exercise 7.9 case study history and physical examination findings

The written History and Physical (H&P) serves several purposes:

• It outlines a plan for addressing the issues which prompted the hospitalization. This information should be presented in a logical fashion that prominently features all of the data that’s immediately relevant to the patient's condition.
• It is a means of communicating information to all providers who are involved in the care of a particular patient.
• It allows students and house staff an opportunity to demonstrate their ability to accumulate historical and examination-based information, make use of their medical fund of knowledge, and derive a logical plan of attack.

The H&P is not:

• An instrument designed to torture Medical Students and Interns.
• Meant to cover unimportant/unrelated information.
• Should not require so much time to write that by the time it’s submitted, the information contained within is obsolete!

Knowing what to include and what to leave out will be largely dependent on experience and your understanding of illness and pathophysiology. If, for example, you were unaware that chest pain is commonly associated with coronary artery disease, you would be unlikely to mention other coronary risk-factors when writing the history. As you gain experience, your write-ups will become increasingly focused. You can accelerate the process by actively seeking feedback about all the H&Ps that you create as well as by reading those written by more experienced physicians. Several sample write-ups are presented at the end of this section to serve as reference standards.

The core aspects of the H&P are described in detail below.

"CC: Mr. Smith is a 70 year-old male admitted for the evaluation of increasing chest pain."

The HPI should provide enough information to clearly understand the symptoms and events that lead to the admission. This covers everything that contributed to the patient's arrival in the ED (or the floor, if admission was arranged without an ED visit). Events which occurred after arrival can be covered in a summary paragraph that follows the pre-hospital history.

A commonly used pneumonic to explore the core elements of the chief concerns is OLD CARTS, which includes: O nset, L ocation, D uration, C haracteristics, A ggravating/ A lleviating factors, R elated symptoms, T reatments, and S ignificance.

Some HPIs are rather straight forward. If, for example, you are describing the course of a truly otherwise healthy 40-year-old who presents with 3 days of cough, fever, and shortness of breath as might occur with pneumonia, you can focus on that time frame alone. Writing HPIs for patients with pre-existing illness(es) or a chronic, relapsing problems is a bit trickier. In such cases, it’s important to give enough relevant past history "up front," as having an awareness of this data will provide the contextual information that allows the reader to fully understand the acute issue. If, for example, a patient with a long history of coronary artery disease presents with chest pain and shortness of breath, an inclusive format would be as follows:

"HIP: Mr. S is a 70 yr old male presenting with chest pain who has the following coronary artery disease related history: -Status Post 3 vessel CABG in 2008. -Suffered recurrent chest pain in December 2015, which ultimately lead to catheterization and stent placement in a mid-LAD lesion. -He was re-cathed in January 2017 for recurrent chest pain at rest; at that time there was no significant change compared to catheterization of 12/15. The patient was therefore continued on medical therapy. -Known to have an Ejection Fraction of 40% with inferior and lateral akinesis by echo in January 2018 -No prior episodes of heart failure. -Last Exercise Tolerance Test was performed in January of 2018 and showed no ischemia at 8 METS of activity. Mr. S was in his usual state of health until last week (~ Saturday, November 18), when he began to experience recurrent episodes of chest pain, exactly like his past angina, after walking only one block. This represented a significant change in his anginal pattern, which is normally characterized as mild discomfort which occurs after walking vigorously for 8 or 9 blocks. In addition, 1 day prior to admission, the pain occurred while he was reading a book and resolved after taking a nitroglycerin tablet. It lasted perhaps 1 minute. He has also noted swelling in his legs over this same time period and has awakened several times in the middle of the night, gasping for breath. In order to breathe comfortably at night, Mr. S now requires the use of 3 pillows to prop himself up, whereas in the past he was always able to lie flat on his back and sleep without difficulty. Mr. S is known to have poorly controlled diabetes and hypertension. He currently smokes 2 packs of cigarettes/day. He denies fevers, chills, cough, wheezing, nausea vomiting, recent travel, or sick contacts."

That's a rather complicated history. However, it is obviously of great importance to include all of the past cardiac information "up front" so that the reader can accurately interpret the patient's new symptom complex. The temporal aspects of the history are presented in an easy to follow fashion, starting with the most relevant distant event and then progressing step-wise to the present.

From a purely mechanical standpoint, note that historical information can be presented as a list (in the case of Mr. S, this refers to his cardiac catheterizations and other related data). This format is easy to read and makes bytes of chronological information readily apparent to the reader. While this data is technically part of the patient's "Past Medical History," it would be inappropriate to not feature this prominently in the HPI. Without this knowledge, the reader would be significantly handicapped in their ability to understand the patient's current condition.

Knowing which past medical events are relevant to the chief concern takes experience. In order to gain insight into what to include in the HPI, continually ask yourself, "If I was reading this, what historical information would I like to know?" Note also that the patient's baseline health status is described in some detail so that the level of impairment caused by their current problem is readily apparent.

The remainder of the HPI is dedicated to the further description of the presenting concern. As the story teller, you are expected to put your own spin on the write-up. That is, the history is written with some bias. You will be directing the reader towards what you feel is/are the likely diagnoses by virtue of the way in which you tell the tale. If, for example, you believe that the patient's chest pain is of cardiac origin, you will highlight features that support this notion (e.g. chest pressure with activity, relieved with nitroglycerin, preponderance of coronary risk factors etc.). These comments are referred to as "pertinent positives." These details are factual and no important features have been omitted. The reader retains the ability to provide an alternative interpretation of the data if he/she wishes. A brief review of systems related to the current complaint is generally noted at the end of the HPI. This highlights "pertinent negatives" (i.e. symptoms which the patient does not have). If present, these symptoms might lead the reader to entertain alternative diagnoses. Their absence, then, lends support to the candidate diagnosis suggested in the HPI. More on the HPI can be found here: HPI .

Occasionally, patients will present with two (or more) major, truly unrelated problems. When dealing with this type of situation, first spend extra time and effort assuring yourself that the symptoms are truly unconnected and worthy of addressing in the HPI. If so, present them as separate HPIs, each with its own paragraph.

This includes any illness (past or present) that the patient is known to have, ideally supported by objective data. Items which were noted in the HPI (e.g. the cardiac catheterization history mentioned previously) do not have to be re-stated. You may simply write "See above" in reference to these details. All other historical information should be listed. Important childhood illnesses and hospitalizations are also noted.

Detailed descriptions are generally not required. If, for example, the patient has hypertension, it is acceptable to simply write "HTN" without providing an in-depth report of this problem (e.g. duration, all meds, etc.). Unless this has been a dominant problem, requiring extensive evaluation, as might occur in the setting of secondary hypertension.

Also, get in the habit of looking for the data that supports each diagnosis that the patient is purported to have. It is not uncommon for misinformation to be perpetuated when past write-ups or notes are used as the template for new H&Ps. When this occurs, a patient may be tagged with (and perhaps even treated for) an illness which they do not have! For example, many patients are noted to have Chronic Obstructive Pulmonary Disease (COPD). This is, in fact, a rather common diagnosis but one which can only be made on the basis of Pulmonary Function Tests (PFTs). While a Chest X-Ray and smoking history offer important supporting data, they are not diagnostic. Thus, "COPD" can repeatedly appear under a patient's PMH on the basis of undifferentiated shortness of breath coupled with a suggestive CXR and known smoking history, despite the fact that they have never had PFTs. So, maintain a healthy dose of skepticism when reviewing notes and get in the habit of verifying critical primary data.

Past Surgical History (PSH):

All past surgeries should be listed, along with the rough date when they occurred. Include any major traumas as well.

Medications (MEDS):

Includes all currently prescribed medications as well as over the counter and non-traditional therapies. Dosage, frequency and adherence should be noted.

Allergies/Reactions (All/RXNs):

Identify the specific reaction that occurred with each medication.

Social History (SH): This is a broad category which includes:

• Alcohol Intake: Specify the type, quantity, frequency and duration.
• Cigarette smoking: Determine the number of packs smoked per day and the number of years this has occurred. When multiplied this is referred to as "pack years." If they’ve quit, make note of when this happened.
• Other Drug Use: Specify type, frequency and duration.
• Marital/Relationship Status; Intimate Partner Violence (IPV) screen.
• Sexual History, including: types of activity, history of STIs.
• Work History: type, duration, exposures.
• Other: travel, pets, hobbies.
• Health care maintenance: age and sex appropriate cancer screens, vaccinations.
• Military history, in particular if working at a VA hospital.

Family History (FH): This should focus on illnesses within the patient's immediate family. In particular, identifying cancer, vascular disease or other potentially heritable diseases among first degree relatives

Obstetrical History (where appropriate):

Included the number of pregnancies, live births, duration of pregnancies, complications. As appropriate, spontaneous and/or therapeutic abortions. Birth control (if appropriate).

Review of Systems (ROS): As mentioned previously, many of the most important ROS questions (i.e. pertinent positives and negatives related to the chief concern) are generally noted at the end of the HPI. The responses to a more extensive review, covering all organ systems, are placed in the "ROS" area of the write-up. In actual practice, most physicians do not document an inclusive ROS. The ROS questions, however, are the same ones that are used to unravel the cause of a patient's chief concern. Thus, early in training, it is a good idea to practice asking all of these questions so that you will be better able to use them for obtaining historical information when interviewing future patients. A comprehensive list can be found here: ROS

Physical Exam: Generally begins with a one sentence description of the patient's appearance. Vital Signs: HEENT: Includes head, eyes, ears, nose, throat, oro-pharynx, thyroid. Lymph Nodes: Lungs: Cardiovascular: Abdomen: Rectal (as indicated): Genitalia/Pelvic: Extremities, Including Pulses:

Neurologic:

• Mental Status
• Cranial Nerves
• Sensory (light touch, pin prick, vibration and position)
• Reflexes, Babinski
• Coordination
• Observed Ambulation

Lab Results, Radiologic Studies, EKG Interpretation, Etc.:

Assessment and Plan:

It's worth noting that the above format is meant to provide structure and guidance. There is no gold standard, and there’s significant room for variation. When you're exposed to other styles, think about whether the proposed structure (or aspects thereof) is logical and comprehensive. Incorporate those elements that make sense into future write-ups as you work over time to develop your own style

SAMPLE WRITE UP #1

ADMISSION NOTE

CC: Mr. B is a 72 yo man with a history of heart failure and coronary artery disease, who presents with increasing shortness of breath, lower extremity edema and weight gain.

HPI: His history of heart failure is notable for the following:

• First MI was in 2014, when he presented w/a STEMI related to an LAD lesion. This was treated w/a stent. Echo at that time remarkable for an EF 40%.
• Despite optimal medical therapy, he had a subsequent MI in 2016. At that time, cardiac catheterization occlusions in LAD, OMB, and circumflex arteries. No lesions were amenable to stenting. An echo was remarkable for a dilated LV, EF of 20-25%, diffuse regional wall motion abnormalities, 2+MR and trace TR.
• Heart failure symptoms of DOE and lower extremity edema developed in 2017. These have been managed medically with lisinopril, correg, lasix and metolazone.

Over the past 6 months he has required increasing doses of lasix to control his edema. He was seen 2 weeks ago by his Cardiologist, Dr. Johns, at which time he was noted to have worsening leg and scrotal edema. His lasix dose was increased to 120 bid without relief of his swelling.

Over the past week he and his wife have noticed a further increase in his lower extremity edema which then became markedly worse in the past two days. The swelling was accompanied by a weight gain of 10lb in 2 days (175 to 185lb) as well as a decrease in his exercise tolerance. He now becomes dyspneic when rising to get out of bed and has to rest due to SOB when walking on flat ground. He has 2 pillow orthopnea, but denies PND.

Denies CP/pressure, palpitations or diaphoresis. Occasional nausea, but no vomiting. He eats normal quantities of food but does not salt or fluid intake. He also admits to frequently eating canned soup, frozen meals, and drinking 6-8 glasses liquid/day. He has increased urinary frequency, but decreased total amount of urine produced. He denies urinary urgency, dysuria or hematuria. He has not noted cough, sputum, fever or chills. He states he has been taking all prescribed medications on most days – missing a few (? 2-3) doses a week.

