Endothelial progenitor cells are related to glycemic control in children with type 1 diabetes over time.

OBJECTIVE: The risk of cardiovascular death before the age of 40 is 20-fold higher in patients with type 1 diabetes mellitus (T1DM). Endothelial progenitor cells (EPCs) predict cardiovascular morbidity and mortality in patients without diabetes. We hypothesized that EPCs are modified in children with T1DM and are related to characteristics of T1DM such as glycemic control. RESEARCH DESIGN AND METHODS: Children (n = 190; 156 T1DM subjects and 34 control subjects) were included in an observational cohort study and matched for age and sex. EPCs were enumerated by flow cytometry at the beginning (cross-sectional) and 1 year later (longitudinal). To analyze changes of variables during the observation, Δ values were calculated. RESULTS: EPCs were significantly reduced in T1DM children versus control subjects (609 ± 359 vs. 1,165 ± 484, P < 0.001). Multivariate regression modeling revealed that glycated hemoglobin A1c (HbA1c) was the strongest independent predictor of EPCs (ß = -0.355, P < 0.001). Overall glycemic control at the beginning and end of study did not differ (7.8 ± 1.2 vs. 7.8 ± 1.2 relative %, P = NS), but we observed individual HbA1c changes of -4.30/+3.10 relative %. The strongest EPC increase was observed in the patients with the most favorable HbA1c lowering during the 1-year follow-up. Accordingly, the strongest EPC decrease was demonstrated in the patients with the strongest HbA1c worsening during the time period. CONCLUSIONS: This is the first prospective study demonstrating diminished EPCs in children with T1DM. The association of better glycemic control with an increase in EPC numbers within 1 year suggests that a reduction of the high cardiovascular disease burden might be mediated likewise.

Correlation of different circulating endothelial progenitor cells to stages of diabetic retinopathy: first in vivo data.

PURPOSE: To investigate vasculogenic circulating progenitor cells (CPCs), endothelial progenitor cells (EPCs), and mature EPCs in patients with type 1 diabetes mellitus (T1DM) with or without diabetic retinopathy (DR). METHODS: A case-control study comparing 90 patients with T1DM with and without DR was performed. Patients were studied and staged for retinopathy according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) classification. Ninety patients were included: 30 without DR (control [CO]), 30 with mild nonproliferative DR (mNPDR), 10 with moderate-severe NPDR (msNPDR), 10 with mild-moderate proliferative diabetic retinopathy (mmPDR), and 10 with high-risk PDR (hrPDR). CPCs (CD34/CD133), EPCs (CD34/CD133/CD309), and mature EPCs (CD34/CD133/CD309/CD31) were enumerated by flow cytometry. RESULTS: EPCs were reduced in mNPDR (114 +/- 66; P < 0.001) and msNPDR (77 +/- 40; P = 0.042) compared with CO (244 +/- 115). In contrast, EPCs were unchanged in mmPDR (248 +/- 155) compared with CO. Strikingly, EPCs were augmented in hrPDR (389 +/- 124) compared with all other stages. Numbers of undifferentiated progenitor cells (CPCs) did not differ among CO, mmPDR, and hrPDR. Augmentation (3x) of mature EPCs in hrPDR (325 +/- 118; P < 0.001) compared with CO (100 +/- 49) but against all other stages of DR was observed. The percentage of mature EPCs/EPCs was augmented in an ETDRS classification-dependent manner. CONCLUSIONS: In patients with T1DM with DR, EPCs undergo stage-related regulation. In nonproliferative retinopathy, a reduction of EPCs was observed, and in proliferative retinopathy, a dramatic increase of mature EPCs was observed.

Circulating levels of MCP-1 are increased in women with gestational diabetes.

OBJECTIVE: We investigated whether gestational diabetes mellitus is associated with monocyte-chemoattractant-protein-1 (MCP-1) and soluble CD40 ligand (sCD40L), the functional relevant proteins in the inflammatory process. METHODS: In all 32 women with gestational diabetes mellitus, 18 women without gestational diabetes mellitus and 40 nonpregnant women were included. MCP-1 and sCD40L were measured at the time of the oral glucose tolerance test (second trimester), in the third trimester and postpartum. RESULTS: MCP-1 was higher in pregnant women (women with gestational diabetes mellitus and without) than in nonpregnant women (p < 0.001) in the third trimester, and also in the second trimester and postpartum. MCP-1 was elevated in patients with gestational diabetes mellitus in the third trimester compared to healthy pregnant women (p = 0.007). In gestational diabetes mellitus, MCP-1 increased from the second to the third trimester (p = 0.003). We found no association of sCD40L and gestational diabetes mellitus. CONCLUSION: The elevation of MCP-1 in the third trimester in gestational diabetes mellitus suggests an association between inflammation and GDM.

Effect of massive weight loss induced by bariatric surgery on serum levels of interleukin-18 and monocyte-chemoattractant-protein-1 in morbid obesity.

BACKGROUND: Morbid obesity is associated with insulin resistance (IR), chronic inflammation and premature atherosclerosis. Since vascular inflammation may contribute to the increased risk of cardiovascular morbidity and mortality of these patients, we studied circulating Interleukin-18 (L-18) and monocyte-chemoattractant-protein-1 (MCP-1) levels in 37 patients with morbid obesity before and after significant weight loss induced by bariatric surgery and their preoperative and postoperative associations with C-reactive protein (CRP) and IR-associated factors. METHODS: High sensitivity assays were used to measure concentrations of fasting CRP, IL-18 and MCP-1. Differences between patients before and after bariatric surgery were analyzed by Student's paired t-test. To investigate the associations of the observed reductions of values, delta of parameters were calculated and preoperative, postoperative and delta data were tested by univariate and multivariate linear regression. RESULTS: After a mean follow-up period of 26.5 months and a massive weight loss of 35 kg induced by bariatric surgery, circulating IL-18 levels decreased by 37% (P<0.001) and circulating MCP-1 levels by 47% (P<0.001). Multiple linear regression of delta values of IL-18 showed that only 2-hour glucose (P=0.008) remained independently and significantly associated with IL-18, whereas multiple linear regression analysis of delta values of MCP-1 revealed that only delta of HOMA-IR (P<0.001) remained independently and significantly associated with MCP-1, respectively. CONCLUSIONS: Because both biomarkers have been shown to play an important role in the development and progression of atherosclerosis, the observations presented in this study could be of clinical relevance for morbidly obese patients undergoing bariatric surgery.