Clinical perspective: Pharmacologic approaches to the prevention of type 2 diabetes in high risk pediatric patients

Journal of Clinical Endocrinology and Metabolism

Volumn 88, Issue 1, 2003, Pages 3-13

  Freemark, Michael ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACARBOSE; ALPHA GLUCOSIDASE INHIBITOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; FATTY ACID; GLUCOSE; GLUCOSE TRANSPORTER 4; GROWTH FACTOR; HIGH DENSITY LIPOPROTEIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; METFORMIN; PRAVASTATIN; RAMIPRIL; THIAZOLIDINE DERIVATIVE; TRIACYLGLYCEROL; TROGLITAZONE; TUMOR NECROSIS FACTOR ALPHA; VERY LOW DENSITY LIPOPROTEIN;

ADIPOCYTE; ANEMIA; BODY MASS; CARBOHYDRATE ABSORPTION; CHILD GROWTH; CLINICAL TRIAL; CYTOKINE PRODUCTION; DIABETES CONTROL; DIABETIC OBESITY; DIARRHEA; DISEASE PREDISPOSITION; EDEMA; ENVIRONMENTAL FACTOR; FLATULENCE; FOOD INTAKE; GASTROINTESTINAL SYMPTOM; GENETIC RISK; GENETIC VARIABILITY; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; HEREDITY; HIGH RISK PATIENT; HUMAN; HYPERINSULINEMIA; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; INSULIN SENSITIVITY; JUVENILE DIABETES MELLITUS; LIFESTYLE; LIPID METABOLISM; LIVER TOXICITY; LOW CALORY DIET; NON INSULIN DEPENDENT DIABETES MELLITUS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN SECRETION; REVIEW; TREATMENT OUTCOME; TRIACYLGLYCEROL BLOOD LEVEL; WEIGHT REDUCTION; DRUG THERAPY; GENETIC PREDISPOSITION; GENETICS; METHODOLOGY; PEDIATRICS; RISK FACTOR;

DIABETES MELLITUS, TYPE 2; DISEASE SUSCEPTIBILITY; DRUG THERAPY; GENETIC PREDISPOSITION TO DISEASE; HUMANS; PEDIATRICS; RISK FACTORS;

EID: 0037242507     PISSN: 0021972X     EISSN: None     Source Type: Journal    
DOI: 10.1210/jc.2002-021033     Document Type: Review

References (119)

1. Rosenbloom AL, Joe JR, Young RS, Winter WE 1999 Emerging epidemic of type 2 diabetes in youth. Diabetes Care 22:345-354
2. Fagot-Campagna A, Pettitt DJ, Engelgau MM, Burrows NR, Geiss LS, Valdez R, Beckles GLA, Saaddine J, Gregg EW, Williamson DF, Narayan KMV 2000 Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 136:664-672
3. Ludwig DS, Ebbeling CB 2001 Type 2 diabetes in children: primary care and public health considerations. JAMA 286:1427-1430
4. Caprio S 2002 Insulin resistance in childhood obesity. J Pediatr Endocrinol Metab 15(Suppl 1):487-492
5. Berenson GS, Srinivasan SR 2001 Emergence of obesity and cardiovascular risk for coronary artery disease: the Bogalusa Heart Study. Prev Cardiol 4:116-121
6. Tounian P, Aggoun Y, Dubern B, Varille V, Guy-Grand B, Sidi D, Girardet JP, Bonnet D 2001 Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet 358:1400-1404
7. McGill Jr HC, McMahan CA, Herderick EE, Malcom GT, Tracy RE, Strong JP 2000. Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr 72:1307S-1315S
8. McGill Jr HC, McMahan CA, Zieske AW, Sloop GD, Walcott JV, Troxclair DA, Malcom GT, Tracy RE, Oalmann MC, Strong JP 2000 Associations of coronary heart disease risk factors with the intermediate lesion of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Arterioscler Thromb Vasc Biol 20:1998-2004
9. Dean H, Flett B, Natural history of type 2 diabetes diagnosed in childhood: long term followup in young adult years [Abstract 99-OR]. Proc 62nd Annual Meeting of the American Diabetes Association, San Francisco, CA, 2002
10. Lindhal B, Weinehall L, Asplund K, Hallmans G 1999 Screening for impaired glucose tolerance. Results from a population-based study of 21, 057 individuals. Diabetes Care 22:1988-1992
