Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men

OBJECTIVE: In men, hypoandrogenism is associated with features of the metabolic syndrome, but the role of sex hormones in the pathogenesis of the metabolic syndrome and diabetes is not well understood. We assessed the association of low levels of testosterone and sex hormone-binding globulin (SHBG) with the development of the metabolic syndrome and diabetes in men. RESEARCH DESIGN AND METHODS: Concentrations of SHBG and total and calculated free testosterone and factors related to insulin resistance were determined at baseline in 702 middle-aged Finnish men participating in a population-based cohort study. These men had neither diabetes nor the metabolic syndrome. RESULTS: After 11 years of follow-up, 147 men had developed the metabolic syndrome (National Cholesterol Education Program criteria) and 57 men diabetes. Men with total testosterone, calculated free testosterone, and SHBG levels in the lower fourth had a severalfold increased risk of developing the metabolic syndrome (odds ratio [OR] 2.3, 95% CI 1.5-3.4; 1.7, 1.2-2.5; and 2.8, 1.9-4.1, respectively) and diabetes (2.3, 1.3-4.1; 1.7, 0.9-3.0; and 4.3, 2.4-7.7, respectively) after adjustment for age. Adjustment for potential confounders such as cardiovascular disease, smoking, alcohol intake, and socioeconomic status did not alter the associations. Factors related to insulin resistance attenuated the associations, but they remained significant, except for free testosterone. CONCLUSIONS: Low total testosterone and SHBG levels independently predict development of the metabolic syndrome and diabetes in middle-aged men. Thus, hypoandrogenism is an early marker for disturbances in insulin and glucose metabolism that may progress to the metabolic syndrome or frank diabetes and may contribute to their pathogenesis.     

Sex hormone-binding globulin levels in middle-aged premenopausal women. Associations with visceral obesity and metabolic profile.

OBJECTIVE: Low sex hormone-binding globulin (SHBG) levels in women are associated not only with hyperinsulinemia, increased risk for cardiovascular disease, and type 2 diabetes but also with excess body fatness and abdominal obesity. We tested the hypothesis that an elevated total or intra-abdominal adipose tissue accumulation mediates the relationship between low SHBG levels and an altered metabolic profile. RESEARCH DESIGN AND METHODS: We measured body composition (dual-energy X-ray absorptiometry [DEXA]) and body fat distribution (computed tomography) in 52 middle-aged (46.7 +/- 0.4, mean +/- SEM) premenopausal women. Insulin and glucose responses to a 75-g oral glucose load and plasma lipid-lipoprotein levels were also measured. RESULTS: Low plasma SHBG concentrations were associated with increased total body fat mass (r = -0.41, P < 0.005) and subcutaneous abdominal (r = -0.39, P < 0.005) and intra-abdominal (r = -0.37, P < 0.008) adipose tissue area. Low SHBG was also associated with a greater insulin response to oral glucose (r = -0.40, P < 0.005), higher triglyceride levels (r = -0.29, P < 0.05), higher cholesterol/HDL cholesterol ratio (r = -0.51, P < 0.005), but lower HDL cholesterol concentrations (r = 0.65, P < 0.005). When matched for intra-abdominal fat or total fat mass, subjects with either low or high SHBG showed no difference in the insulin response to an oral glucose challenge. Statistical adjustment for differences in intra-abdominal adipose tissue accumulation or total body fat mass also eliminated the associations between SHBG levels and metabolic variables, with the exception of the association between SHBG and HDL cholesterol levels (r = 0.52, P < 0.005). CONCLUSIONS: Our results suggest that the previously reported relationship between low SHBG levels and increased metabolic disease risk in women is mediated, to a large extent, by concomitant variation in body fatness and intra-abdominal adipose tissue accumulation.     

Low serum adiponectin is independently associated with both the metabolic syndrome and angiographically determined coronary atherosclerosis

BACKGROUND: We aimed at investigating serum adiponectin in patients with the metabolic syndrome (MetS), in patients with angiographically diagnosed coronary artery disease (CAD), and in patients who had both, the MetS and CAD. METHODS: We enrolled 687 consecutive patients undergoing coronary angiography for the evaluation of CAD. RESULTS: From our patients, 178 had neither the MetS (Adult Treatment Panel III definition) nor significant CAD (MetS-/CAD-), 91 had the MetS, but not significant CAD (MetS+/CAD-), 251 did not have the MetS but had significant CAD (MetS-/CAD+), and 167 had both, the MetS and significant CAD (MetS+/CAD+). Serum adiponectin was highest (12.1+/-8.3 microg/ml) in MetS-/CAD- subjects. It was significantly lower in MetS+/CAD- (9.5+/-7.3 microg/ml; p=0.001) and in MetS-/CAD+ patients (9.2+/-5.3 microg/ml; p<0.001) and lowest in MetS+/CAD+ patients (6.7+/-3.8 microg/ml) in whom it was significantly lower than in MetS-/CAD-, MetS+/CAD-, and MetS-/CAD+ patients (p<0.001 for all comparisons). In analysis of covariance the MetS and significant CAD proved associated with serum adiponectin in a mutually independent manner. CONCLUSIONS: Low serum adiponectin is independently associated with both the MetS and coronary atherosclerosis.     

