Insulin Resistance In Men Research Articles

Leptin Indicates Obesity and Insulin Resistance in Men

Leptin Indicates Obesity and Insulin Resistance in Men

Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen‐deprivation therapy

Prostate carcinoma (PCa) is one of the most common malignancies in men. Androgen-deprivation therapy (ADT) is used frequently in the treatment of recurrent and metastatic PCa, rendering these men hypogonadal. Because male hypogonadism is associated with an unfavorable metabolic profile, and men with PCa have high cardiovascular mortality, the authors evaluated the effects of long-term ADT on fasting glucose levels, insulin levels, and insulin resistance. To evaluate the long-term effects of ADT on fasting glucose and insulin resistance in men with PCa who received ADT and to determine whether these metabolic alterations are a result of hypogonadism, the authors conducted a cross-sectional study at a university-based research institution in the United States. In total, 53 men were evaluated, including 18 men with PCa who received ADT for at least 12 months prior to the onset of the study (the ADT group), 17 age-matched men with nonmetastatic PCa who had undergone prostatectomy and/or received radiotherapy and who were not receiving ADT (the non-ADT group), and 18 age-matched controls (the control group). None of the men had a known history of diabetes mellitus. The mean age was similar in all 3 groups (P=0.33). Serum total testosterone levels (P<0.0001) and free testosterone levels (P<0.0001) were significantly lower in the ADT group compared with the other groups. Men in the ADT group had a higher BMI compared with the other groups (overall P=0.005). After adjustment for age and BMI, men in the ADT group had significantly higher fasting levels of the following parameters: 1) Glucose levels were 131.0+/-7.43 mg/dL in the ADT group compared with 103.0+/-7.42 mg/dL in the non-ADT group (P=0.01) and 99.0+/-7.58 mg/dL in the control group (P<0.01). 2) Insulin levels were 45.0+/-7.25 uU/mL in the ADT group compared with 24.0+/-7.24 uU/mL in the non-ADT group (P=0.05) and 19.0+/-7.39 uU/mL in the control group (P=0.02). 3) Leptin levels were 25.0+/-2.57 ng/mL in the ADT group compared with 12.0+/-2.56 ng/mL in the non-ADT group (P<0.01) and 6.0+/-2.62 ng/mL in the control group (P<0.01). 4) The homeostatic model assessment for insulin resistance (HOMAIR)=17.0+/-2.78 in the ADT group compared with HOMAIR=6.0+/-2.77 in the non-ADT group (P<0.01) and HOMAIR=5.0+/-2.83 in the control group (P=0.01). There was a significant negative correlation between total and free testosterone levels with fasting glucose, insulin, leptin, and HOMAIR. The current data suggested that men with PCa who are receiving long-term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease. This adverse metabolic profile developed independent of age and BMI and appeared to be a direct result of androgen deprivation.

Insulin Resistance in HIV-Infected Men and Women in the Nutrition for Healthy Living Cohort

We evaluated insulin resistance (IR) in an HIV-infected cohort and compared our results with those of the National Health and Nutrition Examination Survey III (NHANES III). Using a cross-sectional study design, we determined the Quantitative Insulin Sensitivity Check Index (QUICKI) in 378 nondiabetic participants in the Nutrition for Healthy Living (NFHL) study and evaluated the association of the QUICKI with demographic, socioeconomic, body composition, lipid, liver function, HIV-associated factors (CD4 cell count, viral load, highly active antiretroviral therapy type, and years infected), and injection drug use. The prevalence of IR (QUICKI <0.350) and the mean QUICKI were ascertained for nondiabetic persons aged 25 to 65 years in the NHANES III and compared with those in the NFHL study. Protease inhibitor (PI) highly active antiretroviral therapy (HAART) and nonnucleoside reverse transcriptase inhibitor (NNRTI) HAART were associated with worse IR in HIV-infected men. Greater waist circumference, triglycerides, age, and alanine aminotransferase were associated with worse IR, and higher high-density lipoprotein, low-density lipoprotein, and smoking were associated with less IR in the NFHL study; CD4 cell count, viral load, and years HIV infected were not associated with IR. There was no significant difference in the prevalence of IR in the NFHL study versus the NHANES III (51% vs. 47%; P = 0.27). NFHL participants were not more IR than NHANES III participants. IR in the NFHL study was quite common but not significantly different than in the NHANES III and was associated with similar factors as in the general population. PI HAART and NNRTI HAART were associated with worse IR in men.