11. Paris RM, Bedno SA, Krauss MR, Keep LW, Rubertone MV 2001 Weighing in on type 2 diabetes in the military: characteristics of US military personnel at entry who develop type 2 diabetes. Diabetes Care 24:1894-1898
12. Hu FB, van Dam RM, Liu S 2001 Diet and risk of type 2 diabetes: the role of fat and carbohydrate. Diabetologia 44:805-817
13. Legro RS, Kunselman AR, Dodson WC, Dunaif A 1999 Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 84:265-169
14. Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 345:790 -797
15. Ronnemaa T, Koskenvuo M, Marniemi J, Koivunen T, Sajantila A, Rissanen A, Kaitsaari M, Bouchard C, Kaprio J 1997 Glucose metabolism in identical twins discordant for obesity: the critical role of visceral fat. J Clin Endocrinol Metab 82:383-387
16. Caprio S, Hyman LD, Limb C, McCarthy S, Lange R, Sherwin RS, Shulman G, Tamborlane WV 1995. Central adiposity and its metabolic correlates in obese adolescent girls. Am J Physiol E118-E126
17. Caprio S 1999 Relationship between abdominal visceral fat and metabolic risk factors in obese adolescents. Am J Hum Biol 11:259-266
18. Cruz ML, Bergman RN, Goran MI 2002 Unique effect of visceral fat on insulin sensitivity in obese Hispanic children with a family history of type 2 diabetes. Diabetes Care 25:1631-1636
19. Gower BA, Nagy, TR, Goran MI 1999 Visceral fat, insulin sensitivity, and lipids in prepubertal children. Diabetes 48:1515-1521
20. Goran MI, Bergman RN, Gower BA 2001. Influence of total vs. visceral fat on insulin action and secretion in African American and white children. Obesity Res 9:423-431
21. Arslanian S, Suprasongsin C 1996 Insulin sensitivity, lipids and body composition in childhood: is "syndrome X" present? J Clin Endocrinol Metab 51:1058-1062
22. Srinivasan ST, Myers L, Berenson GS 1999 Temporal association between obesity and hyperinsulinemia in children, adolescents and young adults: The Bogalusa Heart Study. Metab Clin Exp 48:928-934
23. Sinha R, Fisch G, Teague B, Tamboralne WV, Banyas B, Allen K, Savoye M, Rieger V, Taksali S, Barbetta G, Sherwin RS, Caprio S 2002 Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 346:802-810
24. Sinaiko AR, Donahue RP, Jaeobs Jr DR, Prineas RJ 1999 Relation of weight and rate of increase in weight during childhood and adolescence to body size, blood pressure, fasting insulin and lipids in young adults: The Minneapolis Children's Blood Pressure Study. Circulation 99:1471-1476
25. Srinivasan SR, Myers L, Berenson GS 2002 Predictability of childhood adiposity and insulin for developing insulin resistance syndrome (syndrome X) in young adulthood: The Bogalusa Heart Study. Diabetes 51:204-209
26. Vanhala MJ, Vanhala PT, Keinanen-Kiukaanniemi SM, Kumpusalo EA, Takala JK 1999 Relative weight gain and obesity as a child predict metabolic syndrome as an adult. Int J Obes 23:656-659
27. Pettitt DJ, Moll PP, Knowler WC, Mott DM, Nelson RG, Saad MF, Bennett PH, Kottke BA 1993 Insulinemia in children at low and high risk of NIDDM. Diabetes Care 16:608-615
28. McCance DR, Pettitt DJ, Hanson RL, Jacobsson TH, Bennett PH, Knowler WC 1994 Glucose, insulin concentrations and obesity in childhood and adolescence as predictors of NIDDM. Diabetologia 37:617-623
29. Innes KE, Byers TE, Marshall JA, Baron A, Orleans M, Hamman RF 2002 Association of a woman's own birth weight with subsequent risk for gestational diabetes. JAMA 287:2534-2541
30. Looker HC, Knowler WC, Hanson RL 2001 Changes in BMI and weight before and after the development of type 2 diabetes. Diabetes Care 24:1917-1922
31. Rich-Edwards JW, Coldltz GA, Stampfer MJ, Willett WC, Gillman MW, Hennekens CH, Speizer FE, Manson JE 1999 Birthweight and the risk for type 2 diabetes mellitus in adult women. Ann Intern Med 130:278-284
