Cardiovascular risk and glycemic control

• Published in: Canadian Medical Association journal (CMAJ) 2009-04, Vol.180 (9), p.907-908
• Main Authors: Cheng, Alice Y Y, Leiter, Lawrence A
• Format: Article
• Language: English
• Subjects: Biomarkers - metabolism; Blood Glucose; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Care and treatment; Causality; Clinical Trials as Topic; Comorbidity; Complications and side effects; Control; Diabetes; Diabetes Complications - epidemiology; Diabetes Complications - prevention & control; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Glycemic index; Health aspects; Humans; Hyperglycemia - epidemiology; Hyperglycemia - prevention & control; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - therapeutic use; Insulin Resistance; Protein C - metabolism; Research Design; Risk Assessment; Risk factors; Studies; Treatment Outcome
• ISSN: 0820-3946; 1488-2329
• DOI: 10.1503/cmaj.090252

Glycemic control instituted early in the course of type 2 diabetes thus appears to have a "legacy effect" (or "metabolic memory") whereby reductions in the risk of microvascular complications are seen early and persist over time and reductions in the risk of macrovascular complications may take years to manifest. A similar phenomenon was observed among patients with type 1 diabetes in another post-trial follow- up study.8 This apparent legacy effect raises the possibility that the degree of glycemic control does indeed play a role in reducing the risk of cardiovascular complications of diabetes but that glucose-lowering therapy needs to be administered early in the course of the disease and that benefits become evident only after a long period. Greater reductions in cardiovascular events were also observed among participants with no prior cardiovascular disease and those with a baseline hemoglobin A1c concentration of 8% or less in a prespecified subgroup analysis of the ACCORD trial. This finding, too, supports the hypothesis that earlier glycemic intervention is associated with greater cardiovascular benefit. Elevated endogenous insulin levels represent a compensatory response to insulin resistance, which is associated with numerous metabolic disturbances. These disturbances are known to increase the risk of cardiovascular events and include elevated blood pressure, dyslipidemia, endothelial dysfunction, increased inflammatory and prothrombotic factors and microalbuminuria.10 The findings of [Ko] and colleagues support the evidence for an association between insulin resistance and these clinical conditions. Study participants who had high C peptide levels also had lower baseline levels of highdensity lipoprotein levels and higher baseline blood pressure, triglyceride levels, weight and waist circumference. Also, those in the insulin-treated, high-C-peptide group had worse glycemic control, longer duration of diabetes and more microvascular complications at baseline compared with the patients in the other groups. It is therefore not surprising that these baseline characteristics were associated with worse outcomes. In fact, the analysis by Ko and colleagues supports the alternate interpretation that the higher incidence of cardiovascular disease in the insulin-treated, high-C-peptide group was due to other metabolic factors. After control for confounders, only age, duration of diabetes and albuminuria were independent predictors for all-cause mortality, a