Brain Insulin Sensitivity Predicts Adiposity—Nine-Year Results of the Tulip Study

Abstract

Lifestyle intervention reduces body weight and prevents type 2 diabetes. One crucial modulator of food intake and whole body energy metabolism is insulin action in the brain. We now test whether brain insulin sensitivity is a long-term predictor of weight and body fat distribution during and after a lifestyle intervention program. Before, after 9 months, at the end of lifestyle intervention at 24 months, as well as after 8.7 ±1.6 years follow-up, participants of the Tuebingen Lifestyle Intervention Program underwent a 75g OGTT, and whole body MRI. Brain insulin sensitivity was measured at baseline by changes in neuronal signals (theta frequency band) with magnetoencephalography during a hyperinsulinemic-euglycemic clamp in a subgroup of 28 participants of whom long-term follow-up was available in 15 persons. Higher brain insulin sensitivity before lifestyle intervention was associated with a more pronounced reduction in total and visceral fat during the lifestyle intervention (all p<0.01). High brain insulin sensitivity was also associated with less regain of fat mass during the long-term follow-up. In contrast to visceral fat, changes in subcutaneous adipose tissue were independent of the brain insulin responsiveness. Our results extend previous findings on the role of brain insulin for the success of lifestyle intervention to a long-term perspective. Insulin action in the human brain appears to be not only important for weight loss, but seems to determine regain of body weight and especially total and visceral fat mass thereafter. Experimental findings demonstrated that insulin administration to the brain modulates peripheral energy fluxes in humans. In line, our results indicate fat depots specific effects of brain insulin with particular benefits in the visceral compartment. These findings support the role of brain insulin in the regulation of body fat distribution and body weight. Disclosure V. Schmid: None. O. Tschritter: None. J. Machann: None. R. Wagner: None. N. Stefan: Consultant; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, OmniaMed Ltd.. H. Preissl: None. H. Haering: None. A. Fritsche: Advisory Panel; Self; Sanofi-Aventis Deutschland GmbH, Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim GmbH. M. Heni: Research Support; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc..