Insulin Resistance In Men Research Articles

Pathomechanism of Insulin Resistance in Men with Central Obesity: Correlation of GGT, GPx, hs-CRP and Plasma Total Cysteine

BACKGROUND: Gamma glutamyltransferase (GGT) was reported recently to be associated with inflammation, oxidative stress and increased amino acid. However, role of GGT in insulin resistance pathomechanism is not exactly known. Therefore correlation of GGT with inflammation, oxidative stress and elevated amino acid, in men with central obesity need to be confirmed.METHODS: A cross-sectional study was designed. Men with central obesity were recruited and selected. Anthropometric parameters, creatinine, hs-CRP, fasting glucose, fasting insulin, glutathione peroxidase (GPx) activity, GGT, plasma total cysteine (tCys) and fatty liver were measured. Subjects were then divided in 4 groups based on waist circumference (WC) and fatty liver: Group I: WC ≤100 cm, without fatty liver; Group II: WC ≤100 cm, with fatty liver; Group III: WC >100 cm, without fatty liver; Group IV: WC >100 cm, with fatty liver. All biochemical characteristics in each group were then statistically analyzed.RESULTS: Seventy-two men with central obesity were selected. Numbers of subjects in each group were: Group I: n=33; Group II: n=5; Group III: n=17; Group IV: n=17. We found significant difference of HOMA-IR between Group I and IV, significant correlation between GGT and HOMAIR, and significant negative correlation between tCys with HOMA-IR in Group IV.CONCLUSION: GGT was significantly correlated with HOMA-IR in men with WC >100 cm and fatty liver. Further investigation with more subjects is necessary to determine clear GGT cut-off to distinguish subjects with fatty liver and insulin resistance.KEYWORDS: GGT, hs-CRP, GPx, tCys, HOMA-IR, insulin resistance

Insulin resistance and adipokines serum levels in a caucasian cohort of hiv-positive patients undergoing antiretroviral therapy: a cross sectional study

BackgroundInsulin resistance is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy. Cytokines secreted by adipose tissue (adipokines) are linked to insulin sensitivity. The present study is aimed to assess the prevalence of insulin resistance (IR) and its association with several adipokines, in a non-diabetic Romanian cohort of men and women with HIV-1 infection, undergoing combination antiretroviral therapy (cART).MethodsA cross-sectional study was conducted in an unselected sample of 89 HIV-1-positive, non-diabetic patients undergoing stable cART for at least 6 months. Metabolic parameters were measured, including fasting plasma insulin, and circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Insulin resistance was estimated by measuring the Quantitative Insulin Sensitivity Check Index (QUICKI), using a cut-off value of 0.33. A linear regression model was fitted to QUICKI to test the association of IR and adipokines levels.ResultsA total of 89 patients (aged 18–65, median: 28 years) including 51 men (57.3%) and 38 women (42.7%) were included in the study. Fifty nine patients (66.3%) were diagnosed with IR based on QUICKI values lower than the cut-off point. IR prevalence was 72.5% in men and 57.6% in women. The presence of the IR was not influenced by either the time of the HIV diagnosis or by the duration of cART. Decreased adiponectin and increased serum triglycerides were associated with increased IR in men (R=0.43, p=0.007). Hyperleptinemia in women was demonstrated to be associated with the presence of IR (R=0.33, p=0.03).ConclusionsGiven the significant prevalence of the IR in our young non-diabetic cohort with HIV infection undergoing antiretroviral therapy reported in our study and the consecutive risk of diabetes and cardiovascular events, we suggest that the IR management should be a central component of HIV-infection therapeutic strategy. As adipokines play major roles in regulating glucose homeostasis with levels varying according to the sex, we suggest that further studies investigating adipokines should base their analyses on gender differences.

Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance

Recent studies linked circulating pigment epithelium-derived factor (PEDF) to obesity-associated insulin resistance, but the main source of circulating PEDF is unknown. We aimed to investigate liver and adipose tissue PEDF gene expression in association with obesity and insulin resistance. Three (two cross-sectional and one longitudinal) independent cohorts have been studied, for adipose tissue (n=80 and n=30) and liver gene expression (n=32 and n=14). Effects of high glucose and cytokines on HepG2 cell line were also investigated. PEDF gene expression and circulating PEDF were analyzed using real-time PCR and ELISA, respectively. In a first cohort of subjects, PEDF relative gene expression was higher in subcutaneous (SC) than in omental (OM) adipose tissue (P<0.0001) being also higher in mature adipocytes compared with stromo-vascular cells (P<0.0001). However, OM PEDF relative gene expression was decreased in morbidly obese subjects (P=0.01). Both OM PEDF and OM PEDF receptor (PEDFR) correlated positively with lipogenic and lipolytic genes, and with genes implicated in the lipid vacuole formation. Circulating PEDF levels were not associated with fat PEDF gene expression. In the second cohort, SC PEDF was decreased in subjects with type 2 diabetes and did not change significantly after weight loss. We next explored circulating PEDF in association with markers of liver-related insulin resistance injury (alanine aminotransferase, r=0.59, P=0.001). Interestingly, liver PEDF gene expression increased with obesity and insulin resistance in men, being significantly associated with fasting glucose and glycated hemoglobin in two independent cohorts. In fact, high glucose led to increased PEDF in HepG2 cells, while inflammatory stimuli present in the adipose tissue environment downregulated PEDF. Liver, but not adipose tissue, might be the source of increased circulating PEDF linked to insulin resistance.

A Prospective Study of Epicardial Adipose Tissue and Incident Metabolic Syndrome: The ARIRANG Study

Increased epicardial adipose tissue (EAT) may be closely associated with the development of metabolic abnormalities. We investigated whether EAT predicts the incident metabolic syndrome in a community-based, middle-aged population. The study subjects were comprised of 354 adults (134 men and 220 women) aged 40 to 70 yr without metabolic syndrome. Baseline EAT thickness, measured by echocardiography, was compared between subjects who developed new-onset metabolic syndrome at follow-up survey and those who did not. After an average of 2.2 yr of follow-up, 32 men (23.9%) and 37 women (16.8%) developed metabolic syndrome. Median EAT thickness at baseline was significantly higher in male subjects who developed metabolic syndrome than those who did not (1.52 mm vs 2.37 mm, P<0.001). The highest quartile of EAT thickness (≥2.55 mm) was associated with increased risk of progression to metabolic syndrome (Odds ratio [OR], 3.09; 95% confidence interval [CI], 1.11-8.66) after adjustment for age, smoking, alcohol intake, regular exercise, total energy intake, high sensitive C-reactive protein and homeostasis model assessment of insulin resistance in men. A significant association of EAT with incident metabolic syndrome was not seen in women (OR, 1.25; 95% CI, 0.54-2.90). In conclusion, increased EAT thickness is an independent predictor for incident metabolic syndrome in men.

Asymmetric dimethylarginine predicts decline of glucose tolerance in men with stable coronary artery disease: a 4.5-year follow-up study

