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Patients with hypopituitarism have an increased mortality from cardiovascular events. Reduced nocturnal blood pressure decline (non-dipping) and impaired glucose tolerance are considered as cardiovascular risk factors. To evaluate the role of these risk factors in patients with hypopituitarism we determined the 24-hour blood pressure regulation and glucose tolerance status in hypopituitary patients with and without growth hormone (GH) deficiency. Sixty-one hypopituitary subjects 5 +/- 3 years after brain surgery because of macroadenoma, 61 patients with type 2 diabetes mellitus (T2DM), and 20 healthy controls were included. Forty-four hypopituitary patients were GH deficient and 28 of these on GH treatment. Non-dipping was observed in 41 % (n = 7) of hypopituitary subjects with normal GH release, in 46 % (n = 13) of patients on GH therapy, and in 69 % (n = 11) of untreated GH deficient patients. Untreated GH deficient patients had a higher systolic night/day ratio (1.00 +/- 0.03) compared to non GH deficient (0.92 +/- 0.02; p < 0.02) and GH treated hypopituitary patients (0.93 +/- 0.01; p < 0.02). The rate of non-dipping in hypopituitarism was comparable to that in T2DM. Pathologic glucose tolerance was diagnosed in 30 % of the hypopituitary patients. The prevalence of non-dipping was independent of glucose metabolism in hypopituitary patients. All controls had normal night time blood pressure fall and glucose metabolism. The high prevalence of nocturnal non-dipping and glucose intolerance detected in this cohort might contribute to the increased cardiovascular risk of hypopituitary patients.

Low Sex-Hormone-Binding Globulin (SHBG) levels--indicating a state of hyperandrogenicity--are associated with a higher risk for the development of non-insulin dependent diabetes (NIDDM) in women and are accepted as a marker of muscular insulin resistance. To analyze whether low SHBG values are also present in patients with gestational diabetes, we investigated levels of SHBG in 42 patients with gestational diabetes mellitus (GDM) in comparison with 48 pregnant women with normal glucose tolerance (NGT). Beside maternal parameters like body-mass index (BMI), HbA1c, fasting, 1- and 2-hour blood glucose and insulin concentrations, parameters of the new-borns (head-circumference, body weight, height and sex) were recorded. Maternal and neonatal variables were then related to SHBG levels. Both groups showed no differences in BMI, height, weight or age of gestation. Patients with GDM revealed significantly lower levels of SHBG than pregnant women with NGT(512 +/- 249 nmol/l vs. 643 +/- 137 nmol/l; p < 0.01). In patients with severe GDM and insulin therapy significantly lower levels of SHBG than in those with dietary treatment only were found (223 +/- 210 nmol/l vs. 592 +/- 102 nmol/l; p < 0.001). SHBG was inversely correlated to BMI (r = - 0.30; p < 0.01), 1-hour (r = - 0.20; p < 0.05) and 2-hour blood glucose levels (r = - 0.30; p <0.01). In summary, we found significantly lower levels of SHBG in patients with GDM, especially in those who developed severe GDM and required insulin therapy during the last months of pregnancy.

LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults and represents a considerable proportion (about 5-10%) of all diabetic patients. Associations with high risk HLA genotypes and autoimmune phenomena (GAD, IA2, ICA) show similarities with type 1 diabetes, but phenotypical characteristics of these patients do not allow the correct identification without screening of GAD antibodies. The relatively low antibody titers against islet-cell antigens in LADA patients may be sign of a less aggressive form of autoimmune diabetes and could be responsible for the long non-insulin requirement phase of this diabetes type. Similar as in prediabetic relatives of type 1 diabetic patients the risk for beta cell failure in adult "type 2 diabetic" patients increases with the number of antibodies positive. Consequently, low titers of GAD--in particular in elderly patients--do not predict a progressive and rapid loss of beta-cell failure, when associations with high risk genotypes or other islet-cell antibodies are lacking. Patients with LADA share insulin resistance with type 2 diabetic patients, but display a more severe defect in stimulated beta-cell capacity than patients with classical type 2 diabetes. With respect to features of the metabolic syndrome, patients with LADA have lower BMI, blood pressure and triglyceride levels compared with classical type 2 diabetes patients. Early identification of LADA patients will be mandatory, when effective immune interventions are available for prevention of the beta-cell destructive process and insulin requirement of these patients.

Endothelial cell activations and/or dysregulations of the coagulation system are crucial parameters for the prognosis of disease in patients with IDDM. Recent data suggest that expression of the adhesion molecules E-selectin and P-selectin are markers of endothelial cell activation and/or platelet activation and might modify immunologic responses after shedding from cell membranes. In patients with newly diagnosed IDDM only limited data on circulating selectins are available. This has prompted us to measure levels of soluble (s) forms of P-selectin and E-selectin in 18 patients with newly diagnosed IDDM and two years after the onset of insulin substitution therapy in comparison to 18 age-matched healthy control subjects. HbA1c and blood glucose levels were significantly higher in patients with new onset diabetes, compared to the same patients after two years of insulin therapy (HbA1c: 12 +/- 3% vs. 7.8 +/- 2%; p < 0.01; blood-glucose: 409 +/- 163 mg/dl vs. 131 +/- 23 mg/dl; p < 0.01), but no correlation between these metabolic parameters and soluble forms of E- and P-selectins were noted. Levels of sP-selectin decreased from 210 +/- 120 ng/ml in newly diagnosed IDDM patients to 127 +/- 75 ng/ml after two years of therapy (p < 0.01) and were similar to those of the control subjects (110 +/- 31 ng/ml). Serum concentrations of circulating E-selectin showed no differences in the three groups (newly diagnosed IDDM: 42 +/- 17 ng/ml; two years later: 43 +/- 19 ng/ml; control subjects: 41 +/- 14 ng/ml; n.s.). Increased levels of sP-selectin together with normal levels of sE-selectin at the onset of IDDM suggest enhanced platelet activation during the initial phase of the autoimmune process and return to baseline levels within two years of the disease.