32. Dabelea D, Pettitt D, Hanson R, Imperatore G, Bennett P, Knowler W 1999 Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults. Diabetes Care 22:944-950
33. Egeland GM, Skjaerven R, Irgens LM 2000 Birth characteristics of women who develop gestational diabetes: population study. Br Med J 321:546-547
34. Lucas A, Fewtrell M, Cole T 1999 Fetal origins of adult disease: the hypothesis revisited. Br Med J 319:245-249
35. Pettitt DJ, Bennett PH, Saad MF, Charles MA, Nelson RG 1991 Abnormal glucose tolerance during pregnancy in pima Indian women: long-term effects on offspring. Diabetes 40:126-130
36. Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM, Roumain J, Bennett PH, Knowler WC 2000 Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 49:2208-2211
37. Silverman B, Rizzo T, Cho N, Metzger B 1998 Long-term effects of the intrauterine environment. Diabetes Care 21:B142-B149
38. Eriksson J, Franssila-Kallunki A, Ekstrand A, et al. 1989 Early metabolic defects in persons at increased risk for non-insulin dependent diabetes mellitus. N Engl J Med 321:337-343
39. Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR 1990 Slow glucose removal rate and hyperinsulinemia precede the development of type 2 diabetes in the offspring of diabetic parents. Ann Intern Med 113:909-915
40. Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR 1992 Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 340:925-929
41. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C 1993 Insulin resistance and insulin secretory dysfunction as precursors of non-insulin dependent diabetes mellitus: prospective studies of Pima Indians. N Engl J Med 329:1988-1992
42. Lewis GF, Carpentier A, Adeli K, Giacca A 2002 Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23:201-229
43. Poitout V, Robertson RP 2002 Minireview: secondary β cell failure in type 2 diabetes: a convergence of glucotoxicity and lipotoxicity. Endocrinology 143: 339 -342
44. Boden G, Shulman GI 2002 Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β cell dysfunction. Eur J Clin Invest 32(Suppl 3):14-23
45. Weyer C, Bogardus C, Pratley RE 1999 Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance. Diabetes 48:2197-2203
46. Paquot N, Scheen AJ, Dirlewanger M, Lefebvre PJ, Tappy L 2002 Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic subjects. Obes Res 10:129-134
47. Pratipanawatr T, Pratipanawatr W, Rosen C, Berria R, Bajaj M, Cusi K, Mandarino L, Kashyap S, Belfort R, DeFronzo RA 2002 Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects. Am J Physiol 282:E1360-E1368
48. Mauvais-Jarvis F, Kulkami RN, Kahn CR 2002 Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistance. Clin Endocrinol (Oxf) 57:1-9
49. Sinha R, Dufour S, Petersen KF, LeBon V, Enoksson S, Ma YZ, Savoye M, Rothman DL, Shulman GI, Caprio S 2002 Assessment of skeletal muscle triglyceride content by (1)H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Diabetes 51:1022-1027
50. Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin MF, Surwit RS, Ricquier D, Warden CH 1997 Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15:269-272
51. Lameloise N, Muzzin P, Prentki M, Assimacopoulos-Jeannet F 2001 Uncoupling protein-2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion? Diabetes 50:803-809
52. Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal-Puig AJ, Boss O, Kim YB, Zheng XX, Wheeler MB, Shulman GI, Chan CB, Lowell BB 2001 Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, β cell dysfunction and type 2 diabetes. Cell 105:745-755
