Person:

Roshan, Bijan

The results of recent outcome trials challenge hypotheses that tight control of both glycohemoglobin and blood pressure diminishes macrovascular events and survival among type 2 diabetic patients. Relevant questions exist regarding the adequacy of glycohemoglobin alone as a measure of diabetes control. Are we ignoring mechanisms of vasculotoxicity (profibrosis, altered angiogenesis, hypertrophy, hyperplasia, and endothelial injury) inherent in current antihyperglycemic medications? Is the polypharmacy for lowering cholesterol, triglyceride, glucose, and systolic blood pressure producing drug interactions that are too complex to be clinically identified? We review angiotensin-aldosterone mechanisms of tissue injury that magnify microvascular damage caused by hyperglycemia and hypertension. Many studies describe interruption of these mechanisms, without hemodynamic consequence, in the preservation of function in type 1 diabetes. Possible interactions between the renin-angiotensin-aldosterone system and physiologic glycemic control (through pulsatile insulin release) suggest opportunities for further clinical investigation.

OBJECTIVE - The purpose of this study was to examine prospectively whether renal hyperfiltration is associated with the development of microalbuminuria in patients with type 1 diabetes, after taking into account known risk factors. RESEARCH DESIGN AND METHODS - The study group comprised 426 participants with normoalbuminuria from the First Joslin Kidney Study, followed for 15 years. Glomerular filtration rate was estimated by serum cystatin C, and hyperfiltration was defined as exceeding the 97.5th percentile of the sex-specific distribution of a similarly aged, nondiabetic population (134 and 149 ml/min per 1.73 m2 for men and women, respectively). The outcome was time to microalbuminuria development (multiple albumin excretion rate >30 μg/min). Hazard ratios (HRs) for microalbuminuria were calculated at 5, 10, and 15 years. RESULTS - Renal hyperfiltration was present in 24% of the study group and did not increase the risk of developing microalbuminuria. The unadjusted HR for microalbuminuria comparing those with and without hyperfiltration at baseline was 0.8 (95% CI 0.4–1.7) during the first 5 years, 1.0 (0.6–1.7) during the first 10 years, and 0.8 (0.5–1.4) during 15 years of follow-up. The model adjusted for baseline known risk factors including A1C, age at diagnosis of diabetes, diabetes duration, and cigarette smoking resulted in similar HRs. In addition, incorporating changes in hyperfiltration status during follow-up had minimal impact on the HRs for microalbuminuria. CONCLUSIONS - Renal hyperfiltration does not have an impact on the development of microalbuminuria in type 1 diabetes during 5, 10, or 15 years of follow-up.