Intensive glycemic control and cardiovascular disease: an update

Abstract

Cardiovascular complications constitute the major cause of morbidity and mortality in patients with diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) provided consistent evidence that intensive glycemic control prevents the development and progression of microvascular complications in patients with type 1 or type 2 diabetes. However, whether intensive glucose lowering also prevents macrovascular disease and major cardiovascular events remains unclear. Extended follow-up of participants in these studies demonstrated that intensive glycemic control reduced the long-term incidence of myocardial infarction and death from cardiovascular disease. By contrast, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, and Veterans Affairs Diabetes Trial (VADT) results suggested that intensive glycemic control to near normoglycemia had either no, or potentially even a detrimental, effect on cardiovascular outcomes. This article discusses the effects of intensive glycemic control on cardiovascular disease, and examines key differences in the design of these trials that might have contributed to their disparate findings. Recommendations from the current joint ADA, AHA, and ACCF position statement on intensive glycemic control and prevention of cardiovascular disease are highlighted.

Gene Silencing of the Mitochondrial Adaptor p66 Shc Suppresses Vascular Hyperglycemic Memory in Diabetes

“…Animals were divided into 5 experimental groups: (1) control; (2) diabetic; (3) diabetic mice treated with insulin after 3 weeks from the induction of diabetes; (4) diabetic mice treated with insulin plus p66 Shc siRNA; and (5) diabetic mice treated with insulin plus scrambled siRNA. Insulin administration was started 3 weeks after the induction of diabetes and continued for a period of 3 weeks (groups [3][4][5]. Groups 1 and 2 received placebo instead of insulin (microrecrystallized Plamitic acid, LinShin Canada, Inc., Toronto, Canada).…”

Management of Atherosclerotic Cardiovascular Disease Risk Factors in the Older Adult Patient With Diabetes

“…Although the AGS recommends an upper limit for HbA 1c up to 75 mmol/mol (9%), there is evidence that many elderly adults are being treated more aggressively (10). The modified targets for HbA 1c in older adults are based in part on the lack of evidence for ASCVD risk reduction as well as concern for harm with tight glycemic targets in older adults (10,66,67). Several large randomized controlled trials with relevance to an elderly population (average age at baseline 60-66 years) were unable to identify any ASCVD benefit with glycemic management strategies targeting HbA 1c values of #42 to 48 mmol/mol (#6-6.5%) (68).…”

Pyrrolidine dithiocarbamate enhances hepatic glycogen synthesis and reduces FoxO1-mediated gene transcription in type 2 diabetic rats

“…Persistent high level of blood glucose is considered to be a key factor in the development of several chronic complications, such as renal failure, microvasculopathy, and peripheral neuropathy, that contribute to the high morbidity and mortality observed in diabetes (15). A better control of blood glucose reduces diabetic complications sharply (5). Under normal conditions, the secretion of insulin is increased after ingestion of a meal, which enables glucose entry into target tissues via facilitative glucose transporters.…”