Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS)

Abstract

Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with prediabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomized controlled intervention over 12 months with 2 years’ follow-up. A total of 1,105 individuals with prediabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In HR individuals, the difference between conventional and intensified LI in postchallenge glucose change was −0.29 mmol/L [95% CI −0.54; −0.04], P = 0.025. Liver fat (−1.34 percentage points [95% CI −2.17; −0.50], P = 0.002) and cardiovascular risk (−1.82 percentage points [95% CI −3.13; −0.50], P = 0.007) underwent larger reductions with intensified than with conventional LI. During a follow-up of 3 years, intensified compared with conventional LI had a higher probability of normalizing glucose tolerance (P = 0.008). In conclusion, it is possible in HR individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk phenotype–based LI may be beneficial for the prevention of diabetes.

Short‐Term Variability of Proton Density Fat Fraction in Pancreas and Liver Assessed by Multiecho Chemical‐Shift Encoding‐Based MRI at 3 T

“…Quantification of ectopic lipids, for example, in skeletal muscle (IMCL), liver (IHL) or pancreas (PF) has gained a lot of interest in cross‐sectional and longitudinal studies as ectopic lipid accumulation is a well‐known important contributor to the pathogenesis of metabolic diseases 2,4,8–11 . Thus, noninvasive MR‐based phenotyping including fat quantification is increasingly being applied in large‐scale epidemiological studies as well as in interventional prospective studies 1,4,5,13 .…”

“…8 Adipose tissue volume and distribution throughout the body, as well as ectopic fat accumulation in parenchymal tissues are important markers for, and presumably causative contributors to, individual metabolic risk. 4 In this context, pancreatic fat (PF) and intrahepatic lipids (IHL) are of major interest, as they are linked to impaired glucose metabolism. [9][10][11][12][13] For PF, an inverse correlation with insulin secretion has been shown in subjects with prediabetes [9][10][11] and it has been hypothesized that PF modulates islet function in concert with further metabolic factors of the prediabetic milieu.…”

Does the Effect of a 3-Year Lifestyle Intervention on Body Weight and Cardiometabolic Health Differ by Prediabetes Metabolic Phenotype? A Post Hoc Analysis of the PREVIEW Study

“…those with IFG+IGT) had a smaller reduction in 2-hour plasma glucose after a 9-month lifestyle intervention. Fritsche et al (36) demonstrated that an intensified lifestyle intervention with doubling of required exercise in high-risk individuals with prediabetes improved cardiometabolic risk factors. In the present study we also showed that individuals with both prediabetic hyperglycemia and intermediate HbA1c had higher diabetes incidence than those with normal HbA1c.…”

Observation on clinical effect of Huoxue-Jiangtang decoction formula granules in treating prediabetes: a randomized prospective placebo-controlled double-blind trial protocol

“…The Diabetes Prevention Program has shown that lifestyle intervention can decrease the occurrence of prediabetes conversion by 58% [14]. In addition, lifestyle interventions require no additional financial costs or time requirements, so patients can do corresponding exercise in their free time, which remains the main measure and first choice for the prevention and treatment of prediabetes [15][16][17]. However, it's not easy for some people to change a long-standing diet or lifestyle, and the lack of a consistently effective lifestyle intervention is also less effective in prediabetes.…”