Diabetes at the crossroads: relevance of disease classification   to pathophysiology and treatment.
Diabetes is not a single homogeneous disease but composed of many diseases with hyperglycaemia as a common feature. Four factors have, historically, been used to identify this diversity: the age at onset; the severity of the disease, i.e. degree of loss of beta cell function; the degree of insulin resistance and the presence of diabetes-associated autoantibodies. Our broad understanding of the distinction between the two major types, type 1 diabetes mellitus and type 2 diabetes mellitus, are based on these factors, but it has become apparent that they do not precisely capture the different disease forms. Indeed, both major types of diabetes have common features, encapsulated by adult-onset autoimmune diabetes and maturity-onset diabetes of the young. As a result, there has been a repositioning of our understanding of diabetes. In this review, drawing on recent literature, we discuss the evidence that autoimmune type 1 diabetes has a broad clinical phenotype with diverse therapeutic options, while the term non-autoimmune type 2 diabetes obscures the optimal management strategy because it encompasses substantial heterogeneity. Underlying these developments is a general progression towards precision medicine with the need for precise patient characterisation, currently based on clinical phenotypes but in future augmented by laboratory-based tests.
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK. r.d.g.leslie@qmul.ac.uk.
R David
RD
Leslie
University of Washington, VA Puget Sound Health Care System, Seattle, USA.
Jerry
J
Palmer
Institute for Clinical Diabetology at the German Diabetes Center, Heinrich-Heine University, Düsseldorf, Germany.|Lilly Deutschland GmbH, Bad Homburg, Germany.
Nanette C
NC
Schloot
Department of Clinical Sciences, Lund University/CRC, Malmö, Sweden.
Ake
A
Lernmark
D000367:Age Factors; D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D002096:C-Peptide / Q000097:blood; D003920:Diabetes Mellitus / Q000175:diagnosis* / Q000503:physiopathology* / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D010641:Phenotype
D001323:Autoantibodies; D002096:C-Peptide; D007328:Insulin