title: Type 2 diabetes across generations: from pathophysiology to prevention and management.
abstract: Type 2 diabetes is now a pandemic and shows no signs of abatement. In this Seminar we review the pathophysiology of this disorder, with particular attention to epidemiology, genetics, epigenetics, and molecular cell biology. Evidence is emerging that a substantial part of diabetes susceptibility is acquired early in life, probably owing to fetal or neonatal programming via epigenetic phenomena. Maternal and early childhood health might, therefore, be crucial to the development of effective prevention strategies. Diabetes develops because of inadequate islet β-cell and adipose-tissue responses to chronic fuel excess, which results in so-called nutrient spillover, insulin resistance, and metabolic stress. The latter damages multiple organs. Insulin resistance, while forcing β cells to work harder, might also have an important defensive role against nutrient-related toxic effects in tissues such as the heart. Reversal of overnutrition, healing of the β cells, and lessening of adipose tissue defects should be treatment priorities.
authors.affiliation: Department of Endocrinology, Canberra Hospital and Australian National University Medical School, Canberra, ACT, Australia. christopher.nolan@anu.edu.au
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nolan
authors.forename: Peter
authors.initials: P
authors.lastname: Damm
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology* / Q000517:prevention & control / Q000628:therapy*; D016640:Diabetes, Gestational / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000453:epidemiology; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development; D020022:Genetic Predisposition to Disease; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D054795:Incretins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology; D008019:Life Style; D008099:Liver / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology; D011236:Prediabetic State / Q000503:physiopathology; D011247:Pregnancy
chemical_list: D001786:Blood Glucose; D054795:Incretins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon