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Recent information suggests that insulin may regulate myosin synthesis in muscle in the direction of the changes observed. Therefore, it is possible that muscle fiber composition abnormalities in insulin-resistant conditions are secondary to hyperinsulinemia. However, the low capillary density, hypothetically, may contribute to insulin resistance.

Middle-aged men with abdominal obesity were treated in a double-blind study with moderate doses of transdermal preparations of testosterone (T), dihydrotestosterone (DHT), or placebo. This resulted in moderately elevated T concentrations and marked decreases in follicle stimulating and luteinizing hormones in the group treated with T, while the DHT group showed elevated DHT, markedly lower T values, and less diminution of gonadotropin concentrations. In the group treated with T visceral fat mass decreased (measured by computerized tomography) without significant changes in other depot fat regions. Lean body mass did not change. In the group treated with T, glucose disposal rate, measured with the euglycemic hyperinsulinemic clamp method, was markedly augmented. Plasma triglycerides, cholesterol, and fasting blood glucose concentrations as well as diastolic blood pressure decreased. There were no such changes in the DHT or placebo treatment groups. The men treated with T reported increased well-being and energy. In none of the groups did prostate volume, specific prostate antigen concentration, genito-urinary history, or urinary flow measurement change. It is suggested that supplementation of abdominal obese men with moderate doses of T might have several beneficial effects.

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ROSMOND, ROLAND, LEIF LAPIDUS, PER MARIN AND PER BJORNTORP. Mental distress, obesity and body fat distribution in middle-aged men. Obes Res. 1996;4:245~252. Previous epidemiological studies have suggested that psychiatric symptoms are associated with obesity and abdominal distribution of body fat in women. The aim of the present study was to examine this in middle-aged men.In 1992 a cluster selected cohort of 1040 men born in 1944 (participation rate 79.9%) was examined. Registrations of symptoms of depression and anxiety, sleep disturbances, psychosomatic disease as well as degree of life satisfaction were analyzed in relation to body mass index (BMI) and the waistlhip circumference ratio (WHR). In univariate analyses both BMI and WHR correlated with these factors. BMI and WHR were, however, closely interrelated (p=0.61), necessitating analyses of separate, independent relationships in multivariate analyses.When adjusted for WHR all the significant relationships with BMI disappeared. In contrast the WHR, adjusted for BMI, showed remaining significant associations with the use of anxiolytics (p=0.018), hypnotics (p=0.029), antidepressive drugs (p=0.008), degree of melancholy (p=0.002), and life satisfaction (p=0.002, negative), difficulties to sleep (p=0.014) and fall asleep (p=0.047), tendency to wake up from sleep (borderline, p=0.070) and dyspepsia (p

Women with NIDDM have high levels of free testosterone and low levels of SHBG. Insulin resistance is closely correlated with these signs of hyperandrogenicity as well as with obesity. Men with NIDDM also have low levels of SHBG and, in contrast to women, low testosterone values. Insulin values correlate negatively with these hormonal factors. Based on the results of experimental work and intervention studies, we suggest that these androgen abnormalities might be causally related to insulin resistance in NIDDM.

LJUNG, THOMAS, BJORN ANDERSSON, BENGT-AKE BENGTSSON, PER BJORNTORP AND PER MARIN. Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution, a dose-response study. Obes Res. 1996;4:277-282. There is now evidence of a hypersensitive hypothalamo-pituitary-adrenal (lIPA) axis in subjects with an elevated waisUhip circumference ratio (WHR), an indicator of the centralization of body fat stores. The activity of the lIPA axis is regulated by central glucocorticoid receptors, whose activity can be tested by the administration of exogenous glucocorticoids, which normally inhibit cortisol secretion.In this study, dexamethasone (dex) was administered in random order in doses of 0.05, 0.125, 0.25 and 0.5 mg at 10 p.rn. with measurements of serum cortisol in the morning (8 a.m.) of this and the following day. The test was performed on 22 apparently healthy men, 40 to 60 years of age, recruited from laboratory personnel, outpatient clinics or advertisements in a newspaper. Eight had a body mass index (BMI) (kglm 2 ) of <25 and 14 of >25. Twelve men had a waist hip ratio (WHR) of <1.0 and 10 men had a WHRof>I.0.Cortisol values at baseline were correlated inversely with WHR and were usually lower in men with a high (>1.0) rather than a low than low «1.0) WHR after dex inhibition. There was apparently no inhibition by dex at 0.05 and 0.125 mg on average in men with a WHR of >1.0. In addition, the inhibition at 0.5 mg dex correlated negatively with the WHR and was significantly lower (p<0.05) in men with a WHR of >1.0 than in men with a WHR of <1.0. None of these differences or relationships was found to be dependent on BMI.It is concluded that men with an elevated WHR experience a decrease in the inhibition of cortisol secretion by dex, It is suggested that this could explain or contribute to the elevated sensitivity of their HPA axis. Furthermore, lower morning cortisol concentrations suggest a change in diurnal secretion patterns.

Studies on regional differences of adipose tissue metabolism have mainly been performed in vitro. To allow measurements of lipid uptake in vivo in man, radioactive label from [9,10-3H]oleic acid in 80 g orally administered milk fat was measured after 4 h in abdominal and femoral sc adipose tissues in 28 middle-aged, abdominally obese men. Radioactivity was measured in adipose tissue triglycerides extracted from needle biopsies. Lipoprotein lipase (LPL) activity was also measured. Uptake of label in triglycerides and LPL activity were higher (20% and 15%, respectively; P < 0.05) in the abdominal compared to the femoral adipose tissue region. The men were then randomly assigned to three groups, receiving testosterone (T), dihydrotestosterone, or placebo, for 9 months. After 2 months of treatment, the procedure of administration of label was repeated, this time using [U-14C]oleic acid as a marker. Measurements of radioactive label was then performed after 4 h and monthly up to 7 months. Supplementation with T was followed by an inhibited uptake of label in triglycerides (34%; P < 0.05), lower LPL activity (48%; P < 0.05), and a shorter t1/2 (30%; P < 0.05) in the abdominal adipose tissue region compared with the dihydrotestosterone and placebo groups. No significant effect of T on triglyceride uptake, LPL activity, or t1/2 was found in sc femoral adipose tissue. It was concluded that the turnover rate of depot triglycerides is more rapid in abdominal compared to femoral sc adipose tissue in men. Furthermore, T supplementation inhibits triglyceride uptake and LPL activity and causes a more rapid turnover of triglycerides only in the sc abdominal adipose tissue region. These results demonstrate the marked effects of T on adipose tissue metabolism in vivo and suggest that T is an important regulator of the proportion of depot fat mass in central and peripheral adipose tissue in men.