No abstract

Aim:Postprandial release of intact proinsulin (IP) is an independent marker for β-cell dysfunction in patients with type 2 diabetes. This open-label, parallel-group, two-arm, pilot study compared the β-cell protective effect of adding insulin glargine (GLA) vs. NPH insulin to ongoing metformin.Material and methods:Overall, 28 insulin-naive type 2 diabetes subjects (mean ± SD age, 61.5 ± 6.7 years; diabetes duration, 9.8 ± 6.5 years; HbA1c, 7.1 ± 0.5%; BMI, 30.7 ± 4.3 kg/m2) treated with metformin and sulfonylurea were randomized to add once-daily GLA or NPH at bedtime. At baseline and after 3 months, subjects received a standardized breakfast, lunch and dinner, with pre- and postprandial blood sampling to measure plasma IP, total insulin and blood glucose (BG).Results:Insulin dose after 3 months was comparable in both groups (GLA vs. NPH: 23.6 ± 13.4 vs. 23.3 ± 12.7; p = NS ). Both treatments significantly reduced fasting BG levels (GLA: 158 ± 19 to 121 ± 23 mg/dl; NPH: 156 ± 34 to 119 ± 29 mg/dl; both p < 0.01 vs. baseline). Fasting and postprandial BG levels did not differ between groups. IP levels decreased in both groups (p < 0.05 at all timepoints). Although IP release after breakfast did not differ between treatments, GLA induced a greater reduction in IP release after lunch (p = 0.08) and dinner (p = 0.04). Total plasma insulin levels did not differ between groups.Conclusions:Adding basal insulin to metformin reduces postprandial β-cell load. While GLA and NPH had comparable effects at breakfast, GLA reduces β-cell stress more effectively at dinner, and with a trend at lunch, most probably because of its longer lasting pharmacodynamic profile.

These observational results, obtained from a nonselected patient population under daily routine conditions, confirm the benefits of pioglitazone treatment on blood glucose, lipid metabolism, and blood pressure. The results show that pioglitazone treatment improves chronic vascular inflammation, which may be associated with reduced cardiovascular risk.

The relevance of tumor necrosis factor-alpha (TNF-alpha) inducing early inflammatory reactions in the liver after hemorrhagic shock, for example, leukocyte adhesion, has been well described. This study evaluated the anti-inflammatory effects of a monoclonal antibody against TNF-alpha (TN3.19.12) in terms of the time of application, namely, prior to shock induction, at the time of resuscitation, and after resuscitation. The hepatic microcirculation was investigated by intravital fluorescence microscopy in female Sprague-Dawley rats undergoing severe hemorrhagic shock for 60 min and subsequent resuscitation. TN3.19.12 or placebo was given in a randomized and blinded manner either 60 min prior to shock induction, 1 min prior to resuscitation, or 15 min after the onset of resuscitation. The number of firmly adherent leukocytes in the livers of treated animals depended on the time of application of TN3.19.12. Leukocyte adhesion was significantly reduced when TN3.19.12 was given prior to shock induction or at the time of resuscitation and was less effective when administered after the onset of resuscitation. The results further confirm that TNF-alpha initiates very early pathological leukocyte adhesion in the liver 5 h following shock. Inhibition of leukocyte adhesion after shock, however, depends strongly on the time of TNF-alpha blocking. While TN3.19.12 prior to shock induction resulted in most effective attenuation, only very early treatment allowed limitation of posttraumatically increased leukocyte adhesion.

The metabolic syndrome summarizes a cluster of several disorders associated with an increased risk of type 2 diabetes and cardiovascular disease including dyslipidaemia, hypertension and hyperglycaemia [1]. Obesity and insulin resistance are the two major nominators considered to be the link between the metabolic disorders. Medical treatment with thiazolidinediones, also referred to as insulin sensitizers, is known to improve the overall metabolic profile [2]. This study was designed to investigate the effects of an onset of a pioglitazone therapy on markers of the metabolic syndrome and body weight if patients are treated under daily routine conditions. We collected laboratory data and clinical measures before and after a 20-week-treatment interval from a large patient population throughout Germany. Main inclusion criteria were type 2 diabetes mellitus with an HbA1c value between 6.6 and 9.9%. Main exclusion criteria were all contraindications defined for pioglitazone. Treatment was performed in addition to the existing therapies with 30 mg of pioglitazone. The following observation parameters were collected at weeks 0, 10 and 20 after treatment initiation: fasting blood glucose, lipid profile [triglyceride, high-