Long-term effects of promoting physical activity in obese children

Restrained food consumption may alter metabolic function and contribute to eventual weight gain; however, sex differences in these relationships have not been assessed. The objective of this study was to examine the relationship between restrained eating and insulin resistance and the influence of body mass index and sex on this relationship in a large community sample of both men and women. We hypothesized that restrained eating would be related to insulin resistance and this relationship would be influenced by sex and body mass index.In this cross-sectional, observational study, we studied 487 individuals from the community (men N = 222, women N = 265), who ranged from lean (body mass index 18.5–24.9 kg/m2, N = 173), overweight (body mass index 25–29.9 kg/m2, N = 159) to obese (body mass index > 30 kg/m2, N = 155) weight categories. We assessed restrained eating using the Dutch Eating Behavior Questionnaire and obtained fasting morning plasma insulin and glucose on all subjects.In men, but not in women, restrained eating was related to homeostatic model assessment of insulin resistance (HOMA-IR) (p < 0.0001). Furthermore, HOMA-IR was significantly higher in men who were high- versus low-restrained eaters (p = 0.0006).This study is the first to report sex differences with regard to the relationship between restrained eating and insulin resistance. Our results suggest that high restrained eating is associated with insulin resistance in men but not in women.

Serum leptin in the development of insulin resistance and other disorders in the metabolic syndrome.

The metabolic syndrome mostly represented by obesity and hyperinsulinaemia connected with insulin resistance, presents the main mechanism in the pathogenesis of cardiovascular disease. The aim of this study was to analyze the interrelations between several metabolic variables (including leptin) and factors related to insulin resistance in groups of both normal and non-diabetic hyperlipemic postmenopausal women and men of appropriate age, and to attempt to elucidate the gender differences. Two groups of patients (20 men, 20 women) with hypertriglyceridemia were compared with 30 individuals (10 men, 20 women) with normal serum triacylglycerols. Fasting serum leptin concentration, lipid parameters (triacylglycerols, HDL cholesterol, LDL cholesterol) and BMI were measured and compared with changes in insulin parameters influencing insulin resistance (HOMA IR, insulin, intact proinsulin, C-peptide). Statistical analysis was performed using SAS/STAT software including unpaired Student's t-test, Kolmogorov-Smirnov's test, Spearman's rank-order correlation and multiple regression analysis. In men, the insulin sensitivity correlates with leptin only. In women insulin sensitivity is markedly influenced by a complex of factors: leptin and lipid parameters. Increased insulin resistance in men is followed mainly by the increased correlations between leptin, HOMA IR and insulin parameters. In women correlations between leptin, HOMA IR and insulin parameters were smaller, but the inverse correlation with HDL cholesterol was stronger. In postmenopausal women and also in men, serum leptin concentration contributes to insulin resistance. However in women the effect of increase in serum triacylglycerols in contribution of insulin resistance seems to be more dominant.

Relationship Between Testosterone Levels, Insulin Sensitivity, and Mitochondrial Function in Men

The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity and mitochondrial function in men. A total of 60 men (mean age 60.5 +/- 1.2 years) had a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by measuring maximal aerobic capacity (V(O2max)) and expression of oxidative phosphorylation genes in skeletal muscle. A total of 45% of subjects had normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2 diabetes. Testosterone levels were positively correlated with insulin sensitivity (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had a BMI >25 kg/m(2) and a threefold higher prevalence of the metabolic syndrome than their eugonadal counterparts (n = 50); this relationship held true after adjusting for age and sex hormone-binding globulin but not BMI. Testosterone levels also correlated with V(O2max) (r = 0.43, P < 0.05) and oxidative phosphorylation gene expression (r = 0.57, P < 0.0001). These data indicate that low serum testosterone levels are associated with an adverse metabolic profile and suggest a novel unifying mechanism for the previously independent observations that low testosterone levels and impaired mitochondrial function promote insulin resistance in men.

