insulin-detemir and Diabetic-Angiopathies

Hypoglycemia is a barrier to the achievement of glycemic targets and limits the beneficial effects of improved glucose control on cardiovascular outcomes in type 2 diabetes (T2D). Circulating endothelial progenitor cells (EPCs) participate in cardiovascular homeostasis and predict future cardiovascular events. Therefore, we herein analyzed the association between occurrence of hypoglycemia and EPC changes in T2D patients after optimization of glucose control with basal insulin therapy.. In the NCT00699686 trial, 42 T2D insulin-naïve patients received a 3 + 3-month cross-over therapy with glargine and detemir. There were 43 minor and 2 severe hypoglycemic episodes in 19 patients (45.2 %, 0.54 episodes/patient/year). Changes in EPCs were analyzed in relation to the occurrence of hypoglycemia during the trial.. Patients with hypoglycemia had a higher final HbA1c at 6 months than patients without, although absolute HbA1c changes were not significantly different. Though PCs increased at study end, in patients experiencing at least 1 hypoglycemic episode, the changes in CD34(+), CD133(+) progenitor cells and CD34(+)KDR(+) EPCs were significantly lower than the respective changes in patients without incident hypoglycemia, even after correcting for confounders. During treatment with detemir, which induced >twofold less hypoglycemia than glargine, CD34(+)KDR(+) EPCs increased significantly more than during treatment with glargine.. In naïve T2D patients initiating basal insulin, hypoglycemia prevents the increase in vasculoprotective PCs. Clinically, these data strengthen the importance of avoiding hypoglycemia to improve cardiovascular outcomes during the treatment of T2D.

Topics: Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelial Progenitor Cells; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Male; Middle Aged

Chronic diabetic complications result from an imbalance between vascular damage and regeneration. Several circulating lineage-committed progenitor cells have been implicated, but no data are available on pericyte progenitor cells (PPCs). Based on the evidence that PPCs increase in cancer patients after chemotherapy, we explored whether circulating PPC levels are affected by glucose control in type 2 diabetic patients, in relation to the presence of chronic complications. We enumerated peripheral blood PPCs as Syto16+CD45-CD31-CD140b+ events by flow cytometry at baseline and after 3 and 6 months of glucose control by means of add-on basal insulin therapy on top of oral agents in 38 poorly controlled type 2 diabetic patients. We found that, in patients with microangiopathy (n = 23), the level of circulating PPCs increased about 2 fold after 3 months and then returned to baseline at 6 months. In patients without microangiopathy (control group, n = 15), PPCs remained fairly stable during the whole study period. No relationship was found between change in PPCs and macroangiopathy (either peripheral, coronary, or cerebrovascular). We conclude that glucose control transiently mobilizes PPCs diabetic patients with microangiopathy. Increase in PPCs may represent a vasoregenerative event or may be a consequence of ameliorated glucose control on microvascular lesions.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Flow Cytometry; Humans; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Pericytes; Stem Cells; Treatment Outcome

In diabetes, endothelial damage promotes macroangiopathy and endothelial regeneration is impaired, owing to reduced endothelial progenitor cells (EPCs). Given that insulin influences endothelial biology, we compared the effects of add-on basal insulin analogues on endothelial damage and regeneration in type 2 diabetes (T2D).. This was a 6-month randomized crossover trial comparing add-on insulin detemir versus glargine in poorly controlled T2D with macroangiopathy. At baseline, crossover (3 months) and study end (6 months), we measured HbA1c, EPCs, circulating endothelial cells (CECs), VCAM-1, ICAM-1 and E-selectin. Body weight and hypoglycaemic episodes were also recorded.. Forty-two patients completed the study, randomly assigned to the glargine-detemir (n = 21) or the detemir-glargine (n = 21) schedule. At crossover, EPC levels did not change compared with baseline, but significantly increased at study end. CECs decreased over time and were significantly reduced at study end. ICAM-1, VCAM-1 and E-selectin were significantly reduced at crossover and further decreased at study end. No differences were seen in these effects between detemir and glargine. HbA1c showed a carryover effect and its reduction was similar with detemir and glargine in the first arm. Incidence of hypoglycaemia and weight gain was lower with detemir than with glargine in both arms.. Optimized glycaemic control by add-on basal insulin improved indexes of endothelial damage and regeneration. Compared to glargine, detemir achieved similar endothelial protection with lower weight gain and less hypoglycaemia. These results might have implications for therapy of aging T2D patients with cardiovascular disease.

Topics: Aged; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Endothelial Cells; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome