SDF-1 Genotype Influences Insulin-Dependent Mobilization of Adult Progenitor Cells in Type 2 Diabetes

Abstract

CD34+/CD133+ circulating adult progenitor cells (PCs) play an important role in tissue repair in metabolic disease. PCs have a certain plasticity to differentiate into cells with tissue-specific phenotypes (1–3). In diabetic mice, therapeutic use of PCs in models of hindlimb ischemia and wound healing was particularly effective, suggesting a diabetes-dependent defect in PC function (4,5). Accordingly, in vitro outgrowth and angiogenic function of endothelial PCs differentiating from PCs (1) is diminished in patients with cardiovascular risk factors and in type 1 and type 2 diabetes (6–8). From clinical studies it is evident that insulin therapy is a factor determining cardiovascular complications and mortality in diabetes (9,10). It can therefore be speculated that insulin might influence mobilization of PCs in type 2 diabetes. In view of the strong genetic background for the development of late diabetes complications, we asked whether the SDF1-3′A/G genotype known to enhance PC mobilization (11) might be of influence. In the pilot study presented here, we quantified the number of PCs by flourescence-activated cell sorter (FACS) analysis in 23 patients with poorly controlled type 2 diabetes (HbA1c 10.6 ± 1.6%, fasting glucose 15.9 ± 4.5 mmol/l) and 10 age-matched control subjects (59 ± 14 vs. 58 ± 10 years) without history of diabetes (HbA1c 5.4 ± 0.5%). After 5.4 ± 1.6 weeks of treatment with (additional) insulin, 11 patients from this cohort had a follow-up measurement of PCs. Adequate insulin supplementation was documented by a lowering of HbA …