Comanagement of Obesity-Related Comorbidities: Assessment, Treatment, and Monitoring

Comanagement of Obesity-Related Comorbidities: Assessment, Treatment, and Monitoring

Sharon J. Herring

Keerthana Kesavarapu

Jessica Briscoe


Nearly every organ system is affected by obesity. Cardiovascular disease (CVD) and its risk factors (diabetes, hypertension [HTN], and lipids) are the most commonly treated by primary care providers. Other complications, such as reproductive abnormalities in both men and women, also have huge impacts on health-related quality of life. Obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS) are common complications of obesity and are underdiagnosed. NAFLD is increasingly recognized as a common complication of obesity. Additionally, some mental health disorders such as depression and binge eating disorder (BED) have a complex, bidirectional relationship with obesity and need evaluation and treatment. Thus, comprehensive obesity care should include evaluation for these weight-related conditions along with weight management using a combination of lifestyle/behavioral, pharmacologic, and surgical therapies. The degree of weight loss needed to ameliorate these conditions varies. This chapter covers the evaluation, management, and monitoring for each of the major complications of excess weight.


Healthcare professionals (HCPs) play a critical role in the assessment and treatment of weight-related comorbidities in patients with obesity. Obesity is a leading risk factor for many of the chronic conditions that remain the leading causes of death among US adults.1 Over 230 comorbidities and complications of obesity have been identified, with nearly every body system affected (Figure 4.1).2 The net impact of the increased burden of disease associated with obesity is increased mortality.3 Successful medical management of obesity will result in significant improvements in health outcomes,4 and reductions in mortality occur with substantial weight losses from bariatric surgery.5





The strong association between obesity and the risk of developing HTN is well documented in both men
and women.6 The Framingham Study demonstrated that persons in the highest BMI quintile had a 16 to 17 mm Hg higher systolic blood pressure and an 11 mm Hg higher diastolic blood pressure than persons in the lowest BMI quintile. In this study, a 10-pound weight gain was associated with a 4 mm Hg increase in systolic blood pressure.7 Additionally, just over one-quarter of HTN cases were attributable to excess body weight.8 Numerous mechanisms for the link between obesity and elevations in blood pressure exist and likely operate simultaneously, including low vascular reactivity, renal injury, hyperinsulinemia and insulin resistance, sleep-disordered breathing, the melanocortin pathway, and genetic susceptibility.9


According to the 2015 US Preventive Services Task Force Guidelines (USPSTF), annual blood pressure screening for HTN is recommended in adults aged 18 years or older who are overweight or obesity, first using office blood pressure measurements followed by confirmation with ambulatory blood pressure measurements.10 For accurate in-office measurements, the American College of Cardiology (ACC) and American Heart Association (AHA) stress the use of the correct blood pressure cuff size (cuff bladder should encircle 80% or more of the patient’s arm circumference), particularly in patients with excess adiposity, and no measurements over clothes. HCPs are advised to measure blood pressure in both arms and to use the higher
reading; an average of two to three measurements taken on two to three separate occasions will minimize error and provide a more accurate estimate.11


A variety of lifestyle modifications are beneficial in the treatment of HTN, including reduction of sodium intake, moderation of alcohol consumption, weight loss, increased physical activity, smoking cessation, and a diet rich in fruits, vegetables, legumes, and low-fat dairy products and low in snacks, sweets, meat, and saturated fat (Table 4.2).11 Stage 1 HTN is particularly responsive to weight loss, sodium and alcohol restriction, and increased physical activity.13 The Dietary Approaches to Stop Hypertension (DASH) trial demonstrated the benefit of this eating plan for HTN (see Chapter 5, Dietary Treatment of Obesity, for additional details of the trial).14

Weight loss through caloric reduction is more important than selecting a diet with a specific macronutrient composition for blood pressure lowering. In general, the reduction in blood pressure with weight loss follows a dose-response effect (e.g., greater weight loss produces a greater reduction in blood pressure).15 Antihypertensive agents are necessary if patients cannot achieve normal blood pressures with lifestyle modification. In general, beta blockers are thought to make weight reduction more difficult and should be considered as second-line agents for blood pressure control.