53. Chan CB, De Leo D, Joseph JW, McQuaid TS, Ha XF, Xu F, Tsushima RG, Pennefather PS, Salapatek AM, Wheeler MB 2001 Increased uncoupling protein-2 levels in β cells are associated with impaired glucose-stimulated insulin secretion: mechanism of action. Diabetes 50:1302-1310
54. Bastard JP, Maachi M, Van Nhieu JT, Jardel C, Bruckert E, Grimaldi A, Robert JJ, Capeau J, Hainque B 2002 Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J Clin Endocrinol Metab 87:2084-2089
55. Vozarova B, Weyer C, Hanson K, Tataranni PA, Bogardus C, Pratley RE 2001 Circulating interleukin-6 in relation to adiposity, insulin action and insulin secretion. Obes Res 9:414-417
56. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM 1995 Increased adipose tissue expression of tumor necrosis factor-α in human obesity and insulin resistance. J Clin Invest 95:2409-2415
57. Ruan H, Hacohen N, Golub TR, Van Parijs L, Lodish HF 2002 Tumor necrosis factor-α suppresses adipocyte-specific genes and activates expression of pre-adipocyte genes in 3T3-L1 adipocytes: nuclear factor-κB activation by TNF-α is obligatory. Diabetes 51:1319-1336
58. Ventre J, Doebber T, Wu M, MacNaul K, Stevens K, Pasparakis M, Kollias G, Moller DE 1997 Targeted disruption of the tumor necrosis factor-α gene: metabolic consequences in obese and nonobese mice. Diabetes 46:1526-1531
59. Ofei F, Hurel S, Newkirk J, Sopwith M, Taylor R 1996 Effects of an engineered human anti-TNF-α antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45:881-885
60. Fasshauer M, Klein J, Neumann S, Eszlinger M 2002 Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 290:1084-1089
61. Paschke R, Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA 2001 Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930-1935
62. Stefan N, Bunt JC, Selbe AD, Funahashi T, Matsuzawa Y, Tataranni PA 2002 Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab 87:4652-4656
63. Berg AH, Combs TP, Scherer PE 2002 ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13:84-89
64. Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y 2002 Diet induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 17:17
65. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA 2001 The hormone resistin links obesity to diabetes. Nature 409:307-312
66. Way JM, Gorgun CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver Jr WR, Willson TM, Kliewer SA, Hotamisligil GS 2001 Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor γ agonists. J Biol Chem 276:25651-25653
67. Janke J, Engeli S, Gorzelniak K, Luft FC, Sharma AM 2002 Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res 10:1-5
68. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O'Rahilly S 2001 Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-γ action in humans. Diabetes 50:2199-2202
69. Degawa-Yamauchi M, Bovenkerk JE, Zhu Q, Considine RV, Serum resistin is significantly elevated in obese humans [Abstract 1660-P]. Proc 62nd Annual Meeting of the American Diabetes Association, San Francisco, CA, 2002
70. McTernan PG, McTernan CL, Valsamakis G, Chetty R, Fisher FM, Lauer M, Barnett AH, Kumar S, Characterization of resistin expression and secretion in human adipose tissue [Abstract 1229-P]. Proc 62nd Annual Meeting of the American Diabetes Association, San Francisco, CA, 2002
71. Jequier E 2002 Leptin signaling, adiposity, and energy balance. Ann NY Acad Sci 967:379-388
72. Unger RH, Zhou YT, Orci L 1999 Regulation of fatty acid homeostasis in cells: novel role of leptin. Proc Natl Acad Sci USA 96:2327-2332
73. Ebihara K, Ogawa Y, Masuzaki H, Shintani M, Miyanaga F, Aizaw-Abe M, Hayashi T, Hosoda K, Inoue G, Yoshimasa Y, Gavrilova O, Reitman ML, Nakao K 2001 Transgenic overexpression of leptin rescues insulin resistance and diabetes in a mouse model of lipoatrophic diabetes. Diabetes 50:1440-1448
74. Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, Wagner AJ, DePaoli AM, Reitman ML, Taylor SI, Gorden P, Garg A 2002 Leptin replacement therapy for lipodystrophy. N Engl J Med 346:570-578
75. Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ 2002 Leptin increases fatty acid oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. Am J Physiol 283:E187-E192
76. Hara K, Kubota N, Tobe K, Terauchi Y, Miki H, Komeda K, Tamemoto H, Yamauchi T, Hagura R, Ito C, Akanuma Y, Kadowaki T 2000 The role of PPARγ as a thrifty gene both in mice and humans. Br J Nutr 84(Suppl 2): S235-S239
77. 12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet 26:76-80
78. Koutnikova H, Cock T-A, Auwerx J, PPARγ2 controls adipose tissue development in vivo [Abstract OR-17-1]. Program of the 84th Annual Meeting of The Endocrine Society, San Francisco, CA, 2002
79. Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS 2001 A transgenic model of visceral obesity and the metabolic syndrome. Science 294:2166-2170
80. Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D 2000 The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med 133:176-182
81. Phillips DIW 1998 Birth weight and the future development of diabetes: a review of the evidence. Diabetes Care 21(Suppl 2):B150-B155
82. Lesage J, Blondeau B, Grino M, Breant B, Dupouy JP 2001 Maternal under-nutrition during late gestation induces fetal overexposure to glucocorticoids and intrauterine growth retardation and disturbs the hypothalamo-pituitary adrenal axis in the newborn rat. Endocrinology 142:1692-1702
83. Jensen CB, Storgaard H, Dela F, Holst JJ, Madsbad S, Vaag AA 2002 Early differential defects of insulin secretion and action in 19 year old Caucasian men who had low birth weight. Diabetes 51:1271-1280
84. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV 1997 The Da Qing IGT and Diabetes Study: effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. Diabetes Care 20:537-544
85. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M 2001 Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343-1350
86. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM 2002 Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393-403, and presentation by Kahn S, 62nd Annual Meeting of the American Diabetes Association, San Francisco, CA, 2002
87. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE 2001 Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167-1174
88. Cusi K, Consoli A, DeFronzo RA 1996 Metabolic effects of metformin in non-insulin dependent diabetes mellitus. J Clin Endocrinol Metab 81:4059-4067
89. Bailey CJ, Turner RC 1996 Metformin. N Engl J Med 334:574-579
90. DeFronzo RA 1999 Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 131:281-303
91. Song S, Andrikopoulos S, Filippis C, Thorburn AW, Khan D, Proietto J 2001 Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin. Am J Physiol 281:E275-E282
92. Lupi R, Del Guerra S, Fierabracci V, Marselli L, Novelli M, Patane G, Boggi U, Mosca F, Piro S, Del Prato S, Marchetti P 2002 Lipotoxicity in human pancreatic islets and the protective effect of metformin. Diabetes 51 (Suppl 1):S134-S137
93. Fontbonne A, Charles MA, Juhan-Vague I, Bard JM, Andre P, Isnard F, Cohen JM, Grandmottet P, Vague P, Safar ME, Eschwege E 1996 The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. B1GPRO Study Group. Diabetes Care 19:920-926
