Prediabetes intervention may also help heart, DPP data show

 

September 9, 2013 

Chevy Chase, MD - Obese prediabetics who lose weight and increase their physical activity or take metformin may not only reduce their risk of progressing to full diabetes but could also reduce their risk of heart disease, according to a new study published online August 26 in the Journal of Clinical Endocrinology & Metabolism [1].

The research is the first to employ nuclear magnetic resonance (NMR) imaging in combination with density-gradient ultracentrifugation (DGU) to confirm in two methodological ways that intensive lifestyle change and use of metformin, compared with placebo, have favorable effects on lipoprotein subfactors involved in the development of atherosclerosis.

Dr Ronald Goldberg (University of Miami Miller School of Medicine, FL) and colleagues conducted a randomized clinical trial involving a subset of the Diabetes Prevention Program study population of patients with prediabetes and a mean body-mass index (BMI) of 33.5 to 33.7 at baseline.

"The take-home message is that the lifestyle program was very effective after one year for improving the lipid profile. There was also improvement from metformin, just not as dramatic," coauthor Dr Edward S Horton (Harvard Medical School, Boston, MA) said in an interview.

Lipoprotein particle size altered by intervention

Goldberg and colleagues randomized 1645 patients with impaired glucose tolerance (IGT) to intensive-lifestyle change, metformin 850 mg twice daily, or placebo. They compared baseline blood samples with samples taken a year later to measure metabolic changes over that time period, adjusting for treatment assignment, age at baseline, sex, race, and baseline change in metabolic variables. They also accounted for lipid-modifying medications across all models.

They found that intensive-lifestyle change decreased large and buoyant very low-density lipoprotein (VLDL), small and dense LDL, and small HDL and raised large HDL. Metformin modestly reduced small and dense LDL and raised small and large HDL.

Intensive-lifestyle change also lowered triglycerides from 1.6 to 1.32 mmol/L (p<0 .01="" compared="" p="" placebo="" with="">

Horton explained that, according to the atherogenic profile of obese, insulin-resistant, type 2 diabetes patients, increased VLDL levels—particularly the larger, more buoyant particles like the ones reduced in this study—are associated with high-fat diets and thought to be more atherogenic than the slightly smaller VLDL particles. Also in this population, HDL tends to be low.

"So the bottom line was we got kind of what we expected," he said. "With the intensive-lifestyle program, we asked everybody to lose 7% of their body fat, which they did. We had an improvement in triglycerides, and there was a shift from large VLDL particles to smaller ones. HDL levels went up a little bit, and they shifted from small to larger ones. Total LDL didn't change, but there was a shift from small LDL particles, the atherogenic ones, to larger LDL particles, which are less atherogenic."

Even the metformin group lost some weight, he added, noting, "Metformin's not a bad weight-loss drug."

Findings reinforce value of metformin as diabetes drug

"I think the most interesting part of this paper is the metformin result," Dr Elizabeth Barrett-Connor (University of California, San Diego), another coauthor of the paper, said in an interview. "Metformin is clearly the most interesting of the diabetes medications, with no serious side effects, and it increased both large and small HDL particles. What's [also] hot now is increasing literature suggesting that it may reduce risk of cancer," she added.

The unique contribution of the study, however, is the use of NMR imaging of the lipoprotein sizes and densities. "I thought that was one of the nicest things about the paper. I like the fact that we got parallel results [regardless of] the method. Similar results can be seen two ways. I thought that was a unique contribution."

The researchers attribute improvement in metabolic measures primarily to a reduction in BMI. While placebo-group BMIs remained constant, intensive-lifestyle patients reduced their mean BMI from 33.5 to 30.8 (p<0 .01="" 32.5="" 33.7="" and="" bmi="" from="" mean="" metformin="" p="" patients="" placebo="" reduced="" their="" to="" vs="">

They note also that because the beneficial effects were observed a year after interventions began, there are increased odds that sustained benefits may begin soon after initiation of treatment.

"Overall, the findings offer optimism that these interventions, in addition to slowing diabetes development, may also slow the progression of atherosclerosis," they conclude.