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Plasminogen activator inhibitor-1 (PAI-1) is implicated in the pathophysiology of cardiovascular disease (CVD) and increased in individuals with type 2 diabetes mellitus (T2DM). Adipose tissue produces PAI-1, and pericardial fat is a CVD risk factor. We sought to determine the relationship between PAI-1 and pericardial fat in males and females with well-controlled T2DM.The study population consisted of 32 males and 19 females, aged 35-70 years with T2DM, without clinical evidence of CVD or other active medical problems except for hypertension. Subjects were studied under good cardiometabolic control. Study procedures included fasting blood work and cardiovascular imaging. Cardiac magnetic resonance imaging of the heart was used to identify and quantify pericardial fat from the bifurcation of the pulmonary trunk to the last slice containing cardiac tissue.PAI-1 was positively correlated with pericardial fat (β = 0.72, r = 0.72, P 0.001) as well as with homeostatic model assessment of insulin resistance (r = 0.31, P = 0.03) and serum triglycerides (r = 0.27, P = 0.05). In a multivariable regression model, controlling for insulin sensitivity, triglycerides, and body mass index, pericardial fat was independently associated with PAI-1 (β = 0.80, P 0.001).PAI-1 is positively associated with pericardial fat in individuals with T2DM.

The objective of this study was to evaluate the gonadal function in men with type 2 diabetes with erectile dysfunction.We examine records of 50 patients with type 2 diabetes and erectile dysfunction who had low free testosterone concentrations. All patients had plasma concentrations of luteinizing hormones (LH), follicle-stimulating hormone (FSH), and prolactin measured.Of the 50 patients with low free testosterone concentrations (0.97 +/- 0.4 ng/dL; reference range, 1.30-3.10), 43 had normal (inappropriately low) LH (5.9 +/- 2.9 mIU/mL), FSH (5.6 +/- 2.4 mIU/mL), and testosterone concentrations, five had elevated LH, FSH concentrations (Hypogonadotropic hypogonadism), and two had prolactinoma. Patients with hypogonadotropic hypogonadism were in their mid 50's and had experienced a decline in their testosterone levels much earlier than that expected from the normal age-related decline. Although a majority of the patients were obese, there was no relationship between testosterone (free or total) and BMI, between testosterone and HbA(1c), duration of diabetes or the age of the patient. Patients given testosterone supplementation experienced a subjective improvement in their wellbeing, but reported no significant improvement in their erectile dysfunction.We conclude that patients with erectile dysfunction require careful assessment and that the most frequent gonadal defect in these patients is that of hypogonadotropic hypogonadism, a defect not previously associated with type 2 diabetes. The mechanism underlying this defect requires investigation. The value of testosterone replacement in such patients needs to be assessed critically.

Fasting hyperinsulinemia is associated with an increased risk of atherosclerotic complications of heart attack and stroke. This has resulted in the concept that insulin may promote atherosclerosis in spite of the absence of any evidence that insulin is atherogenic either in the human or in experimental models. Recent evidence shows that insulin exerts vasodilatory, anti-platelet and anti-inflammatory effects at the cellular level in vitro and in the human in vivo. Since atherosclerosis is a chronic inflammatory process of the arterial wall, insulin may be potentially anti-atherosclerotic in the long term. More recent data on experimental atherosclerosis in the mouse shows that (1) insulin administration reduces the number and the size of atherosclerotic lesions in apo E null mice and (2) in IRS-2 null mice, the interruption in insulin signal transduction results in enhanced atherogenicity. Finally, the use of a low dose of insulin infusion in patients with acute myocardial infarction has been shown to markedly improve clinical outcomes, both in diabetic and nondiabetic patients. Our own most recent data show that a low dose infusion of insulin in patients with acute myocardial infarction induces a reduction in inflammation (C-reactive protein and serum amyloid A) and oxidative stress, and promotes fibrinolysis. We conclude that insulin is anti-inflammatory and potentially antiatherogenic and may be of use in the treatment of cardiovascular inflammatory conditions.