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 hormonebinding 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. Diabetes Care 27:1036 -1041, 2004I n cross-sectional studies, low levels of total and free testosterone and sex hormone-binding globulin (SHBG) in men have consistently been associated not only with type 2 diabetes, but also with visceral obesity, insulin resistance or hyperinsulinemia, dyslipidemia (1-7), and, more recently, the metabolic syndrome itself (6). The association of testosterone and SHBG with an altered lipid profile is partly secondary to abdominal fat accumulation, but there also appears to be an independent relationship between low levels of testosterone and hyperinsulinemia (4) and dyslipidemia (8). Low levels of testosterone have also predicted worsening abdominal obesity (9).Testosterone itself may have a central or permissive role in the pathogenesis of the metabolic syndrome and type 2 diabetes by increasing skeletal muscle tissue and decreasing abdominal obesity and nonesterified fatty acids, consequently improving insulin sensitivity (10). Overall or abdominal obesity increases glucocorticoid turnover and production, which disturbs regulation of the hypothalamic-pituitary-adrenal axis (11,12) and may contribute to mild hypoandrogenism in men. An imbalance between levels of testosterone and its metabolite dihydrotestosterone could...

The objective of the study was to evaluate the diagnostic efficiency of laboratory tests, including serum transferrin receptor (TfR) measurements, in the diagnosis of iron depletion. The patient population consisted of 129 consecutive anemic patients at the University Hospital of Turku who were given a bone marrow examination. Of these patients, 48 had iron deficiency anemia (IDA), 64 anemia of chronic disease (ACD), and 17 patients had depleted iron stores and an infectious or an inflammatory condition (COMBI). Depletion of iron stores was defined as a complete absence of stainable iron in the bone marrow examination. Serum TfR concentrations were elevated in the vast majority of the IDA and COMBI patients, while in the ACD patients, the levels were within the reference limits reported earlier for healthy subjects. TfR measurement thus provided a reliable diagnosis of iron deficiency anemia (AUCROC 0.98). Serum ferritin measurement also distinguished between IDA patients and ACD patients. However, the optimal decision limit for evaluation of ferritin measurements was considerably above the conventional lower reference limits, complicating the interpretation of this parameter. Calculation of the ratio TfR/log ferritin (TfR-F Index) is a way of combining TfR and ferritin results. This ratio provided an outstanding parameter for the identification of patients with depleted iron stores (AUCROC 1.00). In anemic patients, TfR measurement is a valuable noninvasive tool for the diagnosis of iron depletion, and offers an attractive alternative to more conventional laboratory tests in the detection of depleted iron stores.

Objective: Mild hypoandrogenism in men is associated with features of the metabolic syndrome, but the association with the metabolic syndrome itself using an accepted definition has not been described. Design: Men with the metabolic syndrome were identified and testosterone and sex hormone-binding globulin (SHBG) levels were determined in a population-based cohort of 1896 non-diabetic middleaged Finnish men. Results: Calculated free testosterone and SHBG were 11% and 18% lower (P , 0.001) in men with the metabolic syndrome (n ¼ 345, World Health Organisation definition). After categorisation by tertiles and adjusting for age and body mass index, total and free testosterone and SHBG were inversely associated with concentrations of insulin, glucose, triglycerides, C-reactive protein (CRP) and CRP-adjusted ferritin and positively associated with high-density lipoprotein cholesterol. Men with free testosterone levels in the lowest third were 2.7 (95% confidence interval (CI) 2.0-3.7) times more likely to have the metabolic syndrome in age-adjusted analyses, and 1.7 (95% CI 1.2 -2.4) times more likely even after further adjusting for body mass index. Exclusion of men with cardiovascular disease did not alter the association. The inverse association of SHBG with the metabolic syndrome was somewhat stronger. Conclusions: Low testosterone and SHBG levels were strongly associated not only with components of the metabolic syndrome, but also with the metabolic syndrome itself, independently of body mass index. Furthermore, sex hormones were associated with inflammation and body iron stores. Even in the absence of late-stage consequences such as diabetes and cardiovascular disease, subtle derangements in sex hormones are present in the metabolic syndrome, and may contribute to its pathogenesis.

Abstract-Development of hypertension has been linked to chronic low-grade inflammation. However, it is not known whether this connection is mediated by features of the metabolic syndrome or smoking, or their changes, which themselves have been linked to inflammation. We studied the predictive value of highly sensitive C-reactive protein (hs-CRP), smoking, and abdominal obesity to the development of hypertension in an 11-year follow-up of a population-based study cohort comprising 379 middle-aged normotensive men. During the follow-up, 124 men (33%) developed hypertension. Men with hs-CRP Ն3.0 mg/L were 2.8ϫ (95% confidence interval, 1.2 to 6.6) more likely to develop hypertension than with hs-CRP Ͻ1.0 mg/L even after adjustment for features of the metabolic syndrome, lifestyle factors, and their changes. Cigarette smoking was also associated with development of hypertension independently of inflammation and other confounders. Waist girth increased more in men who quit smoking than in other men. An increase in waist girth during follow-up strongly predicted incident hypertension. The decrease in smoking was not associated with a lower risk of hypertension in age-adjusted analyses. Hypertension is preceded by low-grade chronic inflammation in middle-aged white men independently of smoking or features of the metabolic syndrome. Furthermore, smoking may be a risk factor for hypertension. Although stopping smoking is beneficial with respect to health outcomes, the subsequent increase in weight and waist girth associated with smoking cessation may offset the decrease in the risk of hypertension that one may otherwise expect. Key Words: obesity Ⅲ smoking Ⅲ prospective studies Ⅲ insulin resistance C hronic low-grade inflammation seems to be an early feature of many chronic degenerative disorders, including atherosclerosis, abdominal obesity, and type 2 diabetes. 1-3 These disorders are also commonly associated with hypertension, which itself has also been linked recently to inflammation. The most compelling evidence comes from the Women's Health Study, in which C-reactive protein (CRP) as a marker of low-grade inflammation predicted the development of hypertension in a cohort of 20 525 female US health professionals during a follow-up of 7.8 years. 4 This effect was seen even in those with low baseline blood pressure levels and in those without other conventional cardiovascular risk factors, but no adjustment could be made for the presence of the metabolic syndrome, a possible mediator of this connection. 5 Smoking causes an acute rise in blood pressure, whereas the connection between chronic smoking and development of hypertension is still unclear. Smoking in its own right increases inflammation, 6 but smoking cessation may not reverse it. 7 Furthermore, stopping smoking commonly leads to weight gain. Weight gain is a well-established risk factor for hypertension. Moreover, weight gain and obesity, especially abdominal, appear to not only cause inflammation but may be preceded by inflammation. 8 Complicating the pictur...