Relationship of Chronic Vascular Complications with Beta-Cell Dysfunction and Insulin Resistance in Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)

The prevalence of vascular complications in newly-diagnosed type 2 diabetes (NDT2D) and their relationships with beta cell function (BF) and insulin sensitivity (IS) defects are poorly known. In 712 GADA-negative, drug naïve, consecutive VNDS participants we measured: 1) IS, by euglycemic insulin clamp; 2) BF, by mathematical modeling of 5h-OGTT; 3) microvascular complications (MIC): diabetic retinopathy, cardiac autonomic and sensorymotor neuropathy (SMN, by biothesiometer and tendon reflexes), e-GFRMDRD <60 mL/min/1.73 m2 or albuminuria >30 mg/24 h; and 4) macrovascular complications (MAC): prior cardiovascular disease, ischemic ECG, lowerlimb artery stenosis or carotid stenosis >40% at US-scans. Thresholds for defective BF and IS were the 25th percentiles of BF and IS assessed with the same methods of VNDS in subjects with normal glucose regulation of the GENFIEV (n=340) and GISIR (n=386) studies, respectively. The prevalence of combined BF and IS defects was 78.9%, while that of isolated BF and IS was 10.8% and 8.8%, respectively. Overall, the prevalence of MIC andMAC was 48.2% and 18.6%. The most frequent MIC and MAC were SMN (28.5%) and prior cardiovascular disease (11%), respectively. Notably, the prevalence of isolated or combined IS and BF defects did not significantly differ between patients with and without complications. Logistic regression analysis revealed that reduced IS, older age, male sex and smoking independently predicted MAC, but not MIC, after adjusting for BMI, blood pressure, LDL-cholesterol and A1c. BF was not associated with any complication. Our study shows that patients with NDT2D have a high prevalence of MIC and MAC, the latter being independently associated with reduced IS. These findings highlight the clinical importance of a systematic screening for chronic complications in the earliest disease stages. ClinicalTrial.gov ID: NCT00879801, NCT01526720.