Citations

OBJECTIVE—Insulin resistance is associated with visceral adiposity, and interventions that reduce this depot, e.g., diet and exercise, improve insulin resistance. Thiazolidinediones (TZDs) also improve insulin action but paradoxically increase total fat mass, perhaps through remodeling (recruitment of smaller fat cells) and redistribution of adipose tissue. We assessed the effects of pioglitazone versus diet and exercise on fat distribution and the relationship between fat distribution and insulin sensitivity in upper body obesity. RESEARCH DESIGN AND METHODS—Thirty-nine upper body obese, insulin-resistant, nondiabetic men and premenopausal women were randomly assigned to receive either 30 mg/day pioglitazone or a diet and exercise program for 20 weeks. Before and after the intervention, insulin sensitivity, body composition, body fat distribution (waist-to-hip ratio [WHR], computed tomography abdomen, and dual-energy X-ray absorptiometry), and abdominal and femoral fat cell size were assessed. RESULTS—Diet and exercise resulted in an 11.8 ± 1.1 kg weight loss. Both diet and exercise and pioglitazone improved insulin sensitivity, but only the former was associated with loss of intra-abdominal fat. Pioglitazone increased total body fat, which preferentially accumulated in the lower body depot in both men and women. WHRs decreased in both groups. Abdominal fat cell size decreased (P = 0.06) after diet and exercise. No statistically significant changes in fat cell size were observed in pioglitazone-treated volunteers. CONCLUSIONS—In nondiabetic upper body obese subjects, increasing insulin sensitivity via diet and exercise accompanies reductions in visceral fat. Pioglitazone treatment also improves insulin sensitivity and lowers WHR, but this is due to a selective increase in lower body fat. This confirms a site-specific responsiveness of adipose tissue to TZD and suggests that improvements in insulin sensitivity by pioglitazone are achieved independent of changes in intra-abdominal fat.

OBJECTIVE: Elevated urinary albumin excretion (UAE) has been associated with insulin resistance and is suggested to be elevated in prediabetic individuals. Upper body obesity, especially visceral obesity, predicts insulin resistance and development of type 2 diabetes. We examined whether UAE clusters with obesity-associated insulin resistance traits in healthy glucose-tolerant normotensive subjects. RESEARCH DESIGN AND METHODS: There were 49 volunteers with a wide range of body fat and body fat distribution studied. All had normal blood pressure and glucose tolerance and were maintained on a controlled diet for 2 weeks. UAE was assessed from three overnight urine collections, and body composition was assessed by whole-body dual-energy X-ray absorptiometry scanning and abdominal computed tomography scanning. RESULTS: Fasting insulin and insulin responses to oral glucose were significantly increased in obese subjects, who also tended to have more dyslipidemia, greater blood pressure, and more visceral fat than lean subjects. These differences were more apparent in upper body obese subjects. UAE was normal in obese and upper body obese subjects and not different from that of lean subjects. UAE ranged from 0.3 to 8.3 micrograms/min in lean subjects and from 0.2 to 7.2 micrograms/min in obese subjects. UAE was not significantly correlated with body composition, plasma insulin, glucose, or lipids. CONCLUSIONS: Obese subjects (even upper body obese subjects) with increased visceral and total body fat, high plasma insulin and triglycerides, and low HDL cholesterol concentrations do not have elevated UAE. This suggests that UAE is not closely associated with these characteristics and implies a later onset of abnormal albuminuria in the course of the insulin resistance syndrome.

To determine if dehydroepiandrosterone (DHEA) replacement improves insulin secretion, insulin action, and/or postprandial glucose metabolism, 112 elderly subjects with relative DHEA deficiency ingested a labeled mixed meal and underwent a frequently sampled intravenous glucose tolerance test before and after 2 years of either DHEA or placebo. Despite restoring DHEA sulphate concentrations to values observed in young men and women, the changes over time in fasting and postprandial glucose concentrations, meal appearance, glucose disposal, and endogenous glucose production were identical to those observed after 2 years of placebo. The change over time in postmeal and intravenous glucose tolerance test insulin and C-peptide concentrations did not differ in men treated with DHEA or placebo. In contrast, postmeal and intravenous glucose tolerance test change over time in insulin and C-peptide concentrations were greater (P < 0.05) in women after DHEA than after placebo. However, since DHEA tended to decrease insulin action, the change over time in disposition indexes did not differ between DHEA- and placebo-treated women, indicating that the slight increase in insulin secretion was a compensatory response to a slight decrease in insulin action. We conclude that 2 years of replacement of DHEA in elderly men and women does not improve insulin secretion, insulin action, or the pattern of postprandial glucose metabolism.

