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OBJECTIVE -The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organizationdefined metabolic syndrome, independent of conventional cardiovascular risk factors. -up (1991-2001), 1,565 patients were regularly examined with centralized measurements of HbA 1c . The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. RESEARCH DESIGN AND METHODS -During the followRESULTS -At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6 -77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16 -7.33), independent of other risk factors.CONCLUSIONS -We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components.

OBJECTIVE -Incidence of type 1 diabetes is considered to be low in adults, but no study has been performed in Mediterranean countries.RESEARCH DESIGN AND METHODS -We extended the study base of the registry of the province of Turin, Italy, to subjects aged 30 -49 years in the period 1999 -2001 to estimate the incidences of type 1 and type 2 diabetes. Diagnosis of type 1 diabetes was based on permanent insulin treatment or a fasting C-peptide level Յ0.20 nmol/l or islet cell (ICA) or GAD (GADA) antibody positivities.RESULTS -We identified 1,135 case subjects with high completeness of ascertainment (99%), giving an incidence rate of 58.0 per 100,000 person-years (95% CI 54.7-61.5). The incidence of type 1 diabetes was 7.3 per 100,000 person-years (6.2-8.6), comparable with the rates in subjects aged 0 -14 and 15-29 years (10.3 [9.5-11.2] and 6.8 [6.3-7.4]). Male subjects had a higher risk than female subjects for both type 1 (rate ratio [RR] CONCLUSIONS -Risk of type 1 diabetes between age 30 and 49 years is similar to that found in the same area between age 15 and 29 years. Further studies are required to allow geographical comparisons of risks of both childhood and adulthood autoimmune diabetes, the latter being probably higher than previously believed.

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OBJECTIVE -Dehydroepiandrosterone (DHEA) has been shown to prevent oxidative stress in several in vivo and in vitro models. This study aimed to evaluate the effects of DHEA administration on oxidative stress, pentosidine concentration, and tumor necrosis factor (TNF)-␣/ TNF-␣ receptor system activity in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -Twenty patients were enrolled in the study and randomly assigned to the DHEA (n ϭ 10) or placebo (n ϭ 10) group. Twenty healthy sexand age-matched subjects with normal glucose levels served as control subjects. DHEA was given as a single daily dose of 50 mg for 12 weeks.RESULTS -Oxidative stress parameters were significantly higher in diabetic patients versus control subjects. Pentosidine levels, as well as soluble TNF receptor (sTNF-R)I and sTNF-RII, were also higher in diabetic patients. After DHEA, plasma levels of reactive oxygen species and hydroxynonenal dropped by 53 and 47%, respectively, whereas the nonenzymatic antioxidants glutathione and vitamin E increased (ϩ38 and ϩ76%, respectively). The same changes in oxidative parameters were detected in peripheral blood mononuclear cells (PBMCs). DHEA treatment also induced a marked decrease of pentosidine plasma concentration in diabetic patients (Ϫ50%). Moreover, the TNF-␣/TNF-␣ receptor system was shown to be less activated after DHEA treatment, in both plasma and PBMCs.CONCLUSIONS -Data indicate that DHEA treatment ameliorates the oxidative imbalance induced by hyperglycemia, downregulates the TNF-␣/TNF-␣ receptor system, and prevents advanced glycation end product formation, suggesting a beneficial effect on the onset and/or progression of chronic complications in type 2 diabetic patients. Diabetes Care 30:2922-2927, 2007T he onset and progression of diabetes complications involves a complex interplay between ranges of pathogenic mechanisms. However, emerging evidence suggests that a single early phenomenon, i.e., the overproduction of superoxide by the respiratory chain, plays a key role in the pathogenesis of both microvascular and macrovascular chronic complications (1-3).The production of advanced glycation end products (AGEs) is among the main mechanisms recruited by oxidative stress and is involved in the pathogenesis of tissue injury (3,4). AGEs progressively accumulate with time at the sites of diabetic microvascular disease and mediate tissue damage by activation of specific receptors at distant sites, via circulation (3,5). Moreover, the AGE/AGE receptor interaction, along with hyperglycemiainduced oxidative stress, possibly serves as a key activator of upstream kinases, leading to increased production of inflammatory cytokines thought to be involved in the progression of chronic diabetes complications (6).Interruption of free radical overproduction by antioxidants counteracts AGE formation (2). Nevertheless, despite convincing experimental results, clinical trials with traditional antioxidants have been disappointing (7)-the activity of the antioxidants used in those trials is limited to...