Insulin resistance in men with treated hypertension at increased risk for cardiovascular disease: Results of a 3-year study

Insulin resistance is an independent risk factor for cardiovascular disease. The aim of this research was to establish the frequency of insulin resistance in a normoglycemic, hypertensive, male population to determine whether insulin resistance could be predicted by assessment of conventional risk factors and to assess the rate of deterioration. Insulin resistance was calculated in hypertensive patients and healthy control subjects using a homeostasis model assessment for insulin resistance (HOMA-IR) and was correlated with routinely measured clinical variables. A total of 106 patients and 18 healthy control subjects were recruited. The healthy control subjects were similar to the patients in age and body mass index (BMI) but had a lower fasting glucose, insulin, and HOMA-IR. Of the patients, 36 were insulin sensitive (IS, HOMA-IR <1.5) and 21 were insulin resistant (IR, HOMA-IR >3.0). Mean blood pressure and type and number of antihypertensive medications did not differ between the groups. Compared with IS patients, IR patients were younger, had a higher BMI, higher triglycerides, and lower HDL, but there was substantial overlap of these risk factors between the groups. More IR than IS patients developed an impaired fasting glucose after 1 year (48% v 11%, P < .001). After 3 years of follow-up, 10% of the IR group and none from the IS group were confirmed as having type 2 diabetes mellitus. In this study, insulin resistance was common (20%) and could not be reliably diagnosed using conventional risk factors. One-half of the IR patients developed an impaired fasting glucose by 1 year, and, of these individuals, 20% were confirmed as having type 2 diabetes mellitus by 3 years.

Abstract #14: Increased Incidence of Insulin Resistance in Men with Erectile Dysfunction Causes Increased Cardiac Risk

Abstract #14: Increased Incidence of Insulin Resistance in Men with Erectile Dysfunction Causes Increased Cardiac Risk

Insulin action, regional fat, and myocyte lipid: altered relationships with increased adiposity.

Abdominal fat and myocyte triglyceride levels relate negatively to insulin sensitivity, but their interrelationships are inadequately characterized in the overweight. Using recent methods for measuring intramyocyte triglyceride, these relationships were studied in men with a broad range of adiposity. Myocyte triglyceride content ((1)H-magnetic resonance spectroscopy of soleus and tibialis anterior muscles and biochemical assessment of vastus lateralis biopsies), regional fat distribution (DXA and abdominal magnetic resonance imaging), serum lipids, insulin action (euglycemic hyperinsulinemic clamp), and substrate oxidation rates (indirect calorimetry) were measured in 39 nondiabetic men (35.1 +/- 7.8 years) with a broad range of adiposity (BMI 28.6 +/- 4.1 kg/m(2), range 20.1 to 37.6 kg/m(2)). Relationships between insulin-stimulated glucose disposal and regional body fat depots appeared more appropriately described by nonlinear than linear models. When the group was subdivided using median total body fat as the cut-point, insulin-stimulated glucose disposal correlated negatively to all regional body fat measures (all p < or = 0.004), serum triglycerides and free fatty acids (p < 0.02), and both soleus intramyocellular lipid (p = 0.003) and vastus lateralis triglyceride (p = 0.04) in the normal/less overweight group. In contrast, only visceral abdominal fat showed significant negative correlation with insulin-stimulated glucose disposal in more overweight men (r = -0.576, p = 0.01), some of whom surprisingly had lower than expected myocyte lipid levels. These findings persisted when the group was subdivided using different cut-points or measures of adiposity. Interrelationships among body fat depots, myocyte triglyceride, serum lipids, and insulin action are generally absent with increased adiposity. However, visceral abdominal fat, which corresponds less closely to total adiposity, remains an important predictor of insulin resistance in men with both normal and increased adiposity.

Oxidative stress is associated with adiposity and insulin resistance in men.

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2alpha (PGF2alpha) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2alpha than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2alpha were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2alpha and glucose infusion rate in obese men (r = -0.552; P < 0.05) and all men (r = -0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2alpha were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2alpha are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.

Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women.