SAMPLE WRITE-UP #2

ADMISSION NOTE CC: Mr. S is a 65-year-old man who presents with 2 concerns: 1. Acute, painless decline in vision 2. Three day history of a cough.

HPI: 1. Visual changes: Yesterday morning, while eating lunch, the patient had the sudden onset of painless decrease in vision in both eyes, more prominent on the right. Onset was abrupt and he first noted this when he "couldn't see the clock" while at a restaurant. He also had difficulty determining the numbers on his cell phone. He denied pain or diplopia. Did not feel like a “curtain dropping” in front of his eyes. He had nausea and vomiting x2 yesterday, which has resolved. He did not seek care, hoping that the problem would resolve on its own. When he awoke this morning, the same issues persisted (no better or worse) and he contacted his niece, who took him to the hospital. At baseline, he uses prescription glasses without problem and has no chronic eye issues. Last vision testing was during visit to his optometrist 2 year ago. Notes that his ability to see things is improved when he moves his head to bring things into better view. Denies dizziness, weakness, headache, difficulty with speech, chest pain, palpitations, weakness or numbness. No history of atrial fibrillation, carotid disease, or heart disease that he knows of.

2. Cough: Patient has history of COPD with 60+ pack year smoking history and most recent PFT's (2016) consistent with moderate disease. Over the past few days he has noted increased dyspnea, wheezing, and sputum production. Sputum greenish colored. He uses 2 inhalers, Formoterol and Tiotropium every day and doesn’t miss any dosages. He was treated with antibiotics and prednisone a few years ago when he experienced shortness of breath. He has not had any other breathing issues and no hospitalizations or ED visits. Denies hemoptysis, fevers, orthopnea, PND, chest pain or edema.

ED course: given concern over acute visual loss and known vascular disease, a stroke code was called when patient arrived in ER. Neurology service evaluated patient and CT head obtained. Data was consistent with occipital stroke, which occurred > 24 hours ago. Additional details re management described below.

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Clinical pearls, case study: a woman with type 2 diabetes and severe hypertriglyceridemia sensitive to fat restriction.

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Deborah Thomas-Dobersen; Case Study: A Woman With Type 2 Diabetes and Severe Hypertriglyceridemia Sensitive to Fat Restriction. Clin Diabetes 1 October 2002; 20 (4): 202–203. https://doi.org/10.2337/diaclin.20.4.202

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L.S. is a 52-year-old Caucasian woman who was diagnosed with type 2 diabetes in 1988. She developed hypertriglyceridemia 3 years later and hypertension 9 years later. Other medical problems include obesity and diverticulosis. She presents now for screening to determine eligibility for a clinical research protocol using once-daily insulin.

Physical exam reveals a height of 64 inches, a weight of 181 lb, a body mass index of 31 kg/m 2 , and a waist circumference of 40 inches. Blood pressure, well controlled on 20 mg lisinopril (Prinivil) daily, is 104/70 mmHg.

Laboratory results reveal a fasting lipid panel as follows: total cholesterol 214 mg/dl, triglycerides 940 mg/dl, direct HDL cholesterol 24 mg/dl, an invalid LDL cholesterol unobtainable because of the hypertriglyceridemia, and a free fatty acid of 1.1 mEq/l (normal range 0.1–0.6 mEq/l). Hemoglobin A 1c (A1C) is 9.5%, and fasting blood glucose (FBG) is 304 mg/dl. When called to discuss the finding of severe hypertriglyceridema, the patient commented that she had previously had fasting triglycerides as high as 3,000 mg/dl.

L.S. is currently taking metformin (Glucophage), 1,000 mg twice daily, and glipizide (Glucatrol XL), 10 mg twice daily, to control her blood glucose. She is also on gemfibrizol (Lopid), 600 mg twice daily, for hypertriglyceridemia and estradiol (Estraderm) for menopause (topical estrogen does not induce hypertriglyceridemia).

What nutritional modification would be effective in rapidly lowering serum triglycerides when the patient is at risk of pancreatitis?

What treatment strategies can be employed to lower triglycerides, and how effective are they?

How can nutritional modifications improve insulin resistance?

Type 2 diabetes carries a two- to fourfold excess risk of coronary heart disease. The most common pattern of dyslipidemia in patients with type 2 diabetes is elevated triglycerides and decreased HDL levels. 1 Although coexistent increases in small, dense LDL cholesterol particles—not the triglycerides themselves—may be responsible for the increase in cardiovascular risk, hypertriglyceridemia poses a significant burden on society. 2  

In type 2 diabetes, characterized by insulin resistance and insulin deficiency, the pathophysiology of hypertriglyceridemia is an increased hepatic production of triglycerides as well as a decreased lipoprotein lipase activity leading to slower breakdown of VLDL cholesterol and chylomicrons. 3 The American Diabetes Association (ADA) Clinical Practice Recommendations list serum triglycerides ≥400 mg/dl and an HDL level <45 mg/dl for women as indicative of high risk of coronary heart disease. 1  

By both ADA and National Cholesterol Education Program (NCEP III) guidelines, the first goal for this patient is to lower triglycerides to prevent pancreatitis, which not only can result in hospitalization, but also is potentially lethal. 4 Although L.S. is already on the maximum dose of gemfibrozil, her triglycerides are still inadequately controlled.

With triglycerides in this range, she should be alerted immediately to the fact that any alcohol, even that found in over-the-counter cold remedies can trigger pancreatitis until her serum triglycerides are brought down to a safer range (<500 mg/dl). In addition, a single high-fat meal can also trigger pancreatitis.

A severely restricted fat intake (<10% of daily kcal) can effectively bring down serum triglycerides by 20% per day until triglycerides are <500 mg/dl. A diet in which fat is so severely restricted usually brings about weight loss as well. A loss of 2.5 kg body weight would bring an expected 15–20% decrease in serum triglycerides. In addition, aerobic exercise can help to lower serum triglycerides by 10–15%. 2  

Interventions to further decrease serum triglycerides to <200 mg/dl, increase HDL to 45 mg/dl, and decrease LDL to <100 mg/dl should be attempted to decrease the risk of coronary heart disease.

At the first clinic visit, L.S. was advised of the risk of pancreatitis and advised to forego any alcohol and to adhere to severe fat restriction until she has a fasting serum triglyceride level <400 mg/dl. She and her husband are both from the South, and their traditional Southern fare used quite a bit of salt pork, which deleteriously augmented the saturated as well as total fat in her diet. She had been advised to “watch her weight” when her triglycerides were in the 3,000 mg/dl range, but she had been unable to follow that recommendation.

Between clinic visits, L.S. was given written information about a low-fat (10% of kcal) diet, including lists of foods to restrict and foods to encourage until a more thorough meal plan could be developed based on an assessment of her previous dietary patterns. She was advised that this was a short-term, severe dietary change. She had already instituted an exercise program, walking for 1 hour, five times a week regularly.

Two weeks later, when L.S. returned to clinic after following the suggested fat restriction, her lab results showed the following lipid profile: serum total cholesterol 193 mg/dl, serum triglycerides 355 mg/dl, direct HDL cholesterol 32 mg/dl, and LDL cholesterol 90 mg/dl. Her A1C had dropped to 8.8% with no change in therapy for her diabetes, and her FBG was 158 mg/dl. Her fasting free fatty acid level was 0.7 mEq/l. Her weight had dropped by 3 lb.

At this visit, medical nutrition therapy (MNT) was initiated, and the patient was put on 10 units of 75/25 insulin before dinner.

Six weeks later, her A1C had dropped further, to 7%, her FBG was 110 mg/dl, and her weight was down another 2 lb. Her lipid profile was as follows: total cholesterol 181 mg/dl, triglycerides 299 mg/dl, direct HDL cholesterol 32 mg/dl, and LDL cholesterol 89 mg/dl. Her fasting free fatty acid level was now 0.6 mEq/l, the upper level of normal. Meal plan records showed that she was consuming ∼1,500 kcal/day and getting ∼25% of daily kcal from fat.

Commonly, controlling hyperglycemia leads to a decrease in triglycerides. 1 However, in this patient, the clearing of serum triglycerides, the restricted saturated fat, and the weight loss had a substantial impact on improving glucose tolerance without adding further diabetes oral agents. Studies have shown that dietary fat, primarily saturated fat, has adverse effects on insulin sensitivity. 5 Restricting fat intake, especially saturated fat, resulted in a better metabolic profile in regard to both glucose tolerance and fasting serum triglycerides.

Lifestyle changes had been recommended previously; why was L.S. successful this time when she hadn’t been before? The patient offered the following comments when asked this question.

“I was handed written information, but concern about the numbers (hypertriglyceridemia) was never conveyed.”

“They tell you what you need to do, but not how or why to do it.”

“No one sat down and talked with me. I never received individualized attention.”

“If my triglycerides were potentially harmful, why did they not see me sooner than 3 months? Three months was the usual time between visits and again they conveyed no concern.”

In previous attempts to encourage this patient make lifestyle changes, the compliance approach was used, but the benefits of self-care, the costs of not complying, the susceptibility to pancreatitis and cardiovascular disease, and the severity of such elevated triglycerides were not conveyed. A referral to an educator, time spent in assessing eating patterns and teaching alternatives, and more frequent visits or follow-up serve to convey the importance of recommended lifestyle changes. MNT coupled with an empowerment approach through which patients are the primary decision makers is important.

Although lifestyle changes are always recommended as first-line therapy, the approach to helping patients achieve these lifestyle changes in busy office practices is too often insufficient. A new Medicare benefit effective January 2002 allows patients with diabetes access to insurance coverage for MNT. Evidence-based research shows that MNT provided by a registered dietitian experienced in the management of diabetes is clinically effective. 6  

Reducing dietary fat improves body weight, which in turn improves glucose tolerance and hypertriglyceridemia. 7 – 9  

There is evidence that saturated fat may elevate plasma glucose by way of increasing insulin resistance.

MNT for hypertriglyceridemia may be divided into three parts:

  1. When fasting triglycerides are ≥1,000 mg/dl, restrict dietary fat to 10% of kcal until fasting triglycerides fall to <500 mg/dl.

  2. For fasting triglycerides between 1,000 and 500 mg/dl, a ) reduce saturated fat to <7% of energy and dietary cholesterol to 200 mg/day; b ) increase viscous (soluble) fiber to 10–25 mg/day; c ) encourage modest weight loss (5–7% of body weight); and d ) increase physical activity. 10 Monounsaturated fats or carbohydrates can be used to substitute for the decrease in saturated fats.

  3. For fasting triglycerides <500 mg/dl, encourage weight loss and a decrease in simple sugars in addition to the above reduction in saturated fat.

Deborah Thomas-Dobersen, RD, MS, CDE, is a professional research assistant and certified diabetes educator in the Endocrinology Department of the University of Colorado Health Sciences Center in Aurora.

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7.3 General Endocrine System Assessment

When evaluating a client for possible disorders of the endocrine system, the nurse assesses individual and population risk factors, cultural influences, and socioeconomic factors that may impact health. Client health history, physical examination findings, and diagnostic test results also play an important role in endocrine system assessment.

Risk Factors

Understanding the risk factors associated with endocrine system alterations is important for identifying potential endocrine disorders facing many individuals. Risk factors can be diverse and vary depending on the specific endocrine disorder or condition.

