Hyperglycemia is a major risk factor for both the microvascular and macrovascular complications in patients with Type 2 diabetes. This review summarizes the cardiovascular results of large outcomes trials in diabetes and presents new evidence on the role of hyperglycemia, with particular emphasis on postprandial hyperglycemia, in adverse cardiovascular outcomes in patients with Type 2 diabetes….
Treatment options, including the new dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 mimetics that primarily target postprandial hyperglycemia, are also discussed.
Hyperglycemia increases cardiovascular mortality, and reducing hyperglycemia lowers cardiovascular risk parameters. Control of both fasting and postprandial hyperglycemia is necessary to achieve optimal glycated hemoglobin control. Therefore, antihyperglycemic agents that preferentially target postprandial hyperglycemia, along with those that preferentially target fasting hyperglycemia, are strongly suggested to optimize individual diabetes treatment strategies and reduce complications.
Several landmark clinical trials have convincingly demonstrated that hyperglycemia is associated with the microvascular complications of diabetes. These trials, along with epidemiological evidence, have provided the basis for treatment targets and algorithms recommended by the American Diabetes Association (ADA), the American Association of Clinical Endocrinologists (AACE), and the European Association for the Study of Diabetes (EASD). Adequacy of glycemic control is almost universally assessed by glycated hemoglobin (HbA1c) — a measure of hemoglobin glycation over the erythrocyte life span that is proportional to the mean plasma glucose level over the preceding 2 to 3 months. An HbA1c of 7% is recommended by the ADA/EASD and 6.5% by the AACE. The mean value for individuals with normal glucose tolerance is 5.0% (upper limit of normal is 6.0%).
In addition to HbA1c, patients and physicians usually monitor and treat fasting plasma glucose (FPG) levels, but ignore or de-emphasize postprandial glucose (PPG) levels. There is no evidence that fasting hyperglycemia is more deleterious than postprandial hyperglycemia. Recent evidence, however, strongly suggests that control of postprandial hyperglycemia may be necessary to achieve HbA1c targets of less than 7%. Considerable data have accumulated indicating that elevated PPG levels, even in the absence of fasting hyperglycemia, increase the risk for cardiovascular disease (CVD).
Substantial evidence has accumulated indicating that chronic hyperglycemia is a risk factor for micro- and macrovascular disease. Observational studies indicate that isolated postprandial hyperglycemia increases CV mortality. Various antihyperglycemic agents now exist that preferentially target postprandial hyperglycemia (meglitinides, rapid-acting insulin analogs, GLP-1 agonists, and DPP-4 inhibitors) and afford physicians a choice of treatment options that can now be based on individual patient profiles. Controlling and achieving target goals early in the course of diabetes has been shown to provide better outcomes in terms of CV risk. Postprandial glucose should be normalized along with FPG to achieve the currently recommended goal of HbA1c of less then 7%. As reflected in recent trials, a less intense goal may be needed for certain subpopulations of patients with diabetes who have a history of severe CVD, severe hypoglycemia, advanced age, or advanced microvascular or macrovascular complications.
Target levels of glucose control should be individualized by focusing on both FPG and PPG and by optimizing other risk factors of CVD, including high blood pressure, hyperlipidemia, obesity, smoking, and poor exercise and dietary habits.
Vascular Health and Risk Management, March 5, 2010