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Effective guidelines for diabetes prevention

Robin Wulffson MD's picture
type 2 diabetes, metformin, glucose resistance, obesity, fatty liver

The incidence of type 2 diabetes is on the increase in the United States. New research has zeroed in on causative factors as well as how to reduce them. Most are aware that increased weight—and particularly obesity––increase the risk. However, a new study has evaluated overweight/obesity and two other factors and their relationship to diabetes risk. Another study has reported that long-term ingestion of an anti-diabetic medication is not only safe but also can prevent being stricken with the condition. Both studies were published in the April 2012 edition of the journal Diabetes Care.

Researchers in South Korea and the United Kingdom evaluated three risk factors for type 2 diabetes: insulin resistance overweight/obesity, and fatty liver. Insulin resistance is a condition in which the natural hormone insulin becomes less effective at lowering the blood sugar (glucose) level. Fatty liver (steatosis) is the accumulation of fat in liver cells. In any of these conditions, the resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. The researchers noted that dissociation exists between the three risk factors, which suggested that different mechanisms are involved. Therefore, the aim of the study was to: quantify diabetes risk with different combinations of these risk factors at baseline and to determine whether each is an independent risk factor for diabetes.

The study group was comprised of 12,853 South Koreans without diabetes. Patients with insulin resistance, fatty liver, and overweight/obesity were identified at baseline. At follow-up, five years later, cases of type 2 diabetes were identified.

At follow-up, the researchers identified 223 cases of diabetes. Of these cases, 26 subjects had none of the three risk factors, 37 had one, 56 had two, and 104 had three. They found that insulin resistance was linked to an almost four-fold increased risk for diabetes, fatty liver increased the risk by 2.4, and overweight/obesity increased the risk by 1.74. Of those individuals with two risk factors, the combination of overweight/obesity and fatty liver was associated with the lowest risk for diabetes. In contrast the combination of insulin resistance and fatty liver was associated with the highest risk. The highest risk was found among subjects with all three risk factors. They were found to have a more than 14-fold increased risk for diabetes.

Although avoiding excess pounds is a proven method for the reduction of type 2 diabetes risk, failures far outweigh the successes for individuals embarking on a weight loss program. For those individuals, help is available with the antidiabetic medication metformin. A new study has found that the medication is safe, well tolerated, and also facilitates weight loss.

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Investigators affiliated with the Diabetes Prevention Program Research Group evaluated the safety, tolerability, weight loss, and change in waist circumference following long-term follow-up. They accessed new data from the open-label Diabetes Prevention Program Outcomes Study (DPPOS). The study was a randomized double-blind clinical trial of metformin (850 mg twice daily) vs. placebo; follow-up was done after an average of 2.8 years. (Randomization refers to random assignment of the patients to the two groups. Double-blind means that neither the subjects nor the researchers were aware of whether metformin or placebo was taken.)

The researchers did not uncover any significant safety issues. The most common side effect was gastrointestinal problems such as indigestion; however, the symptoms decreased over time. During the trial period, hemoglobin and hematocrit levels (indicative of the number of red blood cells in the circulation) were slightly lower in the metformin group, compared to the placebo group. These decreases in in the metformin group occurred during the first year of the study, with no further changes after that time. Compared to the placebo group, the subjects taking metformin had reduced body weight and waist circumference (metformin; 2.06 ± 5.65% weight loss and 2.13 ± 7.06 cm waist circumference; placebo: 0.02 ± 5.52% weight loss and 0.79 ± 6.54 cm waist circumference). In addition, the degree of weight loss at follow-up was directly related to compliance (taking the medication as prescribed). Following the double-blind period, the study continued in an un-blinded fashion. During this period, weight loss remained significantly greater in the metformin group than in the placebo group; furthermore, the weight loss correlated with compliance.

The authors concluded that metformin used for diabetes prevention is safe and well tolerated. In addition, weight loss is related to metformin compliance and is safe for at least 10 years of treatment.

Take home message:
These two studies clarify the risk factors for diabetes and point out the risk reduction of type 2 diabetes from a metformin regimen. Although metformin reduced diabetes risk and facilitated weight loss, the greatest risk reduction would occur in individuals who consumed a healthy diet and were not overweight.

Diabetes Care
Diabetes Care

See Also:
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Weight loss drug reported to reverse diabetes