Common risk factors for endocrine system alterations include the following:

• Age: Many endocrine disorders, such as diabetes and thyroid disorders, are more common in certain age groups. [1] For example, type 1 diabetes is often diagnosed in childhood, while type 2 diabetes is more common in adults. Thyroid disorders are also more prevalent with age.
• Genetics: A family history can increase an individual’s risk. Many endocrine conditions, such as diabetes, have a genetic component. [2]
• Autoimmune Conditions: Autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues, can affect the endocrine system. Conditions like Hashimoto’s thyroiditis and Addison’s disease are autoimmune disorders that impact the thyroid and adrenal glands, respectively. [3]
• Obesity: Obesity is a significant risk factor for type 2 diabetes. It can also lead to insulin resistance, a condition where the body’s cells don’t respond effectively to insulin. [4]
• Environmental Factors: Exposure to environmental toxins, such as certain chemicals or radiation, can increase the risk of endocrine disorders. For example, exposure to radiation can increase the risk of thyroid cancer. [5]
• Diet and Lifestyle: Poor dietary habits and sedentary lifestyles can contribute to endocrine disorders. Unhealthy eating habits and lack of physical activity can lead to conditions like obesity, which is a risk factor for diabetes. [6]
• Stress: Chronic stress can disrupt the endocrine system, particularly the hypothalamic-pituitary-adrenal (HPA) loop. This disruption can lead to conditions like adrenal fatigue and alterations in cortisol levels. [7]
• Medications: Some medications, such as corticosteroids, can affect the functioning of the endocrine system. Long-term use of these drugs can lead to conditions like Cushing’s syndrome. [8]
• Pregnancy: Pregnancy can lead to temporary alterations in the endocrine system, such as gestational diabetes or thyroid dysfunction. Some women may develop permanent endocrine disorders following pregnancy. [9]
• Underlying Health Conditions: Some preexisting health conditions, such as polycystic ovary syndrome (PCOS) or pituitary tumors, can affect the endocrine system directly or indirectly. [10]

Cultural Factors

Cultural risk factors refer to aspects of a person’s culture or lifestyle that can contribute to an increased risk of endocrine-related health issues. Cultural dietary practices can have a significant impact on endocrine health. For example, high consumption of sugary foods and processed carbohydrates can increase the risk of obesity and type 2 diabetes. In contrast, diets rich in fruits, vegetables, and whole grains can have a protective effect. Some cultures also have dietary restrictions or fasting practices as part of their religious or cultural traditions. These practices can impact blood sugar regulation and management. [11]

Norms regarding alcohol and substance use can vary significantly across cultural groups. For example, some cultural groups abstain from alcohol and drug use, whereas other cultural groups may commonly use alcohol and other substances. Excessive alcohol consumption and substance use can harm the endocrine system, leading to conditions like liver damage or hormone imbalances. Additionally, some cultures may rely heavily on traditional medicines and healing practices, which is important to consider as the treatment plan is developed. [12] Nurses must consider cultural factors when developing a nursing care plan.

Socioeconomic Factors

Socioeconomic status can affect access to health care, nutrition, and education. Lower socioeconomic status is associated with a higher risk of endocrine-related conditions, such as obesity, diabetes, and cardiovascular diseases. People with lower incomes or inadequate health insurance may delay seeking medical attention, miss regular check-ups, or forgo preventive care. This can result in undiagnosed or poorly managed endocrine disorders. Additionally, many endocrine disorders require lifelong medication management. The cost of medications can be a barrier for those with limited financial resources. Skipping or rationing medication due to cost concerns can lead to poor disease control and complications. [13]

Individuals with low-income levels may have limited access to nutritious foods, which can contribute to obesity and diet-related endocrine disorders like type 2 diabetes. Food insecurity can also lead to irregular meal patterns and unhealthy eating habits. Additionally, socioeconomic factors can impact opportunities for physical activity. People in lower-income communities may have limited access to safe recreational spaces, gym facilities, or affordable sports activities. A sedentary lifestyle is also a risk factor for endocrine disorders. [14]

Education levels are closely tied to socioeconomic status. Individuals with lower levels of education may have less health literacy and awareness about endocrine disorders, preventive measures, and effective management of these conditions. Lower health literacy levels can lead to misunderstandings about endocrine alterations and the importance of adherence to treatment plans. [15]

General Endocrine System Assessment

A comprehensive evaluation of overall health status is important due to identifying potential alterations within the endocrine system. The endocrine system controls many different body functions, and signs and symptoms of potential dysfunction can be seen in many different areas. Endocrine dysfunction can result in improper hormone regulation, which subsequently can impede growth, metabolism, mood, and other imbalances within the body.

Health History

Several health history factors can significantly impact endocrine function. Examination of current symptoms, family history, medications and allergies, as well as past medical history, including surgeries and radiation therapy, may help identify undiagnosed endocrine disorders.

The health history should begin by assessing current symptoms. Common endocrine symptoms, such as unexplained weight changes; fatigue; mood swings; and changes in appetite, thirst, or urine output, can provide valuable clues to potential endocrine disorders. Additionally, menstrual irregularities and reproductive disorders can indicate endocrine abnormalities. It is important to also note the client’s current and past medications, especially those affecting hormones (e.g., steroids, birth control pills), that can influence endocrine function. Finally, exposure to substances that can disrupt normal endocrine function should be examined. Examples of endocrine disruptors include occupational exposure to chemicals or pesticides, fabrics treated with flame retardants, and ingestion of soy-based products containing phytoestrogens. [16]

Physical Assessment

Conducting a thorough examination of each body system provides the nurse with cues regarding potential endocrine disorders. Early identification of abnormal findings and notification of the health care provider can lead to prompt intervention. Table 7.3 summarizes abnormal findings in each body system that can potentially be related to the endocrine system.

Table 7.3. Abnormal Findings by Body System Potentially Related to the Endocrine System [17] , [18]

Diagnostic Testing

The aim of diagnostic testing is to identify abnormalities or dysfunction related to endocrine gland functioning and the release of hormones. Health care providers order diagnostic tests based on signs and symptoms exhibited that reflect potential endocrine disorders.

Laboratory Studies

One of the most definitive signs of an endocrine alteration is an abnormal hormone level in blood tests. Read more about specific hormone blood tests under each endocrine system alteration discussed later in this chapter.

Imaging Studies

Imaging studies such as an ultrasound, CT scan, MRI, and nuclear medicine scan may be used to visualize the endocrine glands and identify structural abnormalities or tumors.

• Young, W. F. (2022, September). Effects of aging on the endocrine system. Merck Manual Professional Version. https://www.merckmanuals.com/home/hormonal-and-metabolic-disorders/biology-of-the-endocrine-system/effects-of-aging-on-the-endocrine-system ↵
• Centers for Disease Control and Prevention. (2022, April 5). Diabetes risk factors. https://www.cdc.gov/diabetes/basics/risk-factors.html ↵
• National Institute of Environmental Health Sciences. (2022, May 31). Autoimmune diseases . National Institutes of Health. https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm#:~:text=Introduction,and%20even%20turning%20life%2Dthreatening ↵
• United States Environmental Protection Agency. (2023, March 13). Overview of endocrine disruption. https://www.epa.gov/endocrine-disruption/overview-endocrine-disruption ↵
• Endocrine Society. (2022, January 25). Adrenal fatigue. https://www.endocrine.org/patient-engagement/endocrine-library/adrenal-fatigue ↵
• Khowaja, A., Alkhaddo, J. B., Rana, Z., & Fish, L. (2018). Glycemic control in hospitalized patients with diabetes receiving corticosteroids using a neutral protamine hagedorn insulin protocol: A randomized clinical trial. Diabetes Therapy, 9 , 1647–1655. https://doi.org/10.1007/s13300-018-0468-3 ↵
• Mora, N., & Golden, S. H. (2017). Understanding cultural influences on dietary habits in Asian, Middle Eastern, and Latino patients with type 2 diabetes: A review of current literature and future directions. Current Diabetes Reports, 17 (126). https://doi.org/10.1007/s11892-017-0952-6 ↵
• Kyrou, I., Tsigos, C., Mavrogianni, C., et al. (2020). Sociodemographic and lifestyle-related risk factors for identifying vulnerable groups for type 2 diabetes: A narrative review with emphasis on data from Europe. BMC Endocrine Disorders 20 , 134. https://doi.org/10.1186/s12902-019-0463-3 ↵
• Endocrine Society. (n.d.). Hormones and endocrine disrupting chemicals: What you need to know [Handout]. https://www.endocrine.org/-/media/endocrine/files/patient-engagement/hormones-and-series/hormones_and_edcs_what_you_need_to_know.pdf ↵
• Crafa, A., Condorelli, R. A., Cannarella, R., Aversa, A., Calogero, A. E., & La Vignera, S. (2022). Physical examination for endocrine diseases: Does it still play a role? Journal of Clinical Medicine, 11 (9), 2598. https://doi.org/10.3390/jcm11092598 ↵
• National Institute of Diabetes and Digestive and Kidney Diseases. (n.d.). Endocrine diseases. National Institutes of Health. https://www.niddk.nih.gov/health-information/endocrine-diseases ↵

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JAMES MACDONALD, MD, MPH, MARIE SCHAEFER, MD, AND JUSTIN STUMPH, DO

Am Fam Physician. 2021;103(9):539-546

Related editorial : Clinical Considerations in Caring for Transgender Athletes

Author disclosure: No relevant financial affiliations.

The preparticipation physical evaluation (PPE) is a common reason for young athletes to see a primary care physician. An annual PPE is required by most state high school athletic associations for participation in school-based sports, although there is limited evidence to support its effectiveness for detecting conditions that predispose athletes to injury or illness. In 2019, the American Academy of Pediatrics, with representatives from the American Academy of Family Physicians and other organizations, published updated PPE recommendations (PPE5). According to the guideline, the general goals of the PPE are determining general physical and psychological health; evaluating for life-threatening or disabling conditions, including risk of sudden cardiac arrest and other conditions that may predispose the athlete to illness or injury; and serving as an entry point into the health care system for those without a medical home or primary care physician. The guideline recommends that the evaluation take place in the physician's office rather than in a group setting. The PPE should include a structured physical examination that focuses on the cardiovascular, musculoskeletal, and neurologic systems. Screening for depression, anxiety disorders, and attention-deficit/hyperactivity disorder is also recommended. Clinicians should recognize any findings suggestive of the relative energy deficiency in sport syndrome. Additional consideration is required to address the needs and concerns of transgender athletes and athletes with physical and intellectual disabilities. Finally, guidelines have been published regarding return to play for athletes who have had COVID-19.

Approximately 60 million children and adolescents, including 7.9 million high school students, participate in some form of sports in the United States. 1 , 2 The preparticipation physical evaluation (PPE) has long been used to determine medical eligibility for youth sports in the United States, with the first PPE recommendations published in 1992 by a task force of five physician organizations. 3

The intent of the PPE is to promote the health and safety of young athletes participating in training and competition and to identify those who may need additional evaluation before participation or, rarely, exclusion from sports. The American Academy of Pediatrics has published the fifth edition of the most comprehensive, up-to-date guideline on the PPE, referred to as PPE5. 4 It contains consensus recommendations from representatives of multiple stakeholder medical societies, including the American Academy of Family Physicians, American Academy of Pediatrics, American College of Sports Medicine, American Medical Society for Sports Medicine, American Orthopaedic Society for Sports Medicine, and American Osteopathic Academy of Sports Medicine. 4 In addition to information about physical examinations, the PPE5 contains new recommendations regarding mental health in athletes. It also addresses the specific needs of certain groups, including athletes experiencing relative energy deficiency, transgender athletes, and athletes with disabilities. 4

Controversies and Concerns

A long-standing debate has surrounded the use of the PPE. This is primarily because there is limited evidence to support its effectiveness for detecting conditions that predispose athletes to injury or illness. 5 , 6

Another concern is that requiring a PPE may be a barrier to sports participation, especially in socioeconomically or medically disadvantaged communities in which PPEs may not be readily available. 4 Even for individuals with medical insurance, PPEs may be an out-of-pocket expense (Z02.5 is the current International Classification of Diseases [ICD] code for a sports-related PPE 7 ). Billing for the PPE as though it is a routine health maintenance visit may allow for coverage; however, doing so may preclude additional covered preventive visits for the patient during the calendar year. It may also be difficult to incorporate a PPE into a routine wellness visit because of time limitations, lack of a standardized approach, and gaps in physician knowledge related to appropriate questions and recommended examinations. 8

Despite these ongoing debates, PPEs are widely performed. The Special Olympics requires a PPE for all athletes before participation. 4 PPEs are recommended by the National Federation of State High School Associations and the National Collegiate Athletic Association. 9 , 10 Most state high school athletic associations require an annual PPE for participation in school-based athletics 11 ; however, the PPE5 recommends a full evaluation every two to three years with annual updates only as needed to address potential areas of concern. 4 Clinicians should be aware of their own state's recommendations regarding the required frequency of PPEs. 4

General Goals and Recommendations

The general goals of a PPE are determining the general physical and psychological health of the athlete; evaluating for life-threatening or disabling conditions, including risk of sudden cardiac arrest and other conditions that may predispose the athlete to illness or injury; and serving as an entry point into the health care system for those without a medical home or primary care physician. 4

The PPE5 and the American Academy of Family Physicians recommend that the PPE take place in the athlete's primary care medical home, during an office visit and not in a group setting. 4 , 12 Despite the insurance coverage limitations noted previously, the PPE may be an athlete's only contact with a physician in any given year, allowing an opportunity for the physician to incorporate routine preventive health care into the visit when possible. 5 , 13

Medical History

The medical history is an important component of the PPE. The history alone can detect up to 88% of general medical conditions and 67% to 75% of musculoskeletal conditions pertinent to sports participation. 14 Providing history forms before evaluation allows the athlete and family time to complete an accurate medical history and to reduce errors. The PPE5 recommends using forms that are simpler and shorter than those previously recommended 4 ( Table 1 15 ) .

