The Prediabetes Lifestyle Intervention Study (PLIS) - a multicenter study conducted by the German Center for Diabetes Research - showed that intensified compared to conventional lifestyle intervention led to higher probability to normalize glucose regulation. Here, we examined clinical traits determining remission of prediabetes in PLIS participants with a clinically relevant weight loss of ≥5% of their initial body weight after 12 months of lifestyle intervention. Of 11participants, 298 achieved a weight loss of ≥5 %. We classified individuals as responders, who returned to normal glucose regulation by fasting glucose, 2h OGTT plasma glucose and HbA1c (n=128) and compared them to non-responders (n =170) . There were no differences in BMI change (-3.43 ±2.02 kg/m2 in responders, -2.83 ±1.37 in non-responders, p = 0.68) , whole body fat mass loss (6.7 ± 4.9 l vs. 5.9 ±4.5, p = 0.25) or reduction in liver fat (6.1 ±6.3 percentage points vs. 6.6 ±6.4, p = 0.59) . Similarly, there was no difference in change of insulin secretion between responders and non-responders. In contrast, responders improved insulin sensitivity significantly more than non-responders (Insulin Sensitivity Index +4.5 ±4.7, vs. +2.3 ±3.1, p < 0.01) . We conclude that, in prediabetes, weight loss induced return to normal glucose regulation primarily depends on improvements in insulin sensitivity, contrasting recently reported mechanisms of diabetes remission.

Disclosure

A.Sandforth: None. K.D.Lange: None. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. German center for diabetes research: n/a. A.F.Pfeiffer: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. R.Jumpertz von schwartzenberg: None. A.L.Birkenfeld: None.

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