Why Are Incretin-Based Therapies More Efficient in East Asians? Perspectives from the Pathophysiology of Type 2 Diabetes and East Asian Dietary Habits

*Daisuke Yabe,1,2,3,4 Hitoshi Kuwata,1 Masahiro Iwasaki,2,4 Yutaka Seino1

1. Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan
2. Center for Metabolism and Clinical Nutrition, Kansai Electric Power Hospital, Osaka, Japan
3. Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Osaka, Japan
4. Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
*Correspondence to ydaisuke-kyoto@umin.ac.jp

Disclosure: Daisuke Yabe received consulting and/or speaker fees from Eli Lilly, Merck, Sanofi, Novo Nordisk, Boehringer Ingelheim, Takeda, and Taisho Pharmaceutical Co., Ltd. Daisuke Yabe received clinical commissioned/joint research grants from Nippon Boehringer Ingelheim, K.K., Eli Lilly and Company, and MSD, K.K. Yutaka Seino received consulting and/or speaker fees from Eli Lilly, Sanofi, Novo Nordisk, GSK, Taisho Pharmaceutical Co., Ltd., Astellas Pharma Inc., BD, Boehringer Ingelheim, Johnson & Johnson, and Takeda. Yutaka Seino received clinical commissioned/joint research grants from Nippon Boehringer Ingelheim, K.K., Eli Lilly and Company, and MSD, K.K. Hitoshi Kuwata and Masahiro Iwasaki have declared no conflicts of interest.
Received: 08.12.14 Accepted: 17.02.15
Citation: EMJ Diabet. 2015;3[1]:57-65.

Abstract

Type 2 diabetes mellitus (T2D) is one of the most serious global health problems. This is partly a result of its drastic increase in East Asia, which now comprises more than a quarter of the global diabetes population. Ethnicity and lifestyle factors are two determinants in the aetiology of T2D, and changes such as increased animal fat intake and decreased physical activity link readily to T2D in East Asians, which is characterised primarily by β-cell dysfunction that is evident immediately after ingestion of glucose or a meal, and less adiposity compared with T2D in Caucasians. These pathophysiological differences have an important impact on therapeutic approaches. Incretin-based therapies, such as dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), have become widely available for the management of T2D. Incretins, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1 are secreted from the gut in response to the ingestion of various nutrients, including carbohydrates, proteins, and fats, and enhance insulin secretion via a glucose-dependent pathway to exert their glucose-lowering effects. Recent meta-analyses of clinical trials of DPP-4i and GLP-1RA found the drugs to be more effective in East Asians, most likely due to amelioration of the primary β-cell dysfunction by increased stimulation through incretin activity. In addition, our finding that the glycosylated haemoglobin-lowering effects of DPP-4i are enhanced by fish intake, and possibly worsened by animal fat intake, suggests that dietary habits such as eating more fish and less meat can affect the secretion of incretins, and supports the greater efficacy of incretin-based therapies in East Asians.

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