OBJECTIVE—Pioglitazone, a peroxisome proliferator–activated receptor agonist and glipizide, an insulin secretagogue, are commonly used to treat type 2 diabetes. Our study was designed to examine the effects of pioglitazone versus glipizide on body water, body composition, and hemodynamic parameters in the presence of comparable glycemic control between groups. RESEARCH DESIGN AND METHODS—We studied 19 diabetic subjects randomly assigned to either 45 mg pioglitazone (n = 8) or 10 mg (median dose) glipizide (n = 11) for 12 weeks. Body water content was measured with deuterated water, body composition by dual-energy X-ray absorptiometry and computed tomography, and cardiac output and systemic vascular resistance by acetylene rebreathing technique both before and after therapy. RESULTS—Pioglitazone increased (P < 0.001 from baseline) total body water (+2.4 ± 0.5 l) accounting for 75% of the total weight gain (+3.1 ± 2.0 kg) but did not alter vascular endothelial growth factor concentrations. Total abdominal (−32.2 ± 19 cm2) and visceral fat area (−16.1 ± 8 cm2) tended to decrease with pioglitazone but increased (P < 0.02 for differences between groups) with glipizide (+38.4 ± 17 cm2 abdominal; +19.1 ± 9 cm2 visceral). Pioglitazone tended to reduce (P = 0.05) diastolic (−8.4 ± 4 mmHg) and mean (−9.5 ± 5 mmHg; P = 0.08) blood pressure and reduced (P < 0.001) systemic vascular resistance (2,785 ± 336 vs. 2,227 ± 136 dynes/s per m2), while there were no differences in these parameters with glipizide. Neither therapy altered circulating catecholamine concentrations. CONCLUSIONS—When pioglitazone and glipizide are given in doses sufficient to achieve equivalent glycemic control in people with type 2 diabetes, pioglitazone increases total body water, thereby accounting for the majority of weight gain, tended to decrease visceral and abdominal fat content and blood pressure, and reduces systemic vascular resistance.

AbstractThe records of patients treated at the Mayo Clinic for toxic multinodular goiter during 1950–1954, 1960–1964, and 1970–1974 were reviewed to compare results of surgical and131I therapy, to define trends in treatment policy and outcome, and to attempt to elucidate factors associated with posttreatment hypothyroidism. The series involved 446 patients who underwent thyroidectomy as initial treatment and 89 who initially received131I. The time to success was significantly shorter (p=0.001) in surgically treated patients than in patients initially receiving131I. Compared with patients treated medically, patients treated initially with surgery were much less likely to require a second treatment (0% versus 24%) during the first year after initial treatment. The probability of postthyroidectomy hypothyroidism increased from approximately 12% in the 1950s to more than 70% in the 1970s at 2 years after surgery. Neither more aggressive surgery nor use of more sensitive tests to diagnose hypothyroidism accounted for the increased probability in recent years.

Obesity occurs when energy intake exceeds energy expenditure. Humans expend energy through purposeful exercise and through changes in posture and movement that are associated with the routines of daily life [called nonexercise activity thermogenesis (NEAT)]. To examine NEAT's role in obesity, we recruited 10 lean and 10 mildly obese sedentary volunteers and measured their body postures and movements every half-second for 10 days. Obese individuals were seated, on average, 2 hours longer per day than lean individuals. Posture allocation did not change when the obese individuals lost weight or when lean individuals gained weight, suggesting that it is biologically determined. If obese individuals adopted the NEAT-enhanced behaviors of their lean counterparts, they might expend an additional 350 calories (kcal) per day.

Upper body obesity is associated with insulin resistance, hypertension, and endothelial dysfunction. We examined forearm vascular function in response to vasodilator (endothelium-dependent and endothelium-independent) and vasoconstrictor stimuli in 8 normotensive, upper body/viscerally obese men with a positive family history of hypertension and 8 age-matched nonobese men. We also measured body composition and insulin regulation of free fatty acid (FFA) and glucose metabolism. Forearm blood flow was measured before and during brachial artery infusions of acetylcholine (Ach), sodium nitroprusside (NTP), and angiotensin II (±nitric oxide synthase [NO]) synthase blockade with N G -monomethyl l -arginine [ l -NMMA]). On a separate day, baseline and insulin-regulated glucose ([3- 3 H]glucose) and FFA ([9,10- 3 H]palmitate) turnover were measured. The vasoconstrictor response to angiotensin II was greater ( P <0.05) in obese men than in nonobese men, whereas endothelium-dependent vasodilation was similar. The slope of the angiotensin II dose-response curve correlated significantly with the basal plasma palmitate concentration. Basal and insulin-mediated glucose disposal was significantly reduced and FFA turnover significantly increased in viscerally obese men. No differences in endothelium-independent vasodilation or relationships between vascular responsivity and palmitate and glucose kinetics or body composition were found. Angiotensin II–stimulated forearm vasoconstriction is increased in viscerally obese normotensive men.