Sustained Diabetes Prevention Achieved With Lifestyle Changes

Marlene Busko

November 06, 2017

In a meta-analysis of 43 international studies of adults with prediabetes, lifestyle changes and certain medications prevented diabetes, although the effect was sustained only in those following the lifestyle-modification intervention.

"Diet with physical activity or weight loss and insulin-sensitizing medications prevent progression to diabetes in individuals at risk, with 25 persons needing to be treated to prevent a single diabetes case," J Sonya How, MD, of Emory University, Atlanta, Georgia, and colleagues report, in their study published November 6 in JAMA Internal Medicine.

The interventions were associated with a 36% to 39% lower risk of progressing to diabetes during treatment, but the reduced risk was not sustained after stopping the medications, whereas it was sustained after stopping the lifestyle intervention, although the effect waned over time.

Across all interventions, "weight loss appears to be the key factor associated with reduced diabetes progression," the researchers note. They found that every kilogram of weight lost was associated with an additional 7% decrease in risk of progression to diabetes.

"Overall, our findings suggest that lifestyle modification interventions are promising long-term diabetes-prevention strategies; however, maintenance interventions, even if intermittent, may be needed for prolonged intervention effects," Dr Haw and colleagues summarize.

Seeking Specific Strategies to Ward Off Diabetes

Primary prevention of diabetes has been shown to be cost-effective in different populations and is crucial to reduce the growing diabetes burden, according to Dr Haw and colleagues, "but there are conflicting results regarding which type, frequency, and intensity of [lifestyle modification] or medications are most enduring that would inform clinical practice."

To investigate this, they identified 43 randomized controlled trials of adults (age 18 or older) with prediabetes: 19 trials evaluated single or multiple medications; 19 tested lifestyle modifications; and five tested both.

They excluded trials that involved bariatric surgery, gestational diabetes, type 1 diabetes, or unconfirmed prediabetes.

Forty of the studies had a follow-up ranging from half a year to 6.3 years, with the remaining three having a much longer follow-up: the US Diabetes Prevention Program (DPP) at 10 years, the Finnish Diabetes Prevention Study (DPS), at 13 years, and the Da Qing Diabetes Prevention Study (Da Qing) had 20 years since randomization.

The 43 trials had a total of 49,029 participants from Asia, Europe, and North America. The participants had a mean age of 57 and a mean BMI of 30.8 kg/m2, and just under half (48%) were men.

In the 19 trials with lifestyle modification, during a mean intervention of 2.6 years, overall, the patients who had been randomized to dietary changes, exercise, or both had a 39% lower risk of being diagnosed with diabetes compared with controls (relative risk [RR], 0.61; 95% CI, 0.54–0.68).

Combined dietary and physical-activity strategies seemed best, with a 41% risk reduction.

In the 21 medication trials, during a mean intervention of 3.1 years, overall, patients who had been randomized to medication had a 36% lower risk of being diagnosed with diabetes compared with patients who had been randomized to control (RR, 0.64; 95% CI, 0.54–0.76).

The reduction was greatest with weight-loss drugs (orlistat, combination phentermine-topiramate; 63%), followed by insulin sensitizers (metformin, rosiglitazone, and pioglitazone; 53%).

Among renin-angiotensin system blockade drugs, only valsartan achieved a significant 10% risk reduction; α-glucosidase inhibitors (acarbose, voglibose) achieved a 38% risk reduction, which was significant in two of five studies. A lipid-lowering drug (bezafibrate) and an insulin analog (glargine) achieved risk reductions of 32% and 21%, respectively.

Hormone therapy with estrogen or progestin and insulin secretagogues (glipizide, nateglinide) were not associated with a significantly reduced relative risk of a diabetes diagnosis.

Sustainability, Future Research Direction

To explore whether diabetes-prevention efforts were sustained after treatment withdrawal, the researchers estimated the risk for a diabetes diagnosis at the end of the washout or follow-up period, in trials that reported this (five testing medication, three testing lifestyle modifications, and one testing both).

After a mean follow-up of 7.2 years, patients who had had lifestyle modifications had a 28% lower risk of being diagnosed with diabetes compared with the control patients (RR, 0.72; 95% CI, 0.60–0.86).

After a mean follow-up of 17 weeks, patients who had received medication did not have a greater reduction in risk of diabetes diagnosis compared with controls (RR, 0.95; 95% CI, 0.79–1.14).

Since intervention effects decrease over time, future research should identify cost-effective, successful maintenance strategies to prevent or delay progression to diabetes, the authors indicate.

"Additionally, more studies identifying the differences in intervention effects for those with isolated impaired glucose tolerance (IGT), isolated impaired fasting glucose (IFG), or both are needed to develop better individualized prevention approaches," Dr Haw and colleagues write.

"Dissemination and real-world implementation of [lifestyle modification] with strategies for long-term sustainability on a large-scale is critical in addressing the global diabetes burden," they urge.

The study was funded by a Disease Control Priorities Network grant to the Institute for Health Metrics and Evaluation from the Bill & Melinda Gates Foundation and by grants from the Georgia Center for Diabetes Translation Research. Dr Haw has no relevant financial relationships. Disclosures for the coauthors are listed in the paper.

JAMA Intern Med. Published online November 6, 2017. Abstract

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