Managing postprandial glucose levels in patients with diabetes

Journal of Family Practice, Jan, 2008 by Penny Tenzer-Iglesias, Stephen Brunton

Of the many factors influencing insulin secretion, the most important treatment target is control of the amount of glucose transported from the blood into the beta cells of the pancreas. Even in healthy people, carbohydrate intake can lead to small increases in blood glucose and increased insulin secretion. If pancreatic beta cells can detect glucose levels and produce insulin, the insulin secretion usually is sufficient to maintain a fasting plasma glucose (FPG) level between 70 and 110 mg/dL and a postprandial glucose (PPG) level below 140 mg/dL. Diabetes leads to increasing resistance to insulin's effects and, early in the disease, greater output of endogenous insulin. Over time, beta cells fail to keep up; later, diabetes is characterized by both insulin resistance and insulin deficiency. Many patients are not diagnosed until both defects occur.

Is diagnosis based solely on fasting plasma glucose sufficient?

Nearly a third of affected individuals are unaware that they have type 2 diabetes. (1) FPG--the preferred method for diagnosis--may not identify all individuals with diabetes: 33% of patients diagnosed by PPG levels have normal FPG levels (2) and would have been missed by reliance on FPG measurements alone. Other diagnostic methods include a postprandial component or a postchallenge glucose measurement (75-g oral glucose tolerance test). (2-4)

[FIGURE 1 OMITTED]

Challenges in achieving glycemic control: Are current strategies adequate?

Currently, only 1 out of 3 patients achieves or maintains recommended glycemic levels. (5) Treatment approaches that focus on FPG levels may be inadequate. Type 2 diabetes results from both insulin resistance and impaired insulin secretion, primarily characterized by a gradual decline in insulin secretion in response to nutrient loads. (6) Thus, it is a disorder of PPG regulation. (2) In the progression to diabetes, PPG levels often rise before FPG levels do. FIGURE 1 shows the insulin curve, with increased time required for normalization of PPG.

Postprandial hyperglycemia (PPHG) may contribute significantly to overall glucose exposure in patients who can achieve normal or near-normal HbA1c levels. The lower the HbA1c level, the greater the contribution of PPG. (7) For example, at HbA1c levels <7.3%, PPG contributes approximately 70% to elevated HbA1c levels; at HbA1c levels of 7.3% to 8.4%, approximately 50% of the HbA1c contribution comes from PPG. These findings may explain the inability of patients to achieve target HbA1c goals even when FPG levels appear to be controlled. Ideally, FPG and PPG levels should be determined at different time points during the day; many patients will not test often enough to reveal daily glucose patterns. It may be helpful for patients with higher HbA1c levels to measure their FPG levels more often, while those who are closer to achieving HbA1c goals measure mostly PPG levels.

The postprandial state is the norm for patients. The true fasting state typically exists only in the 2 hours before breakfast (for those who consume 3 meals a day at relatively fixed times). (8) During the postprandial periods, insulin secretion in patients with type 2 diabetes does not fully compensate for insulin resistance. Monnier et al confirmed that worsening diabetes control is preceded by changes in daytime postprandial control, followed by changes during the morning (the dawn phenomenon, ie, the early morning rise in blood glucose, typically between 4 AM and 8 AM), and finally by changes in nocturnal fasting control (FIGURE 2). As HbA1c levels exceed 6.5%, patients with near-normal FPG levels have abnormal elevations in PPG levels. (9) This supports the finding in recent treat-to-target trials that similar decreases in FPG levels did not result in similar improvements in HbA1c levels. (10,11) In these trials, the use of a premixed insulin analog, which provides both fasting and postprandial coverage, resulted in superior HbA1c reductions compared with the combined use of basal insulin and oral agents. Whereas FPG reductions were similar, PPG reductions were greater when the premixed analog was used. (10,11)

Although HbA1c level remains the primary target for glycemic control, the American Diabetes Association and the American Association of Clinical Endocrinologists have set specific goals for both FPG and PPG levels (TABLE). (3,4) PPG concentrations measured at midmorning will, for most patients, correspond to the highest glucose concentrations of daytime. Postprandial measurements taken 2 hours after lunch have been shown to provide an evaluation of overall glycemic control and to be excellent predictors of HbA1c levels (PPG <126 mg/dL predicts an HbA1c <7%). (12)

Summary

While normalizing FPG values may be an important goal of therapy in patients with type 2 diabetes, especially for those with very poorly controlled disease, there is strong evidence in support of monitoring and treating PPG elevations as well.

Penny Tenzer-lglesias, MD

Associate Professor of Clinical Family Medicine