A parent or guardian should be involved in completion of the history form. A study of high school athletes undergoing PPEs found that only about 19% of students' answers were in concordance with their parents' responses. 16

Of particular importance is personal history of possible cardiovascular symptoms (e.g., exertional chest pain) or family history of premature serious cardiac conditions or sudden death before 50 years of age. 4 Other inquiries about potentially disqualifying conditions include a history or symptoms of spinal injuries, brachial plexus injuries, concussions, neurologic disorders, diabetes mellitus, loss of a paired organ (e.g., kidney), skin conditions, asthma or exercise-induced bronchospasm, hematologic disorders, and musculoskeletal injuries. 4 Answers to these questions may prompt consideration for further evaluation through a structured examination or additional testing to determine eligibility for sports participation.

The history should also include questions about mental health, substance use, and high-risk behavior. These issues should ideally be discussed with the athlete alone to increase the likelihood of honest answers. 17

Physical Examination and Testing

Elevated blood pressure and visual acuity problems are among the most common abnormalities noted during the physical examination portion of the PPE. 4 , 18 The evidence is lacking for performing any other routine screening tests in asymptomatic athletes as part of the PPE, but expert consensus recommends a structured physical examination. 4 In particular, the American Heart Association and American College of Cardiology provide recommendations that should be followed with regard to various cardiovascular abnormalities, considering intensity of the sport and disease severity with the potential of sudden cardiac death. 19

The cardiovascular portion of the examination should focus on identifying concerning findings, such as pathologic heart murmurs or the stigmata of Marfan syndrome (e.g., long arms and legs, tall and thin body, flexible joints). 19 Worldwide, there is considerable debate about whether electrocardiography or echocardiography should be part of the PPE. 20 , 21 The American Heart Association continues to recommend its 14-element cardiovascular history and physical examination as opposed to electrocardiogram screening ( Table 2 ) . 22 It is unknown whether detection of disease by these screening tests leads to a reduction in sudden cardiac deaths. 23

When a condition is identified that may restrict an athlete's medical eligibility for participating in a certain sport, consultation with a specialist may be warranted. If it is determined that there is risk to participation, shared decision-making should occur, including a discussion among the athlete, the athlete's family, and an interdisciplinary health care team about the risks and benefits of participation. It may be appropriate to consider an alternative activity in which the athlete could participate. 19 It is also important to consider that athletes restricted from participating in their chosen sport may be upset; they should be monitored and provided with appropriate emotional support.

Mental Health Screening

Mental health is increasingly recognized as a major issue for young athletes and is emphasized in the PPE5. 4 In addition to screening for and evaluating mental health disorders, the PPE can be used as an opportunity to screen for and educate patients on bullying, hazing, sexual abuse, and sleep disorders, all of which can affect mental health in athletes. 17 , 24

DEPRESSION AND ANXIETY

The PPE5 recommends screening athletes for depression and anxiety disorders and maintaining an awareness of local resources that can assist patients. 4 Suggested screening tools include the Patient Health Questionnaire-9 ( https://www.mdcalc.com/phq-9-patient-health-questionnaire-9 ) and the Generalized Anxiety Disorder-7 scale ( https://www.mdcalc.com/gad-7-general-anxiety-disorder-7 ). 4

Illness and sports-related injury can cause psychological distress, and conversely, psychological distress may be an independent risk factor for injury. 25 Depression is also a risk factor for suicide, which is the second-leading cause of death among all college students but only the fourth-leading cause of death in college athletes, suggesting that sports participation may have a protective effect. 26 , 27 In the absence of suicidal ideation, depression or anxiety should not preclude sports participation, although sports participation should not delay appropriate treatment.

ATTENTION-DEFICIT/HYPERACTIVITY DISORDER

Attention-deficit/hyperactivity disorder is another common condition affecting athletes. It is not a disqualifier for sports participation, but academic accommodations and treatment should be provided as needed after diagnosis. At the collegiate and elite level, a therapeutic use exemption may be required for patients taking attention-deficit/hyperactivity disorder medications at the same time as sports participation. 28 , 29

Substance Abuse Screening

Screening should be performed for substance use disorders, including tobacco, vaping/electronic cigarettes, performance-enhancing supplements, alcohol, marijuana, and prescription analgesics. 4 One method for substance abuse screening is the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) tool, which is intended for use in individuals 12 to 21 years of age ( https://crafft.org/ ).

Special Considerations

Female athlete triad and relative energy deficiency in sport.

The female athlete triad (the triad) and relative energy deficiency in sport (RED-S) are syndromes that occur when energy expenditure is disproportionately high relative to caloric intake. The triad refers to girls and women who have long-term manifestations of low energy availability, disordered eating, decreased bone mineral density, and menstrual dysfunction. The RED-S syndrome is characterized by relative energy deficiency (sometimes due to an eating disorder); low bone mineral density; and impaired cardiovascular, immune, and psychological health. 30 , 31 Although it is more often reported in female athletes, the syndrome also occurs in male athletes. 32 There is ongoing discussion about the degree of overlap and differences between RED-S and the triad. 33

Endocrine abnormalities may also occur, resulting in menstrual dysfunction in female athletes and low testosterone levels and erectile dysfunction in male athletes. 30 , 31 , 34 – 36

Screening for the triad and RED-S is challenging because many of its features are not readily apparent until they have progressed to serious clinical concerns. Consequently, it is important to discuss potential early symptoms during the PPE.

Menstrual dysfunction is an important symptom. It is two to three times more common in athletes than nonathletes, with as many as 10% to 15% of female athletes having amenorrhea or oligomenorrhea. 37 Use of hormonal oral contraceptives may mask menstrual dysfunction.

Other findings that suggest the possibility of the triad or RED-S include eating disorders, history of bone stress injuries, symptoms of low testosterone in males, and symptoms of low energy (e.g., fatigue, difficulty in recovering from training). Other conditions that may mimic low-energy symptoms should be excluded, notably pregnancy and iron deficiency anemia.

Treatment of the triad or RED-S includes increasing caloric intake and/or decreasing energy expenditure. In female athletes, normalization of menses suggests that the treatment is working. Taking oral contraceptives, however, restores menses without correcting the underlying energy imbalance. This should not preclude the physician from prescribing oral contraceptives to patients with the triad or RED-S if needed for contraception, assuming no contraindications exist. If sports participation would cause serious harm to the athlete's health or compromise appropriate treatment of the syndrome, disqualification may be considered. 30

TRANSGENDER ATHLETES

Many sports have traditionally been organized by biologic sex rather than gender identification, and policy on sports participation by transgender athletes has been controversial. A safe and supportive relationship should be established between the athlete and physician, ideally before the PPE. It is important to address patients by their preferred pronoun or gender, which can be identified on a history intake form with a simple question (i.e., What pronouns do you use? or How do you identify your gender?). See a previously published article in American Family Physician on caring for transgender patients for more information. 38 An editorial on caring for transgender athletes appears in this issue of American Family Physician . 39

As with all athletes, mental health screening and guidance should be thoroughly discussed during the PPE with transgender athletes. However, clinicians should avoid assuming that any concerns are secondary to being transgender. 40

As part of the PPE, clinicians should be advocates for transgender athletes to promote inclusivity and to support access to sports participation for all. Clinicians can help improve the health care experience for transgender patients by becoming aware of regulations from local sports governing bodies and by advocating for athletes as they navigate these regulations. 41

ATHLETES WITH A DISABILITY

Athletes with a physical or intellectual disability represent a growing number of participants in sports. 42 The Americans with Disabilities Act defines disability as an impairment that limits a major life activity. 43 Common disabilities in athletes include cerebral palsy, blindness, deafness, paralysis, cognitive impairment, amputation, muscular dystrophy, and multiple sclerosis. Athletes with disabilities derive similar benefits from sports participation as other athletes and should be encouraged to participate. 44 , 45

The PPE of athletes with a disability includes the same components as athletes without a disability but may require closer examination of specific systems. Ocular function should be assessed closely because athletes with a disability commonly have poor visual acuity, refractive errors, astigmatism, or strabismus. 46 Assessing the cardiovascular system may require specialty consultation because some underlying disabilities are associated with comorbid congenital heart issues (e.g., patients who have Down syndrome have a high incidence of atrioventricular septal defects). 47 Dermatologic abnormalities should be assessed and discussed with athletes who use wheelchairs or who may lie prone during activity. A comprehensive neuromuscular examination is important for athletes with a disability because they may have difficulty with strength, flexibility, or spasticity or may use prosthetic devices.

The PPE of athletes with a disability should ideally use a multidisciplinary approach, with the athlete's medical specialists and service providers available to help assess the athlete's medical condition and functional abilities and the demands of the sport to determine medical eligibility.

The COVID-19 pandemic poses new challenges to conducting PPEs. Adherence to physical distancing guidelines makes it imperative that PPEs are conducted in the patient's medical home as opposed to group settings. 7

Another challenge relates to cardiovascular risk after COVID-19. Recommendations for addressing return to play after COVID-19 continue to evolve as new evidence accumulates. The National Federation of State High School Associations, American Medical Society for Sports Medicine, and American Academy of Pediatrics are among several organizations recommending that athletes with COVID-19–related illness be evaluated by a medical professional before returning to participation because potential cardiac and pulmonary risks following the disease can occur. 48 – 50 Specific details of this evaluation are beyond the scope of this review but are addressed in interim guidance from the American Medical Society for Sports Medicine. 7

This article updates previous articles by Mirabelli, et al. 51 ; Giese, et al. 52 ; and Kurowski and Chandran . 53

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• v.47(5); 2024 May
• PMC11043226

Timing of Moderate to Vigorous Physical Activity, Mortality, Cardiovascular Disease, and Microvascular Disease in Adults With Obesity

Angelo sabag.

1 Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia

2 Faculty of Medicine and Health, School of Health Sciences, The University of Sydney, Sydney, New South Wales, Australia

Matthew N. Ahmadi

3 Mackenzie Wearables Research Hub @ Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia

Monique E. Francois

4 School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia

Svetlana Postnova

5 School of Physics, The University of Sydney, Sydney, New South Wales, Australia

Peter A. Cistulli

6 Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia

Luigi Fontana

7 Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

8 Faculty of Medicine and Health, Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia

Emmanuel Stamatakis

To assess the association between timing of aerobic moderate to vigorous physical activity (MVPA) and risk of cardiovascular disease (CVD), microvascular disease (MVD), and all-cause mortality in adults with obesity and a subset with obesity and type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS

Participants included adults with obesity (BMI ≥30 kg/m 2 ) and a subset of those with T2D from the UK Biobank accelerometry substudy. Aerobic MVPA was defined as bouts of MVPA lasting ≥3 continuous minutes. Participants were categorized into morning, afternoon, or evening MVPA based on when they undertook the majority of their aerobic MVPA. The reference group included participants with an average of less than one aerobic MVPA bout per day. Analyses were adjusted for established and potential confounders.

The core sample included 29,836 adults with obesity, with a mean age of 62.2 (SD 7.7) years. Over a mean follow-up period of 7.9 (SD 0.8) years, 1,425 deaths, 3,980 CVD events, and 2,162 MVD events occurred. Compared with activity in the reference group, evening MVPA was associated with the lowest risk of mortality (hazard ratio [HR] 0.39; 95% CI 0.27, 0.55), whereas afternoon (HR 0.60; 95% CI 0.51, 0.71) and morning MVPA (HR 0.67; 95% CI 0.56, 0.79) demonstrated significant but weaker associations. Similar patterns were observed for CVD and MVD incidence, with evening MVPA associated with the lowest risk of CVD (HR 0.64; 95% CI 0.54, 0.75) and MVD (HR 0.76; 95% CI 0.63, 0.92). Findings were similar in the T2D subset ( n = 2,995).

