Background
Remission of type 2 diabetes can occur as a result of weight loss and is characterized by a reduction in liver and pancreas fat and a return to insulin secretion.
In this analysis, we aimed to investigate the mechanisms of weight loss-induced remission in people with prediabetes .
Methods
In this prespecified post-hoc analysis, resolution of prediabetes induced by weight loss was evaluated in the multicenter, randomized, controlled Prediabetes Lifestyle Intervention Study (PLIS), and the results were validated with Diabetes Prevention Program (DPP) study participants .
For PLIS, between March 1, 2012 and August 31, 2016, participants were recruited at eight clinical study sites (including seven university hospitals) in Germany and randomly assigned to receive a control intervention, a style intervention of standard living (i.e., DPP-based intervention), or an intensified lifestyle intervention for 12 months.
For the DPP, participants were recruited at 23 clinical trial sites in the US between July 31, 1996 and May 18, 1999, and were randomly assigned to receive a standard lifestyle intervention, metformin or placebo.
In both PLIS and DPP, only participants who were randomly assigned to receive lifestyle intervention or placebo and who lost at least 5% of their body weight were included in this analysis.
Responders were defined as individuals who returned to normal fasting plasma glucose (FPG; <5.6 mmol/L), normal glucose tolerance (<7.8 mmol/L), and HbA 1c less than 39 mmol/L . mol after 12 months of treatment with lifestyle intervention or placebo or control intervention.
Non -responders were defined as individuals who had FPG, 2-h glucose, or HbA 1c above these thresholds.
The main outcomes of this analysis were insulin sensitivity, insulin secretion, visceral adipose tissue (VAT), and intrahepatic lipid content (IHL) and were evaluated using linear mixed models.
Results
Of 1160 participants recruited into PLIS, 298 (25.7%) had a weight loss of 5% or more of their body weight at baseline. 128 (43%) of 298 participants responded and 170 (57%) did not respond.
Responders were younger than nonresponders (mean age 55.6 years [SD 9.9] vs. 60.4 years [8.6]; p<0.0001) . The DPP validation cohort included 683 participants who lost at least 5% of their body weight at baseline. Of them, 132 (19%) responded and 551 (81%) did not respond.
In PLIS, BMI reduction was similar between responders and non-responders (responders mean at baseline 32.4 kg/m 2 [SD 5.6] to 12-month mean 29.0 kg/m 2 [4.9] versus non-responders 32.1 kg/m 2 [5.9] to 29.2 kg/m 2 [5.4]; p=0.86).
However, whole-body insulin sensitivity increased more in responders than in nonresponders (mean at baseline 291 ml/[min × m 2 ], SD 60 to mean at 12 months 378 ml /[min × m 2 ], 56 versus 278 mL/[min × m 2 ], 62, to 323 mL/ [ min differed within groups over time or between groups (mean responders at baseline 175 pmol/mmol [SD 64] to mean at 12 months 163.7 pmol/mmol [60.6] versus non-responders 158.0 pmol/mmol [55.6] to 154.1 pmol/mmol [56.2] ;p=0·46).
Intrahepatic lipid (IHL) content decreased in both groups, with no differences between groups (mean of responders at baseline 10.1% [SD 8.7] to mean at 12 months 3.5% [ 3.9] versus non-responders 10.3% [8 ·1] to 4.2% [4.2];p=0.34); However, visceral adipose tissue (VAT) decreased more in responders than in non-responders (mean at baseline 6.2 L [SD 2.9] to mean at 12 months 4.1 L [2 .3] versus 5.7 L [2.3] to 4.5 L [2.2]; p=0.0003).
Responders had a 73% lower risk of developing type 2 diabetes than non-responders within 2 years of completing the intervention.
Interpretation Unlike the remission of type 2 diabetes , the resolution of prediabetes was characterized by an improvement in insulin sensitivity and a reduction in visceral adipose tissue (VAT) . Because return to normal glucose regulation (NGR) prevents the development of type 2 diabetes, we propose the concept of prediabetes remission in analogy with type 2 diabetes. We suggest that prediabetes remission should be the goal main therapeutic in individuals with prediabetes. |
Money
German Federal Ministry of Education and Research through the German Center for Diabetes Research; the Ministry of Science, Research and Arts of Baden-Württemberg; the Helmholtz Association and Helmholtz Munich; the Cluster of Excellence in Microbe Control to Fight Infections; and the German Research Foundation.
