Don't Put Away Those Glucose Monitors: Glycemic Variability May Be Harming Our Diabetic Patients

Abstract & Commentary

By Joseph E. Scherger, MD, MPH, Clinical Professor, University of California, San Diego. Dr. Scherger reports no financial relationships to this field of study.

Synopsis: Glycemic variability may be an independent cause of diabetic complications. Wide fluctuations of blood glucose may not be detected by HbA1c measurement. High blood glucose levels, even if brief, may cause oxidative damage to endothelial tissue leading to atherosclerosis.

Source: Monnier L, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patient with type 2 diabetes. JAMA. 2006;295:1707-1708.

The biochemical mechanism of glucose toxicity in diabetics is being elucidated. In this French study of 21 patients with type 2 diabetes, the investigators demonstrated that blood glucose fluctuations caused oxidative stress independent of HbA1c levels. Specifically, in patients with the same HbA1c levels, those with greater glucose fluctuations had more production of the reactive free radical molecule superoxide. The potential damage is directly related to high blood glucose levels, which triggers the oxidative free radical production in mitochondria. The authors call for interventional trials which not only target HbA1c levels, but also acute glucose swings.

In an accompanying editorial, Brownlee and Hirsch call these findings new, yet the study was too small to confirm that the increased free radical production was enough to cause clinically significant damage. They cite several studies which found that diabetic complications such as retinopathy varied among patients with similar HbA1c levels, and that these complications are reduced with more intensive control of blood glucose.1 Self-monitoring of blood glucose (SMBG), especially postprandial levels, is likely to remain important in the monitoring of diabetic control. This is well established in type 1 diabetes. These data suggest that SMBG will remain important for type 2 diabetics also.

Commentary

In a previous issue of Internal Medicine Alert, I wrote an article entitled "Getting practical with monitoring type 2 diabetes."2 A meta-analysis showed that self-monitoring of blood glucose by type 2 diabetics did not improve control of the disease compared with regular monitoring of HbA1c. Much time and expense is required for frequent blood glucose monitoring, and there are large numbers of patients with type 2 diabetes in our practices. The clinical implications of the decision how best to monitor this disease are enormous. Is regular monitoring of HbA1c good enough? What do these results do to the previous recommendation?

Nothing is clinical medicine is ever simple. It would have been nice to think that HbA1c measurement, as useful as it is, would be the whole story. The important new information from this data is that glycemic variability is important. High glucose levels, even if brief, may be harmful. Measuring postprandial glucose levels is still important. But how often?

What is not discussed in this study and editorial is the diet of the patients. The glycemic index of certain foods, how rapidly they cause a rise in blood glucose, becomes very important and may shift from the popular diet books to mainstream medicine. A wise approach to diabetic patient care is for patients to know their glucose response to eating certain meals. Self-monitoring of blood glucose postprandially may become more about understanding the patient's response to food than monitoring the disease.

As this knowledge develops, we may have more refined target postprandial glucose levels that we want patients to stay below. Armed with the knowledge of high glycemic foods to avoid or eat sparingly, patients may sporadically check their 1-2 hour postprandial glucose levels. The combination of regular HbA1c levels and periodic postprandial glucose levels to monitor fluctuations and response to certain meals may emerge as the best way to manage type 2 diabetes. This approach preserves patient empowerment in monitoring and managing their disease.

References

1. Brownlee M, Hirsch IB. Glycemic variability: A hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006;295:1707-1708.

2. Scherger J. Getting practical with monitoring type 2 diabetes. Internal Medicine Alert. 2005;27:163-164.