CONCLUSIONS

Aerobic MVPA bouts undertaken in the evening were associated with the lowest risk of mortality, CVD, and MVD. Timing of physical activity may play a role in the future of obesity and T2D management.

Graphical Abstract

Introduction

Obesity is a significant and independent risk factor for the development of type 2 diabetes (T2D) ( 1 ), cardiovascular disease (CVD), microvascular disease (MVD) ( 2 ), and premature mortality ( 3 ). These associations are fueled, in part, by obesity-related imbalances in adipokines, chronic inflammation, insulin resistance, and ensuing impaired glucose tolerance ( 4 , 5 ).

Engaging in moderate to vigorous physical activity (MVPA), particularly aerobic activity ( 6 ), is widely acknowledged as a therapeutic strategy for improving cardiometabolic risk factors ( 7 ). Although historically all MVPA, regardless of bout length, has been considered reflective of aerobic activity, very short MVPA bouts may not truly engage the aerobic energy system. Skeletal muscle predominantly relies on anaerobic energy pathways to meet sudden energy demand up to the first 3 min of MVPA, beyond which aerobic metabolism dominates ( 8 ). Recent evidence suggests that accumulating aerobic MVPA bouts is associated with a lower cardiovascular morbidity and mortality risk compared with accumulating shorter nonaerobic bouts ( 9 ).

Because obesity and T2D are associated with circadian misalignment and impaired metabolic processes ( 10 ), particularly during the evening ( 11 ), modulating the timing of MVPA may offset diurnal variations in glucose tolerance and insulin sensitivity ( 12 ), potentially leading to durable improvements in cardiovascular morbidity. Recent randomized trials have indicated that undertaking late-afternoon or evening aerobic exercise yields superior improvements in glucose control than that generated by morning aerobic exercise ( 13 – 15 ). However, it is unclear whether aerobic MVPA timing is associated with longer-term outcomes, such as morbidity and mortality, among individuals with exacerbated diurnal variations in glucose intolerance. Therefore, this study aimed to determine the association between the timing of MVPA, mortality, and incidence of CVD and MVD among adults with obesity and a subset also diagnosed with T2D.

Research Design and Methods

Study participants.

This study included participants from the UK Biobank study, all of whom were enrolled between 2006 and 2010 and provided written informed consent. Ethical approval was obtained from the National Research Ethics Service of the U.K. National Health Service (NHS; ref. no. 11/NW/0382; London, U.K.). Participants underwent physical examinations conducted by trained staff and completed touchscreen questionnaires. The inclusion criteria were as follows: individuals with prevalent obesity (BMI ≥30 kg/m 2 ; ascertained through health linkage of general practitioner records), including those with T2D (ascertained through health linkage of medication prescription history, general practitioner records, and UK Biobank physical examination) ( Supplementary Table 1 ). Exclusion criteria were as follows: individuals with missing covariate data or those experiencing an event within the initial 24 months of follow-up ( 9 , 16 , 17 ). In analyses considering CVD and MVD as outcomes, participants with prevalent CVD (ascertained through self-report and hospital admission records) or MVD (ascertained through hospital admission records) were excluded where appropriate ( Supplementary Fig. 1 ).

Physical Activity Assessment

Between 2013 and 2015, a total of 103,684 participants wore an Axivity AX3 accelerometer (Axivity, Ltd, Newcastle Upon Tyne, U.K.) on their dominant wrist continuously for 24 h per day over a period of 7 days. Standard procedures were used for device calibration, and nonwear periods were detected using established methods ( 18 ). Participants with a minimum of 3 valid wear days, defined as wearing the accelerometer for at least 16 h per day, were included in the analysis. Physical activity intensity was determined in 10-s intervals using a validated machine-learning accelerometer-based two-level random forest classifier. Physical activity was first classified into one of four activity classes: sedentary, standing utilitarian movements (e.g., ironing a shirt, washing dishes), walking (e.g., active commuting, mopping floors), or running/high-energy activities (active play with children). These activity classes were then assigned to one of four activity intensities: sedentary, light, moderate, or vigorous ( 16 , 17 , 19 ). Walking activities were classified as light (an acceleration value of <100 mg), moderate (≥100 mg), or vigorous (≥400 mg) intensity. As described previously ( 9 ), this two-level physical activity classification scheme minimized the possibility of false-positive MVPA from stationary activities with high wrist movement, such as ironing or cleaning dishes, because an activity had to be classified first by level 1 as an ambulatory activity and then by level 2 as moderate or vigorous. Similar to in a previous study ( 20 ), to assess physical activity timing, participants were categorized into morning (6 a.m. to <12 p.m. ), afternoon (12 p.m. to <6 p.m. ), and evening MVPA (6 p.m. to <12 a.m. ) groups based on when the majority of their MVPA occurred in bouts lasting ≥3 min (e.g., participants undertaking 40%, 30%, and 30% of their total MVPA bouts in the morning, afternoon, and evening, respectively, would be assigned to morning MVPA). Although a previous study categorized morning MVPA as 5 a.m. to 11 a.m. , midday-afternoon MVPA as 11 a.m. to 5 p.m. , and evening MVPA as 5 p.m. to 12 a.m. ( 21 ), we elected to categorize participants into one of three 6-h time windows, as per a previous study ( 20 ), to allow for three even 6-h timing windows. The choice of the ≥3-min bout length aimed to better capture aerobic-based MVPA, known for its established benefits in improving cardiometabolic health in adults with obesity ( 22 ), as well as its association with reduced cardiovascular risk ( 9 ). Participants who did not accumulate at least one MVPA bout lasting ≥3 min in the morning, afternoon, or evening were categorized as having no aerobic physical activity bouts, irrespective of the total minutes of physical activity accumulated. Additionally, we calculated the total time spent undertaking MVPA (regardless of bout length) and MVPA accrued from bouts lasting <3 min.

Mortality, CVD, and MVD Ascertainment

Participants were observed through to 30 November 2022, with deaths obtained through linkage with NHS Digital of England and Wales or the NHS Central Register and National Records of Scotland. Inpatient hospitalization data were sourced from the Hospital Episode Statistics for England, the Patient Episode Database for Wales, or the Scottish Morbidity Record for Scotland. Detailed methods for CVD and MVD assessment are outlined in Supplementary Table 2 . In short, CVD was defined as a disease of the circulatory system, excluding hypertension and diseases of the arteries or lymph nodes ( 23 ). MVD was defined as neuropathy, nephropathy, or retinopathy ( 24 ). Follow-up time was calculated as the time in years from accelerometer wear to the first occurrence of event or censoring.

Covariates considered in the analysis included age, sex, smoking status, alcohol intake, fruit and vegetable consumption, sedentary time, total MVPA, sleep duration, education, medication use (cholesterol, antihypertensive, and/or diabetes medication), waist circumference, and prevalent CVD (all-cause mortality analysis only). Complete definitions for all covariates are provided in Supplementary Table 3 .

Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs for all-cause mortality. For CVD and MVD analyses, participants with prevalent CVD (ascertained through self-report and hospital admission records) or MVD (ascertained through hospital admission records) were excluded where appropriate. Additionally, the Fine-Gray subdistribution method was used, treating deaths resulting from non-CVD or non-MVD causes as competing risks when appropriate. Cox proportionality assumptions were assessed using Schoenfeld residuals, with no observed violations. The association between physical activity timing and risk of all-cause mortality, CVD, and MVD was examined, using the “no aerobic bouts” group as the referent. The analysis also included an examination of adjusted 5-year absolute risk and age- and sex-adjusted incidence rate ratios. A dose-response analysis of activity bout frequency and total duration per day was conducted using restricted cubic splines with knots at the 10th, 50th, and 90th percentiles, with the reference group set to zero bouts and minutes per day. Additionally, the association of physical activity timing with each outcome was explored among participants with T2D, with the no aerobic bouts group as the referent.

Sensitivity Analyses

To assess residual confounding, a negative control outcome of death or hospitalization resulting from an accident (excluding cycling, self-harm, and falls) was used as this outcome does not have an explicit mechanistic link to physical activity ( 25 ). If the negative control had an association pattern similar to that of the primary outcomes, it would be more plausible that the associations were due to bias and confounding than to causality. A sensitivity analysis for total mortality was conducted, excluding participants with prevalent CVD and cancer, recognizing that adjustment for prevalent disease may not fully capture confounding. Additional analyses were performed, categorizing the no aerobic bouts group based on meeting or not meeting physical activity guidelines (150 min of MVPA/week). Additional analyses included assessments for total MVPA and MVPA accrued from bouts lasting <3 min. To assess the influence of more even temporal distributions of aerobic MVPA, sensitivity analyses were conducted for mortality, CVD, and MVD incidence in which participants were only assigned to morning, afternoon, or evening MVPA if >50% of their total daily aerobic MVPA occurred during the same time window; otherwise, they were classified as having mixed MVPA, similar to in previous studies ( 21 , 26 ). Additional analyses were conducted, adjusting for LDL and HDL, blood pressure, ethnicity, Townsend deprivation index, season of accelerometer wear time, ethnicity, and employment status. To assess the influence of diet quality on the primary results, a sensitivity analysis was conducted using the dietary quality index ( 23 ). Finally, sensitivity analyses were also conducted to determine the association of the exposure with all outcomes among nonshift workers. All analyses were conducted using R statistical software, and reporting adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guideline.

Data and Resource Availability

The UK Biobank data that support the findings of this study can be accessed by bona fide researchers when applying to access the UK Biobank research resource to conduct health-related research.

Our sample for all-cause mortality included 29,836 participants, with a mean age of 62.2 years (SD ±7.7) at baseline; 53.2% were female, and 46.8% were either current or previous smokers. A total of 2,995 participants had a prevalent T2D diagnosis at baseline. During an average follow-up time of 7.9 years (SD ±0.8), corresponding to 236,387 person-years, 1,425 deaths occurred. The sample for CVD analyses included 24,660 participants with 3,980 events, and the MVD analysis sample included 28,455 participants with 2,162 events ( Supplementary Fig. 1 ). Throughout the week, participants in the reference group averaged fewer than one MVPA bout per day, whereas the morning MVPA group averaged 4.8 bouts per day in the morning, the afternoon MVPA group averaged 5.0 bouts per day in the afternoon, and the evening MVPA group averaged 3.4 bouts per day in the evening. Participant characteristics by physical activity timing group are listed in Table 1 .

Participant characteristics by physical activity timing group

Data are reported as mean (SD) or median (interquartile range) unless otherwise specified.

Adjusted 5-year absolute risk and incidence rate ratio are presented in Supplementary Table 4 . The 5-year all-cause mortality risk was 25–32% lower for participants in the evening MVPA group (1.79%; 95% CI 2.31%, 1.27%) than for those in the morning (2.64%; 95% CI 3.08%, 2.21%) or afternoon MVPA (2.43%; 95% CI 2.81%, 2.05%) group. Participants in the reference group had a 5-year mortality risk of 4.02% (95% CI 4.48%, 3.57%). This pattern was consistent for the 5-year risk of CVD incidence. For MVD incidence, the 5-year risk was similar between morning, afternoon, and evening MVPA groups and 20–24% lower than that of the reference group (e.g., 5-year risk 5.86%; 95% CI 6.59%, 5.13% vs. 7.78%; 95% CI 8.44%, 7.12% for morning MVPA group vs. reference group). Supplementary Figs. 2 and 3 show the dose-response association for aerobic MVPA (≥3 min) bout duration and frequency. Overall, the magnitude of association was stronger for activity bout frequency (e.g., nadir of the curve HR 0.39 for all-cause mortality) than for activity bout duration (nadir of the curve HR 0.59 for all-cause mortality).

All-Cause Mortality

Compared with the reference group, evening MVPA was associated with the lowest mortality risk (HR 0.39; 95% CI 0.27, 0.55) ( Fig. 1 ). Mortality risk was similar for participants in the afternoon (HR 0.60; 95% CI 0.51, 0.71) and morning MVPA (HR 0.67; 95% CI 0.56, 0.79) groups. Among participants diagnosed with obesity and T2D, evening MVPA was again associated with the lowest mortality risk (HR 0.24; 95% CI 0.08, 0.76), followed by afternoon MVPA (HR 0.44; 95% CI 0.28, 0.72) ( Supplementary Fig. 4 ). Notably, there was no observed association for participants in the morning MVPA (HR 0.86; 95% CI 0.57, 1.29) when compared with those in the reference group.

Association of aerobic MVPA bout (≥3 min) timing with all-cause mortality in adults with obesity. No aerobic bouts group represents participants who did not accumulate an average of one or more aerobic MVPA bout (≥3 min) per day over the week.

CVD Incidence

The findings for CVD incidence among participants with diagnosed obesity mirrored the pattern observed for all-cause mortality ( Fig. 2 ). Evening MVPA was associated with the lowest CVD incidence risk (HR 0.64; 95% CI 0.54, 0.75). Morning MVPA was associated with a CVD incidence risk of 0.83 (95% CI 0.76, 0.91), and afternoon MVPA was associated with an incidence risk of 0.84 (95% CI 0.77, 0.91). Among participants with obesity and T2D, evening MVPA was associated with a CVD incidence risk of 0.54 (95% CI 0.34, 0.86), whereas morning and afternoon MVPA showed smaller or null associations, with HRs of 0.73 (95% CI 0.56, 0.94) and 0.85 (95% CI 0.69, 1.06), respectively ( Supplementary Fig. 5 ).

Association of aerobic MVPA bout (≥3 min) timing with the incidence of CVD in adults with obesity. No aerobic bouts group represents participants who did not accumulate an average of one or more aerobic MVPA bouts (≥3 min) per day over the week.

MVD Incidence

Regarding the incidence of nephropathy, neuropathy, and retinopathy, we observed a similar magnitude of association across each of the three physical activity timing groups. Participants in the morning, afternoon, and evening MVPA groups had respective HRs of 0.79 (95% CI 0.70, 0.89), 0.84 (95% CI 0.75, 0.93), and 0.76 (95% CI 0.63, 0.92) ( Fig. 3 ). Among participants with diagnosed T2D, the strength of association was greatest among those in the evening MVPA group (HR 0.52; 95% CI 0.32, 0.86), with null or smaller associations observed in the morning (HR 0.89; 95% CI 0.69, 1.14) and afternoon MVPA groups (HR 0.75; 95% CI 0.59, 0.95) ( Supplementary Fig. 6 ).

Association of aerobic MVPA bout (≥3 min) timing with the incidence of MVD in adults with obesity. No aerobic bouts group represents participants who did not accumulate an average of one or more aerobic MVPA bouts (≥3 min) per day over the week.

Additional and Sensitivity Analyses

The analyses for negative control outcomes suggested that residual and unmeasured confounding likely had a minimal impact on the findings. Specifically, with the negative control outcome, the HR point estimate pattern was inconsistent relative to the main analyses, with no significant associations for any of the physical activity timing groups ( Supplementary Fig. 7 ). Additional analyses controlling for LDL and HDL, blood pressure, ethnicity, Townsend deprivation index, season of accelerometer wear time, ethnicity, employment status, and diet quality index were consistent with our main analyses ( Supplementary Tables 5 and 6 ). Consistent results for all-cause mortality were observed after excluding participants with prevalent CVD and cancer ( n = 5,258) ( Supplementary Fig. 8 ). The mortality risk ranged from 0.48 (95% CI 0.36, 0.65) for evening MVPA to 0.66 (95% CI 0.56, 0.78) for morning MVPA. Furthermore, separating the no aerobic bouts reference group into those meeting and not meeting physical activity guidelines (i.e., <150 min of MVPA/week) showed that meeting physical activity guidelines did not lower the risk of mortality or CVD or MVD incidence, if no aerobic bouts were undertaken ( Supplementary Figs. 9 , 10 , and 11 ). Physical activity timing from bouts lasting <3 min was not associated with a lower risk of mortality or CVD or MVD incidence ( Supplementary Figs. 12 , 13 , and 14 ). The sensitivity analyses in nonshift workers yielded consistent results ( Supplementary Table 7 ). When undertaking sensitivity analyses to control for more even temporal distributions of aerobic MVPA (i.e., participants not undertaking >50% of total aerobic MVPA in one of the three time windows), the results showed that evening MVPA was associated with the lowest incidence rates in all outcomes relative to afternoon and morning MVPA, although similar to the primary analyses, there was little difference between timing groups for MVD. When compared with activity in the mixed MVPA group, evening MVPA was associated with the lowest risk of mortality, and with a similar incidence of CVD. Mixed MVPA was associated with the lowest incidence of MVD ( Supplementary Figs. 15 , 16 , and 17 ). Finally, there was an inverse dose-response association between total MVPA, including both aerobic and nonaerobic bouts (any bout length), and all-cause mortality and CVD and MVD incidence ( Supplementary Fig. 18 ).

Conclusions

Increasing MVPA is a proven strategy for effectively managing cardiometabolic risk in adults with obesity and related disorders. This study, to our knowledge, is the first to determine the associations between objectively measured aerobic MVPA timing, all-cause mortality, and incidence of CVD and MVD in adults with obesity. These findings demonstrate a compelling connection between MVPA timing and a lower risk of morbidity and mortality in adults with obesity, including those with T2D. Building upon previous clinical studies ( 14 , 15 ), our analyses underscore the consistent association of evening MVPA with the lowest risk in mortality, as well as strong associations with the incidence of CVD and MVD, when compared with not undertaking aerobic MVPA bouts. These findings are robust and extend to the subset of participants with T2D, in whom evening MVPA exhibited even more pronounced associations with mortality and cardiovascular morbidity. Sensitivity analyses demonstrated that when controlling for more even temporal distributions of aerobic MVPA, evening MVPA was associated with the greatest reduction in mortality, whereas more evenly spread MVPA was associated with the greatest reduction in MVD incidence. Finally, the frequency of aerobic bouts seems to be a more important factor in their association with mortality and CVD and MVD incidence than the duration of aerobic MVPA. Although additional well-designed clinical studies are required to confirm these findings, these observational data suggest that MVPA timing may play a significant role in optimizing MVPA-related interventions among adults contending with obesity and T2D.

Insulin resistance, a common feature in both obesity and T2D, denotes impairments in insulin-mediated processes such as glucose uptake, metabolism, and storage across diverse cell types, including adipocytes, hepatocytes, and skeletal muscle ( 27 ). Recognized as a key driver of obesity-related disease and aging ( 27 , 28 ), insulin resistance maintains an inverse association with mortality, independent of body weight ( 29 ). Although MVPA per se exhibits an inverse relationship with insulin resistance ( 30 ) and is linked to a lower mortality risk among individuals with or susceptible to T2D ( 31 , 32 ), the potential impact of undertaking MVPA during specific time windows on morbidity and mortality remains unclear. Previous findings have shown that MVPA performed in the evening is associated with the greatest improvement in insulin sensitivity (+25%) among adults with or without T2D ( 20 ). Our findings add to previous reports by showing that when controlling for total MVPA volume, the timing of MVPA, particularly in the evening, is linked with the lowest risk in all-cause mortality. Additionally, the frequency of aerobic MVPA bouts demonstrated a greater inverse association with mortality risk than the total volume of MVPA, highlighting that accumulating bouts of MVPA within specific timing windows or throughout the day may lead to improved health outcomes.

The robust findings of this study are in line with previously published cohort ( 20 ) and clinical studies ( 14 , 15 ). However, it is important to note that these findings differ from those of other similar studies ( 21 ). For example, a recent study by Feng et al. ( 21 ) showed that afternoon or mixed MVPA but not evening MVPA was associated with a lower mortality risk and CVD incidence than morning MVPA. These seemingly disparate findings may be explained by methodological differences. Firstly, Feng et al. selected morning MVPA as the reference group, whereas in our study, the reference group reflected individuals who did not undertake any aerobic MVPA. Furthermore, where our study focused on individuals with obesity, Feng et al. included individuals from the general population with and without obesity, which likely affected the results, given the association between obesity, circadian misalignment, and metabolic dysfunction ( 10 , 11 ). This may explain why, even when undertaking a sensitivity analysis to account for more even temporal distributions of MVPA, evening MVPA was still associated with a greater reduction in mortality and equal reduction in CVD incidence compared with activity in the mixed group.

Among adults with T2D, more than half of all deaths are related to CVD-related events, including myocardial infarction and ischemic stroke ( 33 ). The results of this study showed that when compared with other MVPA timing windows, evening MVPA was associated with the lowest incidence of CVD among adults with obesity, including those with T2D. Although further research is needed to uncover the precise mechanism behind this association, our findings align with previous studies indicating that moderate- or vigorous-intensity exercise performed in the evening may be linked to lower mean arterial blood pressure, whereas among morning exercisers, it was increased ( 34 ). Similarly, research suggests that evening, but not morning, aerobic exercise can lead to significant reductions in clinic and ambulatory blood pressure, through improvements in systemic vascular resistance and vasomotor sympathetic modulation, as demonstrated in a 10-week randomized trial involving 50 men with hypertension ( 35 ).

An important finding of this study was that aerobic MVPA, regardless of timing, was linked to a reduced risk of MVD. Although the sensitivity analyses revealed that mixed MVPA, followed by evening MVPA, was associated with the greatest reduction in MVD incidence, the differences between the timing windows (morning, afternoon, and evening) were minimal and nonsignificant. This finding highlights the role of MVPA in MVD prevention, and may be explained, in part, by the effects of MVPA on hyperglycemia and oxidative stress, which directly contribute to MVD development and progression ( 36 ). For example, findings from a previous clinical study demonstrated that moderate- to vigorous-intensity exercise directly improved microvascular function through improvements in redox balance via increased nitric oxide production ( 37 ). Furthermore, in addition to the well-established effects of chronic exercise on glycemia ( 38 ), it may be that more frequent episodes of contraction-stimulated glucose uptake into skeletal muscle may reduce hyperglycemic excursions throughout the day. This hypothesis is further supported by the significant association between frequency of MVPA and MVD demonstrated in our results. Thus, it seems plausible that these separate mechanistic pathways may have an additive interaction, thereby reducing the risk of MVD; however, additional studies are required to confirm this hypothesis.

For adults with obesity and T2D, where blood glucose regulation is an ongoing challenge, the results of this study highlight that evening MVPA may yield the greatest benefits in terms of cardiovascular morbidity and mortality. Although the precise mechanisms driving this observation remain unclear, the concept of the dawn phenomenon, suggesting that T2D impairs the circadian rhythm, may offer insights. Individuals with T2D, partly due to desynchronized rhythms, often experience relatively better insulin sensitivity and glycemia in the evening, which progressively worsens overnight to the early morning ( 12 , 39 ). Therefore, engaging in MVPA later in the afternoon or evening, when postprandial glycemia is highest and hepatic insulin sensitivity begins to decline, may elicit the greatest metabolic benefits by directly influencing these pathways and leading to lower morning fasting glucose levels ( 12 ). Additionally, because β-cell function and glucose tolerance are reduced in the circadian evening ( 11 ), particularly in individuals with T2D, MVPA at this time may improve β-cell function when it is needed most. Additional well-designed clinical studies are required to delve deeper into these findings; however, this theory finds support, in part, in a recent prospective study and meta-analysis indicating that MVPA/exercise performed later in the day was associated with the greatest improvements in glucose control ( 13 , 40 ).

Strengths and Limitations

Strengths of our study include the large sample of participants with obesity and a subset concurrently diagnosed with T2D, which allowed for an in-depth exploration of associations with objectively measured physical activity timing using accelerometer-based wearable devices. The extended follow-up duration was instrumental in mitigating the risk of reverse causality by excluding participants with pre-existing CVD or MVD or events within the initial 2 years of follow-up. Despite these robust measures, the potential for reverse causation stemming from prodromal disease and unmeasured or residual confounding cannot be entirely ruled out because of the observational design of the study. However, our use of negative control outcomes suggests minimal impact on our observed associations. There was a median lag of 5.5 years between the UK Biobank baseline, when covariate measurements were taken, and the accelerometry study, although covariates remained generally stable over time, except for medication. The UK Biobank had a low response rate; however, previous work indicates that this factor of poor representativeness does not materially influence associations between physical activity and all-cause or CVD mortality ( 41 ).

