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. 2020 Jul;11(4):1020-1076.
doi: 10.1111/jdi.13306.

Japanese Clinical Practice Guideline for Diabetes 2019

Eiichi Araki  1 , Atsushi Goto  2 , Tatsuya Kondo  3 , Mitsuhiko Noda  4 , Hiroshi Noto  5 , Hideki Origasa  6 , Haruhiko Osawa  7 , Akihiko Taguchi  8 , Yukio Tanizawa  8 , Kazuyuki Tobe  9 , Narihito Yoshioka  10
Affiliations

Japanese Clinical Practice Guideline for Diabetes 2019

Eiichi Araki et al. J Diabetes Investig. 2020 Jul.
No abstract available

Keywords: Diabetes; Diagnosis; Guideline; Treatment.

PubMed Disclaimer

Conflict of interest statement

Eiichi Araki received honoraria from AstraZeneca, Daiichi Sankyo, Kowa, Mitsubishi Tanabe Pharma, MSD, Novo Nordisk, Ono Pharmaceutical and Sanofi, also received subsidies or donations from Astellas Pharma, Bayer Yakuhin, Daiichi Sankyo, Eli Lilly Japan, Kowa, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk, Pfizer Japan, Sanofi, Sumitomo Dainippon Pharma, Taisho Pharmaceutical and Takeda Pharmaceutical, and belongs to endowed departments by MSD, Ono Pharmaceutical and Terumo. Mitsuhiko Noda received subsidies or donations from Astellas Pharma, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly Japan, Mitsubishi Tanabe Pharma, MSD, Novo Nordisk Pharma, Ono Pharmaceutical, Sumitomo Dainippon Pharma, Takeda Pharmaceutical and Teijin Pharma. Hiroshi Noto received honoraria from Eli Lilly Japan and MSD. Haruhiko Osawa received research funding from Daiichi Sankyo, Ono Pharmaceutical, Sysmex, Taisho Toyama Pharmaceutical and Takeda Pharmaceutical. Yukio Tanizawa received honoraria from Astellas Pharma, MSD, Novo Nordisk Pharma, Ono Pharmaceutical and Takeda Pharmaceutical, also received research funding from Seastar, also received subsidies or donations from Astellas Pharma, Daiichi Sankyo, Eli Lilly Japan, Kyowa Kirin, Mitsubishi Tanabe Pharma, MSD, Nippon Boehringer Ingelheim, Sanofi, Sumitomo Dainippon Pharma and Takeda Pharmaceutical. Kazuyuki Tobe received honoraria from Novo Nordisk Pharma, Kowa Pharmaceutical and Astellas Pharma, also received research funding from The Uehara Memorial Foundation and The Naito Foundation, also received subsidies or donations from Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Daiichi Sankyo, MSD, Asahi Kasei Pharma, Teijin Pharma, Boehringer Ingelheim, Ono Pharmaceutical, Novo Nordisk Pharma, Eli Lilly Japan, Fuji Chemical Industries and Arkray. Narihito Yoshioka received honoraria from Novo Nordisk Pharma and Takeda Pharmaceutical. Atsushi Goto, Tatsuya Kondo, Hideki Origasa, Akihiko Taguchi have nothing to declare.

