Advertisement

REPRINT OF: CLASSIFICATION OF DIABETES MELLITUS

      Abstract

      Executive Summary
      This document updates the 1999 World Health Organization (WHO) classification of diabetes. It prioritizes clinical care and guides health professionals in choosing appropriate treatments at the time of diabetes diagnosis, and provides practical guidance to clinicians in assigning a type of diabetes to individuals at the time of diagnosis. It is a compromise between clinical and aetiological classification because there remain gaps in knowledge of the aetiology and pathophysiology of diabetes.
      While acknowledging the progress that is being made towards a more precise categorization of diabetes subtypes, the aim of this document is to recommend a classification that is feasible to implement in different settings throughout the world. The revised classification is presented in Table 1.
      Unlike the previous classification, this classification does not recognize subtypes of type 1 diabetes and type 2 diabetes and includes new types of diabetes (“hybrid types of diabetes” and “unclassified diabetes”).
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Diabetes Research and Clinical Practice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Diabetes mellitus. Report of a WHO Expert Committee. Geneva: World Health Organization; 1965.

      2. World Health Organization: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and Classification of Diabetes Mellitus. Geneva: World Health Organization; 1999.

        • Leslie R.D.
        • Palmer J.
        • Schloot N.C.
        • Lernmark A.
        Diabetes at the crossroads: relevance of disease classification to pathophysiology and treatment.
        Diabetologia. 2016; 59: 13-20
        • Zimmet P.
        • Alberti K.G.M.M.
        • Shaw J.
        Global and societal implications of the diabetes epidemic.
        Nature. 2001; 414: 782-787
      3. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia. Geneva: World Health Organization; 2006.

      4. Report of a World Health Organization consultation. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Diabetes Res Clin Pract. 2011;93: 299–309.

      5. Global report on diabetes. Geneva: World Health Organization; 2016.

      6. 8th Edition. International Diabetes Federation, Brussels2017
        • Tuomi T.
        • Santoro N.
        • Caprio S.
        • Cai M.
        • Weng J.
        • Groop L.
        The many faces of diabetes: a disease with increasing heterogeneity.
        Lancet. 2014; 383: 1084-1094
        • Schwartz S.S.
        • Epstein S.
        • Corkey B.E.
        • Grant S.F.A.
        • Gavin J.R.
        • Aguilar R.B.
        The time is right for a new classification system for diabetes: rationale and implications of the β-cell-centric classification schema.
        Diabetes Care. 2016; 39: 179-186
        • Kahn S.E.
        • Cooper M.E.
        • Del Prato S.
        Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future.
        Lancet. 2014; 383: 1068-1083
        • Skyler J.S.
        • Bakris G.L.
        • Bonifacio E.
        • Darsow T.
        • Eckel R.H.
        • Groop L.
        • et al.
        Differentiation of diabetes by pathophysiology, natural history, and prognosis.
        Diabetes. 2017; 66: 241-255
        • Perl S.
        • Kushner J.A.
        • Buchholz B.A.
        • Meeker A.K.
        • Stein G.M.
        • Hsieh M.
        • et al.
        Significant human β cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating.
        J Clin Endocrinol Metab. 2010; 95: E234-E239
      7. Hocking S. Systematic review of the association between inherited genetic variants and response to blood glucose lowering therapies. 2017 (https://sydney.edu.au/content/dam/corporate/documents/faculty-of-medicine-and-health/research/centres-institutes-groups/boden/2018-Hocking-S-Systematic-review-association-between-inherited-genetic-variants-and-response-to-blood-glucose-lowering-therapies.pdf, accessed 1 March 2019).

        • Ng E.
        • Vanderloo S.E.
        • Geiss L.
        • Johnson J.A.
        Concordance between self-report and a survey-based algorithm for classification of type 1 and type 2 diabetes using the 2011 population-based Survey on Living with Chronic Diseases in Canada (SLCDC)-Diabetes component.
        Can. J. Diabetes. 2013; 37: 249-253
      8. Bellatorre A, Jackson SH, Choi K. Development of the diabetes typology model for discerning Type 2 diabetes mellitus with national survey data. PloS One. 2017;12:e0173103.

        • Johansson B.B.
        • Irgens H.U.
        • Molnes J.
        • Sztromwasser P.
        • Aukrust I.
        • Juliusson P.B.
        • et al.
        Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry.
        Diabetologia. 2017; 60: 625-635
        • Davis T.ME.
        • Makepeace A.E.
        • Ellard S.
        • Colclough K.
        • Peters K.
        • Hattersley A.
        • et al.
        The prevalence of monogenic diabetes in Australia: the Fremantle Diabetes Study Phase II.
        MJA. 2017; 207: 344-347
        • Woodmansey C.
        • McGovern A.P.
        • McCullough K.A.
        • Whyte M.B.
        • Munro N.M.
        • Correa A.C.
        • et al.
        Incidence, demographics, and clinical characteristics of diabetes of the exocrine pancreas (Type 3c): a retrospective cohort study.
        Diabetes Care. 2017; 40: 1486-1493
        • Karamanou M.
        • Protogerou A.
        • Tsoucalas G.
        • Androutsos G.
        • Poulakou-Rebelakou E.
        Milestones in the history of diabetes mellitus: the main contributors.
        World J Diabetes. 2016; 7: 1-7
      9. WHO Expert Committee on Diabetes Mellitus. Second Report. Technical report Series 646. Geneva, World Health Organization; 1980.

      10. Diabetes mellitus: report of a WHO Study Group. Technical Report Series 727. Geneva: World Health Organization; 1985.

      11. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58:773–795.

        • Patterson Christopher C
        • Dahlquist Gisela G
        • Gyürüs Eva
        • Green Anders
        • Soltész Gyula
        EURODIAB study group incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study.
        Lancet. 2009; 373: 2027-2033
        • Maahs David M.
        • West Nancy A.
        • Lawrence Jean M.
        • Mayer-Davis Elizabeth J.
        Epidemiology of type 1 diabetes.
        Endocrinol Metab Clin North Am. 2010; 39: 481-497
        • Centers for Disease Control and Prevention
        National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014.
        U.S. Department of Health and Human Services, Atlanta2014
      12. Livingstone SJ, Levin D, Looker HC, Lindsay RS, Wild SH, Joss N et al. Scottish Diabetes Research Network epidemiology group; Scottish Renal Registry. Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA. 2015;313:37–44.