Coronary Artery Disease/Cerebrovascular Disease



Obesity is associated with a number of physiologic and metabolic changes that contribute to increased cardiovascular morbidity and mortality, including insulin resistance and glucose intolerance, systolic and diastolic HTN, hypertriglyceridemia, reduced high-density lipoprotein-cholesterol (HDL-C), and increased systemic inflammation (e.g., C-reactive protein, interleukin-6 and tumor necrosis factor-alpha). There is consistent epidemiologic evidence for an association between obesity and coronary artery disease (CAD), particularly in individuals with increased abdominal adiposity, and significant CAD risk associated with obesity beginning as early as childhood.16,17 A publication from the Framingham Heart Study suggested that obesity in middle-aged adults could account for as much as 23% of cases of CAD in men and 15% in women.8 Obesity is additionally associated with an increased risk of stroke, and stroke risk is mitigated by weight loss.18


Most asymptomatic adults do not need routine screening for CAD/CVD. However, as described in the 2013 American Heart Association/American College of Cardiology/The Obesity Society (AHA/ACC/TOS) Guideline for the Management of Overweight and Obesity in Adults, patients with obesity should undergo risk assessment for cardiovascular risk factors, including lipids, blood pressure measurement, and fasting blood glucose. A waist circumference measurement is recommended for individuals with BMI 25 to 34.9 kg/m2 to provide additional information on risk. It is unnecessary to measure waist circumference in patients with BMI ≥35 kg/m2 because the waist circumference will likely be elevated and will add no additional risk information. Cut points of (≥88 cm [≥35 inches] for women and ≥102 cm [≥ 40 inches] for men) are indicative of

increased cardiometabolic risk.19 While there is little evidence to support routine exercise testing in asymptomatic adults, ACC/AHA guidelines suggest that exercise electrocardiogram (ECG) testing may be of benefit in patients with multiple risk factors for CAD in the following situations: as a guide to risk reduction therapy; men ≥45 years of age and women ≥55 years of age who are sedentary and planning to begin a vigorous exercise program; or patients who are involved in occupations linked to public safety.20 If stress testing reveals an abnormal result, referral to a cardiologist and aggressive treatment is needed with secondary prevention measures (e.g., statin therapy, aspirin, tight blood pressure control). The use of computed tomography (CT) to obtain a coronary artery calcium (CAC) score may be useful to further risk stratify and to guide a discussion regarding statin therapy in adults at borderline (5% to < 7.5%) or intermediate (7.5% to < 20%) 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Chapter 3 contains an in-depth discussion of how cardiovascular risk factors can be used to risk stratify patients with obesity.


In adults who are overweight or have obesity with cardiovascular risk factors (HTN, hyperlipidemia, and hyperglycemia), lifestyle changes that produce even modest, sustained weight losses of 3% to 5% result in clinically meaningful reductions in triglycerides, blood glucose, HBA1C, and the risk of developing T2D. Greater amounts of weight loss will reduce blood pressure, improve low-density lipoprotein-cholesterol (LDL-C) and HDL-C, and reduce the need for medications to control blood pressure, blood glucose, and lipids as well as further reduce triglycerides and blood glucose.19

Observational studies suggest significant benefits of a Mediterranean diet on reduction in cardiovascular mortality—this diet is typically high in fruits, vegetables, whole grains, beans, nuts, and seeds, includes extra-virgin olive oil as an important source of monounsaturated fat, and allows low to moderate wine consumption. It generally includes low to moderate amounts of fish, poultry, and dairy products, but little red meat. In a meta-analysis of randomized trials, a Mediterranean diet reduced the risk of stroke compared with a low-fat diet (HR 0.60, 95% CI 0.45-0.80) but did not reduce the incidence of cardiovascular or overall mortality.21 Data additionally support high-quality plant-based diets that include whole grains as the main form of carbohydrate, unsaturated fats as the predominate form of dietary fat, an abundance of fruit and vegetables, and adequate n−3 fatty acids as important components in preventing CVD.22 Randomized trials support the use of vegetarian diets for weight loss.

Statin therapy may be necessary if 10-year ASCVD risk is ≥7.5%. Lipid-lowering therapy with statins reduces relative cardiovascular risk by approximately 20% to 30% regardless of baseline LDL-C.23 HCPs can quickly calculate ASCVD risk and need for medication management beyond lifestyle changes using the ASCVD Risk Estimator Plus from the ACC/AHA:!/calculate/estimate/.