The Japan Diabetes Society: Organizational Conflict of Interest

Co‐sponsored seminar: Abbott Diagnostics Medical, Abbott Japan, Abbott Vascular Japan, Aegerion Pharmaceuticals, Ajinomoto, AR Brown, Arkray, Arkray Global Business, Asahi Kasei Pharma, ASKA Pharmaceutical, Astellas Pharma, AstraZeneca, Bayer Yakuhin, Cosmic Corporation, Covidien Japan, Daiichi Sankyo, Eiken Chemical, Eizai, Eli Lilly Japan, Fujifilm Pharma, Fujifilm Toyama Chemical, Fukuda Colin, Fukuda Denshi, Gilead Sciences, Hakubaku, Healthy Network, Hitachi Chemical Diagnostics Systems, Horiba, InBody Japan, Johnson & Johnson, Kaken Pharmaceutical, Kissei Pharmaceutical, Kotobuki Pharmaceutical, Kowa, Kracie Pharmaceutical, Kyowa Kirin, LifeScan Japan, LSI Medience, Medtronic Japan, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Mylan EPD, Nikkiso, Nippon Becton Dickinson, Nippon Boehringer Ingelheim, Nipro, Novartis Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Rizap Group, Roche DC Japan, Sanofi, Santen Pharmaceutical, Sanwa Kagaku Kenkyusho, SRL, Sumitomo Dainippon Pharma, Taisho Pharma, Taisho Pharmaceutical, Takeda Pharmaceutical, Terumo, Unex, Welby.

Supporting member: Abbott Japan, Arkray Global Business, Astellas Pharma, AstraZeneca, Bunkodo, Chugai Pharmaceutical, Daiichi Sankyo, EA Pharma, Eizai, Eli Lilly Japan, H + B Life Science, Horiba, Japan Tobacco, Johnson & Johnson, Kaken Pharmaceutical, Kissei Pharmaceutical, Kowa, Kyowa Kirin, LifeScan Japan, Medtronic Japan, Mitsubishi Tanabe Pharma, MSD, Nippon Boehringer Ingelheim, Nipro, Novo Nordisk Pharma, Ono Pharmaceutical, PHC, Roche DC Japan, Sanofi, Sanwa Kagaku Kenkyusho, Sekisui Medical, Shionogi, SRL, Sumitomo Dainippon Pharma, Sysmex, Taisho Pharma, Taisho Pharmaceutical, Takeda Pharmaceutical, Terumo, Tosoh.

Research grant: Abbott Japan, Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Sanofi, Takeda Pharmaceutical.

Award system: Eli Lilly Japan, Novo Nordisk Pharma, Sanofi.

Funding statement: The society received no specific funding for this work.

