PMID- 28067320 OWN - NLM STAT- MEDLINE DCOM- 20181004 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 DP - 2017 Jan 9 TI - Relationship between frequency of hypoglycemic episodes and changes in carotid atherosclerosis in insulin-treated patients with type 2 diabetes mellitus. PG - 39965 LID - 10.1038/srep39965 [doi] LID - 39965 AB - The effect of hypoglycemia on the progression of atherosclerosis in patients with type 2 diabetes mellitus (T2DM) remains largely unknown. This is a post hoc analysis of a randomized trial to investigate the relationship between hypoglycemic episodes and changes in carotid intima-media thickness (IMT). Among 274 study subjects, 104 patients experienced hypoglycemic episodes. Increases in the mean IMT and left maximum IMT of the common carotid arteries (CCA) were significantly greater in patients with hypoglycemia compared to those without hypoglycemia. Classification of the patients into three groups according to the frequency of hypoglycemic episodes showed that high frequency of hypoglycemic events was associated with increases in mean IMT-CCA, and left max-IMT-CCA and right max-IMT-CCA. In addition, repetitive episodes of hypoglycemia were associated with a reduction in the beneficial effects of sitagliptin on carotid IMT. Our data suggest that frequency of hypoglycemic episodes was associated with changes in carotid atherosclerosis. FAU - Mita, Tomoya AU - Mita T AD - Department of Metabolism &Endocrinology, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. FAU - Katakami, Naoto AU - Katakami N AD - Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. AD - Department of Metabolism and Atherosclerosis, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. FAU - Shiraiwa, Toshihiko AU - Shiraiwa T AD - Shiraiwa Medical Clinic, 4-10-24 Houzenji, Kashiwara, Osaka 582-0005, Japan. FAU - Yoshii, Hidenori AU - Yoshii H AD - Department of Medicine, Diabetology &Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center, Shinsuna 3-3-20, Koto-ku, Tokyo 136-0075, Japan. FAU - Kuribayashi, Nobuichi AU - Kuribayashi N AD - Misaki Naika Clinic, 6-44-9 Futawahigashi, Funabashi, Chiba 274-0805, Japan. FAU - Osonoi, Takeshi AU - Osonoi T AD - Naka Memorial Clinic, 745-5, Nakadai, Naka City, Ibaraki 311-0113, Japan. FAU - Kaneto, Hideaki AU - Kaneto H AD - Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. FAU - Kosugi, Keisuke AU - Kosugi K AD - Osaka Police Hospital, 10-31 Kitayamacho, Tennoji-ku, Osaka 543-0035, Japan. FAU - Umayahara, Yutaka AU - Umayahara Y AD - Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka 558-8558, Japan. FAU - Gosho, Masahiko AU - Gosho M AD - Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan. FAU - Shimomura, Iichiro AU - Shimomura I AD - Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. FAU - Watada, Hirotaka AU - Watada H AD - Department of Metabolism &Endocrinology, Juntendo University Graduate School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170109 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulins) RN - TS63EW8X6F (Sitagliptin Phosphate) SB - IM MH - Aged MH - Carotid Artery Diseases/complications/*physiopathology MH - Carotid Artery, Common/physiopathology MH - Carotid Intima-Media Thickness MH - Diabetes Mellitus, Type 2/complications/*drug therapy/pathology MH - Disease Progression MH - Female MH - Humans MH - Hypoglycemia/complications/*pathology MH - Hypoglycemic Agents/*therapeutic use MH - Insulins/*therapeutic use MH - Male MH - Middle Aged MH - Risk Factors MH - Sitagliptin Phosphate/therapeutic use PMC - PMC5220284 COIS- TM received research funds from MSD and Takeda Pharma K.K. and has received lecture fees from AstraZeneca K.K., Boehringer Ingelheim, Eli Lilly, Kowa Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., MSD, Ono Pharmaceutical Co., and Takeda Pharmaceutical Co. NKa is a staff member of the endowed chair (Department of Metabolism and Atherosclerosis) established by funds from Kowa Pharmaceutical Co., has received research funds from MSD and lecture fees from Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim, Daiichi Sankyo Inc., Dainippon Sumitomo Pharma Co., Eisai Co., Eli Lilly, Kowa Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., Novartis Pharmaceuticals, Novo Nordisk Pharma, Ono Pharmaceutical Co., Otsuka Pharmaceutical, Shionogi & Co., Takeda Pharmaceutical Co., Sanofi-Aventis, and Shionogi & Co. TS has received lecture fees from Boehringer Ingelheim, Sanofi-Aventis, Novo Nordisk Pharma, Novartis Pharmaceuticals, Eli Lilly, Abbott Japan, Takeda Pharmaceutical Co., Sanwakagaku Kenkyusho, Mitsubishi Tanabe Pharma Co., Daiichi Sankyo Inc., Astellas Pharma Inc., Ono Pharmaceutical Co., MSD, Shionogi, Pharma, and Taisho Toyama Pharmaceutical Co. NKu has received lecture fees from Sanofi-Aventis and Novartis Pharmaceuticals. TOs has received lecture fees from Novo Nordisk, Inc., Astellas Pharma, Inc., Mitsubishi Tanabe Pharma, Sanwakagaku Kenkyusho, Takeda Pharmaceutical Co., Kowa Co. and research funds from Novo Nordisk, Inc., Astellas Pharma, Inc., Mitsubishi Tanabe Pharma, Sanwakagaku Kenkyusho, Kowa Co. Novo Nordisk Pharma, Dainippon Sumitomo Pharma., Eli Lilly Taisho Pharmaceutical Co., Ltd., GlaxoSmithKline, Sumitomo Dainippon Pharma Co., Ltd., Astellas Pharma US, Inc., Bayer HealthCare, and AbbVie GK. KK has received lecture fees from Boehringer Ingelheim, Sanofi-Aventis, Novo Nordisk Pharma, Novartis Pharmaceuticals, Eli Lilly, Takeda Pharmaceutical Co., MSD, Kowa Co., Mitsubishi Tanabe Pharma and research funds from Sysmex Co. HK has received lecture fees from Boehringer Ingelheim, Sanofi-Aventis, Ono Pharmaceutical Co., MSD, Novo Nordisk Pharma, Novartis Pharmaceuticals, Daiichi Sankyo Inc., Takeda Pharmaceutical Co., Kissei Pharmaceutical Co., Dainippon Sumitomo Pharma Co., Mitsubishi Tanabe Pharma Co., Kyowa Kirin, Eli Lilly, Pfizer, Astrazeneca, Astellas Pharma Inc. and research funds from Takeda Pharmaceutical Co., MSD, Mochida Pharmaceutical Co. Sanofi-Aventis, Novartis Pharmaceuticals, Novo Nordisk Pharma, Eli Lilly, Daiichi Sankyo Inc., Shionogi Pharma, Teijin Pharma, Dainippon Sumitomo Pharma Co., Otsuka Pharmaceutical, Kissei Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., Astrazeneca, Astellas Pharma Inc., and Kyowa Hakko Kirin Co. KK has received lecture fees from Boehringer Ingelheim, Sanofi-Aventis, Novo Nordisk Pharma, Novartis Pharmaceuticals, Eli Lilly, Takeda Pharmaceutical Co., MSD, Kowa Co., Mitsubishi Tanabe Pharma and research funds from Sysmex Co. MG received lecture fees from Novartis and Tiho Pharma K.K. and received travel fees from Takeda Pharmaceutical Co. and writing fee from Kowa Co., Ltd. IS has received lecture fees from Astellas Pharma Inc., AstraZeneca K.K., MSD K.K., Ono Pharmaceutical Co., Kyowa Hakko Kirin Co., Kowa Pharmaceutical Co., Sanofi K.K., Sanwa Kagaku Kenkyusho Co., Daiichi Sankyo Co., Takeda Pharma K.K., Mitsubishi Tanabe Pharma Co., Teijin Pharma, Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Novartis Pharma K.K., Novo Nordisk Pharma, Bayer Yakuhin, Pfizer Japan Inc., Bristol-Myers K.K., Mochida Pharmaceutical Co., Shionogi & Co., Taisho Toyama Pharmaceutical Co., Shionogi & Co., and research funds from Astellas Pharma Inc., AstraZeneca K.K., Eisai Co., MSD K.K, Otsuka Pharmaceutical Co., Ono Pharmaceutical Co., Kaken Pharmaceutical Co., Kissei Pharmaceutical Co., Kyowa Hakko Kirin Co., Sanofi K.K., Shionogi & Co., Daiichi Sankyo Co., Dainippon Sumitomo Pharma Co., Takeda Pharma K.K., Mitsubishi Tanabe Pharma Co., Teijin Pharma, Nippon Boehringer Ingelheim Co., Novartis Pharma K.K., Novo Nordisk Pharma, Pfizer Japan Inc., Bristol-Myers K.K., Mochida Pharmaceutical Co., Eli Lilly Japan K.K, Kowa Co., Ltd., Kowa Pharmaceutical Co., and Taisho Toyama Pharmaceutical Co. HW has received lecture fees from Novo Nordisk, Inc., Eli Lilly and Company, Sanofi, Dainippon Sumitomo Pharma Co., Fujifilm, Bayer Health Care, Kissei Pharmaceutical Company, Mochida Pharmaceutical Company, MSD, Takeda Pharmaceutical Company, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi-Sankyo, Ono Pharmaceutical Co., Ltd., Novartis Pharmaceuticals Corporation, Mitsubishi Tanabe Pharma Corporation, AstraZeneca LP, Kyowa Hakko Kirin Comapany, Ltd, Sanwa Kagaku Kenkyusyo Company, Ltd., Kowa Company Ltd, Astellas Pharma, Inc., advisory fees from Novo Nordisk, Inc., Mochida Pharma Company, AstraZeneca LP, Kowa Company, Astellas Pharma, Inc., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc., MSD, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Dainippon Sumitomo Pharma Co, Takeda Pharmaceutical Company, Ono Pharmaceutical Co, Pfizer, Inc., Kowa Company and research funds from Boehringer Ingelheim, Pfizer, Mochida Pharmaceutical Co., Sanofi-Aventis, Novo Nordisk Pharma, Novartis Pharmaceuticals, Sanwakagaku Kenkyusho, Terumo Corp. Eli Lilly, Mitsubishi Tanabe Pharma, Daiichi Sankyo Inc., Takeda Pharmaceutical Co., MSD, Shionogi, Pharma, Dainippon Sumitomo Pharma, Kissei Pharma, and Astrazeneca. EDAT- 2017/01/10 06:00 MHDA- 2018/10/05 06:00 PMCR- 2017/01/09 CRDT- 2017/01/10 06:00 PHST- 2016/06/03 00:00 [received] PHST- 2016/11/29 00:00 [accepted] PHST- 2017/01/10 06:00 [entrez] PHST- 2017/01/10 06:00 [pubmed] PHST- 2018/10/05 06:00 [medline] PHST- 2017/01/09 00:00 [pmc-release] AID - srep39965 [pii] AID - 10.1038/srep39965 [doi] PST - epublish SO - Sci Rep. 2017 Jan 9;7:39965. doi: 10.1038/srep39965.