There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. We studied the effect of the association between circulating interleukin 6 (IL-6) levels, one of the major mediators of inflammation, and C-reactive protein on insulin resistance and blood pressure in 228 healthy volunteers. The plasma IL-6 concentration was significantly and similarly associated with systolic (SBP) and diastolic (DBP) blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI) in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r = 0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter associations persisted after controlling for body mass index (r = 0.15 and r = 0.19; P = 0.02 and P: = 0.0004 for SBP and DBP, respectively; r = 0.24 and r = 0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively). Gender and smoking status significantly influenced the results. Although IL-6 levels were significantly associated with fasting insulin and FIRI in men, these significant correlations were not observed in women. Conversely, although IL-6 levels were significantly associated with SBP and DBP in women, these coefficients were not statistically significant in men. All of these associations were lost among smokers and remained significant in nonsmokers. As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum CRP levels correlated significantly with IL-6 in all the subjects, but mainly in nonsmokers and men. Of note was that this significant relationship was lost among smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike IL-6, the associations between CRP and these parameters were similar in men and women and in smokers and nonsmokers. For insulin and FIRI they were stronger in women and in nonsmokers. CPR significantly correlated with the WHR only in men (r = 0.22; P = 0.01). Using multiple linear regression in a stepwise manner to predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03), but not fat mass or SBP, independently contributed to 11% of its variance in men. When CRP was introduced into the model, the latter (P < 0.0001) and smoking status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its variance. When CRP was introduced into the model, again only SBP (P = 0.01) contributed to 10% of the variance in IL-6 levels. In 25 of these subjects, insulin sensitivity was determined using the frequently sampled iv glucose tolerance test with minimal model analysis, and circulating IL-6 levels were strongly associated with the insulin sensitivity index (r = -0.65; P < 0.0001). Again, this relationship was even stronger in men (r = -0.75; P < 0.001) and was not significant in women (r = -0.26; P = NS). In all of these subjects, only insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the variance of IL-6 levels in a multiple linear regression analysis. In summary, circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitute a significant proatherogenic cytokine. The mechanisms of these associations should be further investigated.

High plasma leptin concentrations in hypertensive men but not in hypertensive women.

Previous studies on humans have reported higher leptin levels in women than in men, independent of body fat, and leptin has been correlated with insulin resistance in men but not in women. Since insulin resistance is thought to play a role in raising blood pressure, we investigated sex differences in leptin concentrations between hypertensive and normotensive individuals. Ninety-two nondiabetic hypertensive patients (48 men and 44 women) and 92 age, body mass index (BMI)-matched normotensive control individuals were studied. Fasting plasma glucose, insulin, leptin and lipoprotein concentrations, glucose and insulin responses to 75 g oral glucose tolerance test (OGTT) and insulin suppression tests were determined. Fasting plasma leptin concentrations were higher in hypertensive men than in normotensive men (5.1 +/- 0.5 versus 3.9 +/- 0.4 ng/ml, P = 0.015). However, fasting plasma leptin concentrations were not significantly different between hypertensive and normotensive women (11.8 +/- 1.0 versus 10.9 +/- 1.0 ng/ml, P = 0.440). Fasting plasma leptin concentrations showed good correlation with BMI, body fat, fasting plasma insulin concentrations, and insulin area to OGTT in both men and women (all P < 0.001). However, fasting plasma leptin concentrations were related to steady-state plasma glucose (SSPG) concentrations, a measure of insulin sensitivity by insulin suppression test, in men only (P < 0.001). After adjustment for body fat amount, age and duration of hypertension, fasting plasma leptin levels still correlated significantly with SSPG concentrations in men. These four variables together accounted for a 67.9% variation in fasting plasma leptin levels in men. In women, body fat amount was the only significant determinant for plasma leptin levels. These four variables accounted for a 78.2% variation in plasma leptin levels in women. Our study confirmed a sex difference in leptin levels both in hypertensive and normotensive subjects. Higher plasma leptin concentrations in hypertensive men but not in hypertensive women when compared with normotensive control individuals was also demonstrated. These observations are consistent with the findings that plasma leptin is correlated with insulin sensitivity in men but not in women. Further studies are needed to understand the causes and consequences of sex effects on leptin in blood pressure regulation.

Gender differences in relation to leptin concentration and insulin sensitivity in nondiabetic Chinese subjects.

