Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control.

The role of intact proinsulin and adiponectin in endothelial dysfunction and insulin resistance has been receiving increasing attention. This study investigates the effect of PPARgamma stimulation or beta-cell stimulation on metabolic and vascular parameters in patients with type 2 diabetes. In our study, 173 type 2 diabetic patients were recruited and randomly assigned to pioglitazone 45 mg or glimepiride 1 - 6 mg treatment. Intima media thickness of the carotid artery, glycemic control, insulin resistance, adiponectin and intact proinsulin levels were assessed at baseline and after six months of treatment. Despite similar improvements in metabolic control (HbA (1c) after 24 weeks: - 0.8 +/- 0.9% [pioglitazone] vs. - 0.6 +/- 0.8% [glimepiride]; mean +/- SD; p < 0.0001, respectively), improvements in intima media thickness (- 0.033 +/- 0.052 mm; p < 0.0001), proinsulin intact (- 5.92 +/- 10.04 pmol/l; p < 0.0001), adiponectin (10.9 +/- 6.3 microg/ml; p < 0.0001) and HOMA score (- 2.21 +/- 3.40; p < 0.0001) were observed by pioglitazone but not glimepiride treatment. Reduction in intima media thickness was correlated with improved insulin sensitivity (r = 0.29; p = 0.0003), and proinsulin intact levels (r = 0.22; p = 0.006), while an inverse correlation was found with adiponectin levels (r = - 0.37; p < 0.0001). Measurement of adiponectin and intact proinsulin enables characterization of the metabolic situation and an estimation of atherosclerotic risk in patients with type 2 diabetes.

OBJECTIVE -To investigate the effect of insulin glulisine on postprandial microvascular blood flow in type 2 diabetes.RESEARCH DESIGN AND METHODS -A total of 15 patients with type 2 diabetes received insulin glulisine or human insulin before a liquid meal test. Thereafter, skin microvascular blood flow was measured by laser Doppler fluxmetry and blood samples were taken for measurement of plasma levels of glucose, insulin, intact proinsulin, asymmetric dimethylarginine, nitrotyrosine, interleukin-18, matrix metalloproteinase-9, oxidized LDL, and free fatty acids.RESULTS -Insulin glulisine injections resulted in higher postprandial insulin levels (means Ϯ SEM area under the curve [AUC] 0 -120 51.0 Ϯ 6.8 vs. 38.2 Ϯ 5.4 mU/l; P ϭ 0.004), while plasma glucose (AUC 0 -240 158 Ϯ 9 vs. 180 Ϯ 9 mg/dl; P Ͻ 0.05) and intact proinsulin (AUC 0 -240 26.2 Ϯ 3.5 vs. 31.2 Ϯ 4.3 pmol/l; P ϭ 0.002) were lower. Microvascular blood flow increased after insulin glulisine injection (27.9 Ϯ 3.1 to 51.7 Ϯ 9.9 arbitrary units [AU]; P Ͻ 0.05), while only a minor increase was found during human insulin (27.9 Ϯ 3.1 to 34.4 Ϯ 7.8 AU; not significant). Asymmetric dimethylarginine and nitrotyrosine levels were reduced after insulin glulisine (P Ͻ 0.05).CONCLUSIONS -Insulin glulisine is superior to human insulin in restoring postprandial metabolic and microvascular physiology. Diabetes Care 31:1021-1025, 2008S everal epidemiological studies have demonstrated an association between glucose spikes and the development of vascular complications in patients with type 2 diabetes. Postprandial generation of oxidative stress and impaired endothelial function are major contributors in the development of early vascular damage and atherosclerosis. Recent studies have shown that microvascular blood flow increases after a meal in gut, skin, heart, and adipose tissues (1-5). Postprandial regulation of microvascular blood flow is a complex process inversely affected by postprandial glucose and insulin excursions (2,6,7).Diminished prandial insulin secretion and an increase in postprandial plasma glucose excursions with increased postprandial oxidative stress and impaired endothelial function are early features of type 2 diabetes. Insulin glulisine attenuates the postprandial increase in plasma levels of intact proinsulin compared with regular human insulin, which may lead to a corresponding reduction in cardiovascular risk and ␤-cell protection. Therefore, the pharmacokinetics of prandial insulin formulations may be important not only in controlling postprandial glucose excursions, but also in the maintenance of normal endothelial function and microvascular blood flow. The aim of this study was to compare the effect of insulin glulisine with regular human insulin in terms of postprandial microvascular blood flow and several laboratory markers of endothelial function and oxidative stress in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS -This investigation wasa single-center, open-label, randomized, two-way crossover study of patients with type 2 ...

Fragestellung: Veränderungen in der Koagulation ist eines der wesentlichen physiologischen Merkmale des Diabetes mellitus Typ 2. Das oft als "Schwangerschafts"-Hormon bezeichnete Peptid Relaxin könnte auf molekularer Ebene in die Koagulationskaskade eingreifen. Deshalb haben wir die Relaxinexpression in Korrelation zu Fibrinogenexpression bei Typ-2-Diabetespatienten untersucht und stratifiziert nach Geschlecht analysiert. Material und Methodik: Insgesamt nahmen 192 Patienten an der Studie teil. Die Patienten erhielten randomisiert entweder Pioglitazon oder Glimepirid für 26 Wochen zur oralen antidiabetischen Therapie. Blutproben wurden zu Beginn und am Ende der Studie entnommen, und die Serumkonzentrationen von Relaxin (per ELISA) und Fibrinogen (per Turbimetrie) bestimmt. Zusätzlich wurden die Thrombozytenzahlen erhoben. Ergebnisse: Insgesamt wurden die Daten von 157 Patienten (Durchschnittsalter 62,5 ± 8,2 Jahre), darunter 57 Frauen und 100 Männer analysiert. Die Basisdaten lagen im Mittel bei 27,9 pg/ml Relaxinkonzentration, 3 g/l Fibrinogengehalt und 220 000 Thrombozyten/µl. Der Therapieverlauf wurde für jeden Patienten individuell durch Anstieg bzw. Abfall der Parameter im Vergleich zum Basiswert erfasst. In der Subgruppe der weiblichen Diabetespatientinnen korrelierte die Änderungen im Relaxingehalt mit den Änderungen der Fibrinogenkonzentration (p < 0,05). Diese Korrelation war unabhängig von der Art der antidiabetischen Medikation. Schlussfolgerung: Die Daten lassen einen Zusammenhang zwischen der Relaxinexpression und Fibrinogenspiegeln bei Frauen vermuten. Es ist denkbar, dass die Relaxinexpression aufgrund eines pathologischen Fibrinogenanstiegs aktiv erhöht wird, und somit die bekannten kardioprotektiven Eigenschaften von Relaxin zum Tragen