Prediabetes/Diabetes Mellitus Type 2


Prevalence of Prediabetes and T2D in Populations With Obesity

The prevalence of both diabetes and obesity have continued to rise from 1999/2000 to 2013/2014 using the most recent NHANES data.24 More than 88% of people with T2D have overweight or obesity with 26% of adults being overweight, 44% having obesity, and 18% having severe obesity.25 The risk of T2D rises with increasing body weight, with the prevalence of T2D being three to seven times higher in those with obesity than normal weight adults. Obesity-associated insulin resistance, particularly in patients with visceral adiposity, is the primary mechanism of T2D in populations with obesity.

Symptoms and Physical Examination Findings Associated With Insulin Resistance

Patients may complain of symptoms from hyperglycemia, which include polydipsia, polyuria, polyphagia, fatigue, nausea/vomiting, and abdominal pain, or symptoms from microvascular complications, such as sensory loss (peripheral neuropathy) and vision changes (retinopathy). Physical examination should include a comprehensive foot examination observing for skin integrity, foot deformities, ulcerations, pedal pulses for peripheral arterial disease, and a 10 g monofilament examination for sensation. Skin changes seen in T2D include acanthosis nigricans, which is defined as dark, coarse, and thickened skin commonly located at the back of the neck, and acrochordons (skin tags), defined as small, soft, pedunculated, and benign skin tumors found on the neck, axilla, or groin. These lesions are a sign of insulin resistance and impaired carbohydrate metabolism.26


Testing for prediabetes and T2D in asymptomatic individuals should be considered in adults of any age who have overweight or obesity (BMI ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans) and who have one or more additional risk factors for diabetes (Table 4.3). As per the USPSTF, all adults aged 40 to 70 years should be screened at least once for prediabetes and T2D.

Definition of Prediabetes and Diabetes

Diabetes and prediabetes may be diagnosed based on plasma glucose, with either fasting plasma glucose (FPG) or 2-hour plasma glucose (2-h PG) value during a 75-g oral glucose tolerance test (OGTT), or using the HBA1C criteria (Table 4.4). Unless there is a clear clinical diagnosis of diabetes in the case of hyperglycemic crisis, classic symptoms of hyperglycemia, or random plasma blood glucose >200 mg/dL, diagnosis requires two abnormal test results.



The goal of management of prediabetes is prevention or delay in progression to diabetes. The Diabetes Prevention Program (DPP) demonstrated that weight loss achieved through intensive lifestyle modifications can prevent or delay the onset of T2D. In the DPP, the relative incidence of diabetes was reduced by 58% over 3 years in participants randomized to intensive lifestyle intervention.27 The lifestyle intervention arm ran over 1 year. During the first 6 months, patients met weekly for 1 hour to learn about eating healthy, adding physical activity, dealing with stress, coping with challenges, and getting back on track. During the subsequent 6 months, patients focused on sticking to new habits. Follow-up in the Diabetes Prevention Program Outcomes Study has shown a sustained reduction in the rate of developing T2D, by 34% at 10 years and 27% at 15 years.16

Given these findings, the American Diabetes Association (ADA) recommends referral of patients with prediabetes to an intensive lifestyle intervention program modeled on the DPP, with goals to achieve and maintain 7% loss of body weight and to increase moderate intensity physical activity to at least 150 minutes/week. The Center for Medicare and Medicaid Services (CMS) covers the DPP with no patient out-of-pocket cost, if patients meet the criteria and if the HCP uses ICD-10 diagnosis codes for prediabetes or abnormal blood glucose without diabetes. These programs are readily available in the community (e.g., YMCA).

Based on intervention trials, eating patterns that may be helpful for prediabetes include a Mediterranean eating plan and/or a low-calorie, low-fat eating plan, as was employed in the DPP.28 For diabetes prevention, the emphasis should be on whole grains, legumes, nuts, fruits, and vegetables and minimal refined and processed foods.29 Red meats and sugar-sweetened beverages are associated with an increased risk of T2D.29

Physical activity, as modeled in the DPP, should be encouraged with at least 150 minutes/week of moderate-intensity activities, such as brisk walking and resistance training.27,30 This allows for improvement in insulin sensitivity.30 These findings also extend to prevention of gestational diabetes mellitus.31

Lifestyle intervention may be supplemented with pharmacotherapy. Metformin for prevention of diabetes mellitus type 2 (DM2) should be considered in those with prediabetes who are at high risk for progression, especially those with BMI ≥35 kg/m2, those aged <60 years, and women with prior gestational diabetes (ADA recommendations). In the DPP, participants randomized to metformin had a 31% relative reduction in incidence of T2D vs. control. Long-term use of metformin may be associated with vitamin B12 deficiency, and annual measurement should be performed.


