The accelerator hypothesis: a review of the evidence for insulin resistance as the basis for type I as well as type II diabetes (original) (raw)

• Molbak AG, Christau B, Marner B, Borch-Johnsen K, Nerup J . Incidence of insulin-dependent diabetes in age groups over 30 years in Denmark. Diabet Med 1994; 11: 650–655.
  CAS PubMed Google Scholar
• Rosenbloom AL, Joe JR, Young RS, Winter WE . Emerging epidemic of type 2 diabetes in youth. Diabetes Care 1999; 22: 345–354.
  CAS PubMed Google Scholar
• Aizawa T, Funase Y, Katakura M, Asanuma N, Yamauchi K, Yoshizawa K et al. Ketosis-onset diabetes in young adults with subsequent non-insulin-dependency, a link between IDDM and NIDDM? Diabet Med 1997; 14: 989–991.
  CAS PubMed Google Scholar
• Gale EA . Declassifying diabetes. Diabetologia 2006; 49: 1989–1995.
  CAS PubMed Google Scholar
• Wilkin TJ . Changing perspectives in diabetes: their impact on its classification. Diabetologia 2007; 50: 1587–1592.
  CAS PubMed Google Scholar
• Wilkin TJ . The accelerator hypothesis: weight gain as the missing link between type I and type II diabetes. Diabetologia 2001; 44: 914–922.
  CAS PubMed Google Scholar
• Kibirige M, Metcalf B, Renuka R, Wilkin TJ . Testing the accelerator hypothesis: the relationship between body mass and age at diagnosis of type 1 diabetes. Diabetes Care 2003; 26: 2865–2870.
  CAS PubMed Google Scholar
• Betts P, Mulligan J, Ward P, Smith B, Wilkin TJ . Increasing body weight predicts the earlier onset of insulin-dependant diabetes in childhood: testing the ‘accelerator hypothesis’ (2). Diabet Med 2005; 22: 144–151.
  CAS PubMed Google Scholar
• Knerr I, Wolf J, Reinehr T, Stachow R, Grabert M, Schober E et al. DPV Scientific Initiative of Germany and Austria. The ‘accelerator hypothesis’: relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9248 German and Austrian children with type 1 diabetes mellitus. Diabetologia 2005; 48: 2501–2504.
  CAS PubMed Google Scholar
• Kordonouri O, Hartmann R . Higher body weight is associated with earlier onset of type 1 diabetes in children: confirming the ‘Accelerator Hypothesis’. Diabet Med 2005; 22: 1783–1784.
  CAS PubMed Google Scholar
• Clarke SL, Craig ME, Garnett SP, Chan AK, Cowell CT, Cusumano JM et al. Increased adiposity at diagnosis in younger children with type 1 diabetes does not persist. Diabetes Care 2006; 29: 1651–1653.
  PubMed Google Scholar
• Dabelea D, D’Agostino Jr RB, Mayer-Davis EJ, Pettitt DJ, Imperatore G, Dolan LM et al. SEARCH for Diabetes in Youth Study Group. Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1(autoimmune) diabetes. Diabetes Care 2006; 29: 290–294.
  PubMed Google Scholar
• Rosenbloom AL . Obesity, insulin resistance, beta-cell autoimmunity, and the changing clinical epidemiology of childhood diabetes. Diabetes Care 2003; 26: 2954–2956.
  PubMed Google Scholar
• Daneman D . Is the ‘accelerator hypothesis’ worthy of our attention? Diabet Med 2005; 22: 115–117.
  CAS PubMed Google Scholar
• Gale EA . To boldly go—or to go too boldly? The accelerator hypothesis revisited. Diabetologia 2007; 50: 1571–1575.
  CAS PubMed Google Scholar
• Devendra D, Liu E, Eisenbarth GS . Type 1 diabetes: recent developments. BMJ 2004; 27: 750–754.
  Google Scholar
• Gepts W . Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes 1965; 14: 619–633.
  CAS PubMed Google Scholar
• Nerup J, Platz P, Anderssen OO . HLA antigens and diabetes mellitus. Lancet 1974; 2: 864–866.
  CAS PubMed Google Scholar
• Bottazzo GF, Florin-Christensen A, Doniach D . Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 1974; 2: 1279–1283.
  CAS PubMed Google Scholar
• Onkamo P, Vaananen S, Karvonen M, Tuomilehto J . Worldwide increase of type 1 diabetes—analysis of the data on published incidence trends. Diabetologia 1999; 42: 1395–1403.
  CAS PubMed Google Scholar
• Gale EAM . The rise of childhood type 1 diabetes in the 20th century. Diabetes 2002; 51: 3353–3361.
  CAS PubMed Google Scholar
• Shuldiner AR, Yang R, Gong DW . Resistin, obesity and insulin resistance—the emerging role of the adipocyte as an endocrine organ. N Engl J Med 2001; 345: 1345–1346.
  CAS PubMed Google Scholar
• Moller DE, Flier JS . Insulin resistance—mechanisms, syndromes, and implications. N Engl J Med 1991; 325: 938–948.
  CAS PubMed Google Scholar
• Navab M, Gharavi N, Watson AD . Inflammation and metabolic disorders. Curr Opin Clin Nutr Metab Care 2008; 11: 459–464.
  CAS PubMed Google Scholar
• Rastouli N, Kern PA . Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 2008; 93 (11 Suppl 1): S64–S73.
  Google Scholar
• Donath MY, Størling J, Maedler K, Mandrup-Poulsen T . Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med 2003; 81: 455–470.
  CAS PubMed Google Scholar
• Kolb H, Mandrup-Poulsen T . An immune origin of type 2 diabetes? Diabetologia 2005; 48: 1038–1050.
  CAS PubMed Google Scholar
• Pickup JC . Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 2004; 27: 813–823.
  PubMed Google Scholar
• Velho C, Froguel P . Maturity-onset diabetes of the young (MODY), MODY genes and non-insulin-dependent diabetes mellitus. Diabetes Metab 1997; 23 (Suppl 2): 34–37.
  PubMed Google Scholar
• Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med 2006; 355: 467–477.
  CAS PubMed Google Scholar
• Sun Q, Yue P, Jeffrey A, Lumeng CN, Kampfrath T, Mikolaj MB et al. Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation 2009; 119: 538–546.
  CAS PubMed Google Scholar
• Saxena R, Gianniny L, Burtt NP, Lyssenko V, Giuducci C, Sjögren M et al. Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals. Diabetes 2006; 55: 2890–2895.
  CAS PubMed Google Scholar
• Maedler K, Donath MY . Beta-cells in type 2 diabetes: a loss of function and mass. Horm Res 2004; 62 (Suppl 3): 67–73.
  CAS PubMed Google Scholar
• Robertson RP, Harmon J, Tran PO, Poitout V . glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes 2004; 53 (Suppl 1): S119–S124.
  CAS PubMed Google Scholar
• Wilkin TJ, Metcalf B, Jeffery A, Howdle S, Kirkby J, Voss LD . The relative contributions of birth weight, catch-up weight and current weight to the development of insulin resistance in contemporary children (EarlyBird 2). Diabetes 2002; 51: 3468–3472.
  CAS PubMed Google Scholar
• Gardner DS, Metcalf BS, Hosking J, Jeffery AN, Voss LD, Wilkin TJ . Trends, associations and predictions of insulin resistance in prepubertal children (EarlyBird 29). Pediatr Diabetes 2008; 9 (3 Part 1): 214–220.
  CAS PubMed Google Scholar
• Juneja R, Palmer JP . Type 1 1/2 diabetes: myth or reality? Autoimmunity 1999; 29: 65–83.
  CAS PubMed Google Scholar
• Gale EA . The rise of childhood type 1 diabetes in the 20th century. Diabetes 2002; 51: 3353–3361.
  CAS PubMed Google Scholar
• Zimmet P . Globalization, coca-colonization and the chronic disease epidemic: can the Doomsday scenario be averted? J Intern Med 2000; 247: 301–310.
  CAS PubMed Google Scholar
• Wilkin TJ . Early nutrition and diabetes mellitus (Editorial). BMJ 1992; 306: 283–284.
  Google Scholar
• Wilkin TJ . Autoimmunity: attack or defence? Autoimmunity 1989; 3: 57–73.
  CAS PubMed Google Scholar
• Grabar P . Autoantibodies and the physiological role of immunoglobulins. Immunol Today 1983; 4: 337–340.
  CAS PubMed Google Scholar
• Roitt I, Brostoff J, Male D . Immunology. Churchill Livingstone: London, 1995, pp 1.5–1.6.
  Google Scholar
• Bjork E, Kampe O, Karlsson FA, Pipeleers DG, Andersson A, Hellerström C et al. Glucose regulation of the autoantigen GAD65 in human pancreatic islets. J Clin Endocrinol Metab 1992; 75: 574–576.
  Google Scholar
• Judkowski V, Krakowski M, Rodriguez E, Mocnick L, Santamaria P, Sarvetnick N . Increased islet antigen presentation leads to type-1 diabetes in mice with autoimmune susceptibility. Eur J Immunol 2004; 34: 1031–1040.
  CAS PubMed Google Scholar
• Xu P, Krischer JP, Cuthbertson D, Greenbaum C, Palmer JP . Role of insulin resistance in predicting progression to type 1 diabetes. Diabetes Care 2007; 30: 2314–2320.
  PubMed Google Scholar
• Fourlanos S, Harrison LC, Colman PG . The accelerator hypothesis and increasing incidence of type 1 diabetes. Curr Opin Endocrinol Diabetes Obes 2008; 15: 321–325.
  CAS PubMed Google Scholar
• Fourlanos S, Narendran P, Byrnes GB, Colman PG, Harrison LC . Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 2004; 47: 1661–1667.
  CAS PubMed Google Scholar
• Hawa MI, Bonfanti R, Valeri C, Delli Castelli M, Beyan H, Leslie RD . No evidence for genetically determined alteration in insulin secretion or sensitivity predisposing to type 1 diabetes: a study of identical twins. Diabetes Care 2005; 28: 1415–1418.
  CAS PubMed Google Scholar
• Libman IM, Becker DJ . Coexistence of type 1 and type 2 diabetes mellitus: ‘double’ diabetes? Pediatr Diabetes 2003; 4: 110–113.
  PubMed Google Scholar
• Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR . Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes 1993; 42: 359–362.
  CAS PubMed Google Scholar
• Reinehr T, Schober E, Wiegand S, Thon A, Holl R . B-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification? Arch Dis Child 2006; 91: 473–477.
  CAS PubMed PubMed Central Google Scholar
• Onkamo P, Vaananen S, Karvonen M, Tuomilehto J . Worldwide increase of type 1 diabetes—analysis of the data on published incidence trends. Diabetologia 1999; 42: 1395–1403.
  CAS PubMed Google Scholar
• Baum JD, Ounsted M, Smith MA . Weight gain in infancy and subsequent development of diabetes mellitus in childhood. Lancet 1975; ii: 866.
  Google Scholar
• Johansson C, Samuelsson U, Ludvigsson J . A high weight gain in early life is associated with an increased risk of type 1 (insulin-dependent) diabetes. Diabetologia 1994; 37: 91–94.
  CAS PubMed Google Scholar
• Hypponen E, Kenward MG, Virtanen SM, Piitulainen A, Virta-Autio P, Tuomilehto J et al. Infant feeding, early weight gain and risk of type 1 diabetes. Diabetes Care 1999; 22: 1961–1965.
  CAS PubMed Google Scholar
• Bruining GJ . Association between infant growth before onset of juvenile type-1 diabetes and autoantibodies to IA-2. Netherlands Kolibrie study group of childhood diabetes. Lancet 2000; 356: 655–656.
  CAS PubMed Google Scholar
• Hypponen E, Virtanen SM, Kenward MG, Knip M, Akerblom HK, Childhood Diabetes in Finland Study Group. Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care 2000; 23: 1755–1760.
  CAS PubMed Google Scholar
• Pundziute-Lyckå A, Dahlquist G, Nyström L, Arnquist H, Björke E, Blohmé G et al. Swedish Childhood Diabetes Study Group. The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0–34 years group in Sweden 1983–1998. Diabetologia 2002; 45: 783–791.
  PubMed Google Scholar
• Weets I, De Leeuw IH, Du Caju MV, Rooman R, Keymeulen B, Mathieu C et al. Belgian Diabetes Registry. The incidence of type 1 diabetes in the age group 0–39 years has not increased in Antwerp (Belgium) between 1989 and 2000: evidence for earlier disease manifestation. Diabetes Care 2002; 25: 840–846.
  PubMed Google Scholar
• Hermann R, Knip M, Veijola R . Temporal changes in the frequencies of HLA genotypes in patients with type I diabetes—indication of an increased environmental pressure? Diabetologia 2003; 46: 420–425.
  CAS PubMed Google Scholar
• Gillespie KM, Bain SC, Barnett AH, Bingley PJ, Christie MR, Gill GV et al. The rising incidence of type 1 diabetes is associated with a reduced contribution from high-risk HLA haplotypes. Lancet 2004; 364: 1699–1700.
  PubMed Google Scholar
• Leslie RD, Taylor R, Pozzilli P . The role of insulin resistance in the natural history of type 1 diabetes. Diabet Med 1997; 14: 327–331.
  CAS PubMed Google Scholar
• Greenbaum CJ . Insulin resistance and type 1 diabetes. Diabetes Metab Res Rev 2002; 18: 192–200.
  CAS PubMed Google Scholar
• Gale EA . Spring harvest? Reflections on the rise of type 1 diabetes. Diabetologia 2005; 48: 2445–2450.
  CAS PubMed Google Scholar
• Greenbaum CJ, Eisenbarth G, Atkinson M, Yu L, Babu S, Schatz D et al. DPT-1 study group. High frequency of abnormal glucose tolerance in DQA1*0102/DQB1*0602 relatives identified as part of the Diabetes Prevention Trial. Diabetologia 2005; 48: 68–74.
