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Treating postprandial hyperglycemia did not delay diabetes progression
Other factors may play greater role in progression of early type 2 diabetes.
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New research found that ameliorating postprandial hyperglycemia with acarbose did not delay progression of early type 2 diabetes mellitus.
“Type 2 diabetes is a progressive disease, often with an inexorable rise in HbA1c over time and the need for increasingly aggressive multidrug therapy,” the investigators wrote in Diabetes Care. “Because postprandial hyperglycemia is an early abnormality in type 2 diabetes, the resultant glucose toxicity is a potential mediator of progressive beta-cell dysfunction.”
M. Sue Kirkman, MD, associate professor of medicine in the department of endocrinology at Indiana University in Indianapolis, and colleagues conducted a study testing if amelioration of postprandial hyperglycemia in individuals with early diabetes would delay progression of the disease. The study was a randomized, double blind placebo-controlled trial.
Researchers enrolled 219 individuals diagnosed as having early type 2 diabetes, defined as a two-hour postload plasma glucose measurement >200 mg/dL and a fasting plasma glucose <140 mg/dL. Participants were divided into an acarbose group (n=109) and a placebo group (n=110); the study included 74 men and 145 women.
Study characteristics
Participants began with a dose of 25 mg acarbose once daily with the evening meal; this was titrated weekly by 25 mg to a maximum dose of 100 mg daily. The dose was down-titrated in patients who complained of gastrointestinal side effects.
Patients with two consecutive quarterly fasting plasma glucose measurements of >140 mg/dL reached the study’s primary endpoint.
During the five-year trial, 95 participants (53 in the acarbose group, 42 in the placebo group) terminated follow-up prematurely. After one and two years, patients underwent a meal profile study after which researchers obtained blood samples for plasma glucose and insulin measurements.
“Acarbose significantly reduced peak postprandial glucose after both meals at year 1 and at year 2 compared with baseline, whereas there was no significant reduction with placebo; the difference between groups was highly significant at both time points,” the researchers wrote.
Primary outcomes
There were no significant differences, however, in the primary outcome measure. A total of 28 of 96 acarbose patients who completed at least two consecutive quarterly visits after the baseline visit reached the primary outcome (29%) vs. 34 out of 100 placebo patients (34%), and there was “no difference between groups in the survival analysis.”
When starting additional diabetes medication was added to the primary endpoint analysis there was still no difference between groups (P=.41).
Furthermore, there were no significant differences in measures of insulin resistance between the two groups, or in other measures of beta-cell function.
“We still don’t know why type 2 diabetes is such a relentlessly progressive disease,” Kirkman told Endocrine Today. “Our study in early diabetes seems to show that treating postprandial hyperglycemia, which seemed a logical culprit in beta-cell failure, doesn’t affect the rate of progression. There must be other factors, such as genetics, abnormal amounts of free fatty acids in the blood, or factors we haven’t considered or discovered yet, that cause progression of the disease.”
Kirkman said that because hyperglycemia is known to be reversibly toxic to the beta-cell during the short-term, this finding was a surprise.
Postprandial hyperglycemia is possibly just an abnormality in early diabetes, and not an important part of its pathology.
“Diabetes prevention studies suggest that treating postprandial hyperglycemia or hepatic glucose output or insulin resistance helps slow the progression from impaired glucose tolerance to early diabetes,” Kirkman said. “It may be that at some point one crosses a threshold, after which progression can’t be affected as much by these same mechanisms.” –by Dave Levitan
For more information:
- Kirkman MS, Shankar RR, Shankar S, et al. Treating postprandial hyperglycemia does not appear to delay progression of early type 2 diabetes. Diabetes Care. 2006;29:2095-2101.