BackgroundEndothelial dysfunction, largely dependent on impaired nitric oxide bioavailability, has been reportedly associated with incident type 2 diabetes. Our aim was to test the hypothesis that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide formation, might be linked to future deterioration in glucose tolerance in stable coronary artery disease (CAD).MethodsWe studied 80 non-diabetic men (mean age 55 ± 11 years) with stable angina who underwent successful elective complex coronary angioplasty and were receiving a standard medication according to practice guidelines. Plasma ADMA and its structural isomer symmetric dimethylarginine (SDMA) were measured prior to coronary angiography. An estimate of insulin resistance by homeostasis model assessment (HOMA-IR index) was calculated from fasting insulin and glucose. Deterioration in glucose tolerance was defined as development of type 2 diabetes or progression from a normal glucose tolerance to impaired fasting glucose.ResultsOver a median follow-up of 55 months 11 subjects developed type 2 diabetes and 13 progressed to impaired fasting glucose. Incident deterioration of glucose tolerance was associated with ADMA (hazard ratio [HR] per 1-SD increment 1.64 [95% CI: 1.14–2.35]; P = 0.007), log (HOMA-IR index) (HR = 1.60 [1.16–2.20]; P = 0.004) and body-mass index (HR = 1.44 [0.95–2.17]; P = 0.08) by univariate Cox regression. ADMA (HR = 1.65 [1.14–2.38]; p = 0.008) and log (HOMA-IR index) (HR = 1.55 [1.10–2.17]; P = 0.01) were multivariate predictors of a decline in glucose tolerance. ADMA and SDMA were unrelated to body-mass index, HOMA-IR index, insulin or glucose.ConclusionsADMA predicts future deterioration of glucose tolerance independently of baseline insulin resistance in men with stable CAD. Whether this association reflects a contribution of endothelial dysfunction to accelerated decline of insulin sensitivity, or represents only an epiphenomenon accompanying pre-diabetes, remains to be elucidated. The observed relationship might contribute to the well-recognized ability of ADMA to predict cardiovascular outcome.

Relationship between leptin and body mass and metabolic syndrome in an adult population

ObjectiveTo analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population. MethodsThe study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurement of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated. ResultsBMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (p<0.001); BMI was the best predictor of hyperleptinemia on ROC analysis, with area under the curve (AUC)=0.81 in men and 0.84 in women.The association between leptin and obesity (BMI≥30kg/m2) showed high odds ratios (OR) in both sexes (10.11 in men, 6.00 in women) on univariate regression analysis and 9.30 in men and 8.21 in women on multivariate regression analysis.Hyperinsulinemia and IR strongly influenced hyperleptinemia. Leptin was the best predictor of IR in both sexes (AUC=0.89 in men and 0.85 in women), and IR in men (AUC=0.79) and hyperinsulinemia in women (AUC=0.78) were the best predictors of hyperleptinemia after BMI. The correlations between leptin and IR, and leptin and insulinemia, were strong in both sexes.With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased). ConclusionElevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes.

Relação entre a leptina, a massa corporal e a síndrome metabólica numa amostra da população adulta

ObjectiveTo analyze the relationship between leptin and obesity expressed as body mass index (BMI) and certain components of the metabolic syndrome (MS) in an adult population. MethodsThe study included 103 subjects, 42 men and 61 women, aged over 30 years, clinically defined as non-diabetic but with personal or family history of cardiovascular disease. All subjects underwent fasting blood measurements of leptin, insulin, glucose, glucose after ingestion of 75g glucose, HDL cholesterol and triglycerides, and insulin resistance (IR) and BMI were calculated. ResultsBMI as an index of overall adiposity was strongly associated with serum leptin. BMI rose as serum leptin levels increased from the first to the third tertile; the correlation between leptin and BMI was strong, r=0.524 in men and r=0.603 in women, with high statistical significance (p<0.001); BMI was the best predictor of hyperleptinemia on ROC analysis, with area under the curve (AUC)=0.81 in men and 0.84 in women.The association between leptin and obesity (BMI ≥30kg/m2) showed high odds ratios (OR) in both sexes (10.11 in men, 6.00 in women) on univariate regression analysis and 9.30 in men and 8.21 in women on multivariate regression analysis.Hyperinsulinemia and IR strongly influenced hyperleptinemia. Leptin was the best predictor of IR in both sexes (AUC=0.89 in men and 0.85 in women), and IR in men (AUC=0.79) and hyperinsulinemia in women (AUC=0.78) were the best predictors of hyperleptinemia after BMI. The correlations between leptin and IR, and leptin and insulinemia, were strong in both sexes.With regard to MS components, increased serum levels of the study variables were observed as leptin concentrations rose from the first to the third tertile (with the exception of HDL cholesterol, which decreased). ConclusionElevated serum leptin, particularly in obese individuals, should be taken as a warning sign of energy imbalance, poor diet, hyperinsulinemia, insulin resistance, or changes in other metabolic risk factors that are strongly associated with cardiovascular disease and type 2 diabetes.

Whole egg consumption improves lipoprotein profiles and insulin sensitivity to a greater extent than yolk-free egg substitute in individuals with metabolic syndrome

ObjectiveWe investigated if daily egg feeding, along with carbohydrate restriction, would alter lipoprotein metabolism and influence atherogenic lipoprotein profiles and insulin resistance in men and women with metabolic syndrome (MetS). MethodsIn a randomized, single-blind, parallel design, participants consumed either 3 whole eggs/day (EGG, n=20) or the equivalent amount of yolk-free egg substitute (SUB, n=17), as part of a moderately carbohydrate-restricted diet (25%–30% energy) for 12 weeks. Plasma lipids, apolipoproteins (apos), oxidized LDL (oxLDL), cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) activities were assessed at baseline and week 12. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy. ResultsAtherogenic dyslipidemia improved for all individuals as evidenced by reductions in plasma triglycerides, apoC-III, apoE, oxLDL, VLDL particle diameter, large VDL, total IDL, small LDL, and medium LDL particles (P<0.05). Furthermore, there were increases in HDL-cholesterol, large LDL and large HDL particles (P<0.05) for all individuals. However, there were greater increases in HDL-cholesterol and large HDL particles, and reductions in total VLDL and medium VLDL particles for those consuming EGG compared to SUB (P<0.05). Plasma insulin and insulin resistance (HOMA-IR) were reduced, while LCAT activity, and both HDL and LDL diameters increased over time in the EGG group only (P<0.05). ConclusionsIncorporating daily whole egg intake into a moderately carbohydrate-restricted diet provides further improvements in the atherogenic lipoprotein profile and in insulin resistance in individuals with MetS.

Adipose Tissue Dysfunction in Humans: A Potential Role for the Transmembrane Protein ENPP1

Adipose tissue (AT) helps to regulate body fat partitioning and systemic lipid/glucose metabolism. We have recently reported lipid/glucose metabolism abnormalities and increased liver triglyceride content in an AT-selective transgenic model overexpressing ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1), the AdiposeENPP1-Tg mouse. The aim of the study was to test the translational hypothesis that AT-ENPP1 overexpression associates with AT dysfunction (changes in AT gene expression, plasma fatty acid, and adipokine levels), increased liver triglyceride deposition, and systemic insulin resistance in humans. A total of 134 young normoglycemic men and women were subjected to body composition studies, hyperinsulinemic-euglycemic clamps, and AT needle biopsy. Twenty men also had liver/muscle nuclear magnetic resonance spectroscopy. Predetermined measures included AT expression of ENPP1 and other lipid metabolism/inflammation genes, plasma adipokines, and nonesterified fatty acid (NEFA) levels, liver/muscle triglyceride content, and the systemic glucose disposal rate. After statistical adjustment for body fat content, increasing AT-ENPP1 was associated with up-regulation of genes involved in NEFA metabolism and inflammation, increased postabsorptive NEFA levels, decreased plasma adiponectin, increased liver triglyceride content, and systemic insulin resistance in men. In women, there were no changes in plasma adiponectin, NEFAs, or glucose disposal rate associated with increasing AT-ENPP1, despite increased expression of lipid metabolism and inflammation genes in AT. Increased AT-ENPP1 is associated with AT dysfunction, increased liver triglyceride deposition, and systemic insulin resistance in young normoglycemic men. These findings are concordant with the AdiposeENPP1-Tg phenotype and identify a potential target of therapy for health complications of AT dysfunction, including type 2 diabetes and cardiovascular disease.