        • Atkinson Mark A
        • Eisenbarth George S
        • Michels Aaron W
        Type 1 diabetes.
        Lancet. 2014; 383: 69-82
        • Thomas Nicholas J
        • Jones Samuel E
        • Weedon Michael N
        • Shields Beverley M
        • Oram Richard A
        • Hattersley Andrew T
        Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank.
        Lancet Diabetes and Endocrinology. 2018; 6: 122-129
        • Hagopian W A
        • Karlsen A E
        • Gottsäter A
        • Landin-Olsson M
        • Grubin C E
        • Sundkvist G
        • et al.
        Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.
        J. Clin. Invest. 1993; 91: 368-374
        • Jackson W.
        • Hofman P.L.
        • Robinson E.M.
        • Elliot R.B.
        • Pilcher C.C.
        • Cutfield W.S.
        The changing presentation of children with newly diagnosed type 1 diabetes mellitus.
        Pediatr. Diabetes. 2001; 2: 154-159
        • Madsbad S.
        • Krarup T.
        • Regeur L.
        • Faber O.K.
        • Binder C.
        Insulin secretory reserve in insulin dependent patients at time of diagnosis and the first 180 days of insulin treatment.
        Acta Endocrinol (Copenh). 1980; 95: 359-363
        • Eisenbarth G.S.
        Update in type 1 diabetes.
        J Clin Endocrinol Metab. 2007; 92: 2403-2407
        • Gianani R.
        • Campbell-Thompson M.
        • Sarkar S.A.
        • Wasserfall C.
        • Pugliese A.
        • Solis J.M.
        • et al.
        Dimorphic histopathology of long-standing childhood-onset diabetes.
        Diabetologia. 2010; 53: 690-698
        • Hanafusa Toshiaki
        • Imagawa Akihisa
        Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners.
        Nat Clin Pract Endocrinol Metab. 2007; 3: 36-45
        • Imagawa Akihisa
        • Hanafusa Toshiaki
        • Miyagawa Jun-ichiro
        • Matsuzawa Yuji
        Y for the Osaka IDDM Study Group. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies.
        NEJM. 2000; 342: 301-307
        • Imagawa A.
        • Hanafusa T.
        • Awata T.
        • Ikegami H.
        • Uchigata Y.
        • Kobayashi T.
        • et al.
        Report of the Committee of the Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus: new diagnostic criteria of fulminant type 1 diabetes mellitus.
        J Diabetes Investig. 2012; 3: 536-539
        • Cho Y.M.
        • Kim J.T.
        • Ko K.S.
        • Koo B.K.
        • Yang S.W.
        • Park M.H.
        • et al.
        Fulminant type 1 diabetes in Korea: high prevalence among patients with adult onset type 1 diabetes.
        Diabetologia. 2007; 50: 2276-2279
        • Luo Shuoming
        • Zhang Zhenyi
        • Li Xia
        • Yang Lin
        • Lin Jian
        • Yan Xiang
        • et al.
        Fulminant type 1 diabetes: a collaborative clinical cases investigation in China.
        Acta Diabetol. 2013; 50: 53-59
        • Sosenko J.M.
        • Krischer J.P.
        • Palmer J.P.
        • Mahon J.
        • Cowie C.
        • Greenbaum C.J.
        • et al.
        A risk score for type 1 diabetes derived from autoantibody-positive participants in the diabetes prevention trial-type 1.
        Diabetes Care. 2008; 31: 528-533
        • Stumvoll Michael
        • Goldstein Barry J
        • van Haeften Timon W
        Type 2 diabetes: principles of pathogenesis and therapy.
        Lancet. 2005; 365: 1333-1346
        • Bogardus C.
        • Lillioja S.
        • Mott D.M.
        • Hollenbeck C.
        • Reaven G.
        Relationship between degree of obesity and in vivo insulin action in man.
        Am. J. Physiol. 1985; 248: E286-E291
        • Mooy J.M.
        • Grootenhuis P.A.
        • Vries H.d.
        • Valkenburg H.A.
        • Bouter L.M.
        • Kostense P.J.
        • et al.
        Prevalence and determinants of glucose intolerance in a Dutch caucasian population.
        The Hoorn Study. Diabetes Care. 1995; 18: 1270-1273
        • Ma Ronald C.W.
        • Chan Juliana C.N.
        Type 2 diabetes in East Asians: similarities and differences with populations in Europe and the United States.
        Ann N Y Acad Sci. 2013; 1281: 64-91
      13. Narayan KM. Type 2 diabetes: Why we are winning the battle but losing the war. 2015 Kelly West Award Lecture. Diabetes Care. 2016;39:653–663.

        • Kanaya Alka M.
        • Herrington David
        • Vittinghoff Eric
        • Ewing Susan K.
        • Liu Kiang
        • Blaha Michael J.
        • et al.
        Understanding the high prevalence of diabetes in U.S. south Asians compared with four racial/ethnic groups: the MASALA and MESA studies.
        Diabetes Care. 2014; 37: 1621-1628
        • Gujral Unjali P.
        • Narayan K.M. Venkat
        • Kahn Steven E.
        • Kanaya Alka M.
        The relative associations of β-cell function and insulin sensitivity with glycemic status and incident glycemic progression in migrant Asian Indians in the United States: the MASALA study.
        J Diabetes Complications. 2014; 28: 45-50
      14. U.K. Prospective Diabetes Study Group. U.K. prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995;44:1249–58.

