No abstract

Insulin resistance appears to be central to obesity, NIDDM, hyperlipidemia, and cardiovascular disease. While obese women with abdominal (android) fat distribution are more insulin resistant than those with peripheral (gynecoid) obesity, in nonobese women, the relationship between abdominal fat and insulin resistance is unknown. By measuring regional adiposity with dual-energy X-ray absorptiometry and insulin sensitivity by euglycemic-hyperinsulinemic clamp in 22 healthy women, with a mean +/- SE body BMI of 26.7 +/- 0.9 kg/m2 and differing risk factors for NIDDM, we found a strong negative relationship between central abdominal (intra-abdominal plus abdominal subcutaneous) fat and whole-body insulin sensitivity (r = -0.89, P < 0.0001) and nonoxidative glucose disposal (r = -0.77, P < 0.001), independent of total adiposity, family history of NIDDM, and past gestational diabetes. There was a large variation in insulin sensitivity, with a similar variation in central fat, even in those whose BMI was <25 kg/m2. Abdominal fat had a significantly stronger relationship with insulin sensitivity than peripheral nonabdominal fat (r2 = 0.79 vs. 0.44), and higher levels were associated with increased fasting nonesterified fatty acids, lipid oxidation, and hepatic glucose output. Because 79% of the variance in insulin sensitivity in this heterogeneous population was accounted for by central fat, abdominal adiposity appears to be a strong marker and may be a major determinant of insulin resistance in women.

DODDRELL. Effect of rosiglitazone on insulin sensitivity and body composition in type 2 diabetic patients. Obes Res. 2002;10:1008 -1015. Objective: To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes. Research Methods and Procedures:We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment. Results: There was a significant improvement in glycemic control (glycosylated hemoglobin Ϫ0.7 Ϯ 0.7%, p Յ 0.05) and an 86% increase in insulin sensitivity in the RSG group (glucose-disposal rate change from baseline: 17.5 Ϯ 14.5 mol glucose/min/kg free fat mass, p Ͻ 0.05), but no significant change in the placebo group compared with baseline. Total body weight and fat mass increased (p Յ 0.05) with RSG (2.1 Ϯ 2.0 kg and 1.4 Ϯ 1.6 kg, respectively) with 95% of the increase in adiposity occurring in nonabdominal regions. In the abdominal region, RSG increased subcutaneous fat area by 8% (25.0 Ϯ 28.7 cm 2 , p ϭ 0.02), did not alter intra-abdominal fat area, and reduced intrahepatic fat levels by 45% (Ϫ6.7 Ϯ 9.7%, concentration relative to water). Discussion: Our data indicate that RSG greatly improves insulin sensitivity in patients with type 2 diabetes and is associated with an increase in adiposity in subcutaneous but not visceral body regions.

OBJECTIVE:To investigate the effectiveness of intensive innovative methods for implementing dietary prescriptions on weight management and glycaemic control in overweight men with Type II diabetes. DESIGN: A randomised clinical trial with a 12-week intervention period F three isocaloric dietary intervention groups (intermittent energy restriction, pre-portioned meals and self-selected meals) each with weekly dietitian contact F and a followup visit after 18 months. SUBJECTS: A total of 51 men with Type II diabetes (mean age 54 y, mean body mass index (BMI) 31.7 kg/m 2 ). MEASUREMENTS: Weight, body composition, waist circumference, glycaemic control (HbA 1c ) and blood lipids. RESULTS: For all subjects, intensive diet therapy over the 12-week intervention period resulted in a mean reduction in energy intake of 236072780 kJ/day (5647665 kcal/day) and significant reductions in weight (6.474.6 kg), waist circumference (8.174.6 cm), percent body fat (1.971.5%), HbA 1c (1.071.4%) and triglyceride levels (0.370.6 mmol/l) compared to baseline levels. Intervention group did not affect clinical outcomes, with the exception of percent body fat. A total of 27 (52.9%) subjects attended the 18-month follow-up visit. At this visit, none of the improvements in clinical parameters was maintained, with all parameters returning to preintervention levels. CONCLUSIONS: A dietary prescription of 6000-7000 kJ/day (1400-1700 kcal/day) was effective in achieving a 6% weight loss and improving glycaemic control. The method of implementation made no difference to the outcomes between groups at 12 weeks or 18 months. Thus, we propose that it was the intensive weekly contact with a health professional in combination with moderate energy restriction that facilitated the successful short-term results seen.