In summary, our findings underscore the significant health benefits associated with evening MVPA among adults with or at risk of T2D. The results of this study emphasize that beyond the total volume of MVPA, its timing, particularly in the evening, was consistently associated with the lowest risk of mortality relative to other timing windows. Although future trials and device-based cohort studies are required to further explore MVPA timing as a potential factor in lifestyle interventions targeting cardiometabolic disease management, the available evidence suggests that evening MVPA may be a suitable therapeutic strategy.

This article contains supplementary material online at https://doi.org/10.2337/figshare.25306231 .

Article Information

Acknowledgments. The authors thank all the participants and professionals contributing to the UK Biobank.

Funding. This research was conducted using the UK Biobank resource under application 25813. This study was funded by an Australian National Health and Medical Research Council Investigator Grant (APP1194510) and the National Heart Foundation of Australia Postdoctoral Fellowship (APP107158).

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Author Contributions. A.S. and M.N.A. wrote the first draft of the manuscript. A.S., M.N.A., and E.S. were involved in the conception and design of the study and the analysis of the results. M.N.A. and E.S. obtained funding. All authors interpreted the results and edited, reviewed, and approved the final version of the manuscript. A.S. and M.N.A. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Prior Presentation. The abstract of this work was presented at the 2023 Sydney Cardiovascular Symposium, Sydney, New South Wales, Australia.

Handling Editors. The journal editors responsible for overseeing the review of the manuscript were John B. Buse and Alka M. Kanaya.

Funding Statement

This research was conducted using the UK Biobank resource under application 25813. This study was funded by an Australian National Health and Medical Research Council Investigator Grant (APP1194510) and the National Heart Foundation of Australia Postdoctoral Fellowship (APP107158).

This article is featured in podcasts available at diabetesjournals.org/journals/pages/diabetes-core-update-podcasts .

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Article Contents

Introduction, materials and methods, conclusions, declaration, appendix 1. the quadas tool 11 all items to be scored as yes, no or unclear.

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The diagnostic value of history and physical examination for COPD in suspected or known cases: a systematic review

Broekhuizen BDL, Sachs APE, Oostvogels R, Hoes AW, Verheij TJM and Moons KGM. The diagnostic value of history and physical examination for COPD in suspected or known cases: a systematic review. Family Practice 2009; 26: 260–268.

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Berna DL Broekhuizen, Alfred PE Sachs, Rimke Oostvogels, Arno W Hoes, Theo JM Verheij, Karel GM Moons, The diagnostic value of history and physical examination for COPD in suspected or known cases: a systematic review, Family Practice , Volume 26, Issue 4, August 2009, Pages 260–268, https://doi.org/10.1093/fampra/cmp026

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Background. According to current guidelines, spirometry should be performed in patients suspected of chronic obstructive pulmonary disease (COPD) by the results of history taking and physical examination. However, little is known about the diagnostic value of patient history and physical examination for COPD.

Objectives. To review the existing evidence on the diagnostic value of history taking and physical examination in recognizing COPD in patients suspected of COPD.

Methods. A systematic literature search was performed in electronic medical databases. Studies were included after using defined inclusion and exclusion criteria and judged on their methodological quality by using the Quality Assessment of Diagnostic Accuracy Studies criteria. A formal meta-analysis was not performed because all studied items of history and physical examination were investigated in only in a maximum of three studies.

Results. Six studies were included. The history items dyspnoea, wheezing, previous consultation for wheezing or cough, self-reported COPD, age and smoking and the physical examination items wheezing, forced expiratory time, laryngeal height and prolonged expiration were found to have diagnostic value for COPD. These items were studied in maximally three studies and study population studies were heterogenic. The reference test for COPD in five of the six studies concerned obstructive lung disease in general and not COPD.

Conclusion. There is insufficient evidence to assess the value of history taking and physical examination for diagnosing COPD.

Chronic obstructive pulmonary disease (COPD) is one of the most important chronic diseases in terms of frequency, impact on quality of life and mortality. 1 Since 2001, COPD is internationally classified according to the WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines on COPD, in which it is defined as airflow limitation that is not fully reversible. 1 Diagnosing COPD in an early stage is relevant because early and appropriate management, especially smoking cessation interventions but also vaccination against influenza and medication, reduces the number and severity of exacerbations of COPD and improves quality of life of patients. 2–5

International guidelines recommend that COPD should be suspected in patients with recurrent and persistent lower respiratory tract symptoms, such as persistent cough. 1 Despite the high prevalence of these symptoms, especially in primary care, recognizing COPD remains difficult. 6 The current diagnostic pathway in patients suspected of COPD consists of history taking, physical examination and, ultimately, spirometry. Spirometry is a time-consuming test that must be executed by trained personnel. Screening every smoker for COPD with spirometry, however, irrespective of signs and symptoms, has been shown to be neither efficient nor feasible. 7 , 8

There is still little knowledge about which items from history taking and physical examination have independent diagnostic value for COPD and to what extent. It is well known that there are no pathognomonic signs for COPD. Spirometry alone, however, is also not sufficient; without the knowledge of symptoms and signs, the results of spirometry are often not straightforward. 1 Since history and physical examination are always performed in patients with complaints concerning the respiratory tract in medical practice, it is important to know which items are useful. Two earlier overviews on this topic were published >8 years ago, thus, before the GOLD guidelines were introduced. 9 , 10 Therefore, we performed an updated systematic review to quantitatively summarize the diagnostic accuracy of symptoms and signs for COPD in patients suspected of having COPD.

The results of this review may help clinicians decide which patients should undergo spirometry. Moreover, the results are useful for researchers in future diagnostic studies on COPD to determine which items of history and physical examination should be included.

A systematic search for articles on the diagnostic value of items of history and/or clinical examination was performed by RO and BDLB in September 2008 in the following databases: Pubmed, Embase, Cochrane, CINAHL, Clinical Evidence and the Medion Database without restriction in date of publication. The search strategy included [(COPD OR chronic obstructive pulmonary disease OR obstructive lung disease OR obstructive airway disease OR obstructive airways disease OR airflow obstruction) AND (diagnosis OR diagnosing OR diagnostic test OR detecting OR detection OR screening OR case-finding OR differentiation OR identifying OR sensitivity OR specificity OR prediction)]. The search was limited to humans, adults and English language.

Inclusion criteria of relevant papers were

study population consisted at least partially of patients suspected of COPD (thus studies on screening of asymptomatic patients or on patients with known COPD were excluded);

original reports: we excluded letters, editorials, case-reports, commentaries and reviews;

the index tests on which the diagnostic accuracy was assessed were items from history taking and/or physical examination;

spirometry was used as the reference test;

cut-off points of spirometry parameters, i.e. the Forced Expiratory Volume in one second (FEV1), the forced vital capacity (FVC) or ratio between FEV1 and FVC, were clearly defined.

Validity assessment

The methodological quality of the selected original diagnostic accuracy studies was graded independently by two observers (RO and BDLB), using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool, an evidence-based tool for the quality assessment of studies on diagnostic accuracy. 11 In case of doubt, a third reviewer (KGMM) was consulted. The items of the QUADAS tool enabled us to find potential sources of bias in the studies or problems regarding generalizability of the study results (  Appendix 1 ).

Data extraction

The two observers extracted the following elements from the included studies: study objectives; recruitment setting, such as general practice or hospital; population characteristics such as age, gender and smoking behaviour; duration of symptoms or signs; details of the index tests, i.e. description of the physical examination and history items under study; whether the study was cross-sectional or longitudinal; details of the reference test, such as cut-off points used for the spirometry parameters and whether spirometry was executed after administration of bronchodilatators (i.e. reversibility testing to acquire post-bronchodilator values); blinding of the observer of the reference test for the index tests results; whether the observer of the index tests was blinded for the reference test results (if applicable); time interval between the index tests and the reference test; number of patients enrolled; number of patients who underwent the index test and reference test and missing data.

Additionally, the estimated parameters of diagnostic accuracy of the index test—either from univariable or multivariable analysis—were extracted.

Discrepancies were resolved by discussion between the two reviewers or, if agreement could not be reached, by consultation of a third and fourth reviewer (APES and KGMM).

Quantitative data synthesis

Positive and negative predictive value, sensitivity, specificity and likelihood ratios of each of the index tests in relation to the outcome (i.e. diagnosis of COPD by spirometry) were retrieved or otherwise calculated if possible. 12 If only multivariable diagnostic parameters were described in an article and not the univariable data or vice versa, the authors were contacted to obtain the missing information. A meta-analysis could not be performed because each index test was only studied in a maximum of three of the six included studies.

Search results

Our search yielded 4396 potentially eligible articles. After applying the inclusion and exclusion criteria to the abstracts, the number of papers was reduced to 45. Of these, the full texts were retrieved and independently judged by three readers (BDLB, RO and APES). Reference lists of these 45 articles were scanned to find additional studies. Applying our inclusion and exclusion criteria resulted in six relevant articles to address our objective ( Figure 1 ).

Flowchart of the selection of the relevant papers

Study characteristics

In all six studies, the majority of QUADAS criteria were accounted for but none of the studies fulfilled all 14 criteria ( Table 1 ). One criterium, the reporting of uninterpretable or intermediate results, was not fulfilled in five of the six studies.

Summary of the methodological quality of the six retrieved studies on the diagnostic accuracy of history and physical examination items for the diagnosis of COPD, in patients suspected of COPD, reflected by the 14 QUADAS criteria (+, Yes, ?, unclear reported, -, No, n.a., not applicable)

Full text of items are listed in   Appendix 1

The study population existed of patients referred to a pulmonary function test laboratory at a tertiary care hospital for several reasons; it was unclear whether these patients (all) had symptoms suggestive of COPD.

Definition of the physical signs: wheezing, rhonchi and reduced breath sounds was not provided.

The same investigators performed index tests and reference test.

Index tests were documented by a questionnaire, filled in by the patient and not by a physician.

Uninterpretable results of index test or reference test were not reported.

The study population size varied across the six studies from 161 to 703 patients and the age of patients varied from 18 to 85 years old ( Table 2 ). The study population of Straus et al. 16 in 2002 formed part of the study population of Straus et al. in 2000. 14 Both studies were nevertheless included because the index tests (forced expiratory time in 2002 and laryngeal measurements in 2000) and cut-off points for the reference tests were different in both studies. Age of the study participants, recruitment setting and the definition of ‘suspected of COPD’ differed considerably between the six studies.

Characteristics of study population of the six papers included in the systematic review

N , total number of patients.

Of the total study population of this paper, only patients with complaints suggestive of COPD (i.e. 703 of 3158) were included in the review.

These 161 participants form part of the 309 participants of Straus 2000.

Of the total study population of this paper, only patients suspected of COPD were included in this review (i.e. 233 of 309), as this was the aim of our review.

In total, 10 patient history items and 9 physical examination items were evaluated in the six studies ( Table 3 ). Most often studied items were age, gender and the physical examination item wheezing.

Overview of the index tests and reference tests (outcome definition) studied in the six studies included in our review

The definition of the outcome used in the studies varied, including obstructive airways disease 15 , 16 , 18 ; obstructive lung disease 13 , COPD or asthma 17 and COPD 14 . In only one of the six studies, spirometry results after administration of bronchodilators were included ( Table 3 ). 17

In five of the six studies, results of multivariable analysis were provided, reflecting the independent diagnostic value of the index tests ( Table 4 ). 13 , 14 , 16–18 Three studies reported multivariable likelihood ratios and two reported β-coefficients. In four studies, both univariable and multivariable results were specified. Despite contacting the authors of the included articles for more information, it was not possible to report one single diagnostic accuracy measurement in all six studies.

Accuracy parameters of items that were found to have diagnostic value in the included studies

h, patient history; pe, physical examination; FET, forced expiratory time; n.s., not specified in article; β-coeff, β- or regression coefficient; LR+, likelihood ratio of a positive index test; LR−, likelihood ratio of a negative index test; Sens., sensitivity; Spec., specificity; PPV, positive predictive value; NPV, negative predictive value; OR, odds ratio, LR, likelihood ratio.