        • Yoon Kun-Ho
        • Lee Jin-Hee
        • Kim Ji-Won
        • Cho Jae Hyoung
        • Choi Yoon-Hee
        • Ko Seung-Hyun
        • et al.
        Epidemic obesity and type 2 diabetes in Asia.
        Lancet. 2006; 368: 1681-1688
        • Constantino M.I.
        • Molyneaux L.
        • Limacher-Gisler F.
        • Al-Saeed A.
        • Luo C.
        • Wu T.
        • et al.
        Long-term complications and mortality in young-onset diabetes. Type 2 diabetes is more hazardous and lethal than type 1 diabetes.
        Diabetes Care. 2013; 36: 3863-3869
      15. Hamman RF, Bell RA, Dabelea D, D’Agostino Jr RB, Dolan L, Imperatore G, et al for the SEARCH for Diabetes in Youth Study Group. The SEARCH for diabetes in youth study: rationale, findings, and future directions. Diabetes Care. 2014;37:3336–3344.

        • TODAY Study Group
        A clinical trial to maintain glycemic control in youth with type 2 diabetes.
        N Engl J Med. 2012; 366: 2247-2256
        • Flier Jeffrey S.
        • Underhill Lisa H.
        • Polonsky Kenneth S.
        • Sturis Jeppe
        • Bell Graeme I.
        Seminars in medicine of the Beth Israel Hospital, Boston. Non-insulin-dependent diabetes mellitus – a genetically programmed failure of the beta cell to compensate for insulin resistance.
        N Engl J Med. 1996; 334: 777-783
        • Fuchsberger Christian
        • Flannick Jason
        • Teslovich Tanya M.
        • Mahajan Anubha
        • Agarwala Vineeta
        • Gaulton Kyle J.
        • et al.
        The genetic architecture of type 2 diabetes.
        Nature. 2016; 536: 41-47
        • Newton Christopher A.
        • Raskin Philip
        Diabetic ketoacidosis in type 1 and type 2 diabetes mellitus. Clinical and biochemical differences.
        Arch Intern Med. 2004; 164: 1925https://doi.org/10.1001/archinte.164.17.1925
        • Umpierrez G.
        • Casals M.M.C.
        • Gebhart S.S.P.
        • Mixon P.S.
        • Clark W.S.
        • Phillips L.
        Diabetic ketoacidosis in obese African-Americans.
        Diabetes. 1995; 44: 790-795
        • Pasquel Francisco J.
        • Umpierrez Guillermo E.
        Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment.
        Diabetes Care. 2014; 37: 3124-3131
        • Tuomi T.
        • Groop L.
        • Zimmet P.
        • Rowley M.
        • Mackay I.
        Antibodies to glutamic acid decarboxylase (GAD) reveal latent autoimmune diabetes mellitus in adults with a non-insulin dependent onset of disease.
        Diabetes. 1993; 42: 359-362
        • Gale E.A.M.
        Latent autoimmune diabetes in adults: a guide for the perplexed.
        Diabetologia. 2005; 48: 2195-2199
      16. Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, et al. Latent autoimmune diabetes mellitus in adults (LADA): the role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med. 1994;11:299–303.

