Skip to main content
Log in

Pathophysiology of Type 2 Diabetes Mellitus in Children and Adolescents

Treatment Implications

  • Leading Article
  • Published:
Treatments in Endocrinology

Abstract

Type 2 diabetes mellitus was considered an exclusive disease of adulthood until the late 1970s, when reports of an increased prevalence in the pediatric age group emerged in the literature. The concerning upswing in the rate of diagnosis of type 2 diabetes mellitus in children and adolescents has continued, parallel to the increasing rates of obesity. The disease is not specific to the US; it has proven to be a global problem.

The current information on type 2 diabetes mellitus in children and adolescents is mostly extrapolated from studies in adults with type 2 diabetes mellitus, due to the paucity of studies conducted in youth. Obesity, family history of type 2 diabetes mellitus, minority ethnicity and race, polycystic ovary syndrome, maternal diabetes mellitus or impaired glucose tolerance during gestation, and acanthosis nigricans are the major risk factors and markers of youth-onset type 2 diabetes mellitus. The pathophysiology, which involves both an insulin secretion defect and resistance to insulin, needs further clarification in pediatric studies.

Current management approaches involve lifestyle modification (nutritional and exercise) along with pharmacologic agents, such as insulin and oral antihyperglycemic medications, as indicated. A recent study on the use of metformin in childhood-onset type 2 diabetes mellitus demonstrated the drug to be effective and to have a good safety profile in this population. However, the outcomes of ongoing studies and future studies focusing on type 2 diabetes mellitus in the pediatric age group will be crucial in terms of fine-tuning management plans and setting up appropriate prevention strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Fig. 1
Fig. 2
Table III

Similar content being viewed by others

References

  1. Savage PJ, Bennett PH, Senter RG, et al. High prevalence of diabetes in young Pima Indians. Diabetes 1979; 28: 937–42

    Article  PubMed  CAS  Google Scholar 

  2. Kitagawa T, Mano T, Fujita H. The epidemiology of childhood diabetes mellitus in Tokyo metropolitan area. Tohoku J Exp Med 1983; 14: 171–9

    Article  Google Scholar 

  3. Dean HE, Mandy RLL, Miffed M. Non-insulin dependent diabetes mellitus in Indian children in Manitoba. Can Med Assoc J 1992; 147: 52–7

    CAS  Google Scholar 

  4. Harris SB, Perkins BA, Whalenbrough E. Non-insulin dependent diabetes mellitus among First Nations children: new entity among First Nations people of northwestern Ontario. Can Fam Physician 1996; 42: 869–76

    PubMed  CAS  Google Scholar 

  5. Pinhas-Hamiel O, Dolan LM, Daniels SR, et al. Increased incidence of non-insulin dependent diabetes mellitus among adolescents. J Pediatr 1996; 128: 608–15

    Article  PubMed  CAS  Google Scholar 

  6. Scott CR, Smith JM, Cradock MM, et al. Characteristics of youth-onset non-insulin dependent diabetes mellitus and insulin-dependent diabetes mellitus at diagnosis. Pediatrics 1997; 100: 84–91

    Article  PubMed  CAS  Google Scholar 

  7. Neufeld ND, Raffel LJ, Landon C, et al. Early presentation of type 2 diabetes in Mexican-American youth. Diabetes Care 1998; 21: 80–6

    Article  PubMed  CAS  Google Scholar 

  8. Jones KL. Non-insulin dependent diabetes in children and adolescents: the therapeutic challenge. Clin Pediatr (Phila) 1998; 37: 103–10

    Article  CAS  Google Scholar 

  9. Kitagawa T, Owada M, Urakami T, et al. Epidemiology of type 10 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in Japanese children. Diabetes Res Clin Pract 1994; 24 Suppl.: S7–S13

    Article  PubMed  Google Scholar 

  10. Kitagawa T, Owada M, Urakami T, et al. Increased incidence of non-insulin dependent diabetes mellitus among Japanese schoolchildren correlates with an increased intake of animal protein and fat. Clin Pediatr (Phila) 1998; 37:111–5

    Article  CAS  Google Scholar 

  11. Dabelea D, Pettitt DJ, Jones KL, et al. Type 2 diabetes mellitus in minority children and adolescents: an emerging problem. Endocrinol Metab Clin North Am 1999; 28: 709–29