Figures

Figure 1
Figure 1
Flowchart outlining the steps in the clinical diagnosis of diabetes mellitus. OGTT, oral glucose tolerance test (Adapted from Seino Y et al. J Jpn Diabetes Soc 2012; 55: 485–504 4 ).
Figure 2
Figure 2
Categories of glycemia as indicated by fasting plasma glucose levels and 75 g OGTT results. *1 The impaired fasting glucose (IFG) category refers to individuals with fasting plasma glucose (FPG) levels of 110–125 mg/dL and 2‐h plasma glucose (PG) levels of <140 mg/dL in a 75 g OGTT (WHO), with the caveat, however, that IFG is defined as an FPG 100–125 mg/dL and only FPG is used in the diagnosis of IFG in the American Diabetes Association criteria. *2 Individuals with FPG 100–109 mg/dL are defined as the normal high FPG sub‐category as part of the normal FPG category. It is advisable to perform OGTTs in this population who are shown to be quite heterogeneous in their susceptibility to diabetes or the severity of IGT confirmed at OGTT. *3 As one of the definitions included in the diagnostic criteria proposed by the WHO, IGT is diagnosed in individuals with FPG <126 mg/dL or 2‐h 75 g OGTT PG ranging between 140 and 199 mg/dL.
Figure 3
Figure 3
Schematic diagram showing the etiology (mechanisms of onset) and pathophysiological stages (phases) of diabetes mellitus (Adapted from Seino Y, et al. J Jpn Diabetes Soc 2012; 55: 485–504 4 ).
Figure 4
Figure 4
Treatment of type 2 diabetes patients in non‐insulin‐dependent state. This provides a guide to the management of patients without acute metabolic disorder [i.e., those who had a casual blood glucose level of 250–300 mg/dL or less than 250–300 mg/dL with a negative urinary ketone test]. The glycemic goal should be determined individually depending on the disease condition or age of the patient but is generally set at HbA1c <7.0%. ‘Diet therapy’ and ‘exercise therapy’ are referred to as ‘medical nutrition therapy (MNT)’ and ‘physical activity/exercise’, respectively, elsewhere in this guideline.
Figure 5
Figure 5
Glycemic control targets (see Figure 8 for those for patients 65 years of age or older). The glycemic control target should be determined for each individual in light of his/her age, duration of diabetes, presence of organ damage, risk of hypoglycemia, and access to any support available. *1 Intended for individuals capable of achieving glycemic control with appropriate diet therapy (MNT) or exercise therapy or those capable of achieving glycemic control while on pharmacotherapy without developing hypoglycemia. *2 Defined as HbA1c <7.0% for prevention of diabetic complications, which is assumed to correspond to fasting glucose <130 mg/dL and postprandial 2‐h glucose <180 mg/dL as measured glucose values. *3 Intended for individuals deemed less amenable to treatment intensification due to associated hypoglycemia or for some other reason. *4 All these targets are intended for use by adults except for pregnant women.
Figure 6
Figure 6
Blood pressure measurement and procedure for hypertension diagnosis. (Cited from Umemura, S., Arima, H., Arima, S. et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) Hypertens Res. 2019 Sep;42(9):1256. https://doi.org/10.1038/s41440‐019‐0284‐9, with the permission of the JSH).
Figure 7
Figure 7
Treatment plan for hypertension complicated by diabetes mellitus. (Cited from Umemura, S., Arima, H., Arima, S. et al. The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2019) Hypertens Res. 2019 Sep;42(9):1356. https://doi.org/10.1038/s41440‐019‐0284‐9, with the permission of the JSH).
Figure 8
Figure 8
Glycemic control targets (HbA1c values) for elderly patients with diabetes. The glycemic target is to be determined for each patient by taking into account his/her age, duration of diabetes, risk for hypoglycemia, and any support available to the patient, as well as the patient’s cognitive function, basic/instrumental ADL, and comorbidities/functional impairments, while noting the potential risk of hypoglycemia that increases with age in each patient. Note 1: Refer to the Japan Geriatrics Society website (https://www.jpn‐geriat‐soc.or.jp/tool/index.html), for the evaluation of the cognitive function, basic ADL (e.g. self‐care abilities such as dressing, mobility, bathing, and toileting), and instrumental ADL (e.g. abilities to maintain an independent household such as shopping, meal preparation, taking medication, and handling finances). In end‐of‐life care, priority is to be given to preventing significant hyperglycemia and subsequent dehydration and acute complications through appropriate therapeutic measures. Note 2: As in other age groups, the glycemic target is set at <7.0% in the elderly for preventing diabetic complications. However, this could be set at <6.0% for those likely to achieve glycemic control through diet and exercise therapy alone or those likely to achieve glycemic control with drug therapy without adverse reactions, or 8.0% for those in whom intensifying therapy may prove difficult. In either case, no lower limit is specified for the glycemic target. A glycemic target of <8.5% may be allowed in patients thought to be in category III and therefore at risk of developing adverse reactions to multi‐drug combination therapy or in those with serious comorbidities or poor social support. Note 3: In patients in whom priority should be given to preventing the onset/progression of diabetic complications due to their duration of disease, the glycemic control target or its lower limit may be set for each elderly patient with appropriate measures in order to prevent severe hypoglycemia. In patients in whom any of these agents was initiated before the age of 65 and whose HbA1c values are shown to fall below their glycemic control targets described above, current treatments are to be continued, with utmost care being taken to avoid potential severe hypoglycemia. Glinides may be classified as drugs unlikely to be associated with severe hypoglycemia, as the onset of severe hypoglycemia varies depending on the type and amount of glinide used in a particular patient relative to the patient’s glucose level. (Cited from Haneda, M., Inagaki, N., Suzuki, R. et al. Glycemic targets for elderly patients with diabetes. Diabetol Int 7, 331–333 (2016). https://doi.org/10.1007/s13340‐016‐0293‐8).
See this image and copyright information in PMC

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2 GOALS AND STRATEGIES FOR DIABETES MANAGEMENT

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3 MEDICAL NUTRITION THERAPY (MNT)

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4 PHYSICAL ACTIVITY/EXERCISE

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5 TREATMENT WITH GLUCOSE‐LOWERING AGENTS (EXCLUDING INSULIN)

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6 INSULIN THERAPY

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7 DIABETES SELF‐MANAGEMENT EDUCATION AND SUPPORT FOR THE SELF‑MANAGEMENT OF DIABETES

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8 DIABETIC RETINOPATHY

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9 DIABETIC NEPHROPATHY

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10 DIABETIC NEUROPATHY

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11 DIABETIC FOOT

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12 DIABETIC MACROANGIOPATHY

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13 DIABETES AND PERIODONTITIS

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14 DIABETES COMPLICATED BY OBESITY (INCLUDING METABOLIC SYNDROME)

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15 HYPERTENSION ASSOCIATED WITH DIABETES

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16 DYSLIPIDEMIA ASSOCIATED WITH DIABETES

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17 IMPAIRED GLUCOSE METABOLISM IN PREGNANCY

    1. Ray JG, O'Brien TE, Chan WS. Preconception care and the risk of congenital anomalies in the offspring of women with diabetes mellitus: a meta‐analysis. QJM 2001; 94: 435–444 [level 2]. - PubMed
    1. Jensen DM, Korsholm L, Ovesen P, et al Peri‐conceptional A1C and risk of serious adverse pregnancy outcome in 933 women with type 1 diabetes. Diabetes Care 2009; 32: 1046–1048 [level 2]. - PMC - PubMed
    1. Alwan N, Tuffnell DJ, West J. Treatments for gestational diabetes. Cochrane Database Syst Rev 2009; 8: CD003395 [level 1]. - PMC - PubMed
    1. Nachum Z, Ben‐Shlomo I, Weiner E, et al Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. BMJ 1999; 319: 1223–1227 [level 1]. - PMC - PubMed
    1. Griffin ME, Coffey M, Johnson H, et al Universal vs. risk factor‐based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabet Med 2000; 17: 26–32. - PubMed

18 PEDIATRIC/ADOLESCENT DIABETES

    1. ISPAD Clinical Practice Consensus Guidelines for Pediatric and Adolescent Diabetes 2014. Nankodo, Tokyo, 2015.
    1. Ascerini C, Craig ME, de Beaufort C, et al ISPAD clinical practice consensus guidelines 2014 compendium. Introduction. Pediatr Diabetes 2014; 15(Suppl 20): 1–3. - PubMed
    1. Craig ME, Jefferies C, Dabelea D, et al ISPAD clinical practice consensus guidelines 2014 compendium. Definition, epidemiology, and classification of diabetes in children and adlescents. Pediatr Diabetes 2014; 15(Suppl 20): 4–17. - PubMed
    1. White NH, Cleary PA, Dahms W, et al Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT). J Pediatr 2001; 139: 804–812. - PubMed
    1. Urakami T, Morimoto S, Nitadori Y, et al Urine glucose screening program at schools in Japan to detect children with diabetes and its outcome: Incidence and clinical characteristics of childhood type 2 diabetes in Japan. Pediatr Res 2007; 61: 141–145. - PubMed

20 ACUTE METABOLIC COMPLICATIONS OF DIABETES, SICK DAYS, AND INFECTIOUS DISEASES

    1. Nyenwe EA, Kitabchi AE. Evidence‐based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract 2011; 94: 340–351. - PubMed
    1. Kitabchi AE, Umpierrez GE, Miles JM, et al Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32: 1335–1343. - PMC - PubMed
    1. Wolfsdorf JI, Allgrove J, Craig ME, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes 2014; 15(Suppl 20): 154–179. - PubMed
    1. Jeffrey A, Kraut MD, Nicolaos E, et al Lactic acidosis. N Engl J Med 2014; 371: 2309–2319. - PubMed
    1. American Diabetes Association . Standards of medical care in diabetes–2018. Diabetes Care 2018; 41: S1–S157. - PubMed