Vaccenic acid in serum triglycerides is associated with markers of insulin resistance in men

Serum triglyceride levels are associated with metabolic disorders; however, it remains unclear whether the fatty acid (FA) composition of triglycerides is also changed. Although there were no differences in circulating triglyceride levels between normoglycaemic-normoinsulinaemic and hyperglycaemic-hyperinsulinaemic men, inspection of individual FA revealed that vaccenic acid was enriched with hyperglycaemia-hyperinsulinaemia. Moreover, vaccenic acid levels were positively correlated with insulin and HOMA-IR. This reinforces that examination of individual FA in the context of insulin resistance is warranted.

Abdominal fat in association with insulin resistance in men of European and South Asian origin

Abdominal fat in association with insulin resistance in men of European and South Asian origin

Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus

Patients with primary hyperparathyroidism have impaired glucose tolerance more often than do controls, and parathyroid resection sometimes improves this derangement. However, it is unclear whether serum calcium (Ca) or parathyroid hormone (PTH) is more strongly related to impaired glucose metabolism in subjects without primary hyperparathyroidism. In this cross-sectional study, we examined patients with type 2 diabetes mellitus (DM) (271 men and 209 women) and analyzed the relationships between serum concentrations of Ca or intact PTH and DM-related variables. Simple regression analyses showed that the level of serum Ca was significantly and positively correlated with the levels of fasting plasma glucose, immunoreactive insulin, and homeostasis model assessment insulin resistance in men (P < .05), but not in women. In contrast, intact PTH was not significantly correlated with DM-related parameters in either sex. Multiple regression analyses showed that the significant and positive correlations between serum Ca vs fasting plasma glucose and homeostasis model assessment insulin resistance in men still remained after adjustment for intact PTH as well as age, body weight, height, creatinine, albumin, phosphate, bone metabolic markers, and estradiol (P < .05). Serum Ca level is positively associated with impaired glucose metabolism, independent of PTH or bone metabolism, in men with type 2 DM.

Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men

Low circulating testosterone concentrations have been associated with insulin resistance (IR). Androgen action is mediated by the androgen receptor (AR) whose activity is modulated by a polymorphic CAG repeat sequence within exon 1. An interaction between testosterone and CAG repeat length (CAG length) with respect to IR has been described in women. We investigated such a putative interaction between testosterone and the CAG length with respect to IR in men with normal glucose tolerance. Cross-sectional study. In 113 non-diabetic men calculated free testosterone, the CAG length, and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR, as indicated by homeostasis model assessment (HOMA %S). In a multivariate regression analysis adjusted for age and body mass index, free testosterone, CAG length, and a multiplicative interaction term were significantly associated with IR (P=0.001, P=0.001, P=0.01 respectively). The model explained 36.6% of the variation of IR and predicted that in carriers with a CAG length of 23, changes in testosterone would only minimally affect IR. For CAG lengths longer than 23, however, an increase in testosterone would improve IR, namely the longer the CAG length, the greater the effect. In contrast, in the case of CAG lengths shorter than 23, the effect of increasing testosterone would be the opposite. In men, testosterone and the AR CAG repeat length polymorphism interacted with respect to IR. The interpretation of the association between testosterone and IR seems to require consideration of the AR CAG repeat polymorphism.

251 - The relationship between plasma fatty acids and risk factors for insulin resistance in men

251 - The relationship between plasma fatty acids and risk factors for insulin resistance in men

Sex Hormones and Colorectal Cancer: What Have We Learned So Far?

Sex Hormones and Colorectal Cancer: What Have We Learned So Far?

