Patricia Schaaf

Differentiation Between Obesity and Insulin Resistance in the Association With C-Reactive Protein

Background—Plasma C-reactive protein (CRP) concentrations are increased in obese and/or hyperinsulinemic individuals. The goal of this study was to determine if the relation between insulin resistance and CRP was independent of obesity. Methods and Results—Plasma CRP concentrations were measured before and after 3 months of calorie restriction in 38 healthy, obese women. Steady-state plasma glucose (SSPG) concentration during a 180-minute infusion of octreotide, glucose, and insulin was used to stratify participants into insulin-resistant (IR, n=20) or insulin-sensitive (n=18) groups, similar in terms of mean age (46±2 versus 44±2 years), body mass index (32.0±0.4 versus 31.4±0.3 kg/m2), and waist circumference (96±2 versus 95±2 cm). Mean CRP (0.39±0.08 versus 0.12±0.03 mg/dL, P =0.003) concentrations were higher in the IR group, as were day-long plasma glucose and insulin responses (P <0.001). There was a significant correlation at baseline between CRP and day-long plasma integrated insulin response (r =0.47, P =0.001) but not between CRP and body mass index (r =0.14) or waist circumference (r =0.10). Weight loss was similar in the two groups ( 8.7±0.9 versus 8.4±0.8 kg) but was associated with significant (P <0.001) decreases in SSPG and CRP concentrations in the IR group only. Regression analysis showed that SSPG and day-long plasma insulin response were the only significant predictors of CRP concentration. Conclusions—CRP concentrations are elevated predominantly in obese individuals who are also insulin resistant and fall in parallel with weight loss–associated improvements in insulin resistance. The relation between CRP concentrations and insulin resistance is independent of obesity.

Benefits of Liraglutide Treatment in Overweight and Obese Older Individuals With Prediabetes

OBJECTIVE The aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance, cardiovascular disease (CVD) risk factors, and inflammation in a high-risk population for type 2 diabetes (T2DM) and CVD. RESEARCH DESIGN AND METHODS We randomized 68 older individuals (mean age, 58 ± 8 years) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks. All subjects were advised to decrease calorie intake by 500 kcal/day. Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Traditional CVD risk factors and inflammatory markers also were assessed. RESULTS Eleven out of 35 individuals (31%) assigned to liraglutide discontinued the study compared with 6 out of 33 (18%) assigned to placebo (P = 0.26). Subjects who continued to use liraglutide (n = 24) lost twice as much weight as those using placebo (n = 27; 6.8 vs. 3.3 kg; P < 0.001). Liraglutide-treated subjects also had a significant improvement in SSPG concentration (−3.2 vs. 0.2 mmol/L; P < 0.001) and significantly (P ≤ 0.04) greater lowering of systolic blood pressure (−8.1 vs. −2.6 mmHg), fasting glucose (−0.5 vs. 0 mmol/L), and triglyceride (−0.4 vs. −0.1 mmol/L) concentration. Inflammatory markers did not differ between the two groups, but pulse increased after liraglutide treatment (6.4 vs. −0.9 bpm; P = 0.001). CONCLUSIONS The addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance, systolic blood pressure, glucose, and triglyceride concentration in this population at high risk for development of T2DM and CVD.

Clinical Efficacy of Two Hypocaloric Diets That Vary in Overweight Patients With Type 2 Diabetes Comparison of moderate fat versus carbohydrate reductions

Approximately 80% of patients with type 2 diabetes are overweight/obese (1), and weight loss is the mainstay of treatment for these individuals. However, there is growing controversy as to whether reduced-fat or reduced-carbohydrate diets are best suited for this purpose, and results (2–8) in nondiabetic subjects suggest that lower carbohydrate diets are similarly or more efficacious in improving weight, triglycerides, and HDL cholesterol. There are no published randomized studies evaluating the role of dietary macronutrients with respect to weight loss and cardiovascular risk improvement in patients with type 2 diabetes. Thus, we randomized diet-treated patients with type 2 diabetes to hypocaloric diets, moderately restricted in either carbohydrate or fat, to determine whether weight loss or metabolic improvement differed as a function of macronutrient composition. A total of 29 patients with diet-treated type 2 diabetes were recruited from the San Francisco Bay area. All subjects gave written informed consent. Inclusion criteria included BMI 27–36 kg/m2, fasting plasma glucose concentration 7.2–8.3 mmol/l, no use of antihyperglycemic medications, and stable weight for 3 months. Subjects on anti-hypertensive or cholesterol-lowering drugs or aspirin were allowed to continue their medications. Insulin-mediated glucose uptake was quantified by a modification (9) of the insulin suppression test as originally described (10) and validated (11). In this test, a 180-min infusion of somatostatin (0.27 μg/m2 per min), insulin (25 mU/m2 per min), …

Clinical Efficacy of Two Calorie-Restricted Diets in Overweight Patients with Type 2 Diabetes: Comparison of Moderate Fat vs. Carbohydrate Reductions

Approximately 80% of patients with type 2 diabetes are overweight/obese (1), and weight loss is the mainstay of treatment for these individuals. However, there is growing controversy as to whether reduced-fat or reduced-carbohydrate diets are best suited for this purpose, and results (2–8) in nondiabetic subjects suggest that lower carbohydrate diets are similarly or more efficacious in improving weight, triglycerides, and HDL cholesterol. There are no published randomized studies evaluating the role of dietary macronutrients with respect to weight loss and cardiovascular risk improvement in patients with type 2 diabetes. Thus, we randomized diet-treated patients with type 2 diabetes to hypocaloric diets, moderately restricted in either carbohydrate or fat, to determine whether weight loss or metabolic improvement differed as a function of macronutrient composition. A total of 29 patients with diet-treated type 2 diabetes were recruited from the San Francisco Bay area. All subjects gave written informed consent. Inclusion criteria included BMI 27–36 kg/m2, fasting plasma glucose concentration 7.2–8.3 mmol/l, no use of antihyperglycemic medications, and stable weight for 3 months. Subjects on anti-hypertensive or cholesterol-lowering drugs or aspirin were allowed to continue their medications. Insulin-mediated glucose uptake was quantified by a modification (9) of the insulin suppression test as originally described (10) and validated (11). In this test, a 180-min infusion of somatostatin (0.27 μg/m2 per min), insulin (25 mU/m2 per min), …

Lipoprotein risk factors for cardiovascular disease in patients with type 2 diabetes mellitus treated with oral antihyperglycaemic agents

Aims:  To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET.