Understanding Mechanisms of Weight Loss-Induced Remission in Prediabetes: A Post-hoc Analysis of the PLIS

Dec 21, 2023

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The following is a summary of “Mechanisms of weight loss-induced remission in people with prediabetes: a post-hoc analysis of the randomized, controlled, multicentre Prediabetes Lifestyle Intervention Study (PLIS),” published in the December 2023 issue of Primary Care by Sandforth, et al.

Losing liver and pancreatic fat and raising insulin output may treat type 2 diabetes. For a study, researchers evaluated how weight reduction causes prediabetic remission. This prespecified post-hoc research compared the Diabetes Prevention Programme to weight loss-induced prediabetes resolution in the randomized, controlled, multicenter Prediabetes Lifestyle Intervention research (PLIS). PLIS randomly assigned participants from eight German clinical study sites (including seven university hospitals) to receive a control, standard lifestyle (DPP-based), or intensive lifestyle intervention for 12 months between March 1, 2012, and August 31, 2016. DPP randomly allocated patients to metformin, lifestyle intervention, or placebo at 23 US clinical study sites from July 31, 1996, to May 18, 1999. Only individuals randomly allocated to lifestyle intervention or placebo who dropped 5% of their body weight were studied in PLIS and DPP. Responders achieved normal fasting plasma glucose (FPG) <5·6 mmol/L, glucose tolerance <7·8 mmol/L, and HbA_1c <39 mmol/mol following 12 months of lifestyle or placebo/control intervention.

NON-responders had FPG, 2 h glucose, or HbA_1c greater. This linear mixed model research assessed insulin sensitivity, secretion, VAT, and IHL. 298 of 1,160 PLIS participants (25.7%) lost 5% or more of their baseline weight. 128 (43%) of 298 responded, and 170 (57%) did not. The respondents were younger than non-responders (mean age 55·6 years [SD 9·9] vs 60·4 years [8·6]; P<0.0001). Almost 5% of 683 DPP validation cohort participants at baseline lost weight. There were 132 (19%) answers and 551 (81%) non-responders. PLIS revealed comparable BMI declines for responders and non-responders (mean 32·4 kg/m² [SD 5·6] from baseline to 12 months).

29.0 kg/m² [4-9] non-responders 32·1 kg/m² [5·9] to 29·2 kg/m² [5·4]; p Insulin sensitivity increased more in responders than non-responders (mean at baseline 291 mL/[min × m²], SD 60 to 378 mL/[min × m²], 56 vs 278 mL/[min × m²], 62, to 323 mL/[min × m²], 66; P<0.0001), while insulin secretion did not change (mean at baseline 175 pmol/mmol [SD 64] to 163 158·0 pmol/mmol [55·6] Both groups had similar IHL reductions (mean baseline: 10·1% [SD 8·7] to mean 12 months). 3.5% [3.9] vs. non-respond VAT decreased more in responders (mean baseline: 6·2 L [SD 2·9]; mean at 12 months: 4·1 L [2·3] vs. 5·7 L [2·3] to 4·5 L [2·2]; p= After two years, respondents had 73% reduced type 2 diabetes risk than non-responders. Prediabetes remission enhances insulin sensitivity and VAT savings, unlike type 2. They equate NGR to prediabetes remission because it avoids type 2 diabetes. Treatment should target prediabetes remission.