The goal of managing diabetes is to achieve glycemic control and prevent and/or reduce progression of microvascular and macrovascular complications. The Look AHEAD trial, a 12-year multicenter randomized trial of patients with T2D, found that meaningful weight loss (≥5%) achieved with lifestyle intervention led to improved glycemic control and a decrease in antihyperglycemic medications use.32

Nutrition therapy plays an integral role in the treatment of T2D and should be done in collaboration with a registered dietitian nutritionist (RDN). Dietary plans created and delivered by an RDN are associated with improvements in glycemic control with HBA1C decreases of 0.3% to 2% in those with DM2.33

There is no ideal percentage of macronutrient distribution (fat, carbohydrate, and protein) that is suited for all people with obesity and T2D. Meal plans should be individualized, keeping total calorie count low. Studies of reduced calorie interventions show reductions in HBA1C of 0.3% to 2.0% in adults with T2D, as well as reductions in medication doses and improvement in quality of life.34

Carbohydrate Restriction

Data examining the ideal amount of carbohydrate intake is inconclusive. Monitoring carbohydrate intake and the resulting blood glucose response is key to improving postprandial glucose control, regardless of weight loss. The quality of carbohydrates consumed also is important. Specifically, carbohydrate foods with a high glycemic index (rate of breakdown and absorption) lead to higher postprandial blood glucose, compared to carbohydrate foods with lower glycemic index.

The role of low-carbohydrate diets (<130 g/day, compared to 150 to 175 g for a macronutrient balanced but calorie-restricted eating plan) in T2D remains unclear. Some studies show that lowering glycemic load (i.e., reducing both the glycemic index of carbohydrates consumed, as well as overall carbohydrate intake) lowers HBA1C by 0.2% to 0.5%.35 Studies longer than 12 weeks report no significant influence of glycemic index on HBA1C independent of weight loss. Very-low-carbohydrate or ketogenic diets (<50 g/day) have shown similar weight loss after 1 year, as compared with more balanced eating plans.

Fat Restriction

The ideal total dietary fat content for people with obesity and T2D is inconclusive. The types of fat as well as the quantity of fats appear to play an important role in achieving metabolic goals. As described above, eating a Mediterranean-style diet rich in monounsaturated and polyunsaturated fats and avoiding saturated fats can improve glucose metabolism and lower CVD risk.

Physical Activity

Similar to prediabetes, 150 minutes or more of moderate- to vigorous-intensity aerobic activity, spread over at least 3 days/week, with two sessions per week of resistance training on nonconsecutive days, is recommended by the ADA. Shorter durations of vigorous intensity or interval training may be sufficient for younger and more physically fit individuals. Data suggest that the additive benefit of aerobic and resistance exercise improves insulin sensitivity and lowers HBA1C by 0.66% even without a change in BMI.36 More recent research has focused on improving glucose control by interrupting prolonged sitting (sedentary time) with short bouts of physical activity.

Because of the progressive nature of T2D, lifestyle changes may not be enough over time to maintain euglycemia. Many patients with T2D will require pharmacotherapy. Currently there are 10 approved classes of agents for diabetes management (Table 4.5). A patient-centered approach should be taken to guide use of pharmacologic agents considering comorbidities, risk of hypoglycemia, cost/health plan formularies, and side effects.

When considering glucose-lowering agents for patients with obesity and with T2D, medications promoting weight loss or that are weight neutral should ideally be chosen immediately after metformin (Table 4.5). Agents with weight loss effects include biguanides, SGLT2 inhibitors, and GLP-1 agonists. Metformin is the preferred initial pharmacologic agent.37 Once initiated at 500 mg once daily, metformin should be titrated to maximum tolerated dose (assuming normal renal function). Patients with T2D and coexisting chronic kidney disease (CKD) or CAD should be initiated on SGLT2 inhibitors or GLP-1 receptor agonists, as these classes of medications have been shown to decrease the risk of progression of CKD and/or CVD. Insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when HBA1C (≥10%) or blood glucose levels (>300) are very high. Combination drug therapy should be considered in those newly diagnosed with diabetes who have an HBA1C >1.5% above target.

Jun 23, 2022 | Posted by in ENDOCRINOLOGY | Comments Off on Comanagement of Obesity-Related Comorbidities: Assessment, Treatment, and Monitoring
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