    Article  PubMed  CAS  Google Scholar 

  12. Libman I, Arslanian S. Type II diabetes mellitus: no longer just adults. Pediatr Ann 1999; 28: 589–93

    PubMed  CAS  Google Scholar 

  13. Fagot-Campagna A, Pettitt D, Engelgau MM, et al. Type 2 diabetes among North American Children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 2000; 136: 664–72

    Article  PubMed  CAS  Google Scholar 

  14. Kadiki OA, Reddy MR, Marzouk AA. Incidence of insulin-dependent diabetes (IDDM) and non-insulin-dependent diabetes (NIDDM) (0-34 years at onset) in Benghazi, Libya. Diabetes Res Clin Pract 1996; 32: 165–73

    Article  PubMed  CAS  Google Scholar 

  15. American Diabetes Association. Type 2 Diabetes in children and adolescents. Diabetes Care 2000; 23: 381–9

    Article  Google Scholar 

  16. Arslanian SA. Type 2 diabetes mellitus in children: pathophysiology and risk factors. J Pediatr Endocrinol Metab 2000; 13: 1385–94

    PubMed  Google Scholar 

  17. Pinhas-Hamiel O, Dolan LM, Zeitler PS. Diabetic ketoacidosis among obese African-American adolescents with NIDDM. Diabetes Care 1997; 20: 484–6

    Article  PubMed  CAS  Google Scholar 

  18. Dean HE. NIDDM-Y in First Nation children in Canada. Clin Pediatr 1998; 39: 89–96

    Article  Google Scholar 

  19. Freedman DS, Serdula MK, Percy CA, et al. Obesity, levels of lipids and glucose, and smoking among Navajo adolescents. J Nutr 1997; 128 Suppl. 10: 2120–7S

    Google Scholar 

  20. Dabelea D, Hanson RL, Bennett PH, et al. Increasing prevalence of type 2 diabetes in American Indian children. Diabetologia 1998; 41: 904–10

    Article  PubMed  CAS  Google Scholar 

  21. Dean HJ, Young TK, Flett B, et al. Screening of non-type 2 diabetes in aboriginal children in northern Canada [letter]. Lancet 1998; 352: 1523–4

    Article  PubMed  CAS  Google Scholar 

  22. Rios Burrows N, Acton K, Geiss L, et al. Trends in diabetes prevalence among American Indian and Alaska Native children, adolescents, and young adults, 1991–1997.11th Annual Indian Health Service Research Conference; 1999 Apr 26–28; Alburquerque, New Mexico. Albuquerque: Indian Health Service, 1999: 19

    Google Scholar 

  23. Willi SM, Kennedy A, Wojciechowski B, et al. Insulin resistance and defective glucose-insulin coupling in ketosis-prone type 2 diabetes of African-American youth [abstract]. Diabetes 1998; 47 Suppl. 1: A306

    Google Scholar 

  24. Glaser NS, Jones KL. Non-insulin dependent diabetes mellitus in Mexican-American Children. West J Med 1998; 168: 11–6

    PubMed  CAS  Google Scholar 

  25. Hale DE, Danney KM. Non-insulin dependent diabetes in Hispanic youth (type 2Y) [abstract]. Diabetes 1998; 47 Suppl. 1: A82

    Article  Google Scholar 

  26. Neufeld ND, Raffel LJ, Landon C, et al. Early presentation of type 2 diabetes in Mexican-American youth. Diabetes Care 1998; 21: 80–6

    Article  PubMed  CAS  Google Scholar 

  27. karvonen M, Viik-Kajander M, Moltchanova E, et al. Incidence of childhood type 1 diabetes worldwide: the DiaMond Project Group. Diabetes Care 2000; 23: 1516–26

    Article  PubMed  CAS  Google Scholar 

  28. Chan JCN, Cheung C, Swaminathan R, et al. Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin-dependent diabetes mellitus (NIDDM). Postgrad Med 1993; 69: 204–1

    Article  CAS  Google Scholar 

  29. McGrath NM, Parker GN, Dawson P. Early presentation of type 2 diabetes mellitus in young New Zealand Maori. Diabetes Res Clin Pract 1999; 43: 205–9

    Article  PubMed  CAS  Google Scholar 

  30. Ehtisam S, Barrett TG, Shaw NJ. Type 2 diabetes mellitus in UK children: an emerging problem. Diabet Med 2000; 17: 867–71

    Article  Google Scholar 

  31. Pettitt DJ, Bennett PH, Knowler WC, et al. Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Diabetes 1985; 34(2): 119–22

