The metabolic syndrome

The "metabolic syndrome" (MetS) is a clustering of components that reflect overnutrition, sedentary lifestyles, and resultant excess adiposity. The MetS includes the clustering of abdominal obesity, insulin resistance, dyslipidemia, and elevated blood pressure and is associated with other comorbidities including the prothrombotic state, proinflammatory state, nonalcoholic fatty liver disease, and reproductive disorders. Because the MetS is a cluster of different conditions, and not a single disease, the development of multiple concurrent definitions has resulted. The prevalence of the MetS is increasing to epidemic proportions not only in the United States and the remainder of the urbanized world but also in developing nations. Most studies show that the MetS is associated with an approximate doubling of cardiovascular disease risk and a 5-fold increased risk for incident type 2 diabetes mellitus. Although it is unclear whether there is a unifying pathophysiological mechanism resulting in the MetS, abdominal adiposity and insulin resistance appear to be central to the MetS and its individual components. Lifestyle modification and weight loss should, therefore, be at the core of treating or preventing the MetS and its components. In addition, there is a general consensus that other cardiac risk factors should be aggressively managed in individuals with the MetS. Finally, in 2008 the MetS is an evolving concept that continues to be data driven and evidence based with revisions forthcoming.

The Metabolic Syndrome

Background The independent effects of diet- or exercise-induced weight loss on the reduction of obesity and related comorbid conditions are not known. The effects of exercise without weight loss on fat distribution and other risk factors are also unclear. Objective To determine the effects of equivalent diet- or exercise-induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat skeletal muscle mass, and insulin sensitivity in obese men. Design Randomized, controlled trial. Setting University research center. Participants 52 obese men (mean body mass index [+/-SD], 31.3 +/- 2.0 kg/m2) with a mean waist circumference of 110.1 +/- 5.8 cm. Intervention Participants were randomly assigned to one of four study groups (diet-induced weight loss, exercise-induced weight loss, exercise without weight loss, and control) and were observed for 3 months. Measurements Change in total, subcutaneous, and visceral fat; skeletal muscle mass; cardiovascular fitness; glucose tolerance and insulin sensitivity. Results Body weight decreased by 7.5 kg (8%) in both weight loss groups and did not change in the exercise without weight loss and control groups. Compared with controls, cardiovascular fitness (peak oxygen uptake) in the exercise groups improved by approximately 16% (P 0.2). However, these values were significantly greater than those in the control and exercise without weight loss groups (P Conclusions Weight loss induced by increased daily physical activity without caloric restriction substantially reduces obesity (particularly abdominal obesity) and insulin resistance in men. Exercise without weight loss reduces abdominal fat and prevents further weight gain.

Reduction in Obesity and Related Comorbid Conditions after Diet-Induced Weight Loss or Exercise-Induced Weight Loss in Men: A Randomized, Controlled Trial

The National Cholesterol Education Program’s Adult Treatment Panel III (ATP III) report [1] added the metabolic syndrome, a multidimensional risk factor for cardiovascular disease (CVD), as a coequal partner of elevated low-density lipoprotein (LDL) cholesterol for risk-reduction therapies. Interest in the metabolic syndrome has increased greatly since the publication of the ATP III report. There are several aspects to the metabolic syndrome that deserve consideration for clinical practice: 1) major clinical outcomes, 2) metabolic components, 3) pathogenesis, 4) clinical criteria for diagnosis, 5) risk for clinical outcomes, and 6) therapeutic interventions.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)66378-7.pdf

Background and Methods. Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet — low total energy expenditure and underreporting of caloric intake — in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. Results. Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic...

https://www.nejm.org/doi/pdf/10.1056/NEJM199212313272701

Discrepancy between Self-Reported and Actual Caloric Intake and Exercise in Obese Subjects

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and...

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

Controversy regarding defective postprandial thermogenesis in obesity may partly be due to methodological factors such as duration of measurement. To clarify further the role of blunted thermogenesis in obesity, the thermic effect of food was compared in seven lean (mean ± SEM, 15.7% ± 1.5% body fat, by densitometry) and seven obese men (37.3% ± 3% fat) over 3 and 6 hours. The groups were matched for age (35 ± 2 and 33 ± 2 years for the lean and obese groups; range, 25 to 39 years), fat-free mass (FFM), and aerobic fitness. Resting metabolic rate (RMR) was measured by indirect calorimetry for 6 hours on two mornings, in randomized order: (1) after a 720-kcal liquid mixed meal, which was 24% protein, 21% fat, and 55% carbohydrate; and (2) in the postabsorptive state. The thermic effect of food, calculated as postprandial minus postabsorptive RMR, was significantly greater for the lean than obese men for the first 3 hours of measurement (67 ± 6 v 49 ± 3 kcal3 hours; P < .01). During the second 3 hours, the thermic effect of food was marginally, but not significantly, greater for the lean than obese men (34 ± 8 v 20 ± 4 kcal3 hours; P = .10, NS). Over the entire 6 hours, the thermic effect of food was significantly greater for the lean than obese men (100 ± 12 v 69 ± 5 kcal6 hours; P < .05). Three hours after the meal the increment above fasting RMR was greater for the lean than obese men (28% ± 7% v 13% ± 3% above fasting; P < .05). However, 6 hours after the meal the elevation above fasting RMR was not significantly different between the lean (6% ± 3%) and obese men (0% ± 2%). These results indicate that the thermic effect of food is neither delayed nor more prolonged in obese compared with lean men and provide further evidence for defective thermogenesis in obesity.

Thermic effect of a meal over 3 and 6 hours in lean and obese men.

The putative blunted thermogenesis in obesity may be related to insulin resistance, but insulin sensitivity and obesity are potentially confounding factors. To determine the independent effects of obesity and insulin resistance on the thermic effect of food, at rest and after exercise, lean and obese men were matched at two levels of insulin sensitivity determined by insulin-stimulated glucose disposal (milligrams per kilogram fat-free mass [FFM] per minute) during the euglycemic, hyperinsulinemic (40 mU/m2.min) clamp: 5.4 mg/kg FFM for the lean and obese groups with low insulin sensitivity, and 8.1 mg/kg FFM for the groups with high insulin sensitivity. The two lean groups were matched for percent fat (approximately 15 +/- 1% fat), as were the two obese groups (approximately 33 +/- 2% fat). Energy expenditure was measured for 3 h in the fasting state and for 3 h after a 720-kcal mixed meal, each at rest and immediately after 1 h of cycling at 100 W. The thermic effect of food (TEF) was calculated as the postprandial minus fasting energy expenditure (kcal/3 h) during rest and after exercise. During rest, TEF was blunted by both obesity (24 +/- 5 and 34 +/- 6 kcal/3 h for obese groups with low and high insulin sensitivity vs. 56 +/- 6 and 74 +/- 6 kcal/3 h for the lean groups with low and high insulin sensitivity; P less than 0.01 lean vs. obese) and insulin resistance (insulin-resistant less than insulin-sensitive, at both levels of obesity; P less than 0.01). After exercise, TEF was also impaired in the obese (47 +/- 6 and 44 +/- 5 kcal/3 h for the insulin-resistant and -sensitive groups) and in the lean insulin-resistant (55 +/- 5 kcal/3 h), compared with the lean insulin-sensitive men (71 +/- 3 kcal/3 h), P less than 0.01. Compared with rest, TEF after exercise was improved, but not normalized, in both obese groups (P less than 0.05), but unchanged in the lean groups. These results suggest that both insulin resistance and obesity are independently associated with impaired TEF at rest, but the responsiveness of thermogenesis to exercise before a meal is related to the obese state and not independently to insulin resistance per se.

/pdf/independent-effects-of-obesity-and-insulin-resistance-on-38wa6lnt8b.pdf

Independent effects of obesity and insulin resistance on postprandial thermogenesis in men.

Comparison of thermic effects of constant and relative caloric loads in lean and obese men.

To determine the independent impact of physical training on postprandial thermogenesis at rest and after 1 hour of cycling at 100 W, 10 lean (15% +/- 1% body fat), 10 obese (33% +/- 2% fat), and six obese diet-controlled, type II diabetic men (34% +/- 4% fat) underwent 12 weeks of vigorous cycle ergometer training (4 h/wk at approximately 70% of maximum oxygen consumption [VO2max]) while maintaining body weight and composition. Body weight was held constant by refeeding the energy expended in each training session. Cardiorespiratory fitness increased by approximately 27%, but body weight and fat did not change. Before and at least 4 days after the last exercise session, energy expenditure was measured for 3 hours under four conditions: (1) rest, no meal; (2) rest, after a 720-kcal mixed meal; (3) postexercise after 1 hour cycling, no meal; and (4) postexercise, meal after exercise. The thermic effect of food was calculated as postprandial minus postabsorptive energy expenditure at rest and postexercise (kcal/3 h). Before and after training, the thermic effect of food during rest was lower in obese than in lean men, and lower in diabetic than in obese men (P less than .05). Thermogenesis was improved after short-term exercise in obese and diabetic men compared with that at rest, but was not normalized (P less than .05 for lean v obese, diabetic men). A significant effect of training on thermogenesis was due to a small but significant increase after training for diabetic men under the postexercise condition. Thus, while short-term exercise enhances but does not normalize thermogenesis in obese and diabetic men, long-term exercise training leading to increased cardiorespiratory fitness, in the absence of changes in body composition, leads to a small increase in thermogenesis in diabetic men, which manifests only after a short period of exercise.

A. Edano

Papers

Effect of exercise training on insulin sensitivity and glucose metabolism in lean, obese, and diabetic men.

Thermic effect of a meal over 3 and 6 hours in lean and obese men.

Independent effects of obesity and insulin resistance on postprandial thermogenesis in men.

Comparison of thermic effects of constant and relative caloric loads in lean and obese men.

Postprandial thermogenesis at rest and postexercise before and after physical training in lean, obese, and midly diabetic men