Intra-abdominal fat is independently associated with liver fat, whereas subcutaneous fat is not. Liver fat, but not intra-abdominal fat, is independently associated with serum insulin. Men and women with similar amounts of intra-abdominal and liver fat do not exhibit sex differences in markers of insulin resistance (serum insulin, triglycerides, HDL cholesterol and adiponectin).

Our objective was to determine how 8% weight loss influences subcutaneous, intra-abdominal, and liver fat (LFAT), as well as features of insulin resistance, in obese women with high versus low LFAT. A total of 23 women with previous gestational diabetes were divided into groups of high (9.4 ؎ 1.4%) and low (3.3 ؎ 0.4%) LFAT based on their median LFAT (5%) measured with proton spectroscopy. Both groups were similar with respect to age, BMI, and intra-abdominal and subcutaneous fat. Before weight loss, women with high LFAT had higher fasting serum insulin and triglyceride concentrations than women with low LFAT. At baseline, LFAT correlated with the percent of fat (r ‫؍‬ 0.44, P < 0.05) and saturated fat (r ‫؍‬ 0.45, P < 0.05) of total caloric intake but not intra-abdominal or subcutaneous fat or fasting serum free fatty acids. Weight loss was similar between the groups (high LFAT ؊7.4 ؎ 0.2 vs. low LFAT ؊7.7 ؎ 0.3 kg). LFAT decreased from 9.4 ؎ 1.4 to 4.8 ؎ 0.7% (P < 0.001) in women with high LFAT and from 3.3 ؎ 0.4 to 2.0 ؎ 0.2% (P < 0.001) in women with low LFAT. The absolute decrease in LFAT was significantly higher in women with high than low LFAT (؊4.6 ؎ 1.0 vs. ؊1.3 ؎ 0.3%, P < 0.005). The decrease in LFAT was closely correlated with baseline LFAT (r ‫؍‬ ؊0.85, P < 0.001) but not with changes in the volumes of intra-abdominal or subcutaneous fat depots, which decreased similarly in both groups. LFAT appears to be related to the amount of fat in the diet rather than the size of endogenous fat depots in obese women. Women with initially high LFAT lost more LFAT by similar weight loss than those with low LFAT, although both groups lost similar amounts of subcutaneous and intraabdominal fat. These data suggest that LFAT is regulated by factors other than intra-abdominal and subcutaneous fat. Therefore, LFAT does not appear to simply reflect the size of endogenous fat stores.

Research Methods and Procedures:We recruited 27 obese nondiabetic women in whom liver fat (LFAT) content was determined by proton spectroscopy, intra-abdominal and subcutaneous fat by magnetic resonance imaging, and insulin sensitivity by the euglycemic insulin clamp technique. The women were divided based on their median LFAT content (5%) to groups with low (3.2 Ϯ 0.3%) and high (9.8 Ϯ 1.5%) liver fat. The groups were almost identical with respect to age (36 Ϯ 1 vs. 38 Ϯ 1 years in low vs. high-LFAT), body mass index (32.2 Ϯ 0.6 vs. 32.8 Ϯ 0.5 kg/m 2 ), waist-to-hip ratio, intra-abdominal, subcutaneous, and total fat content. Results: Women with high LFAT had features of insulin resistance including higher fasting serum triglyceride (1.93 Ϯ 0.21 vs. 1.11 Ϯ 0.09 mM, p Ͻ 0.01) and insulin (14 Ϯ 3 vs. 10 Ϯ 1 mU/L, p Ͻ 0.05) concentrations than women with low LFAT. The group with high LFAT also had higher 24-hour blood pressures, and lower whole-body insulin sensitivity compared with the low-LFAT group. Discussion: In obese women with previous gestational diabetes, LFAT, rather than any measure of body composition, is associated with features of insulin resistance.

PC associates with severe primary hyperparathyroidism and must be suspected if calcium ≥1.77 mmol/l. The prevalence of CDC73 germline mutations in PC and APA in Finland is 6%. PC has distinct histopathological characteristics and its incidence has increased over the past decades.