    Google Scholar 

  32. Pettitt DJ, Baird HR, Aleck KA, et al. Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N Engl J Med 1983; 308: 242–5

    Article  PubMed  CAS  Google Scholar 

  33. Pettitt DJ, Baird HR, Aleck KA, et al. Diabetes mellitus in children following maternal diabetes during gestation [abstract]. Diabetes 1982; 31: 66A

    Google Scholar 

  34. Pettitt D, Baird H, Carraher M, et al. Genetic and intrauterine environmental effects in transmission of diabetes mellitus [abstract]. Am J Epidemiol 1984; 120: 477

    Google Scholar 

  35. Troiano RP, Flegal KM. Overweight children and adolescents: description, epidemiology, and demographics. Pediatrics 1998; 101s: 497–504

    Google Scholar 

  36. Wang Y. Cross-national comparison of childhood obesity: the epidemic and the relationship between obesity and socioeconomic status. Int J Epidemiol 2001; 30: 1129–36

    Article  PubMed  CAS  Google Scholar 

  37. Seidell JC. Obesity, insulin resistance and diabetes: a worldwide epidemic. Br J Nutr 2000; 83 Suppl. 1: S5–8

    Article  PubMed  CAS  Google Scholar 

  38. Sorensen TI. The changing lifestyle in the world: body weight and what else? Diabetes Care 2000; 23: B1–4

    Article  PubMed  Google Scholar 

  39. Ludvig DS, Peterson KE, Gortmaker SL. Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective observational analysis. Lancet 2001; 357: 505–8

    Article  Google Scholar 

  40. Morton JF, Guthrie JF. Changes in children’s total fat intakes and their food group sources of fat, 1989–91 versus 1994–95: implications for diet quality. FamEcon Nutr Rev 1998; 11:44–57

    Google Scholar 

  41. Obarzanek E, Schreiber GB, Crawford PB, et al. Energy intake and physical activity in relation to indexes of body fat: the National Heart, Lung, and Blood Institute Growth and Health Study. Am J Clin Nutr 1994; 60: 15–22

    PubMed  CAS  Google Scholar 

  42. Kimm SYS, Glyn NW, Kriska AM, et al. Longitudinal changes in physical activity in a biracial cohort during adolescence. Med Sci Sports Exerc 2000; 32: 1445–54

    Article  PubMed  CAS  Google Scholar 

  43. Fujimoto WY, Leonetti DL, Kinyoun JL, et al. Prevalence of diabetes mellitus and impaired glucose tolerance among second-generation Japanese American men. Diabetes 1987; 36: 7212–729

    Google Scholar 

  44. King H, Zimmet P, Pargeter K, et al. Ethnic differences in susceptibility to non-insulin-dependent diabetes: a comparative study of two urbanized Micronesian populations. Diabetes 1984: 33; 1002–1027

    Article  PubMed  CAS  Google Scholar 

  45. Coldtiz GA, Willett WC, Stampfer MJ, et al. Weight as a risk factor for clinical diabetes in women. Am J Epidemiol 1990; 132: 501–13

    Google Scholar 

  46. Manson JE, Nathan DM, Krolewski AS, et al. A prospective study of exercise and incidence of diabetes among male physicians. JAMA 1992; 268: 63–7

    Article  PubMed  CAS  Google Scholar 

  47. Manson JE, Rimm EB, Stampfer MJ, et al. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet 1991; 338: 774–8

    Article  PubMed  CAS  Google Scholar 

  48. West KM, Kalbfleisch JM. Influence of nutritional factors on prevalence of diabetes. Diabetes 1971; 20: 99–108

    PubMed  CAS  Google Scholar 

  49. Rosenbloom AL, Wheeler L, Bianchi R, et al. Age-adjusted analysis of insulin responses during normal and abnormal glucose tolerance tests in children and adolescents. Diabetes 1975; 24: 820–8

    Article  PubMed  CAS  Google Scholar 

  50. Lestradet H, Deschamps I, Giron B. Insulin and free fatty acid levels during oral glucose tolerance tests and their relation to age in 70 healthy children. Diabetes 1976; 25: 505–8

    Article  PubMed  CAS  Google Scholar 

  51. Smith CP, Dunger DB, Williams AJK, et al. Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty and adult life. J Clin Endocrinol Metab 1989; 68: 932–7

    Article  PubMed  CAS  Google Scholar 

  52. Smith CP, Williams AJK, Thomas JM, et al. The pattern of basal and stimulated insulin responses to intravenous glucose in first degree relatives of type 1 (insulin-dependent) diabetic children and unrelated adults aged 5 to 50 years. Diabetologia 1988; 31: 430–4

    Article  PubMed  CAS  Google Scholar 

  53. Hindmarsh P, DiSilvio L, Pringle PJ, et al. Changes in serum insulin concentration during puberty and their relationship to growth hormone. Clin Endocrinol (Oxf) 1988; 28: 381–8

    Article  CAS  Google Scholar 

  54. Amiel SA, Sherwin RS, Simenson DC, et al. Impaired insulin action in puberty. N Engl J Med 1986; 315: 215–9

    Article  PubMed  CAS  Google Scholar 

  55. Block CA, Clemons P, Sperling MA. Puberty decreases insulin sensitivity. J Pediatr 1987; 110: 418–27

    Google Scholar 

  56. Arslanian SA, Kalhan SC. Correlations between fatty acid and glucose metabolism. Potential explanation of insulin resistance of puberty. Diabetes 1994; 43: 908–14

    Article  PubMed  CAS  Google Scholar 

  57. Amiel SA, Caprio S, Sherwin RS, et al. Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism. J Clin Endocrinol Metab 1991; 72: 277–82

    Article  PubMed  CAS  Google Scholar 

  58. Caprio S, Plewe G, Diamond MP, et al. Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J Pediatr 1989; 114: 963–7

    Article  PubMed  CAS  Google Scholar 

  59. Moran A, Jacobs Jr DR, Steinberger J, et al. Insulin resistance during puberty. Diabetes 1999; 48: 2039–44

    Article  PubMed  CAS  Google Scholar 

  60. Cook JS, Hoffman RP, Steine MA, et al. Effects of maturational stage on insulin sensitivity during puberty. J Clin Endocrinol Metab 1993; 77: 725–30

    Article  PubMed  CAS  Google Scholar 

  61. Travers SH, Jeffers BW, Bloch CA, et al. Gender and Tanner stage difference in body composition and insulin sensitivity in early pubertal children. J Clin Endocrinol Metab 1995; 80: 172–8

    Article  PubMed  CAS  Google Scholar 

  62. Arslanian SA, Danadian K, Suprasongsin C. GH treatment in adolescents with non-GH deficient short stature (NGHD-SS): physical, biochemical and metabolic changes [abstract]. Pediatr Res 1999; 45: 84A

    Article  Google Scholar 

  63. Arslanian S, Suprasongsin C. Testosterone treatment in adolescents with delayed puberty: changes in body composition, protein, fat and glucose metabolism. J Clin Endocrinol Metab 1997; 82: 3213–20

    Article  PubMed  CAS  Google Scholar 

  64. Saad RJ, Keenan BS, Danadian K, et al. Dihydrotestosterone treatment in adolescents with delayed puberty: does it explain insulin resistance of puberty? J Clin Endocrinol Metab 2001; 86: 4881–6

    Article  PubMed  CAS  Google Scholar 

  65. Umpaichitra V, Bastian W, Taha D, et al. C-peptide and glucagon profiles in minority children with type 2 diabetes mellitus. J Clin Endocrinol Metab 2001; 86: 1605–9

    Article  PubMed  CAS  Google Scholar 

  66. Kobayashi K, Amemiya S, Higashida K, et al. Pathogenic factors of glucose intolerance in obese Japanese adolescents with type 2 diabetes. Metabolism 2001; 49: 186–91

    Article  Google Scholar 

  67. Kahn CR. Banting Lecture: insulin action, diabetogenes, and the cause of Type II diabetes. Diabetes 1994; 43: 1066–84

    Article  PubMed  CAS  Google Scholar 

  68. Leahy JL. Natural history of β-cell dysfunction in NIDDM. Diabetes Care 1990; 13: 992–1010

    Article  PubMed  CAS  Google Scholar 

  69. Kahn SE. Regulation of β-cell function in vivo: from health to disease. Diabetes Rev 1996; 4: 372–89

    Google Scholar 

  70. Ferrannini E. Insulin resistance is central to the burden of diabetes. Diabetes Metab Rev 1997; 13: 81–6

    Article  PubMed  CAS  Google Scholar 

  71. Taylor SI. Insulin resistance or insulin deficiency: which is the primary cause of NIDDM? Diabetes 1994; 43: 735–40

    PubMed  CAS  Google Scholar 

  72. Home PD. Insulin resistance is not central to the burden of diabetes. Diabetes Metab Rev 1997; 13:87–92

    Article  PubMed  CAS  Google Scholar 

  73. Himsworth H. Diabetes mellitus: a differentiation into insulin-sensitive and insulin-insensitive types. Lancet 1936; I: 127–30