To investigate the relationship between fasting plasma leptin concentrations and insulin resistance in Chinese men and women. Cross-sectional study design. Ninety-six nondiabetic Chinese (51 men and 45 women) with body mass index (BMI) between 18.4-35.8 kg/m2 were studied. Plasma glucose and insulin concentrations were measured every 30 min for 2 h after a 75 g oral glucose load. The degree of insulin resistance was assessed using a modified insulin suppression test. Plasma leptin values were determined by radioimmunoassay. Fasting plasma glucose, glucose areas, fasting insulin, insulin areas, most of the lipoprotein concentrations and steady state plasma glucose (SSPG) concentrations were relatively similar between men and women. Despite the fact that men had higher BMI values (26.1 +/- 0.5 vs 24.7 +/- 0.5 kg/m2, P < 0.05), fasting plasma leptin concentrations were significantly lower in men than in women (4.9 +/- 0.5 vs 9.0 +/- 0.8 ng/ml, P < 0.001). Fasting leptin values were positively related to SSPG concentrations by simple correlation analysis in both sexes. However, this relationship persisted in men (r = 0.513, P < 0.01) but not in women (r = 0.119, P = NS) after adjustment for BMI. Multiple regression analysis showed that SSPG concentrations, BMI, glucose and insulin responses together accounted for 62.5% and 52.2% of the variation in plasma leptin concentrations in Chinese men and women respectively. Fasting plasma leptin concentrations were lower in Chinese men than in Chinese women despite the higher BMI observed in men. After adjustment for BMI, plasma leptin values correlated with the degree of insulin resistance in men but not in women.

Endothelial dysfunction and insulin resistance in men with small LDL particles

Endothelial dysfunction and insulin resistance in men with small LDL particles

Gender differences in the associations between cortisol and insulin in healthy subjects

To investigate the role of cortisol in the etiology of insulin resistance in men and women, we examined 218 healthy non-hospitalized elderly, selected from the Rotterdam Study. Free cortisol was assessed by the ratio of fasting serum cortisol over corticosteroid-binding globulin (CBG), and insulin resistance was estimated by the fasting insulin level. CBG was higher in women and decreased with age. In both men and women, the early morning free cortisol level showed no association with age or waist/hip ratio. In men, an inverse association between cortisol and body mass index was observed. In women, higher cortisol levels were associated with increased insulin levels; an increase of 9.7 mU/l insulin per unit cortisol/CBG (S.E. 3.9, P = 0.01). The association did not change after adjustment for age, body mass index or waist/hip ratio. The results of this study in elderly subjects suggest that in women cortisol may be implicated in the age-associated insulin resistance.

Relationships of generalized and regional adiposity to insulin sensitivity in men.

The relative impacts of regional and generalized adiposity on insulin sensitivity have not been fully defined. Therefore, we investigated the relationship of insulin sensitivity (measured using hyperinsulinemic, euglycemic clamp technique with [3-3H]glucose turnover) to total body adiposity (determined by hydrodensitometry) and regional adiposity. The latter was assessed by determining subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses (using magnetic resonance imaging) and the sum of truncal and peripheral skinfold thicknesses. 39 healthy middle-aged men with a wide range of adiposity were studied. Overall, the intraperitoneal and retroperitoneal fat constituted only 11 and 7% of the total body fat. Glucose disposal rate (Rd) and residual hepatic glucose output (rHGO) values during the 40 mU/m2.min insulin infusion correlated significantly with total body fat (r = -0.61 and 0.50, respectively), subcutaneous abdominal fat (r = -0.62 and 0.50, respectively), sum of truncal skinfold thickness (r = -0.72 and 0.57, respectively), and intraperitoneal fat (r = -0.51 and 0.44, respectively) but not to retroperitoneal fat. After adjusting for total body fat, the Rd and rHGO values showed the highest correlation with the sum of truncal skinfold thickness (partial r = -0.40 and 0.33, respectively). We conclude that subcutaneous truncal fat plays a major role in obesity-related insulin resistance in men, whereas intraperitoneal fat and retroperitoneal fat have a lesser role.

Disparate effects of insulin reduction with diltiazem on serum dehydroepiandrosterone sulfate levels in obese hypertensive men and women.