        • Reinehr T.
        • Schober E.
        • Wiegand S.
        • Thon A.
        • Holl R.
        and the DPV-Wiss Study Group. β-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification?.
        Arch Dis Child. 2006; 91: 473-477
        • Klingensmith G.J.
        • Pyle L.
        • Arslanian S.
        • Copeland K.C.
        • Cuttler L.
        • Kaufman F.
        • et al.
        and the TODAY Study Group. The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study.
        Diabetes Care. 2010; 33: 1970-1975
        • Sørgjerd E.P.
        • Skorpen F.
        • Kvaløy K.
        • Midthjell K.
        • Grill V.
        Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: the HUNT study.
        Norway. Diabetologia. 2012; 55: 1310-1318
        • Williams Georgina M.
        • Long Anna E.
        • Wilson Isabel V.
        • Aitken Rachel J.
        • Wyatt Rebecca C.
        • McDonald Timothy J.
        • et al.
        Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes.
        Diabetologia. 2016; 59: 2722-2726
        • Redondo M.J.
        Time for a New Definition.
        Diabetes. 2013; 62: 339-340
        • Cervin C.
        • Lyssenko V.
        • Bakhtadze E.
        • Lindholm E.
        • Nilsson P.
        • Tuomi T.
        • et al.
        Genetic similarities between latent autoimmune diabetes in adults, type 1 diabetes, and type 2 diabetes.
        Diabetes. 2008; 57: 1433-1437
        • Winter William E.
        • Maclaren Noel K.
        • Riley William J.
        • Clarke Derrel W.
        • Kappy Michael S.
        • Spillar Rebecca P.
        Maturity-onset diabetes of youth in black Americans.
        N Engl J Med. 1987; 316: 285-291
        • Mauvais-Jarvis F.
        • Sobngwi E.
        • Porcher R.
        • Riveline J.-P.
        • Kevorkian J.-P.
        • Vaisse C.
        • et al.
        Ketosis-prone type 2 diabetes in patients of Sub-Saharan African origin. Clinical pathophysiology and natural history of β-cell dysfunction and insulin resistance.
        Diabetes. 2004; 53: 645-653
        • Sobngwi E.
        • Gautier J.-F.
        Adult-onset idiopathic Type I or ketosis-prone type II diabetes: evidence to revisit diabetes classification.
        Diabetologia. 2002; 45: 283-285
        • Sobngwi E.
        • Mauvais-Jarvis F.
        • Vexiau P.
        • Mbanya J.C.
        • Gautier J.F.
        Diabetes in Africans. Part 2: Ketosis-prone atypical diabetes mellitus.
        Diabetes Metab. 2002; 28: 5-12
        • Banerji M.A.
        • Chaiken R.L.
        • Huey H.
        • Tuomi T.
        • Norin A.J.
        • Mackay I.R.
        • et al.
        GAD-antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4.
        Flatbush diabetes. Diabetes. 1994; 43: 741-745
        • Thomas Celeste C.
        • Philipson Louis H.
        Update on Diabetes Classification.
        Med Clin N Am. 2015; 99: 1-16
        • Hattersley A.
        • Bruining J.
        • Shield J.
        • Njolstad P.
        • Donaghue K.C.
        The diagnosis and management of monogenic diabetes in children and adolescents.
        Pediatric Diabetes. 2009; 10: 33-42
      17. Hattersley A, Bruining J, Shield J, Njolstad P, Donaghue K. ISPAD Clinical Practice Consensus Guidelines 2006–2007. The diagnosis and management of monogenic diabetes in children. Pediatric Diabetes. 2006;7:352–360.

        • Tattersall R.B.
        Mild familial diabetes with dominant inheritance.
        Q J Med. 1974; 43: 339-357
        • Shields B.M.
        • Hicks S.
        • Shepherd M.H.
        • Colclough K.
        • Hattersley A.T.
        • Ellard S.
        Maturity-onset diabetes of the young (MODY): how many cases are we missing?.
        Diabetologia. 2010; 53: 2504-2508
        • Hattersley A.T.
        • Pearson E.R.
        Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes.
        Endocrinology. 2006; 147: 2657-2663
      18. Spyer G, Macleod KM, Shepherd M, Ellard S, Hattersley AT. Pregnancy outcome in patients with raised blood glucose due to a heterozygous glucokinase gene mutation. Diabet Med. 2009;26:14–18.

      19. Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, et al. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS.Med. 2007;4:e118.