OBJECTIVE -Effects of weight loss on vascular function are unknown. We compared, in the face of similar weight loss over 3-6 months, effects of orlistat (120 mg t.i.d., n ϭ 23) and placebo (n ϭ 24) on in vivo endothelial function in a high-risk group of obese (BMI 32.1 Ϯ 0.4 kg/m 2 ) premenopausal nondiabetic women with a history of gestational diabetes. RESEARCH DESIGN AND METHODS-Forearm blood flow responses to intraarterial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), body composition, and serum lipids were determined before and after weight loss.RESULTS -Weight loss averaged 7.3 Ϯ 0.2 kg (8.3 Ϯ 0.1%) and 7.4 Ϯ 0.2 kg (8.2 Ϯ 0.1%) of initial body weight in the orlistat and placebo groups, respectively. Forearm and body compositions changed similarly in both groups. Responses to ACh increased by 41% to the low dose (5.9 Ϯ 0.6 vs. 8.3 Ϯ 0.3 for flow in the experimental/control arm, P Ͻ 0.01) and by 33% to the high dose (7.6 Ϯ 0.8 vs. 10.1 Ϯ 0.6, P Ͻ 0.001) in the orlistat group, but they remained unchanged in the placebo group. The blood flow responses to SNP did not differ significantly between the groups. LDL cholesterol decreased significantly in the orlistat group from 3.5 Ϯ 0.2 to 3.0 Ϯ 0.1 mmol/l (P Ͻ 0.01) but remained unchanged in the placebo group. Within the orlistat group, the decrease in LDL cholesterol correlated significantly with the improvement in the blood flow response to ACh (r ϭ Ϫ0.44, P Ͻ 0.05).CONCLUSIONS -Orlistat but not moderate (8%) weight loss per se improves endothelial function in women with previous gestational diabetes. This improvement is associated with a lowering of LDL cholesterol by orlistat. Diabetes Care 26:1667-1672, 2003E ndothelial dysfunction, defined as an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide (NO) bioactivity in the vessel wall, is considered an early functional change preceding atherosclerosis (1). Obesity is associated with endothelial dysfunction (2-7). In these studies, both obesity (2) and associated metabolic abnormalities such as dyslipidemia (4), hypertension (5), insulin resistance (4), and accumulation of fat in intra-abdominal rather than subcutaneous depots (3,6,7) have correlated with altered vascular function. The exact cause of endothelial dysfunction in obesity is, however, unclear.Weight loss has beneficial effects on multiple markers of cardiovascular risk (8). Their magnitude of improvement is proportional to the amount of weight loss (8). Modest weight loss (5-10%) may not always result in significant long-term changes in risk factors. Effects of weight loss of any magnitude on endotheliumdependent and -independent vasodilatory responses have not been studied.Orlistat is a lipase inhibitor that prevents fat absorption, facilitates weight loss, and prevents weight regain (9). Although most effects of orlistat are attributable to weight loss, it lowers LDL cholesterol more than expected from weight loss alone (10). The latter may be beneficial for vascular function because lowering of ...

These data demonstrate that obese insulin-resistant subjects have a blunted response to platelet-inhibitory effect of ASA. If this blunted effect is of a single dose of ASA preserved in continuous use, it could contribute to the increased risk of atherothrombosis in insulin-resistant individuals.

OBJECTIVE -To determine whether large arteries are resistant to insulin.RESEARCH DESIGN AND METHODS -Insulin normally acutely decreases central systolic pressure by decreasing wave reflection in vivo. This effect occurs before any changes in peripheral vascular resistance or heart rate under normoglycemic conditions. We determined whether the ability of insulin to decrease central aortic pressure is altered in uncomplicated type 2 diabetes. The study subjects consisted of 16 type 2 diabetic patients (age 54 Ϯ 2 years, BMI 29 Ϯ 1 kg/m 2 ) and 19 matched nondiabetic individuals (51 Ϯ 2 years, 29 Ϯ 1 kg/m 2 ) studied under normoglycemic-hyperinsulinemic conditions. Central aortic pressure waveforms were synthesized from those recorded in the periphery using applanation tonometry and a validated reverse transfer function to construct the central aortic pressure waveform every 30 min. This method allowed determination of aortic augmentation (the pressure difference between the first and second central systolic pressure waves) and the augmentation index (augmentation divided by pulse pressure).RESULTS -Whole-body insulin sensitivity was 31% lower (P Ͻ 0.05) in the type 2 diabetic patients than in the normal subjects. Basally, before the insulin infusion, augmentation averaged 8.9 Ϯ 1.3 and 11.1 Ϯ 1.2 mmHg (NS) and the augmentation index averaged 23.1 Ϯ 2.1 and 27.5 Ϯ 2.1% (NS) in the normal subjects and diabetic patients, respectively. After 30 min of hyperinsulinemia, augmentation decreased significantly to 6.1 Ϯ 1.1 mmHg (P Ͻ 0.001) in the normal subjects but remained unchanged at 9.1 Ϯ 1.1 mmHg (NS) in type 2 diabetic patients. At 30 min, the augmentation index had decreased significantly (30 Ϯ 7% decrease) to 17.9 Ϯ 2.6% in the normal subjects but remained at 24.4 Ϯ 2.4% in the diabetic patients (13 Ϯ 4% decrease, P Ͻ 0.05 for change vs. normal subjects). Central systolic pressure decreased significantly by 30 min in the normal subjects but only after 120 min in the type 2 diabetic patients. There were no significant changes in heart rate, pulse pressure, or forearm blood flow during the first 120 min of the insulin infusion.CONCLUSIONS -Insulin resistance in type 2 diabetes involves a delay in the ability of insulin to decrease central aortic pressure. This defect could predispose these patients to develop systolic hypertension.

Weight loss rather than inhibition of fat absorption enhances insulin sensitivity. A decrease in fat absorption by orlistat appears to favorably influence the ratio between intraabdominal and subcutaneous fat, which suggests that exogenous fat or its composition influences fat distribution.