Hypoglycemia affects the changes in endothelial progenitor cell levels during insulin therapy in type 2 diabetic patients.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy. gianpaolofadini@hotmail.com.
G P
GP
Fadini
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy.
M
M
Albiero
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy.
S
S
Vigili de Kreutzenberg
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padua, Italy.
A
A
Avogaro
D000368:Aged; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000069057:Insulin Detemir / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000069036:Insulin Glargine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D000069057:Insulin Detemir
Atherosclerosis; Cardiovascular; Regeneration; Trials