title: Type 2 diabetes mellitus.
abstract: Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.
authors.affiliation: Diabetes Division, Department of Medicine, University of Texas Health Science Center, South Texas Veterans Health Care System and Texas Diabetes Institute, 701 S. Zarzamoro, San Antonio, Texas 78207, USA.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.affiliation: CNR Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.affiliation: Department of Clinical Science Malmoe, Diabetes &Endocrinology, Lund University Diabetes Centre, Lund, Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: University of California, San Diego, Section of Diabetes, Endocrinology &Metabolism, Center for Metabolic Research, VA San Diego Healthcare System, San Diego, California, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.affiliation: University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Herman
authors.affiliation: University of Copenhagen, Kobenhavn, Denmark.
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health and Department of Epidemiology, Harvard T.H. Chan School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Harvard Medical School and Joslin Diabetes Center, Boston, Massachusetts, USA.
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.affiliation: Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.affiliation: Howard Hughes Medical Institute and the Departments of Internal Medicine and Cellular &Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.affiliation: Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Simonson
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors.forename: Marcia A
authors.initials: MA
authors.lastname: Testa
authors.affiliation: Department of Human Metabolism and Nutrition, Braun School of Public Health, Hebrew University, Jerusalem, Israel.
authors.forename: Ram
authors.initials: R
authors.lastname: Weiss
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D024821:Metabolic Syndrome / Q000150:complications
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin