Glycemic variability in nondiabetic morbidly obese persons: results of an observational study and review of the literature.

Glycemic variability (GV) is correlated with oxidative stress which may lead to increased cardiovascular risk and poor clinical outcomes in people with prediabetes and diabetes. We sought to understand whether morbidly obese persons without diabetes by standard criteria have dysglycemia as measured by GV. We performed an observational study of GV metrics and carotid intima media thickness (CIMT) in 21 morbidly obese normoglycemic and 15 morbidly obese prediabetic applicants to The Biggest Loser television show. The results were compared to previously published studies in normoglycemic nonobese and obese individuals. Glucose was measured with a masked continuous glucose monitor (CGM) over 3 to 8 days and carotid intima media thickness (CIMT) was determined by ultrasound. CGM-derived GV metrics for GV were coefficient of variation (CV), standard deviation (SD), mean amplitude of glycemic excursions (MAGE), continuous overall net glycemic action-1 hour (CONGA1), and mean of daily differences (MODD). We found that morbidly obese subjects (n = 21) who were normoglycemic by standard criteria had higher GV (CV = 22%, SD = 24.2 mg/dl and MAGE = 48.6 mg/dl) than previous reports of normoglycemic, nonobese individuals (CV = 12-18%, SD = 11.5-15.0 mg/dl, and MAGE = 26.3-28.3 mg/dl). Morbidly obese prediabetic subjects (n = 15) had GV metrics indistinguishable from those morbidly obese subjects who were normoglycemic. CIMT was higher in both morbidly obese groups compared with historical age- and sex-matched controls. Normoglycemic and prediabetic morbidly obese individuals have higher GV compared with normal weight, nondiabetic individuals. We speculate that this may increase the risk for macrovascular disease through excessive oxidative stress.

Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin.

OBJECTIVE: To measure changes in resting metabolic rate (RMR) and body composition in obese subjects following massive weight loss achieved via bariatric surgery or calorie restriction plus vigorous exercise. METHODS: Body composition and RMR were measured in 13 pairs of obese subjects retrospectively matched for sex, body mass index, weight, and age who underwent either Roux-en-Y gastric bypass surgery (RYGB) or participated in "The Biggest Loser" weight loss competition (BLC). RESULTS: Both groups had similar final weight loss (RYGB: 40.2 ± 12.7 kg, BLC: 48.8 ± 14.9 kg; P = 0.14); however, RYGB lost a larger proportion of their weight as fat-free mass (FFM) (RYGB: 30 ± 12%, BLC: 16 ± 8% [P < 0.01]). In both groups, RMR decreased significantly more than expected based on measured body composition changes. The magnitude of this metabolic adaptation was correlated with the degree of energy imbalance (r = 0.55, P = 0.004) and the decrease in circulating leptin (r = 0.47, P = 0.02). CONCLUSIONS: Calorie restriction along with vigorous exercise in BLC participants resulted in preservation of FFM and greater metabolic adaption compared to RYGB subjects despite comparable weight loss. Metabolic adaptation was related to the degree of energy imbalance and the changes in circulating leptin.

Metabolic slowing with massive weight loss despite preservation of fat-free mass.

CONTEXT: An important goal during weight loss is to maximize fat loss while preserving metabolically active fat-free mass (FFM). Massive weight loss typically results in substantial loss of FFM potentially slowing metabolic rate. OBJECTIVE: Our objective was to determine whether a weight loss program consisting of diet restriction and vigorous exercise helped to preserve FFM and maintain resting metabolic rate (RMR). PARTICIPANTS AND INTERVENTION: We measured body composition by dual-energy x-ray absorptiometry, RMR by indirect calorimetry, and total energy expenditure by doubly labeled water at baseline (n = 16), wk 6 (n = 11), and wk 30 (n = 16). RESULTS: At baseline, participants were severely obese (× ± SD; body mass index 49.4 ± 9.4 kg/m(2)) with 49 ± 5% body fat. At wk 30, more than one third of initial body weight was lost (-38 ± 9%) and consisted of 17 ± 8% from FFM and 83 ± 8% from fat. RMR declined out of proportion to the decrease in body mass, demonstrating a substantial metabolic adaptation (-244 ± 231 and -504 ± 171 kcal/d at wk 6 and 30, respectively, P < 0.01). Energy expenditure attributed to physical activity increased by 10.2 ± 5.1 kcal/kg.d at wk 6 and 6.0 ± 4.1 kcal/kg.d at wk 30 (P < 0.001 vs. zero). CONCLUSIONS: Despite relative preservation of FFM, exercise did not prevent dramatic slowing of resting metabolism out of proportion to weight loss. This metabolic adaptation may persist during weight maintenance and predispose to weight regain unless high levels of physical activity or caloric restriction are maintained.

Effects of intense exercise and moderate caloric restriction on cardiovascular risk factors and inflammation.

BACKGROUND: Obesity is associated with insulin resistance, inflammation, metabolic dysfunction, and atherosclerosis. This study investigates the effects of weight loss, intense exercise, and moderate caloric restriction on insulin resistance, lipids, inflammatory biomarkers, carotid artery distensibility index (CaDI), and carotid intima media thickness (CIMT). METHODS: Seventeen sedentary morbidly obese contestants in the "Biggest Loser" television program completed the 7-month intense-exercise and moderate-restricting calories program; 3 were excluded due to lack of follow-up CIMT. Serum insulin level, glucose, lipid profile, high-sensitivity C-reactive protein (CRP), hemoglobin A1c (HbA1c), resistin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor receptor-II (TNFRII), lipoprotein a (Lp[a]), sex hormone binding globulin (SHBG), blood pressure, body fat, weight, CaDI, and CIMT were measured at baseline and 7-month follow-up. CIMT was measured 5-10 mm below the common carotid bifurcation during mid-diastolic phase. CaDI was defined as: (End-systole - End-diastole common-carotid cross-sectional area)/(End-diastole common-carotid cross-sectional-area × systemic pulse pressure) × 1000. Insulin resistance was calculated by homeostatic model assessment (HOMA) index. RESULTS: At 7-month follow-up, major reductions in weight (-39%), body fat (-66%), serum insulin level (-52%), glucose (-21%), high-sensitivity CRP (-81%), HbA1c (-11%), PAI-1 (-49%), TNFRII (-12%), and CIMT (-25%), and increases in CaDI (132%), resistin (344%), adiponectin (94%), Lp(a) (73%), and SHBG (94%) were observed. The improvement in CaDI was positively correlated with increases in adiponectin, Lp(a), SBHG, and resistin (r(2)=0.86, P=.009), but inversely with PAI-1, TNFRII, CRP, and IR (r(2)=-0.64, P=.01). Strong inverse correlation was noted between decreases in CIMT and increases in CaDI (r(2)=0.65, P=.001). CONCLUSION: In morbidly obese individuals, intense exercise with moderate caloric restriction over 7 months is associated with a dramatic improvement in carotid vascular function and atherosclerosis risk factors, as well as a reduction in inflammatory biomarkers, lipids, insulin resistance, and CIMT.