        • Iafusco D.
        • Stazi M.
        • Cotichini R.
        • Cotellessa M.
        • Martinucci M.
        • Mazzella M.
        • et al.
        Permanent diabetes mellitus in the first year of life.
        Diabetologia. 2002; 45: 798-804
        • Edghill E.L.
        • Dix R.J.
        • Flanagan S.E.
        • Bingley P.J.
        • Hattersley A.T.
        • Ellard S.
        • et al.
        HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months.
        Diabetes. 2006; 55: 1895-1898
        • Temple I.K.
        • Gardner R.J.
        • Mackay D.J.
        • Barber J.C.
        • Robinson D.O.
        • Shield J.P.
        Transient neonatal diabetes: widening the understanding of the etiopathogenesis of diabetes.
        Diabetes. 2000; 49: 1359-1366
        • Gloyn Anna L.
        • Pearson Ewan R.
        • Antcliff Jennifer F.
        • Proks Peter
        • Bruining G. Jan
        • Slingerland Annabelle S.
        • et al.
        Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.
        N Engl J Med. 2004; 350: 1838-1849
        • Ellard Sian
        • Flanagan Sarah E.
        • Girard Christophe A.
        • Patch Ann-Marie
        • Harries Lorna W.
        • Parrish Andrew
        • et al.
        Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects.
        Am J Hum Genet. 2007; 81: 375-382
        • Babenko Andrey P.
        • Polak Michel
        • Cavé Hélène
        • Busiah Kanetee
        • Czernichow Paul
        • Scharfmann Raphael
        • et al.
        Activating mutations in the ABCC8 gene in neonatal diabetes mellitus.
        N Engl J Med. 2006; 355: 456-466
        • Stoy J.
        • Edghill E.L.
        • Flanagan S.E.
        • Ye H.
        • Paz V.P.
        • Pluzhnikov A.
        • et al.
        Insulin gene mutations as a cause of permanent neonatal diabetes.
        Proc Natl Acad Sci USA. 2007; 104: 15040-15044
        • Aguilar-Bryan L.
        • Bryan J.
        Neonatal diabetes mellitus.
        Endocr Rev. 2008; 29: 265-291
        • van den Ouweland J.M.W.
        • Lemkes H.H.P.J.
        • Ruitenbeek W.
        • Sandkuijl L.A.
        • de Vijlder M.F.
        • Struyvenberg P.A.A.
        • et al.
        Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness.
        Nat Genet. 1992; 1: 368-371
        • Maassen J.A.
        • Kadowaki T.
        Maternally inherited diabetes and deafness: a new diabetes subtype.
        Diabetologia. 1996; 39: 375-382
        • Kahn C.Ronald
        • Flier Jeffrey S.
        • Bar Robert S.
        • Archer Juanita A.
        • Gorden Phillip
        • Martin Malcolm M.
        • et al.
        The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man.
        N Engl J Med. 1976; 294: 739-745
        • Taylor S.I.
        Lilly Lecture: molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulin-receptor gene.
        Diabetes. 1992; 41: 1473-1490
        • Taylor S.I.
        • Arioglu E.
        Genetically defined forms of diabetes in children.
        Journal of Clinical Endocrinology & Metabolism. 1999; 84: 4390-4396
        • Owen K.R.
        • Groves C.J.
        • Hanson R.L.
        • Knowler W.C.
        • Shuldiner A.R.
        • Elbein S.C.
        • et al.
        Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: association analyses in 9,518 subjects.
        Diabetes. 2007; 56: 879-883
        • Barroso I.
        • Gurnell M.
        • Crowley V.E.
        • Agostini M.
        • Schwabe J.W.
        • Soos M.A.
        • et al.
        Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension.
        Nature. 1999; 402: 880-883
        • Ewald N.
        • Kaufmann C.
        • Raspe A.
        • Kloer H.U.
        • Bretzel R.G.
        • Hardt P.D.
        Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c).
        Diabetes Metab Res Rev. 2012; 28: 338-342
        • Hart PhilA
        • Bellin MelenaD
        • Andersen DanaK
        • Bradley David
        • Cruz-Monserrate Zobeida
        • Forsmark Christopher E
        • et al.
        Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet.
        Gastroenterol Hepatol. 2016; 1: 226-237
        • Permert Johan
        • Larsson Jorgen
        • Westermark Gunilla T.
        • Herrington Margery K.
        • Christmanson Lars
        • Pour Parviz M.
        • et al.
        Islet amyloid polypeptide in patients with pancreatic cancer and diabetes.
        N Engl J Med. 1994; 330: 313-318
        • Dobson L.
        • Sheldon C.D.
        • Hattersley A.T.
        Understanding cystic fibrosis-related diabetes: best thought of as insulin deficiency?.
        J R Soc Med. 2004; 97: 26-35
        • Yajnik C.S.
        • Shelgikar K.M.
        • Naik S.S.
        • Kanitkar S.V.
        • Orskov H.
        • Alberti K.G.M.M.
        • et al.
        The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test.
        Diabetes. Res Clin Pract. 1992; 15: 149-156
      20. MacFarlane IA. Endocrine disease and diabetes mellitus. In: Textbook of diabetes. 2nd ed. Pickup JC, Williams G, Eds. Oxford: Blackwell; 1997; 64.10–64.20.