  CAS PubMed Google Scholar
• Irvine WJ, McCallum CJ, Gray RS, Duncan LJ . Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents. Lancet 1977; 1: 1025–1027.
  CAS PubMed Google Scholar
• Hathout EH, Thomas W, El-Shahawy M, Nahab F, Mace JW . Diabetic autoimmune markers in children and adolescents with type 2 diabetes. Pediatrics 2001; 107: E102.
  CAS PubMed Google Scholar
• Umpaichitra V, Banerji MA, Castells S . Autoantibodies in children with type 2 diabetes mellitus. J Pediatr Endocrinol Metab 2002; 15 (Suppl 1): 525–530.
  CAS PubMed Google Scholar
• Gilliam LK, Brooks-Worrell BM, Palmer JP, Greenbaum CJ, Pihoker C . Autoimmunity and clinical course in children with type 1, type 2, and type 1.5 diabetes. J Autoimmun 2005; 25: 244–250.
  CAS PubMed Google Scholar
• Brooks-Worrell BM, Greenbaum CJ, Palmer JP, Pihoker C . Autoimmunity to islet proteins in children diagnosed with new-onset diabetes. J Clin Endocrinol Metab 2004; 89: 2222–2227.
  CAS PubMed Google Scholar
• Ziegler AG, Hummel M, Schenker M, Bonifacio E . Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes 1999; 48: 460–468.
  CAS PubMed Google Scholar
• Porter JR, Barrett TJ . Braking the accelerator hypothesis? Diabetologia 2004; 47: 352–353.
  CAS PubMed Google Scholar
• Tait BD, Harrison LC, Drummond BP, Stewart V, Varney MD, Honeyman MC . HLA antigens and age at diagnosis of insulin-dependent diabetes mellitus. Hum Immunol 1995; 42: 116–122.
  CAS PubMed Google Scholar
• Bingley PJ, Mahon JL, Gale EA, The European Nicotinamide Diabetes Intervention Trial (ENDIT) Group. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT). Diabetes Care 2008; 31: 146–150.
  CAS PubMed Google Scholar
• Wilkin TJ . Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes: response to Dabelea et al. Diabetes Care 2006; 29: 1462–1463.
  PubMed Google Scholar
• Wilkin TJ . Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT): response to Bingley et al. Diabetologia 2008; 31: e290.
  Google Scholar
• Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 2006; 355: 241–250.
  CAS PubMed PubMed Central Google Scholar
• Field SF, Howson JMM, Smyth DJ, Walker NM, Dunger DB, Todd JA . Analysis of the type 2 diabetes gene TCF7L2 in 13 795 type 1 diabetes cases and control subjects. Diabetologia 2007; 50: 212–213.
  CAS PubMed Google Scholar
• Wilkint TJ . The accelerator hypothesis cannot be tested using the type 2 diabetes gene, TCF7L2. Diabetologia 2007; 50: 1780.
  Google Scholar
• Field SF, Howson JM, Walker NM, Dunger DB, Todd JA . Analysis of the obesity gene FTO in 14 803 type 1 diabetes cases and controls. Diabetologia 2007; 50: 2218–2220.
  CAS PubMed PubMed Central Google Scholar
• O’connell MA, Donath S, Cameron FJ . Major increase in type 1 diabetes—no support for the accelerator hypothesis. Diabet Med 2007; 24: 920–923.
  PubMed Google Scholar
• Wilkin T . Major increase in type 1 diabetes: no support for the accelerator hypothesis (response to O’Connell et al). Diabet Med 2008; 25: 376–377.
  CAS PubMed Google Scholar
• Dahlquist G . The aetiology of type 1 diabetes: an epidemiological perspective. Acta Paediatr 1998; 425 (Suppl): 5–10.
  CAS Google Scholar
• Day C . Thiazolidinediones. Diabetic Med 1999; 16: 179.92.
  PubMed Google Scholar
• Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403.
  CAS PubMed Google Scholar
• Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P et al. Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–1350.
  CAS PubMed Google Scholar
• Harlan DM, von Herrath M . Immune intervention with anti-CD3 in diabetes. Nat Med 2005; 11: 716–718.
  CAS PubMed Google Scholar
• Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D et al. Single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala–Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 2005; 54: 1763–1769.
  CAS PubMed PubMed Central Google Scholar
• Dupre J, Stiller CR, Gent M, Donner A, von Graffenried B, Heinrichs D et al. Clinical trials of cyclosporin in IDDM. Diabetes Care 1988; 11 (Suppl 1): 37–44.
  PubMed Google Scholar
• Wilkin T, Ludvigsson J, Greenbaum C, Palmer J, Becker D, Bruining J . Future intervention trials in type 1 diabetes. Diabetes Care 2004; 27: 996–997.
  PubMed Google Scholar