title: Diabetic microvascular complications: possible targets for improved macrovascular outcomes.
abstract: 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.
authors.affiliation: Renal Unit, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA;
authors.forename: John A
authors.initials: JA
authors.lastname: D'Elia
authors.forename: George
authors.initials: G
authors.lastname: Bayliss
authors.forename: Bijan
authors.initials: B
authors.lastname: Roshan
authors.forename: Manish
authors.initials: M
authors.lastname: Maski
authors.forename: Ray E
authors.initials: RE
authors.lastname: Gleason
authors.forename: Larry A
authors.initials: LA
authors.lastname: Weinrauch