LEPTIN/ADIPONECTIN RATIO AS A MARKER OF CARDIOVASCULAR DISEASES AT THE PATIENTS WITH METABOLIC SYNDROME: PP.34.430

Aim: Optimizing detection of risk factors for cardiovascular disease in patients with metabolic syndrome (MS) and obesity (Ob). Materials and Methods: We examined 88 patients, which divided 5 groups: 1gr. -with excessive body weight; 2 gr.-with Ob.I; 3 gr.- with Ob.II; 4 gr.-with Ob.III; 5 gr. – control with hypertension and normal weight. Depending on the HOMA-index patients were divided into two groups: 1-st- without insulin resistance (IR) (HOMA-index <2.77); 2 gr. with the IR (HOMA-index>2.77). Were observed: the waist circumference, body mass index (BMI), glucose, fasting insulin, HOMA-index, lipid profile, leptin levels, adiponektyn and their ratio (L/A). Results: The most informative indicator of endocrine activity of adipose tissue was the L/A ratio. Progression of BMI in men and women is accompanied by increasing L/A ratio. The minimum value of L/A was determined in control 5 group and was lowest among all groups. The maximum value of this parameter revealed in the 4-th group with the highest BMI. The increase of L/A was associated with progression of abdominal Ob, the development of lipid and carbohydrate disoders. Women without IR had adiponektyn higher than with IR. In contrast, the L/A ratio increased in the group with IR compared with the women without IR. This dependence is observed in male groups. Conclusions: It was found out that clear link between degree of Ob and leptin, adyponektyn levels was not observed in groups of women and men with MS and Ob, while increase in BMI was associated with a linear increase of ratio L/A. Presence of IR in men and women with MS and Ob is accompanied by reduced levels of adiponektyn and increase of the L/A as an important token of formation and detection contingent MS patients with high risk of cardiovascular disease.

Adiposity Factors Influencing Hepatic and Muscle Insulin Resistance in Men with Non-Diabetic Metabolic Syndrome

Adiposity Factors Influencing Hepatic and Muscle Insulin Resistance in Men with Non-Diabetic Metabolic Syndrome

Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women

Increased serum ferritin concentrations in nonpathologic conditions, reflecting subclinical iron overload, have been reported to be associated with insulin resistance and an increased risk of type 2 diabetes mellitus (DM). However, serum ferritin concentrations differ significantly according to sex and ethnicity; and data concerning the relationship between serum ferritin concentrations and glucose metabolism abnormalities in Asian men and women are conflicting. This cross-sectional study investigated the association of serum ferritin concentrations with insulin resistance and impaired glucose metabolism in a large number of subjects with normal fasting glucose (NFG) level, impaired fasting glucose (IFG) level, or type 2 DM. We analyzed clinical and laboratory data from 12 090 subjects (6378 men and 5712 women; age, 20-89 years) who underwent general medical checkups. The study population included 1054 subjects with type 2 DM, 3783 subjects with IFG level, and 7253 subjects with NFG level. Serum ferritin, hemoglobin A 1c, fasting glucose, lipid, and insulin levels were measured. Insulin resistance and β-cell function indices were derived from a homeostasis model assessment. Serum ferritin concentrations were highest in the DM group, followed by the IFG group and the NFG group, in both men and women (186 ± 127, 176 ± 108, and 156 ± 92 ng/mL, respectively, in men; 85 ± 62, 75 ± 55, and 59 ± 47 ng/mL, respectively, in women). After adjustment for other variables using multiple regression analysis, homeostasis model assessment of insulin resistance was independently associated with serum ferritin concentration in men, but not in women. When the fourth quartile of ferritin was compared with the first quartile, the age-adjusted odds ratio (OR) for type 2 DM was 1.71 (95% confidence interval, 1.38-2.12) in men and 1.50 (1.05-2.13) in women. The OR in men was attenuated to 1.27 (1.01-1.60) but remained significant after adjustment for body mass index (BMI), waist circumference, blood pressure, serum lipids, liver enzymes, and high-sensitivity C-reactive protein (hsCRP). In nondiabetic subjects, the age-adjusted OR for IFG in the fourth quartile of ferritin was 1.82 (1.56-2.13) in men and 1.68 (1.40-2.02) in women. The OR was attenuated to 1.31 (1.11-1.55) in men and 1.45 (1.19-1.78) in women after adjustment for BMI, waist circumference, blood pressure, serum lipids, liver enzymes, and hsCRP. In NFG subjects, the age-adjusted OR for metabolic syndrome in the fourth quartile of ferritin concentration was 2.85 (1.99-4.07) in men and 1.21 (0.82-1.79) in women. In men, the OR was attenuated to 1.58 (1.06-2.37) after adjustment for BMI, liver enzymes, and hsCRP. Increased serum concentrations of ferritin are associated with insulin resistance, type 2 DM, IFG, and metabolic syndrome in men, but only with IFG in women. These results suggest that iron overload is associated with insulin resistance in men, but not in women.