Evidence suggests that amelioration of hyperinsulinemic insulin resistance in men with calcium channel blockers of the dihydropyridine class is associated with a fall in serum insulin and a rise in serum dehydroepiandrosterone sulfate (DHEA-S) concentrations. The present study was conducted to determine whether 1) the nondihydropyridine calcium channel blocker diltiazem also reduces circulating insulin levels in humans, and 2) a reduction in circulating insulin with a calcium channel blocker is associated with a rise in serum DHEA-S concentrations in women as well as men. Ten obese hypertensive men and 13 obese hypertensive postmenopausal women were studied. Subjects were assessed at baseline and after the oral administration of diltiazem (60 mg, three times daily) for 18 days. Diltiazem treatment was associated with reductions in fasting serum insulin levels in both the men (from 91 +/- 14 to 56 +/- 12 pmol/L; P < 0.03) and women (from 92 +/- 20 to 48 +/- 9 pmol/L; P = 0.05). Serum glucose levels did not change in either group. In men, concurrent with the fall in serum insulin levels, serum DHEA-S levels rose from 4.05 +/- 1.06 to 6.91 +/- 1.32 mumol/L (P < 0.04), and serum DHEA levels rose from 14.4 +/- 3.0 to 24.3 +/- 4.6 nmol/L (P = 0.05) with diltiazem treatment, whereas serum cortisol did not change. In contrast, diltiazem administration in the women was not associated with any change in serum DHEA-S, DHEA, or cortisol levels. These observations suggest that the action of calcium channel blockers to lower fasting serum insulin levels is not specific for the dihydropyridine class and applies to both men and women. Furthermore, the finding of a sex-based disparity in DHEA-S and DHEA responses to insulin reduction suggests that the metabolism of these steroids may be regulated differently in men than in women.

Testosterone Concentrations in Women and Men With NIDDM

OBJECTIVE--To evaluate androgen concentrations in relation to insulin resistance in men and women with and without NIDDM. Recent studies have indicated the potential importance of the regulation of insulin sensitivity by androgens in both women and men. Low sex hormone binding globulin (SHBG) concentration is an independent risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM) in women and is strongly associated statistically with signs of insulin resistance. RESEARCH DESIGN AND METHODS--We compared measurements of anthropometric variables and SHBG, steroid hormone, and insulin concentrations of women and men who have NIDDM with those of control subjects. RESULTS--Women with NIDDM had somewhat higher plasma insulin concentrations, lower SHBG, and higher free testosterone values than did control subjects with similar body mass index (BMI). Women with NIDDM had marginally higher waist-to-hip ratios (WHR). Plasma insulin concentrations correlated positively with BMI, WHR, and free testosterone and negatively with SHBG. In multivariate analyses, insulin concentrations remained positively associated with BMI and free testosterone. Men with NIDDM had higher fasting plasma insulin concentrations than did the nondiabetic control subjects. Testosterone and SHBG were lower in the diabetic men than in both control groups. The derived value of free testosterone was not different between groups. Univariate correlation analyses revealed tight statistical couplings between plasma insulin on the one hand and SHBG and testosterone concentrations (negative) on the other. In multivariate analyses, only the insulin-testosterone association remained. 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.

Regional obesity and NIDDM.

Obesity and NIDDM are clearly linked. The subgroup of abdominal, visceral obesity has been shown to have a particularly close link to the development of diabetes. This is probably due to the marked insulin resistance of that condition. Epidemiological data show a predictive power for the development of NIDDM in both sexes, in signs of insulin resistance, visceral obesity and, in women, hyperandrogenicity. In men a relative hypogonadism may be of importance. Experimental evidence suggests cause-effect relationships between these factors. In both sexes visceral fat may contribute to insulin resistance in the liver and the periphery by excess production of FFA. Hyperandrogenicity in women may also cause insulin resistance, although the reverse sequence of events cannot be excluded. The relative hypogonadism may well contribute to insulin resistance in men, as well as to the accumulation of visceral fat. There are observations of additional endocrine aberrations in visceral obesity, suggesting a central, neuroendocrine disturbance, which might be a primary factor for the pathogenesis of the syndrome.

Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff.

To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.