Does Aggressive Glycemic Control Benefit Macrovascular and Microvascular Disease in Type 2 Diabetes?: Insights from ACCORD, ADVANCE, and VADT

Abstract

Diabetes is increasing rapidly worldwide and frequently results in severe vascular complications. A target glycated hemoglobin of less than 7% has commonly been recommended in hopes of preventing both macrovascular and microvascular complications. Although results from trials of intensive glycemic control have generally supported the notion that lower glycated hemoglobin values reduce microvascular disease, the evidence for similar benefits for macrovascular disease has been less clear. As macrovascular disease is the major cause of morbidity and mortality in type 2 diabetes, this remains one of the more important unresolved clinical questions. Recent results from the ACCORD, ADVANCE, and VADT studies have challenged the conventional believe that lower glycated hemoglobin values should be pursued in all diabetic patients. Factors that may influence whether intensive glucose management is advisable include duration of diabetes, pre-existing macrovascular disease, hypoglycemic unawareness, and significant comorbidities. Glycated hemoglobin goals should account for these factors and be individualized for each patient.

Diabetes mellitus and risk of sudden cardiac death: A systematic review and meta-analysis

“…Several potential biological mechanisms might explain the association between DM and SCD. First, while a multifactorial control of DMassociated CVD risk factors (particularly blood pressure and dyslipidemia) can significantly reduce CVD risk in DM, recent trials have cast doubt on a beneficial effect of tight glucose control for the prevention of CVD [5], stimulating the research of the other mechanism(s) that may dilute the benefit of intensive glucose control. An increased risk of hypoglycaemic episodes has been suggested as a potential mechanism to explain this apparent lack of efficacy, as hypoglycaemic events are more frequent in intensive-treated diabetic subjects and they have long been associated with arrhythmic abnormalities [5].…”

“…First, while a multifactorial control of DMassociated CVD risk factors (particularly blood pressure and dyslipidemia) can significantly reduce CVD risk in DM, recent trials have cast doubt on a beneficial effect of tight glucose control for the prevention of CVD [5], stimulating the research of the other mechanism(s) that may dilute the benefit of intensive glucose control. An increased risk of hypoglycaemic episodes has been suggested as a potential mechanism to explain this apparent lack of efficacy, as hypoglycaemic events are more frequent in intensive-treated diabetic subjects and they have long been associated with arrhythmic abnormalities [5]. A meta-analysis of about a million diabetic subjects has indeed evidenced a strong association between severe hypoglycaemic episodes and CVD risk [6] and, more recently, a specific increase of SCD events has been reported in intensively treated type 2 DM subjects [7].…”

Nitrates as an Integral Part of Optimal Medical Therapy and Cardiac Rehabilitation for Stable Angina: Review of Current Concepts and Therapeutics

“…10 However, specific targets for hemoglobin A 1c (HbA 1c ) remain unclear, 10 and recent data challenge whether lower glycated hemoglobin values clinically benefit macrovascular disease. 24,25 For example, results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed no significant reduction in macrovascular complications in patients with type 2 diabetes who had received intensive therapy (targeted HbA 1c level <6%) compared with standard therapy (targeted HbA 1c level 7%-7.9%). 25 In addition, patients receiving intensive therapy had increased mortality and a higher rate of hypoglycemia than patients receiving standard therapy.…”

“…25 The decision to initiate intensive glucose management in an individual patient should therefore factor in the duration of diabetes, the presence of preexisting macrovascular disease or significant comorbidities, and hypoglycemic unawareness. 24 …”

The clinical implications of recent studies on the structure and function of the retinal microvasculature in diabetes

“…Microvascular and macrovascular complications are the major causes of morbidity and mortality in diabetic populations [2][3][4]. While intensive glucose control in patients with diabetes has been found to reduce the risk of microvascular complications, such as diabetic retinopathy [5], the beneficial effects of intensive glucose control on macrovascular and cardiovascular endpoints in type 2 diabetes are less clear [6,7].…”