        • Krejs Guenter J.
        • Orci Lelio
        • Conlon J.Michael
        • Ravazzola Mariella
        • Davis Glenn R.
        • Raskin Philip
        • et al.
        Somatostatinoma syndrome. Biochemical, morphologic and clinical features.
        N Engl J Med. 1979; 301: 285-292
        • Pandit M.K.
        • Burke J.
        • Gustafson A.B.
        • Minocha A.
        • Peiris A.N.
        Drug-induced disorders of glucose tolerance.
        Ann Intern Med. 1993; 118: 529-539
        • O'Byrne S.
        • Feely J.
        Effects of drugs on glucose tolerance in non-insulin-dependent diabetics (Part II).
        Drugs. 1990; 40: 203-219
        • Esposti M.D.
        • Ngo A.
        • Myers M.A.
        Inhibition of mitochondrial complex I may account for IDDM induced by intoxication with the rodenticide Vacor.
        Diabetes. 1996; 45: 1531-1534
        • Forrest JillM.
        • Menser MargaretA.
        • Burgess J.A.
        High frequency of diabetes mellitus in young adults with congenital rubella.
        Lancet. 1971; 298: 332-334
        • King MaryL.
        • Bidwell D.
        • Shaikh Aneena
        • Voller A.
        • Banatvala J.E.
        Coxsackie-B-virus-specific IgM responses in children with insulin-dependent (juvenile-onset; type I) diabetes mellitus.
        Lancet. 1983; 321: 1397-1399
      21. Karjalainen J, Knip M, Hyoty H, Leinikki P, Ilonen J, Kaar ML, et al. Relationship between serum insulin autoantibodies, islet cell antibodies and Coxsackie-B4 and mumps virus-specific antibodies at the clinical manifestation of type 1 (insulin-dependent) diabetes. Diabetologia. 1988;31:146–152.

        • Pak ChinY.
        • Mcarthur RobertG.
        • Eun Hyone-Myong
        • Yoon Ji-Won
        Association of cytomegalovirus infection with autoimmune type 1 diabetes.
        Lancet. 1988; 332: 1-4
        • HIRATA YUKIMASA
        • ISHIZU HIROSHI
        Elevated insulin-binding capacity of serum proteins in a case with spontaneous hypoglycemia and mild diabetes not treated with insulin.
        Tohoku J Exp Med. 1972; 107: 277-286
        • Solimena Michele
        • Folli Franco
        • Aparisi Roxanne
        • Pozza Guido
        • De Camilli Pietro
        Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome.
        N Engl J Med. 1990; 322: 1555-1560
        • Levy L.M.
        • Dalakas M.C.
        • Floeter M.K.
        The stiff-person syndrome: an autoimmune disorder affecting neurotransmission of gamma-aminobutyric acid.
        Ann Intern Med. 1999; 131: 522-530
        • Fabris Paolo
        • Betterle Corrado
        • Greggio Nella A.
        • Zanchetta Renato
        • Bosi Emanuele
        • Biasin Maria Raffaella
        • et al.
        Insulin-dependent diabetes mellitus during alpha-interferon therapy for chronic viral hepatitis.
        J Hepatol. 1998; 28: 514-517
        • Kahn C. Ronald
        • Baird Kathleen
        • Flier Jeffrey S.
        • Jarrett David B.
        Effects of autoantibodies to the insulin receptor on isolated adipocytes. Studies of insulin binding and insulin action.
        J Clin Invest. 1977; 60: 1094-1106
        • Rosenstein Elliot D.
        • Advani Sonoo
        • Reitz Richard E.
        • Kramer Neil
        The prevalence of insulin receptor antibodies in patients with systemic lupus erythematosus and related conditions.
        J Clin Rheumatol. 2001; 7: 371-373
        • Robinson S.
        • Kessling A.
        Diabetes secondary to genetic disorders.
        Baillieres Clin Endocrinol Metab. 1992; 6: 867-898
        • Low S.
        • Chin M.C.
        • Deurenberg-Yap M.
        Review on epidemic of obesity.
        Ann Acad Med Singapore. 2009; 38: 57-59
      22. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: a World Health Organization Guideline. Diab Res Clin Pract. 2014;103:341–63.