Accuracy parameters for the items were obtained by pulmonologists and by residents in this study. In this review, we included the accuracy parameters obtained by pulmonologists.

ORs were calculated from the β-coefficients that were stated in the articles.

Of the 10 studied patient history tests, eight were found to have independent diagnostic value for COPD: age ≥45 years, female sex, dyspnoea, wheezing, current smoking, >40 pack years of smoking, previous consultation for wheezing or cough, self-reported history of COPD and symptoms provoked by allergens. Dyspnoea, wheezing and smoking were found to have independent diagnostic value in two studies, the other five tests in only one study. The strongest tests were symptoms provoked by allergens (odds ratio = 4.5), wheezing (odds ratio = 4.4), >40 pack years of smoking (positive likelihood ratio = 11.6) and self-reported history of COPD (positive likelihood ratio = 4.4).

Of the nine studied physical examination items, five were found to have independent diagnostic value for COPD: wheezing, forced expiratory time 9 seconds 14 and 6 seconds 18 , maximum laryngeal height and prolonged expiration. The strongest diagnostic tests were prolonged expiration (odds ratio = 3.7), forced expiratory time >9 seconds (positive likelihood ratio = 4.6) and maximum laryngeal height (the distance between the top of the thyroid cartilage and the suprasternal notch) 16 of ≤4 cm (positive likelihood ratio = 3.6).

The study with only univariable results showed that reduced breath sounds, Hoover sign (paradoxical inspiratory indrawing of the lateral rib margin) and clinical impression on presence versus absence of obstructive airways disease had a significantly increased positive likelihood ratio and decreased negative likelihood ratio. 15

In this review, we summarized all available evidence on the diagnostic accuracy of history and physical examination in patients suspected of COPD. We found only six studies that matched our inclusion and exclusion criteria. In these studies, history items that were found to have independent diagnostic value for ruling in or out COPD were ≥45 years, female sex, dyspnoea, wheezing, current smoking and extensive smoking (>40 pack years), previous consult for wheezing or cough, self-reported history of COPD and allergen-induced symptoms. Physical examination items that were found to have independent diagnostic value were wheezing, forced expiratory time, laryngeal height and prolonged expiration. Most items that were found to have diagnostic value were identified as such in not more than one study.

The number of studies that matched our inclusion criteria was surprisingly low. In contrast, many more adequate diagnostic studies have been published on the diagnostic value of history and physical examination items for other important chronic diseases, such as coronary artery disease or peripheral artery disease. 20 , 21 A possible explanation for the relative lack of diagnostic studies on COPD might be the changing definition of COPD that has occurred over time.

One of the reasons for this review was the development of the GOLD criteria in 2001 to define the presence or absence of COPD, based on spirometry with reversibility testing as reference test. According to these guidelines, COPD is present, when after bronchodilatation the FEV1:FVC ratio is <70%. 1 Hence, our review included only those diagnostic studies with spirometry as reference test. The cut-off values for the spirometry results to define COPD in the six studies varied. None used the GOLD criteria; instead the guidelines of the European Respiratory Society or the American Thoracic Society, both universally accepted prior to the GOLD guidelines, were used. 19 , 22 Moreover, in five of the six studies, the spirometric diagnosis was made without bronchodilatation, which made optimal differentiation between asthma or other reversible airflow obstruction and COPD difficult. Spirometry without bronchodilatation was adequate for the end point of four of the six included studies, namely obstructive airways disease 15 , 16 , 18 and obstructive lung disease 13 , but not for the current definition of COPD.

According to the QUADAS criteria, we found that the overall design, methodology and reporting of the six included studies was adequate. The studies were all cross-sectional and verification of the diagnosis by a reference test was achieved in all included patients. The reporting of uninterpretable or intermediate results, however, was absent in five of the six studies. Suboptimal reporting is not unusual in diagnostic research. 23 Guidelines for the conduct and reporting of diagnostic research have been proposed by the Standards for Reporting of Diagnostic Accuracy steering committee to improve the quality of diagnostic studies, but these guidelines were proposed after the conduct of the six included studies. 24

A possible weakness of this review is the fact that study populations of the six included studies differed considerably in setting and age ( Table 2 ). The difference in setting, e.g. primary, secondary and tertiary care, is usually reflected in disease severity. 25 Concerning age, in three studies, patients <40 years old were also included. 13 , 16 , 17 These are not all necessarily representative for the domain of this review, namely patients suspected of COPD because COPD is rare under the age of 40. Unfortunately, it was not possible to discriminate the younger patients from the others in these papers. Finally, the definitions of ‘patients suspected of COPD’ varied ( Table 2 ). Five of the six study populations consisted of patients with and without known COPD. Preferably, one would rather have included only patients without yet known COPD. But again, it was not possible from the publications to discriminate these patients from the other patients. We did not exclude these studies because at least part of the study populations consisted of our study domain, and we did not want to miss this information. The heterogeneity across the study populations, as well as the diversity in studied items from patient history and physical examination compromise general recommendations for medical practice.

Two overviews, though not systematic reviews, on diagnostic value of history taking and physical examination for COPD have been published previously. 9 , 10 Holleman et al. 9 reviewed 19 articles on the end point ‘airflow obstruction’ and found that no single item of history and physical examination sufficiently ruled in or ruled out airflow obstruction. Combinations of items, like smoking, reduced breath sounds and a peak expiratory flow <350 l/minute, were concluded to be more useful 9 . This is in accordance with our results that also indicate that various items are independent diagnostic determinants of COPD. McAllister et al. 10 wrote an overview about the accuracy of physical examination items for COPD but did not study history items. They showed that the accuracy of the well-known signs for COPD, such as reduced breath sounds, wheezes or hyper resonance, varies greatly between studies and that no sign is sufficiently accurate on its own. 10 Both reviews included more studies than our review because they also included articles with another diagnostic test than spirometry as reference test, articles that formally were not a diagnostic accuracy study comparing an index tests with a reference test, articles evaluating end points other than obstructive pulmonary disease, e.g. emphysema, and text books. Furthermore, both reviews included studies on screening of COPD, meaning testing all people in a population irrespective of signs and symptoms. In regard to this screening, two original diagnostic studies have been performed by Van Schayck et al. 26 and Geijer et al. 27 , both on the detection of chronic obstructive lung disease in smokers. In these studies, cough and age were related to chronic obstructive lung disease.

The available evidence for the diagnostic accuracy of patient history and physical examination for COPD is very limited, let alone the independent diagnostic value of these items. Moreover, existing studies notably studied obstructive lung disease in general, rather than COPD according to current guidelines. Hence, the available evidence cannot yet determine with sufficient confidence which patient history and physical examination items can be used by physicians to select those patients, suspected of COPD, who require spirometry. However, this systematic review does show that dyspnoea, wheezing, cough, self-reported history of COPD, age, smoking, forced expiratory time, laryngeal height and prolonged expiration are the strongest diagnostic parameters from patient history and physical examination among those that have been studied. Future diagnostic studies on COPD are necessary to estimate the true diagnostic accuracy of these items in patients suspected of COPD.

Funding: The Netherlands Organisation for Health Research and Development, ZonMW/NWO research (945-04-015).

Ethical approval: none.

Conflict of interest: none.

Was the spectrum of patients representative of the patients receiving the test in practice?

Were patient selection criteria clearly described?

Is the reference standard likely to correctly classify the target condition?

Is the time period between index test and reference standard short enough to be reasonably sure that the target condition did not change between the two?

Did the whole sample or a random selection of the sample receive verification by the reference standard?

Did patients receive the same reference standard regardless of the index test results?

Was the reference standard independent of the index tests (i.e. the index tests did not form part of the reference standard)?

Was the execution of the index tests described in sufficient detail to permit replication of the tests?

Was the execution of the reference standard described in sufficient detail to permit its replication?

Were the index test results interpreted without knowledge of the results of the reference standard?

Were the reference standard results interpreted without knowledge of the results of the index tests?

Were the same clinical data available when test results were interpreted as would be available when the tests are used in practice?

Were uninterpretable or intermediate test results reported?

Were patient withdrawals from the study explained?

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Author notes

• chronic obstructive airway disease
• physical examination
• forced expiratory volume function
• medical history taking
• medical history
• expiration, function
• self-report

Prof. Badgett regrets that studies on “diminished breath sounds” were excluded and not discussed. We extensively reviewed the studies by Holleman (1) and Badgett (2;3). They were excluded from our analysis, however, because of not meeting our inclusion criteria pertaining to the population studied, i.e. “the study population consisted - at least partially- of patients suspected of COPD (thus studies on screening of asymptomatic people or on subjects that were already known with COPD were excluded)”. We defined this criterium according to the STARD and QUADAS guidelines which advice diagnostic studies to select participants on their indication for testing, or on their suspicion of having the studied disease.(4;5) In our example, the diagnostic problem was which patients, suspected of having COPD by their physician, should undergo spirometry. The study by Badgett included outpatients recruited by notices, who were (former) smokers, or had COPD or asthma. The study of Holleman included patients referred for outpatient medical preoperative risk assessment.

We documented the review of Holleman (6) in our introduction. The study of Melbye et al was excluded because of Norwegian language and the other studies for (again) the studied populations. We agree that we should have made our inclusion criteria more explicit.

Diminished breath sounds was studied in only one of the included studies, which does not suggest that it has no diagnostic value for COPD. Considering the nature of COPD and the results of the mentioned studies, it probably has. Nevertheless, our goal was to summarize the evidence for the diagnostic value of history and physical examination in patients suspected of COPD, and not to overview history and physical examination findings, that are common in COPD.

Recently, we finished a diagnostic study in primary care patients, suspected of having COPD, on the accuracy of history, physical examination and additional tests for COPD. The results of this study, in which diminished breath sounds was included as a potential predictor, will be published soon.

Reference List

(1) Holleman DR, Jr., Simel DL, Goldberg JS. Diagnosis of obstructive airways disease from the clinical examination. J Gen Intern Med 1993; 8(2):63-68.

(2) Badgett RG, Tanaka DJ, Hunt DK, Jelley MJ, Feinberg LE, Steiner JF et al. Can moderate chronic obstructive pulmonary disease be diagnosed by historical and physical findings alone? Am J Med 1993; 94(2):188-196.

(3) Badgett RG, Tanaka DJ, Hunt DK, Jelley MJ, Feinberg LE, Steiner JF et al. The clinical evaluation for diagnosing obstructive airways disease in high-risk patients. Chest 1994; 106(5):1427-1431.

(4) Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig LM et al. The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. Ann Intern Med 2003; 138(1):W1-12.

(5) Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 2003; 3:25.

(6) Holleman DR, Jr., Simel DL. Does the clinical examination predict airflow limitation? JAMA 1995; 273(4):313-319.

Conflict of Interest:

None declared

I believe this review would benefit from more explicit methods and documentation of excluded studies. It is not clear why the authors excluded the studies by Holleman (PMID 8441077 ) and myself (PMID 8430714 ; PMID 7956395 ). In addition, it is not clear why the systematic review (PMID 7815660 ) carefully done by Holleman for the Rational Clinical Examination was not considered systematic by the authors.

Excluding these studies might undersell the value of auscultating diminished breath sounds. Diminished breath sounds were the most sensitive finding in our study as well as in the study of Holleman. Breath sounds were not statistically significant in Holleman's study because they were not added to the protocol until the last third of the study. In addition, diminished breath sounds have been found helpful in other studies with (van Schayck et al, PMID 1792447 ) and without (Hepper et al, PMID 5351681 ; Schneider, PMID 14263096 ; Bohadana, PMID 684671 ; Melbye, PMID 9656782 ; Pardee, PMID 7357938 ) multivariable analysis.

The highest sensitivity for diminished breath sounds was found in our study; we had each examiner attend a session before the study in which they auscultated patients with normal, moderately, and severe airway obstruction. While most doctors will not have this opportunity for training, individual doctors can calibrate their listening by comparing their patients with known, severe obstruction with patients known to be normal.

Admittedly, the sensitivity of diminished breath sound is probably less than 50%, but this is better than the sensitivity of other physical examination findings for airway obstruction and should be noted in a summary of this topic.

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