    Article  Google Scholar 

  74. Reaven GM. Role of insulin resistance in the pathophysiology of non-insulin dependent diabetes mellitus. Diabetes Metab Rev 1993; 9: 5S–12S

    Article  PubMed  Google Scholar 

  75. Knowler WC, Saad MF, Pettitt DJ, et al. Determinants of diabetes mellitus in the Pima Indians. Diabetes Care 1993; 16: 216–27

    Article  PubMed  CAS  Google Scholar 

  76. Haffner SM, Stern MP, Mitchell BD, et al. Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity and body fat distribution. Diabetes 1990; 39: 283–8

    Article  PubMed  CAS  Google Scholar 

  77. Lillioja S, Mott DM, Howard BV, et al. Impaired glucose tolerance as a disorder of insulin action: longitudinal and cross-sectional studies in Pima Indians. N Engl J Med 1988; 318: 1217–25

    Article  PubMed  CAS  Google Scholar 

  78. Lillioja S, Nyomba BL, Saad MF, et al. Exaggerated early insulin release and insulin resistance in a diabetes-prone population: a metabolic comparison of Pima Indians and Caucasians. J Clin Endocrinol Metab 1991; 73: 866–76

    Article  PubMed  CAS  Google Scholar 

  79. Sicree RA, Zimmet PZ, King HOM, et al. Plasma insulin response among Nauruans: prediction of deterioration in glucose tolerance over 6 years. Diabetes 1987; 36: 179–86

    Article  PubMed  CAS  Google Scholar 

  80. Hamman RF. Genetic and environmental determinants of non-insulin-dependent diabetes mellitus (NIDDM). Diabetes Metab Rev 1992; 8: 287–338

    Article  PubMed  CAS  Google Scholar 

  81. Lebovitz HE. Type 2 diabetes: an overview. Clin Chem 1999; 458 (B): 1339–45

    Google Scholar 

  82. Ferrannini E. Insulin resistance versus insulin deficiency in non-insulin dependent diabetes mellitus: problems and prospects. Endocr Rev 1998; 19: 488–90

    Article  Google Scholar 

  83. Gerich JE. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr Rev 1998; 19: 491–503

    Article  PubMed  CAS  Google Scholar 

  84. Lebovitz HE. Diabetes mellitus in adults. In: Rakel RE, editor. Conn’s current therapy 1998. Philadephia (PA): WB Saunders, 1998: 545–53

    Google Scholar 

  85. Polonsky KS, Sturis J, Bell GI. Noninsulin-dependent diabetes mellitus: a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med 1996 Mar 21; 334: 777–83

    Article  PubMed  CAS  Google Scholar 

  86. Blackard WG, Clore JN. Insulin deficiency. In: Davidson JK, editor. Clinical diabetes mellitus: a problem oriented approach. 3rd ed. New York (NY): Thieme Medical Publishers Inc., 2000

    Google Scholar 

  87. Pfeifer MA, Halter JB, Porte Jr D. Insulin secretion in diabetes mellitus. Am J Med 1981; 70(3): 579–88

    Article  PubMed  CAS  Google Scholar 

  88. Banerji MA, Chaiken RL, Huey H, 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: 741–5

    Article  PubMed  CAS  Google Scholar 

  89. Banerji MA, Chaiken RL, Lebovitz HE. Long-term normoglycemic remission in black newly diagnosed NIDDM subjects. Diabetes 1996; 45: 337–41

    Article  PubMed  CAS  Google Scholar 

  90. Umpierrez GE, Casals MMC, Gebhart SSP, et al. Diabetic ketoacidosis in obese African Americans. Diabetes 1995; 44: 790–5

    Article  PubMed  CAS  Google Scholar 

  91. Winter WE, Maclaren NK, Riley WJ, et al. Maturity-onset diabetes of youth in black Americans. N Engl J Med 1987; 316: 285–91

