PracticeUpdate Diabetes March 2019

EDITOR’S PICKS 13

Neurocognitive and Hormonal Correlates of Voluntary Weight Loss in Humans Cell Metabolism Take-home message • In this study involving 24 participants, the authors evaluated the effect of calorie restriction on cognitive control networks measured by functional MRI (fMRI) and associated hormonal signaling changes over time. The participants (mean age of 37.2 years and mean starting BMI of 30.4) were asked to follow a strict calorie-restricted diet for 3 months. The authors determined that increased activity and functional connectivity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3. In addition, weight loss was associated with increased plasma ghrelin and decreased leptin. The authors suggest that activation in pre- frontal regions associated with self-control contributes to successful weight loss and maintenance. • The authors concluded that higher-order processing is responsible for weight main- tenance after dieting by calorie restriction. This is an important component of patient education in order to combat the intense neurohormonal drive to consume calories. Jason Sloane MD Abstract Insufficient responses to hypocaloric diets have been attributed to hormonal adaptations that override self-control of food intake. We tested this hypothesis by measuring circulating energy-balance hormones and brain functional magnetic resonance imaging reactivity to food cues in 24 overweight/obese par- ticipants before, and 1 and 3 months after starting a calorie restriction diet. Increased activity and func- tional connectivity in prefrontal regions at month 1 correlated with weight loss at months 1 and 3. Weight loss was also correlated with increased plasma ghre- lin and decreased leptin, and these changes were associated with food cue reactivity in reward-related brain regions. However, the reduction in leptin did not counteract weight loss; indeed, it was correlated with further weight loss at month 3. Activation in prefrontal regions associated with self-control could contribute to successful weight loss and maintenance. This work supports the role of higher-level cognitive brain func- tion in body-weight regulation in humans. Neurocognitive and Hormonal Correlates of Volun- tary Weight Loss in Humans. Cell Metab 2018 Oct 15;[EPub Ahead of Print], S Neseliler, W Hu, K Larcher, et al. www.practiceupdate.com/c/77965

Abstract OBJECTIVE To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. DESIGN Population based cohort study. SETTING General practices contributing data to the UK Clinical Practice Research Datalink. PARTICIPANTS 154162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018. MAIN OUTCOME MEASURES Use of DPP-4 inhibitors and GLP-1 receptor agonists was mod- elled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc phar- macovigilance analysis was conducted using the World Health Organization’s global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma. RESULTS During 614274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence inter- val 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sul- fonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively). CONCLUSION Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. Incretin Based Drugs and Risk of Cholangiocarcinoma Among Patients With Type 2 Diabetes: Population Based Cohort Study. BMJ 2018 Dec 05;363(xx)k4880, D Abrahami, A Douros, H Yin, et al. www.practiceupdate.com/c/77304

VOL. 3 • NO. 1 • 2019