Comparison of glycemic improvement between intermittent calorie restriction and continuous calorie restriction in diabet

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Comparison of glycemic improvement between intermittent calorie restriction and continuous calorie restriction in diabetic mice Siying Wei1, Jingyu Zhao1, Meijuan Bai1, Chenchen Li1,2, Lingling Zhang1 and Yan Chen1,2*

Abstract Background: Calorie restriction (CR) has been well proved to be a powerful tool to improve metabolic health associated with aging; and many types of CR have been proposed. Intermittent CR has become a trend in recent years due to its better compliance than continuous CR every day. However, there are few studies that directly compare the interventional activity of intermittent CR vs continuous CR in metabolic disorders such as diabetes. Methods: In this study, we analyzed two protocols of intermittent CR with the calorie-matched continuous CR in two diabetic mouse models including db/db and streptozotocin-treated mice. Intermittent CR was carried out by a fasting-mimicking diet (FMD, with 30% calorie intake of the control per day) for 2 days or 5 days (i.e., 2–5 or 5–9 regimes followed by free eating for 5 or 9 days respectively). Results: In the two diabetic mouse models, both intermittent CR and continuous CR significantly reduced fasting blood glucose level and improved insulin sensitivity. However, intermittent CR performed significantly better than continuous CR in improving glycemic control and insulin sensitivity in db/db mice. In addition, intermittent CR improved the glucose homeostasis of the db/db mice without causing loss of body weight. Analyses with the pancreatic islets reveal that intermittent CR profoundly elevated the number of insulin-positive cells in both diabetic mouse models. Conclusions: Our study indicated that both intermittent CR and continuous CR can lower fasting blood glucose level in the diabetic mice, while intermittent CR is better than the latter in improving glucose homeostasis in db/db mice. Keywords: Diabetes, Intermittent fasting, Fasting-mimicking diet, Calorie restriction, Insulin sensitivity

Introduction Weight loss, long considered as a key strategy to ameliorate the progression of type 2 diabetes and calorie restriction (CR), has been widely used to reduce obesity [1, 2]. There are numerous types and regimes of CR used in both animal and human studies. Intermittent CR or intermittent fasting (IF) has gained a lot of popularity in * Correspondence: [email protected] 1 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Rd, Shanghai 200031, China 2 School of Life Sciences and Technology, Shanghai Tech University, Shanghai 200031, China

recent years as it is easily acceptable to patients [3]. Intermittent CR refers to a dietary pattern of extended time period of fasting with low or no energy intake (e.g., 16–48 h), followed by a period of normal food intake, on a recurring basis [4]. It is believed that intermittent CR can induce a metabolic switch f