21 PREVENTION OF TYPE 2 DIABETES

    1. Doi Y, Ninomiya T, Hata J, et al Two risk score models for predicting incident type 2 diabetes in Japan. Diabet Med 2012; 29: 107–114. - PubMed
    1. Nanri A, Nakagawa T, Kuwahara K, et al Development of risk score for predicting 3‐year incidence of type 2 diabetes: Japan Epidemiology Collaboration on Occupational Health study. PLoS One 2015; 10: e0142779. - PMC - PubMed
    1. Heianza Y, Arase Y, Hsieh SD, et al Development of a new scoring system for predicting the 5 year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6). Diabetologia 2012; 55: 3213–3223. - PubMed
    1. Maskarinec G, Erber E, Grandinetti A, et al Diabetes incidence based on linkages with health plans: the multiethnic cohort. Diabetes 2009; 58: 1732–1738. - PMC - PubMed
    1. Chiu M, Austin PC, Manuel DG, et al Deriving ethnic‐specific BMI cutoff points for assessing diabetes risk. Diabetes Care 2011; 34: 1741–1748. - PMC - PubMed

APPENDIX 1. DIABETES AND CANCER

    1. Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta‐analysis. J Natl Cancer Inst 2005; 97: 1679–1687. - PubMed
    1. Larsson SC, Orsini N, Brismar K, et al Diabetes mellitus and risk of bladder cancer: a meta‐analysis. Diabetologia 2006; 49: 2819–2823. - PubMed
    1. Giovannucci E, Harlan DM, Archer MC, et al Diabetes and cancer: a consensus report. CA Cancer J Clin 2010; 60: 207–221. - PubMed
    1. Kasuga M, Ueki K, Tajima N, et al Report of the JDS/JCA Joint Committee on Diabetes and Cancer. Diabetol Int 2013; 2: 81–96. - PMC - PubMed
    1. Goto A, Noto H, Noda M, et al Report of the Japan Diabetes Society (JDS)/Japanese Cancer Association (JCA) Joint Committee on Diabetes and Cancer, Second Report. Diabetol Int 2016; 7: 12–15. - PMC - PubMed

APPENDIX 2. DIABETES AND BONE MINERAL METABOLISM

    1. Guidelines for Prevention and Treatment of Osteoporosis. Life Science Publishing.
    1. Janghorbani M, Van Dam RM, Willett WC, et al Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007; 166: 495–505. - PubMed
    1. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes: a meta‐analysis. Osteoporos Int 2007; 18: 427–444. - PubMed
    1. Weber DR, Haynes K, Leonard MB, et al Type 1 diabetes is associated with an increased risk of fracture across the life span: a population‐based cohort study using The Health Improvement Network (THIN). Diabetes Care 2015; 38: 1913–1920. - PMC - PubMed
    1. Hothersall EJ, Livingstone SJ, Looker HC, et al Contemporary risk of hip fracture in type 1 and type 2 diabetes: a national registry study from Scotland. J Bone Miner Res 2014; 29: 1054–1060. - PMC - PubMed

APPENDIX 3. PANCREAS/ISLET TRANSPLANTATION

    1. Saito T, Gotoh M, Satomi S, et al Islet transplantation using donors after cardiac death: report of the Japan Islet Transplantation Registry. Transplantation 2010; 90: 740–747. - PubMed
    1. Hering BJ, Kandaswamy R, Ansite JD, et al Single‐donor, marginal‐dose islet transplantation in patients with type 1 diabetes. JAMA 2005; 293: 830–835. - PubMed

APPENDIX 4. LARGE‐SCALE CLINICAL TRIALS IN JAPANESE PATIENTS WITH DIABETES

    1. Ueki K, Sasako T, Okazaki Y, et al. Effect of an intensified multifactorial intervention on cardiovascular outcomes and mortality in type 2 diabetes (J‐DOIT3): an open‐label, randomised controlled trial. Lancet Diabetes Endocrinol 2017. - PubMed