A high-risk phenotype associates with reduced improvement in glycaemia during a lifestyle intervention in prediabetes.

Abstract

AIMS/HYPOTHESIS:

Lack of reversal of prediabetes (impaired glucose tolerance and/or impaired fasting glucose) to normal glucose regulation (NGR) during a lifestyle intervention is strongly associated with a higher incidence of diabetes later in life. In the Tübingen Lifestyle Intervention Program (TULIP) we hypothesised that an at-risk phenotype may exist at baseline that associates with this nonresponse to the intervention.

METHODS:

A total of 120 participants of TULIP with prediabetes at baseline were studied. Participants underwent 9 months of lifestyle intervention and had measurements of insulin secretion and insulin sensitivity during a 75 g OGTT, and measurements of liver fat content by proton magnetic resonance spectroscopy.

RESULTS:

During the lifestyle intervention, 55% of the participants did not revert to NGR. Even among participants with the largest body fat loss (upper quartile: -6.9 ± 3.3%, mean ± SD), 40% did not revert to NGR. In this regard, we identified at baseline a high-risk phenotype (n = 72) consisting of low disposition index or low insulin sensitivity + nonalcoholic fatty liver disease (NAFLD) and a low-risk phenotype (n = 48, all other traits). While the adjusted decrease in body fat was almost identical between these phenotypes (-5.7 ± 15.3% vs -7.7 ± 15.2%, p = 0.49), the high-risk phenotype had a smaller decrease in adjusted 2 h blood glucose levels (-3.7 ± 20.3% vs -18.5 ± 20.0%, p = 0.0009). In addition, only 31% of the participants with the high-risk phenotype, but 67% with the low-risk phenotype, reverted to NGR (p < 0.0001). The odds ratio for reaching the status NGR was 4.54 (95% CI 2.08, 9.94) for participants having the low-risk phenotype.

CONCLUSIONS/INTERPRETATION:

Stratification of individuals with prediabetes at baseline into a high-risk and a low-risk phenotype, based on corrected insulin secretion and insulin-resistant NAFLD, may help to determine the effectiveness of a lifestyle intervention to revert individuals to NGR.

• Authors: Norbert Stefan, Harald Staiger, Robert Wagner, Jürgen Machann, Fritz Schick, Hans-Ulrich Häring, Andreas Fritsche
• Journal: Diabetologia (Diabetologia) Vol. 58 Issue 12 Pg. 2877-84 (Dec 2015) ISSN: 1432-0428 [Electronic] Germany
• PMID: 26404062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Fats
• Insulin

Topics

• Adult
• Blood Glucose (metabolism)
• Body Composition
• Cross-Sectional Studies
• Fats (metabolism)
• Female
• Glucose Tolerance Test
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Life Style
• Liver (metabolism)
• Longitudinal Studies
• Male
• Middle Aged
• Motor Activity
• Non-alcoholic Fatty Liver Disease (metabolism)
• Phenotype
• Prediabetic State (blood, therapy)
• Risk