Insulin resistance is associated with the metabolic syndrome and is not directly linked to coronary artery disease

BackgroundInsulin resistance (IR) is the key feature of the metabolic syndrome (MetS). Its association with directly visualized coronary atherosclerosis is unclear. We hypothesised that insulin resistance is associated with both angiographically determined coronary artery disease (CAD) and with the MetS.MethodsIn 986 consecutive patients undergoing coronary angiography for the evaluation CAD, IR was determined by the HOMA index; the MetS was defined according to NCEP-ATPIII criteria; and significant CAD was diagnosed when coronary stenoses ≥ 50% were present.ResultsHOMA IR scores were higher in MetS patients than in subjects without the MetS (4.9 ± 6.4 vs. 2.2 ± 2.0; p < 0.001). HOMA IR did not differ significantly between patients with significant CAD and those who did not have significant CAD. When both, the presence of MetS and of significant CAD were considered, HOMA IR was significantly higher in patients with the MetS both among those who had significant CAD (4.9 ± 6.8 vs. 2.2 ± 1.8; p < 0.001) and among those who did not have significant CAD (5.0 ± 5.8 vs. 2.1 ± 2.3; p < 0.001), it did not differ significantly between patients with significant CAD and subjects without significant CAD among patients with the MetS nor among those without MetS. Similar results were obtained with the IDF definition of the MetS.ConclusionIR is significantly associated with the MetS but not with angiographically determined CAD. IR may play a greater role in the eventual precipitation of thrombosis than in the gradual progression of atherosclerosis.     

Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat

OBJECTIVE: Previous reports of an association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markers of insulin resistance and body fat measures in 221 middle-aged nondiabetic men. RESEARCH DESIGN AND METHODS: Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07-0.1). In contrast, total testosterone correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). RESULTS: Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = -0.15 [P = 0.03], -0.14 [P = 0.03], -0.32 [P < 0.0001], and -0.38 [P < 0.0001], respectively), fasting C-peptide (r = -0.18 [P = 0.009] to -0.41 [P < 0.0001]), HOMA-IR (r = -0.15 [P = 0.03] to - 0.39 [P < 0.0001]), and body fat measures (r = -0.17 [P = 0.008] to -0.44 [P < 0.0001]). Only SHBG and total testosterone were significantly associated with fasting glucose (r = -0.20 [P = 0.003] to -0.21 [P = 0.002]). In multivariate analysis, bioavailable or free testosterone was significantly and inversely associated with insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG. CONCLUSIONS: The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat.     

Frailty is not independently associated with intensive care unit length of stay: An observational study

BackgroundFrailty is independently associated with morbidity and mortality in critically ill patients. However, the association between preadmission frailty and the degree of treatment received in the intensive care unit (ICU) remains unclear.ObjectiveTo describe patient length of stay in an ICU and the treatments provided according to the extent of patient frailty.MethodsSingle-centre retrospective cohort study of adult patients admitted to a tertiary ICU between January 2018 and December 2019. Frailty was assessed using the Clinical Frailty Scale (CFS). The primary outcome was ICU length of stay stratified by CFS score (1–8). Secondary outcomes were the proportion of patients with each CFS score treated with vasoactive agents, invasive ventilation, noninvasive ventilation, renal replacement therapy, and tracheostomy. Poisson regression and competing risks regression was used to analyse associations between ICU length of stay and potential confounders.ResultsThe study cohort comprised 2743 patients, with CFS scores known for 2272 (83%). Length of stay in the ICU increased with each increment in the CFS up to a score of 5, beyond which it decreased with higher frailty scores. After adjusting for age, illness severity, admission type, and treatment limitation, CFS scores were not independently associated with length of stay in the ICU (P = 0.31). The proportion of patients receiving specific ICU treatments peaked at different CFS scores, being highest for vasoactive agents at CFS 5 (47%), invasive ventilation CFS 3 (51%), noninvasive ventilation CFS 6 (11%), renal replacement therapy CFS 6 (8.2%), and tracheostomy CFS 5 (2.2%). Increasing frailty was associated with increased mortality and discharge to a destination other than home.ConclusionsThe extent of frailty is not independently associated with length of stay in the ICU. The proportion of patients receiving specific ICU treatments peaked at different CFS scores.     

Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study

OBJECTIVE: To test the hypothesis that enzymes conventionally associated with liver dysfunction (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase [GGT], and alkaline phosphatase) may predict diabetes. RESEARCH DESIGN AND METHODS: From a population-based diabetes survey, we selected 1,441 men and women in whom serum enzyme levels were < or =3 SDs of the mean population value, alcohol intake was <250 g/week, and hepatitis B and C virus testing was negative. At follow-up (7 years), 94 subjects developed diabetes and 93 impaired glucose tolerance (IGT). RESULTS: At baseline, all four enzymes were related to most of the features of the metabolic syndrome. After controlling for sex, age, adiposity/fat distribution, alcohol intake, serum lipids, and blood pressure, higher alanine aminotransferase and GGT values were significantly (P < 0.01) associated with both IGT and diabetes, whereas alkaline phosphatase was associated with diabetes only (P = 0.0004) and aspartate aminotransferase with IGT only (P = 0.0001). Raised GGT alone was associated with all the features of the metabolic syndrome. Raised GGT was a significant predictor of either IGT or diabetes (odds ratio 1.62 [95% CI 1.08-2.42] top quartile vs. lower quartiles, P < 0.02) after controlling for sex, age, adiposity/fat distribution, alcohol consumption, fasting plasma insulin and proinsulin levels, and 2-h postglucose plasma glucose concentrations. CONCLUSIONS: Although mild elevations in liver enzymes are associated with features of the metabolic syndrome, only raised GGT is an independent predictor of deterioration of glucose tolerance to IGT or diabetes. As GGT signals oxidative stress, the association with diabetes may reflect both hepatic steatosis and enhanced oxidative stress.     

Alanine aminotransferase and gamma-glutamyl transferase are associated with the metabolic syndrome but not with angiographically determined coronary atherosclerosis

BACKGROUND: Recently, elevated liver enzymes have attracted great interest as potential novel markers of cardiovascular risk. Their association with angiographically determined coronary artery disease (CAD) is unknown. METHODS: We enrolled 1000 consecutive patients undergoing coronary angiography for the evaluation of suspected or established stable CAD. The metabolic syndrome (MetS) was defined according to ATP-III criteria; significant CAD was diagnosed in the presence of coronary stenoses with lumen narrowing >/=50%. RESULTS: Serum alanine aminotransferase (ALT), the ALT/aspartate aminotransferase (AST) ratio, and serum gamma-glutamyl transferase (GGT) were significantly higher in patients with the MetS than in subjects without the MetS (34+/-21 vs. 29+/-20 U/l; p<0.001, 1.16+/-0.39 vs. 1.00+/-0.36 U/l, p<0.001; and 53+/-88 vs. 43+/-57 U/l, p=0.001, respectively) but were similar in patients with significant CAD as in those who did not have significant CAD at angiography (p=0.592; p=0.731, and p=0.716, respectively). Analysis of covariance after multivariate adjustment including alcohol consumption confirmed that ALT, ALT/AST ratio, and GGT were significantly and independently associated with the MetS but not with significant CAD. CONCLUSIONS: ALT, the ALT/AST ratio, and GGT are associated with the MetS but not with angiographically determined coronary atherosclerosis.     

中老年男性血清睾酮与代谢综合征的关系

目的 探讨中老年男性代谢综合征(MS)患者血清睾酮下降的原因.方法 选取45～ 83岁的中老年男性56例为研究对象,分别测量其血压、身高、体质量,计算体质量指数(BMI),检测空腹状态下生化指标[血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、空腹胰岛素(FIN)及血清睾酮,并用稳态公式(HOMA)计算胰岛素抵抗指数(HOMA-IR).根据CDS建议的MS诊断标准,将研究对象分为MS组及非MS组,分析睾酮浓度与各指标的关系.结果 中老年男性MS组血清睾酮浓度明显低于非MS组[(9.97±3.87)nmol/L与(13.73±3.93)nmol/L,t=3.337,P＜0.01],多因素回归分析显示,血清睾酮浓度与年龄、腰围、HOMA-IR呈负相关(回归系数分别为-0.214、-0.329、-0.317,标准回归系数分别为-0.730、-0.597、-0.313,t值分别为-5.833、-4.681、-2.686,P均＜0.01).结论 中老年男性MS患者血清睾酮浓度下降,血清睾酮浓度与年龄、腰围、胰岛素抵抗密切相关.