    Article  PubMed  CAS  Google Scholar 

  92. Marcocci C, Chiovato L. Thyroid-directed antibodies. IN: Braveman LE, Utiger RD, editor. Werner and Ingbar’s the thyroid: a fundamental and clinical text. 8th ed. Philadelphia (PA): Lippincott Williams and Wilkins, 2000: 414–32

    Google Scholar 

  93. Savola K, Läärä E, Vähäsalo P, et al. Dynamic pattern of disease-associated autoantibodies in siblings of children with type 1 diabetes: a population-based study. Diabetes 2001; 50: 2625–32

    Article  PubMed  CAS  Google Scholar 

  94. Unger RH, Foster DW. Diabetes mellitus. In: Wilson JD, Foster DW, Kronenberg HM, et al.,editors. Williams textbook of endocrinology. 9th ed. Philadelphia (PA): WB Saunders Co, 1998: 973–1059

    Google Scholar 

  95. Irvine WJ, Gray RS, Steel JM. Islet cell antibody as a marker for early stage type 1 diabetes mellitus. In: Irvine WJ, editor. Immunology of diabetes. Edinburgh: Teviot Scientific Publications, 1980: 117–154

    Google Scholar 

  96. Irvine WJ, McCallum CJ, Gray RS, et al. Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type. Diabetes 1977; 26: 138–47

    Article  PubMed  CAS  Google Scholar 

  97. Tuomi T, Groop LC, Zimmet PZ, et al. Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adults with a non-insulin-dependent onset of disease. Diabetes 1993; 42: 359–62

    Article  PubMed  CAS  Google Scholar 

  98. Seissler J, Sonnaville JJJ de, Morgenthaler NG, et al. Immunological heterogeneity in Type I diabetes: presence of distinct autoantibody patterns in patients with acute onset and slowly progressive disease. Diabetologia 1998; 41: 891–7

    Article  PubMed  CAS  Google Scholar 

  99. Ziegler B, Strebelow M, Rjasanowski I, et al. A monoclonal antibody-based characterization of antibodies against glutamic acid decarboxylase in adults with latent autoimmune diabetes. Autoimmunity 1998; 28: 61–8

    Article  PubMed  CAS  Google Scholar 

  100. Hathout EH, Thomas W, El-Shahawny M, et al. Diabetic autoimmune markers in children and adolescents with type 2 diabetes. Pediatrics 2001; 107: e102

    Article  PubMed  CAS  Google Scholar 

  101. Hattersley AT. Diagnosis of maturity-onset diabetes of the young in the pediatric diabetes clinic. J Pediatr Endocrinol Metab 2000; 13: 1411–7

    PubMed  Google Scholar 

  102. Fajans SS, Bell GI, Polonsky KS. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. N Engl J Med 2001; 345: 971–80

    Article  PubMed  CAS  Google Scholar 

  103. Silverstein JH, Rosenbloom AL. Treatment of Type 2 diabetes mellitus in children and adolescents. J Pediatr Endocrinol Metab 2000; 13: 1403–9

    PubMed  Google Scholar 

  104. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with Type 2 diabetes: UKPDS. BMJ 1998; 317:703–13

    Article  Google Scholar 

  105. Jones KL, Arslanian S, Peterokova VA, et al. Effect of metformin in pediatric patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetes Care 2002; 25(3): 89–94

    Article  PubMed  CAS  Google Scholar 

  106. DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. N Engl J Med 1995; 333: 541–9

    Article  Google Scholar 

  107. Bailey CJ. Biguanides and NIDDM. Diabetes Care 1992; 15: 755–72

    Article  PubMed  CAS  Google Scholar 

  108. Arslanian SA, Lewy V, Danadian K, et al. Metformin therapy in obese adolescents with PCOS and impaired glucose tolerance: Amelioration of exaggerated adrenal response to ACTH with reduction of insulinemia/insulin resistance. J Clin Endocrinol Metab 2002; 87: 1555–9

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by United States Public Health Service grant RO1 HD27503, K24 HD01357, MO1 RR00084 General Clinical Research Center, Renziehausen Trust Fund, Bristol Myers Squibb, and Eli Lilly and Company.

The authors thank Ms Michelle Beckwith and Mrs Pat Antonio for their secretarial assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Silva Arslanian.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gungor, N., Arslanian, S. Pathophysiology of Type 2 Diabetes Mellitus in Children and Adolescents. Treat Endocrinol 1, 359–371 (2002). https://doi.org/10.2165/00024677-200201060-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00024677-200201060-00002

Keywords

Navigation