        • Rosenbloom A.L.
        Obesity, insulin resistance, beta cell autoimmunity, and the changing clinical epidemiology of childhood diabetes.
        Diabetes Care. 2003; 26: 2954-2956
        • Zeitler Phil
        • Haqq Andrea
        • Rosenbloom Arlan
        • Glaser Nicole
        for the Drugs and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Hyperglycemic hyperosmolar syndrome in children: pathophysiological considerations and suggested guidelines for treatment.
        J Pediatr. 2011; 158: 9-14.e2
        • Shields Beverley
        • Colclough Kevin
        Towards a systematic nationwide screening strategy for MODY.
        Diabetologia. 2017; 60: 609-612
        • Shields B.M.
        • McDonald T.J.
        • Ellard S.
        • Campbell M.J.
        • Hyde C.
        • Hattersley A.T.
        The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes.
        Diabetologia. 2012; 55: 1265-1272
      23. NICE guideline. Type 1 diabetes in adults: diagnosis and management. London: National Institute for Healthcare and Excellence; August 2015 (nice.org.uk/guidance/ng17, accessed 9 February 2019).

        • Rewers A.
        • Klingensmith G.
        • Davis C.
        • Petitti D.B.
        • Pihoker C.
        • Rodriguez B.
        • et al.
        Presence of diabetic ketoacidosis at diagnosis of diabetes mellitus in youth: the Search for Diabetes in Youth Study.
        Pediatrics. 2008; 121: e1258-e1266
        • Umpierrez G.E.
        • Woo W.
        • Hagopian W.A.
        • Isaacs S.D.
        • Palmer J.P.
        • Gaur L.K.
        • et al.
        Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis.
        Diabetes Care. 1999; 22: 1517-1523
        • Maldonado M.
        • Hampe C.S.
        • Gaur L.K.
        • D’Amico S.
        • Iyer D.
        • Hammerle L.P.
        • et al.
        Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes.
        J Clin Endocrinol Metab. 2003; 88: 5090-5098
        • Mauvais-Jarvis F.
        • Sobngwi E.
        • Porcher R.
        • Riveline J.P.
        • Kevorkian J.P.
        • Vaisse C.
        • et al.
        Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin: clinical pathophysiology and natural history of β-cell dysfunction and insulin resistance.
        Diabetes. 2004; 53: 645-653
        • Piñero-Piloña Antonio
        • Raskin Philip
        Idiopathic type 1 diabetes.
        J Diabetes Complications. 2001; 15: 328-335
        • Balasubramanyam A.
        • Garza G.
        • Rodriguez L.
        • Hampe C.S.
        • Gaur L.
        • Lernmark A.
        • et al.
        Accuracy and predictive value of classification schemes for ketosis-prone diabetes.
        Diabetes Care. 2006; 29: 2575-2579
        • Ahlqvist Emma
        • Storm Petter
        • Käräjämäki Annemari
        • Martinell Mats
        • Dorkhan Mozhgan
        • Carlsson Annelie
        • et al.
        Novel sub-groups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables.
        Lancet Diabetes Endocrinol. 2018; 6: 361-369