Impact of Acute Biochemical Castration on Insulin Sensitivity in Healthy Adult Men

Introduction. Evidence supports an inverse relationship between serum testosterone (T) and insulin resistance in men. However, data with respect to causality are limited. The aim of this study was to explore the impact of acute biochemical castration on insulin sensitivity in healthy adult men. Methods. Ten healthy, adult males (mean age 41.0 ± 3.9 yr) were studied. Subjects were studied at baseline and after 2 and 4 weeks of biochemical castration. Outpatient hospital research setting. Body composition (dual-energy x-ray absorptiometry), energy expenditure (indirect calorimetry), abdominal and visceral adiposity (MRI), skeletal muscle intramyocellular lipid content ([IMCL] 1H-MR spectroscopy), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed before and after 2 and 4 weeks of biochemical castration induced by a GnRH antagonist (acyline 300 μg/kg subcutaneous every 10–14 days). Serum T, insulin and glucose levels, body composition, abdominal visceral fat, IMCL, and glucose disposal rate (M) were measured. Results and Conclusion. Acyline administration suppressed serum T to frankly hypogonadal levels in all subjects for the duration of the study (P <0.009). No significant changes in body composition, energy expenditure, or M were observed at either 2 or 4 weeks of castration. Acyline is an effective GnRH antagonist inducing acute castration in all subjects. ii) Four weeks of biochemical castration has no impact on insulin sensitivity in healthy men likely due to unchanged body composition variables. iii) Insulin resistance associated with chronic low T levels may be largely driven by decreased fat free mass, increased percent body fat, and/or other metabolic regulatory factors.

Association of Testosterone and Sex Hormone–Binding Globulin With Metabolic Syndrome and Insulin Resistance in Men

OBJECTIVEWe sought to assess the associations of testosterones and sex hormone–binding globulin (SHBG) with metabolic syndrome and insulin resistance in men.RESEARCH DESIGN AND METHODSWe defined metabolic syndrome according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Among men aged ≥20 years who participated in the Third National Health and Nutrition Examination Survey (n = 1,226), the Cox proportional hazards model was used to estimate the prevalence ratio and 95% CI of metabolic syndrome according to circulating concentrations of testosterones and SHBG.RESULTSAfter adjustment for age, race/ethnicity, smoking status, alcohol intake, physical activity level, LDL cholesterol, C-reactive protein, and insulin resistance, men in the first quartile (lowest) (prevalence ratio 2.16 [95% CI 1.53–3.06]) and second quartile of total testosterone (2.51 [1.86–3.37]) were more likely to have metabolic syndrome than men in the fourth quartile (highest, referent group) (P < 0.001 for linear trend). Similarly, men in the first quartile of SHBG (2.17 [1.32–3.56]) were more likely to have metabolic syndrome than men in the fourth quartile (P = 0.02 for linear trend). No significant associations of calculated free testosterone (P = 0.31 for linear trend) and bioavailable testosterone (P = 0.11 for linear trend) with metabolic syndrome were detected after adjustment for all possible confounders.CONCLUSIONSLow concentrations of total testosterone and SHBG were strongly associated with increased likelihood of having metabolic syndrome, independent of traditional cardiovascular risk factors and insulin resistance.