establishing cardiovascular biomarkers to define preferred lantus® use

Conditions: Insulin-requiring Type 2 Diabetes Mellitus

Summary: the aim of this study is to observe changes in cardiovascular biomarkers during treatment with lantus in patients with type 2 diabetes mellitus.

* phase iv * indication: diabetes mellitus type 2 * primary objective: to compare fasting intact proinsulin secretion at the beginning and after a 24 week treatment period. - secondary objectives: to evaluate changes in the parameters * insulin, * glucose, * intact proinsulin (after a glucose challenge), * hscrp, * adiponectin, * mmp-9, * hba1c, * weight after 24 weeks of treatment. to investigate the changes of * glucose, * intact proinsulin, * hscrp, * adiponectin, * hba1c * weight between visit 2 (baseline), visit 6 (12 weeks) and visit 8 (final visit after 24 weeks). to investigate the number of patients with normal values for parameters hscrp, adiponectin, and intact proinsulin after 24 weeks of treatment (responder rates). -primary efficacy variable: fasting intact proinsulin concentration at timepoint visit 2 (baseline) and visit 8 (after 24 week treatment) -secondary efficacy variables: all secondary parameters will be assessed after 24 weeks of treatment and compared versus baseline assessment. * weight * hscrp * adiponectin * mmp-9 * ogtt parameters (insulin, intact proinsulin, glucose at time point 0, 60 and 120 minutes after 24 weeks * homa-ir score * hba1c additionally the following parameters will be assessed at visit 6 and will be compared with visit 2 and visit 8: * weight * hscrp * adiponectin * fasting intact proinsulin * glucose * hba1c * safety variables: * adverse events * hypoglycaemic events medication/dosage: insulin glargine, dose individually adapted to reach treatment goal (fbg ≤ 100 mg/dl)nph insulin, dose individually adapted to reach treatment goal (fbg ≤ 100 mg/dl)insulin glulisine, dose individually adapted to reach treatment goal (fbg ≤ 100 mg/dl)human insulin, dose individually adapted to reach treatment goal (fbg ≤ 100 mg/dl) -study duration: duration of study participation for one patient is approximately 26 weeks. overall total duration of the study is approximately 10 months. design: this is a randomized in four arms, open-label, multi-center study. population patients with type 2 diabetes mellitus, sample size n = 60 (15 per arm)

Eligibility criteria:
inclusion criteria: * give written informed consent. * patient consents that his/her family physician/diabetologist will be informed of trial participation * type-2 diabetes mellitus ≥ 1 year of diagnosis (male and female) * experienced in self blood glucose measurement for ≥ 3 months. * hba1c ≤ 9% and \>6,5% * bmi \> 30 kg/m² * age ≥ 18 years * waist circumference \> 88 cm (female) and \> 102 cm (male) * nph insulin treatment plus 1 or 2 oad (except tzd) exclusion criteria: * history of drug or alcohol abuse within the last five years prior to screening * anamnestic history of hypersensitivity to the study drugs (or any component of the study drug) or to drugs with similar chemical structures * history of severe or multiple allergies * treatment with any other investigational drug within 3 months prior to screening * progressive fatal disease * history of significant cardiovascular, respiratory, gastrointestinal, hepatic (alat and/or asat \> 3 times the normal reference range), renal (creatinine \> 1.3 mg/dl in women and \>1.6 mg/dl in men), neurological, psychiatric and/or hematological disease as judged by the investigator * pregnant or lactating women * sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (iuds), sexual abstinence or vasectomized partner * treatment with glp1-analog or thiazolidinediones (tzd) * hscrp \> 10 mg/l (by rapid test at screening visit). * lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study * type 1 diabetes mellitus * patients already treated with intensified conventional insulin therapy.

Keywords: type 2 diabetes mellitus nph insulin insulin glargine cardiovascular biomarkers hscrp, adiponectin intact proinsulin cardiovascular risk