OBJECTIVES: To investigate the ®bre type composition of skeletal muscle in infants and young children and to compare the ®ndings to an adult population. To relate the ®bre type pro®le of skeletal muscle in adults to measures of adiposity. DESIGN: Cross-sectional studies of skeletal muscle ®bre composition in infants and adults with measures of adiposity in the adults. SUBJECTS: 21 healthy infants and young children (age: 3±21 months) and 40 healthy adult Australian Caucasians (age: 26±62 y; BMI: 18±48 kg/m 2 ). MEASUREMENTS: Skeletal muscle ®bre type composition (by myosin ATPase method) and relative body fatness (BMI, waist circumference and waist/hip ratio (WHR)). RESULTS: Infants and young children had signi®cantly lesser proportions of glycolytic Type 2b ®bres (6.2 AE 1.1%; range 0.3±18.9%) compared with adults (20.5 AE 1.6%; range 4.9±36.0%) (p`0.0001). The percentage of Type 2b ®bres was directly related to BMI (r 0.44, p 0.02), waist circumference (r 0.49, p 0.009) and WHR (r 0.44, p 0.02) in adults. A signi®cant, direct relationship was also found between the proportion of glycolytic Type 2b ®bres and age in the adults (r 0.45, p 0.01). CONCLUSION: Skeletal muscle ®bre type composition is different in infants and adults and there is an age-dependent increase in Type 2b ®bres over the lifespan. An increased proportion of glycolytic Type 2b ®bres is associated with obesity in adults. Results support a gene-environment interaction on ®bre type composition in human skeletal muscle.

Orlistat may have reduced CVD risk, as judged by the favourable changes in individual risk factors and reductions in medication use, but the method used in order to measure absolute CVD risk in this study (Framingham CVD equation) was not sensitive enough to detect the changes in this relatively low-risk group (approximately 10% of risk of a CVD event over 10 years).

The application of magnetic resonance imaging and computed tomography to obesity research has changed the focus from body mass and skinfold thickness to abdominal fat mass and visceral adiposity. Intra-abdominal fat constitutes less than 20% of total body fat but is a major determinant of fasting and postprandial lipid availability because of its physiological (lipolytic rate and insulin resistance) and anatomical (portal drainage) properties. High levels of serum free fatty acids, as a result of abdominal obesity, cause excessive tissue lipid accumulation and contribute to dyslipidaemia, beta cell dysfunction, and hepatic and peripheral insulin resistance. An individual's risk of non-insulin dependent diabetes mellitus and cardiovascular disease relates closely to the inheritance of central obesity and susceptibility to tissue lipotoxicity.

A tryptophan to arginine (Trp64Arg) mutation in the beta 3-adrenergic receptor (beta 3-AR) gene has been implicated in diabetes and obesity. We investigated the relationship of the beta 3-AR gene mutation with total body weight, BMI, central abdominal fat, blood pressure (BP), and reproductive history in 686 elderly subjects (429 women, 257 men; mean age 69.8 +/- 6.9 [+/-SD] years) from a cross section of a normal population in Australia. About 14% of the test population were heterozygote carriers of the Trp64Arg mutation; however, significant effects on clinical parameters were only observed in women. The frequency of the mutation was significantly increased in obese women compared with lean women (BMI > or = 27: 20% compared with BMI < 27: 11%, P = 0.02). Significantly higher total body weight (67.5 +/- 12.9 vs. 64.1 +/- 12.2 kg, P = 0.03) and BMI (26.3 +/- 4.7 vs. 25.1 +/- 4.5 kg/m2, P = 0.03) was observed in heterozygote women compared with normal subjects (homozygous for tryptophan). Central abdominal fat was not significantly different, except in women under 70 years, where heterozygotes had 16% higher abdominal fat compared with normal subjects. Female heterozygotes had significantly higher diastolic BP, even after adjustment for age and BMI (88.9 +/- 11.1 vs. 84.2 +/- 10.8 mmHg, P = 0.003) and a longer reproductive life, with an earlier menarche (12.8 +/- 1.3 vs. 13.4 +/- 1.5 years, P = 0.006), a higher gravidity (4.4 +/- 2.4 vs. 3.5 +/- 2.1, P = 0.01), and higher parity (3.8 +/- 2.0 vs. 3.0 +/- 1.9, P = 0.005). Clearly, the beta 3-AR mutation has pleiotrophic effects on a number of physiological systems, including BMI, BP, and reproductive history, perhaps suggesting evolutionary reasons for its maintenance in the population.