insulin-glulisine and Diabetic-Angiopathies

The insulin analogs lispro, aspart, and glulisine are the only commercially available rapid-acting insulins to treat diabetes. We review the evidence for treating hyperglycemia, using insulin, and specifically using rapid-acting analogs in diabetic individuals, on the prevention of vascular events. We review the beneficial effects of insulin on the vascular system, which include vasodilation and anti-inflammatory actions. The effects of treating hyperglycemia and intensive blood glucose control on vascular outcomes are reviewed.

Topics: Anti-Inflammatory Agents; Blood Glucose; Diabetes Mellitus; Diabetic Angiopathies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Postprandial Period; Treatment Outcome; Vasodilator Agents

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established.. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire.. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores.. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients.

Topics: Adult; Aged; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Patient Satisfaction

To test potential differences between the actions of anti-diabetic medications, we examined the effects of oral hypoglycaemic agents versus glargine-apidra insulin therapy in T2DM.. T2DM subjects were randomized to either oral hypoglycaemic agents (pioglitazone, metformin and glipizide, n = 9) or insulin therapy (n = 12) for 6 months. Carotid intimal media thickness, vascular reactivity (flow-mediated vasodilatation; percent change in brachial artery basal diameter post-ischaemia) and sublingual nitrate were measured with ultrasonography. Euglycemic hyperinsulinemic (80 mU/m(2) ) clamp with [3]-3H-glucose and muscle biopsies were performed.. Fasting plasma glucose (~257 to ~124 mg/dL, oral hypoglycaemic agents and ~256 to ~142 mg/dL, IT) and HbA(1c) (~10.3 to ~6.4%, OHA and ~10.7 to ~7.1%, IT) improved comparably. Endogenous glucose production (~2.1 to ~1.7 mg/kg/min, oral hypoglycaemic agents and ~2.3 to ~2.0 mg/kg/min, insulin therapy) and endogenous glucose production suppression by insulin (~0.4 to ~0.3 mg/kg min, oral hypoglycaemic agents and ~0.5 to ~0.7 mg/kg min, insulin therapy) were different. Total glucose disposal × 100 increased in the oral hypoglycaemic agents group (~5.2 to ~8.1; p = 0.03), but not in insulin therapy (~6.0 to ~5.4 mg/kg/min/µU/mL × 100). OHA reduced CIMT (~0.080 to ~0.068 cm; p < 0.05), whereas insulin therapy did not (~0.075 to ~0.072 cm). After sublingual nitrate, brachial artery basal diameter increased in the OHA group (~8.7 to ~18.2%), but not in insulin therapy (~11.2 to ~15.0%; p < 0.02). Except for plasma adiponectin (~7 to ~15, oral hypoglycaemic agents versus ~6 to ~10, IT), changes in inflammatory markers in the circulation and in muscle (IκBα, super-oxidase dismutase 2, monocyte-chemo-attractant protein 1, p-ERK and JNK) were equivalent.. Oral hypoglycaemic agents and insulin therapy treated patients achieved adequate glycemic control and the effects on circulating and muscle inflammatory biomarkers were similar, but only oral hypoglycaemic agents improved insulin sensitivity, vascular function and carotid intimal media thickness. These findings in a small sample suggest that the use of oral hypoglycaemic agents provides additional benefits to patients with T2DM.

Topics: Adult; Body Mass Index; Carotid Arteries; Carotid Artery Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation Mediators; Insulin; Insulin Glargine; Insulin Resistance; Insulin, Long-Acting; Male; Metformin; Mexican Americans; Middle Aged; Muscle, Skeletal; Myositis; Pioglitazone; Sulfonylurea Compounds; Thiazolidinediones; Tunica Intima

Insulin glulisine has a higher efficacy in reducing postprandial glucose excursions and in restoring normal postprandial microcirculation than rapid human insulin. The aim was to compare the incidence of macro- and microvascular outcomes in Type 2 diabetic patients treated with insulin glulisine or regular human insulin.. Computerized data from 952 glulisine (age: 61 ± 11 y) and 11,157 regular insulin (65 ± 11 y) users in general practices throughout Germany (Disease Analyzer, 11/2004 to 3/2010) were analyzed.. Hazard ratios (HR; Cox regression) for 3.5-year-risk of macro- or microvascular outcomes were adjusted for age, sex, diabetes duration, diabetologist care, hypertension, hyperlipidemia, depression, and comedication (basal insulin, oral antidiabetics). Furthermore, adjustment was carried out for baseline microvascular complications when analyzing macrovascular outcomes and vice versa.. Overall, risk for macro- or microvascular outcomes was 20% lower for insulin glulisine users (p < 0.05). There was a decreased risk for coronary heart disease (HR; 95%CI: 0.78; 0.62 - 0.99), and an indication for a lower risk for incident myocardial infarction (HR: 0.66; 0.43 - 1.02). Also for microvascular complications, the adjusted hazard ratios for retinopathy, nephropathy and neuropathy were below 1.0, indicating a lower risk for the insulin glulisine group, however, which was significant for neuropathy only (HR: 0.74; 0.58 - 0.93).. Prescription of the rapid-acting insulin analog glulisine was associated with a reduced incidence of macro- and microvascular outcomes in Type 2 diabetes under real-life conditions. Given that this was a retrospective database analysis, it is important to confirm this finding in a randomized controlled trial.

Topics: Aged; Chi-Square Distribution; Databases, Factual; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease-Free Survival; Female; General Practice; Germany; Humans; Hypoglycemic Agents; Incidence; Insulin; Kaplan-Meier Estimate; Male; Microcirculation; Microvessels; Middle Aged; Multivariate Analysis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome