A1C and Cardiovascular Outcomes in Type 2 Diabetes

Abstract

OBJECTIVEType 2 diabetes is associated with increased cardiovascular risk. The role of aggressive glycemic control in preventing cardiovascular events is unclear. A nested case-control study design was used to evaluate the association between average A1C and cardiovascular outcomes.RESEARCH DESIGN AND METHODSAdults with type 2 diabetes were identified among members of Kaiser Permanente Southern California. Type 2 diabetes was identified based on ICD-9 diagnosis codes and either A1C >7.5% or prescriptions for hypoglycemic agents. Case subjects were defined based on nonfatal myocardial infarction, nonfatal stroke, or death attributed to cardiovascular events during a 3-year window. Four type 2 diabetes control subjects were matched to each case subject based on age, sex, and index date for the corresponding case. A conditional logistic regression model was used to estimate the odds ratio of cardiovascular events and compare three patient groups based on average A1C measured in the preindex period (≤6, >6–8, >8%).RESULTSA total of 44,628 control subjects were matched to 11,157 case subjects. Patients with an average A1C ≤6% were 20% more likely to experience a cardiovascular event than the group with an average A1C of >6–8% (P < 0.0001). Patients with an average A1C >8% experienced a 16% increase in the likelihood of a cardiovascular event (P < 0.0001). We found evidence of statistical interaction with A1C category and LDL level (P = 0.0002), use of cardiovascular medications (P = 0.02), and use of antipsychotics (P = 0.001).CONCLUSIONSHigh-risk patients with type 2 diabetes who achieved mean A1C levels of ≤6% or failed to decrease their A1C to <8% are at increased risk for cardiovascular events.

Relationship between HbA1c levels and risk of cardiovascular adverse outcomes and all-cause mortality in overweight and obese cardiovascular high-risk women and men with type 2 diabetes

“…Interestingly, post hoc analyses indicated that the risk was not associated with low HbA 1c as such, but was rather driven by a high risk for those who failed to achieve a low HbA 1c , which may have been due to factors such as weight gain; this is nevertheless not well investigated [21]. Several other studies, including two recent meta-analyses, have likewise failed to demonstrate any reduction in risk of mortality for intensified glucose control in patients with established type 2 diabetes and various degrees of cardiovascular disease [22][23][24][25].…”

Glycemic Goals in Diabetes: Trade-off Between Glycemic Control and Iatrogenic Hypoglycemia

“…Finally, an association between low (as well as high) A1C levels and mortality in patients with diabetes has been documented in several reports (58)(59)(60)(61)(62). Again, this could be a marker of impending death, a predictor of the cause of impending death, or both.…”

“…Therefore, it does not provide a convincing rationale for tight glycemic control. The evidence that glycemic control with insulin, a sulfonylurea, or a glinide increases hypoglycemic morbidity and mortality in type 1 and type 2 diabetes is compelling (22,(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62). Unless tight glycemic control empirically can be achieved and maintained safely, the evidence provides a convincing rationale against tight glycemic control, but not for loose glycemic control, during treatment with those drugs.…”

Underlying Autoimmune Activation Rendering Paradoxical Non-Linear Relationship between Biomarkers and Cardiometabolic Risk

“…Though several studies demonstrated a linear relationship between HbA1 c and several outcomes throughout the range of values [12,13], numerous recent studies showed that low HbA1 c in nondiabetic [14,15] or diabetic individuals [16,17] is associated with increased mortality. Such association suggests the involvement of HbA1 c levels in autoimmune activation and may be confined to one gender (e.g.…”