Hemoglobin A1c only part of diabetes risk profile

October 3, 2007

Physicians and patients who focus on controlling hemoglobin A1C levels are missing an important risk factor for the complications of diabetes. Oxidative stress and variations in glycemic levels are more important predictors of problems, such as blindness, kidney disease, cardiovascular disease, foot problems, and other familiar comorbidities associated with diabetes.

Physicians and patients who focus on controlling hemoglobin A1c levels are missing an important risk factor for the complications of diabetes. Oxidative stress and variations in glycemic levels are more important predictors of problems, such as blindness, kidney disease, cardiovascular disease, foot problems, and other familiar comorbidities associated with diabetes.

"A1C is not the main player here," said Jeff Unger, MD, from the Chino Medical Group in Chino, California, and author of Diabetes Management in Primary Care. "Oxidative stress is why people are dying of diabetes complications."

The problem, Dr Unger told the AAFP Scientific Assembly in Chicago on Oct. 3, 2007, is that A1c represents the patient's average glucose level over the previous 90 to 120 days. But exposure to a blood glucose level higher than 180 mg/dL for as little as four hours can damage endothelial cells. What has been considered a relatively unimportant spike in postprandial glucose levels actually triggers long-term endothelial inflammation and degradation.

"It is this transient hyperglycemia that causes the long-term complications of diabetes," Dr Unger said. "This oxidative stress starts a cascade of events that results in microvascular and macrovascular damage and complications that eventually lead to death. We need to fix postprandial glucose levels."

The problem, Dr Unger said, is that variations in glucose levels do not affect A1c. That leaves patients with well-controlled A1C levels at significant risk. The solution, he said, is to minimize variations in glucose levels during the day. Reducing spikes in glucose levels helps prevent endothelial damage, which minimizes oxidative stress and reduces disease complications.

The practical solution is regular self-testing for glucose with data downloaded to the physician for regular evaluation.

"Patient diaries tell you nothing that is useful," he said. "You need to download and evaluate actual glucose levels. You always want to keep that glucose level below 180."

He offered several practical management techniques:

  • avoid hyperglycemia
  • use insulin analogues, not NHP or human regular insulin formulations
  • time insulin injections to account for lag times
  • use inhaled insulin, which has a six-hour duration of action rather than four hours for injected formulations
  • reduce carbohydrate intake
  • exercise regularly
  • consider thiazolidinediones, ACE inhibitors, statins, and angiotensin II inhibitors
  • use a constant glucose monitoring system (CGMS).

CGMS is a key intervention, Dr Unger said. Units deliver an audible alarm when glucose levels exceed a preset level such as 180, which alerts patients to problems they may not have recognized and encourages compliance with other measures.

"Glycemic variability and oxidative stress are significant risk factors for microvascular and macrovascular disease," he said. "We need to treat early and we need to treat aggressively."