Exercise, dietary change, and weight loss can pay off big for people with prediabetes. When lifestyle changes bring blood glucose back to the normal range, the risks for myocardial infarction (MI), heart failure (HF), and premature death are cut roughly in half, according to an international study published in The Lancet Diabetes & Endocrinology that analyzed long-term data from 2402 individuals with prediabetes.

The analysis pooled two of the world’s largest diabetes prevention cohorts: the US Diabetes Prevention Program Outcomes Study (DPPOS) and China’s DaQing Diabetes Prevention Outcomes Study (DaQingDPOS). Researchers from the University Hospital Tübingen, Helmholtz Center Munich, and the German Center for Diabetes Research (DZD) were involved.

Worldwide, millions live with elevated blood glucose without knowing it. Prediabetes has long lacked a clearly defined treatment target. The new analysis suggests the key is not lifestyle change per se but achieving a return to normal blood glucose — a remission of prediabetes. In both cohorts, participants who reached remission had about a 50% lower risk for cardiovascular death, and all-cause mortality also fell significantly.

DPPOS followed participants for 20 years; DaQingDPOS followed participants for 30 years. Led by the Tübingen team, datasets were harmonized and reanalyzed to compare cardiovascular death and HF hospitalizations in those with and without prediabetes remission.

In DPPOS, 275 of 2402 participants (11.5%) achieved remission after 1 year, and 2127 (88.5%) did not. The event rate for cardiovascular death or hospitalization for HF was 1.74 (95% CI, 0.87-3.48) per 1000 person-years among those with remission vs 4.17 (95% CI, 3.55-4.89) per 1000 person-years among those without (P = .013), yielding a hazard ratio (HR) of 0.41 (P = .014). DaQingDPOS confirmed the findings (primary endpoint HR, 0.49; P = .010), and a pooled meta-analysis supported the results.

Normalizing Blood Sugar

Cardiovascular prevention traditionally rests on three pillars: blood pressure control, low-density lipoprotein cholesterol lowering, and smoking cessation. These findings point to a potential fourth pillar: sustained normalization of blood glucose in prediabetes.

“Our results suggest that remission of prediabetes not only delays or prevents the onset of type 2 diabetes — as is already known — but also protects people from serious cardiovascular diseases in the long term — for decades,” said study lead Andreas Birkenfeld, MD, DZD board member and director of the Department of Diabetology, Endocrinology, and Nephrology, University Hospital Tübingen, Tübingen, Germany.

A fasting blood glucose of 97 mg/dL or lower emerged as a simple marker of persistently lower cardiovascular risk — independent of age, weight, or ethnicity. That threshold could be used in primary care worldwide to make prevention more actionable.

Germany lags in prevention. On the current Public Health Index, the country ranks second-to-last among 18 European nations in implementing evidence-based prevention measures. Consistent with that, the risk of dying from cardiovascular disease is significantly higher in Germany than in many other European countries.

The study underscores untapped potential — and how concrete targets can improve public health. “We see a clear therapeutic window: If glucose levels are normalized as early as the prediabetic stage, the long-term risk of heart attack, heart failure, and premature death can be significantly reduced. Our data support explicitly establishing remission as a primary treatment goal in guidelines for the prevention of diabetes and cardiovascular disease,” Birkenfeld said.

This story was translated from Medscape’s German edition.