HeConnection-EquippedAchieving normal glucose regulation even once predicted a lower risk of progression to diabetes for pre-diabetic patients. The evidence points to working hard at pre-diabetes to get rewarded both now and later.

Follow-up data from the Diabetes Prevention Program (DPP) showed that patients who achieved normal glucose regulation on any annual measurement during the DPP were three times as likely to achieve normal glucose regulation at follow-up as patients who remained pre-diabetic.

Leigh Perreault, MD, from the University of Colorado in Aurora, and colleagues reported that, in particular, patients who remained pre-diabetic after intensive lifestyle intervention had a significantly higher risk of progressing to diabetes and a significantly lower likelihood of achieving normal glucose regulation than did patients originally randomized to placebo.

“We conclude that prediabetes is a high-risk state for diabetes, especially in patients who remain with pre-diabetes despite intensive lifestyle intervention,” Perreault and colleagues wrote in conclusion in an article published simultaneously online in The Lancet.

Reversion to normal glucose regulation, even if transient, is associated with a significantly reduced risk of future diabetes, independent of previous treatment group.”

Impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes are characterized by elevated blood glucose concentrations associated with an increased risk of several serious health outcomes.

Several large randomized controlled trials have shown that diabetes can be prevented or delayed in people with IFG or IGT by diet, physical activity, and various drugs. Less well understood is the clinical significance of regression of these conditions to normo-glycemia, which has been noted in several trials.

Perreault and colleagues sought to determine whether regression to normo-glycemia predicted a reduced risk of incident metabolic and vascular diseases or simply reflected glucose fluctuations over time.

Their analysis included 1,990 DPP participants who continued follow-up in the DPP Outcomes Study (DPPOS). The study population comprised 736 patients initially randomized to intensive lifestyle intervention, 647 randomized to metformin, and 607 to placebo. The primary outcome was the proportion of patients who progressed to diabetes during the DPPOS.

Patients who had a confirmed diagnosis of diabetes during DPP were excluded from the analysis. The following definitions were used:

  • Diabetes: fasting plasma glucose (FPG) ≥126 mg/dL or a 2-hour glucose ≥200 mg/dL after a 75-g oral glucose challenge [these were excluded from the program]
  • Normal glucose regulation: FPG <100 mg/dL or a 2-hour glucose <140 mg/dL on at least one annual oral glucose tolerance test (OGTT) during the DPP
  • Pre-diabetes: FPG 100 to 126 mg/dL or 2-hour plasma glucose 140 to 200 mg/dL after OGTT throughout the DPP

The study population included 894 patients who achieved normal glucose regulation at least once during DPP. Those patients had a 56% lower risk of progression to diabetes than did the patients who remained persistently pre-diabetic. The finding was unaffected by DPP treatment assignment.

3 factors had significant associations with achievement of normal glucose regulation during the DPPOS:

  • Increased beta-cell function
  • Normal glucose regulation during the DPP
  • Insulin sensitivity

Among DPP participants who remained persistently pre-diabetic, those assigned to intensive lifestyle intervention had 31% greater risk of progression to diabetes and a 41% lower risk of achieving normal glucose regulation during the DPPOS than did participants randomized to placebo.

Even when overt diabetes is delayed or prevented, both microvascular and macrovascular disease are more prevalent in those with pre-diabetes compared with their normo-glycemic peers,” Natalia Yakubovich, MD, and Hertzel C. Gerstein, MD, from the McMaster University in Hamilton, Ontario, wrote in an accompanying editorial.

“Whether a reduced incidence of diabetes after regression translates into a reduced incidence of diabetes-related health consequences, such as blindness and vascular disease, is unknown, and can be assessed by ongoing follow­-up of this cohort, and by future clinical trials,” they added.

Although some issues remain unresolved, “the findings clearly suggest that transient regression of impaired glucose tolerance to normo-glycemia that is either spontaneous or in response to treatment is of clinical relevance.”

Health-e-Solutions comment: The intensive lifestyle intervention is not defined in this article, but I suspect it contains too many high glycemic carbohydrates for the diabetic-alkaline lifestyle. Our quest to create wellness and support health in our two type 1 diabetic boys (and the rest of our family) has resulted in great blood sugar management, along with a host of other benefits.