94. Paolisso G, Amato L, Eccellente R, Gambardella A, Tagliamonte MR, Varricchio G, Carella C, Giugliano D, D'Onofrio F 1998. Effect of metformin on food intake in obese subjects. Eur J Clin Invest 28:441-446
95. Glueck CJ, Fontaine RN, Wang P, Subbiah MTR, Weber K, Illig E, Streicher P, Sieve-Smith L, Tracy TM, Lang JE, McCullough P 2001 Metformin reduces weight, centripetal obesity, insulin, leptin and low density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30. Metabolism 50:856-861
96. Freemark M, Bursey D 2001 The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Pediatrics 107:e55
97. Kay JP, Alemzadeh R, Langley G, D'Angelo L, Smith P, Holshouser S 2001 Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metabolism 50:1457-1461
98. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y 2001 PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:2094-2099
99. Peraldi P, Xti M, Speigelman BM 1997 Thiazolidinediones block tumor necrosis factor-α-induced inhibition of insulin signaling. J Clin Invest 100: 1863-1869
100. Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, Ochoa C, Tan S, Berkowitz K, Hodis HN, Azen SP 2002 Preservation of pancreatic β-cell functin and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes 51:2796-2803
101. Nakamura T, Funahashi T, Yamashita S, Nishida M, Nishida Y, Takahashi M, Hotta K, Kuriyama H, Kihara S, Ohuchi N, Nishimura T, Kishino BI, Ishikawa K, Kawamoto T, Tokunaga K, Nakagawa C, Mineo I, Watanabe F, Tarui S, Matsuzawa Y 2001 Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation: double-blind placebo-controlled trial. Diabetes Res Clin Pract 54:181-190
102. Chiasson J-L, Josse R, Gomis R, Hanefeld M, Karasik A, Laakso M 2002 Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomized trial. Lancet 359:2072-2077
103. Yusuf S, Gerstein H, Hoogwerf B, Pogue J, Bosch J, Wolffenbuttel BHR, Zinman B 2001 Ramipril and the development of diabetes. JAMA 286:1882-1885
104. Freeman DJ, Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, Shepherd J, Gaw A 2001 Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 103:357-362
105. Sims EAH 2001 Are there persons who are obese, but metabolically healthy? Metabolism 50:1499-1504
106. American Diabetes Association 2002 Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 25:5-20
107. Youssef W, McCullough AJ 2002 Diabetes mellitus, obesity, and hepatic steatosis. Semin Gastrointest Dis 13:17-30
108. Silverstein JH, Rosenbloom AL 2000 Treatment of type 2 diabetes mellitus in children and adolescents. J Pediatr Endocrinol Metab 13(Suppl 6):1403-1409
109. Jones KL, Arslanian S, Peterokova VA, Park JS, Tomlinson MJ 2002 Effect of metformin in pediatric patients with type 2 diabetes: a randomized controlled trial. Diabetes Care 25:89-94
110. Castells S 2002 Management of hyperglycemia in minority children with type 2 diabetes mellitus. J Pediatr Endocrinol Metab 15(Suppl 1):531-540
111. Rosenbloom AL 2002 Increasing incidence of type 2 diabetes in children and adolescents: treatment considerations. Paediatr Drugs 4:209-221
112. Zuhri-Yafi MI, Brosnan PG, Hardin DS 2002 Treatment of type 2 diabetes mellitus in children and adolescents. J Pediatr Endocrinol Metab 15(Suppl 1):541-546
113. Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith LN 2001 Metformin to restore normal menses in oligo-amenorrheic teenage girls with polycystic ovary syndrome (PCOS). J Adolesc Health 29:160-169
114. Arslanian SA, Lewy V, Danadian K, Saad R 2002 Metformin therapy in obese adolescents with polycystic ovary syndrome and impaired glucose tolerance: amelioration of exaggerated adrenal response to adrenocorticotropin with reduction of insulinemia/insulin resistance. J Clin Endocrinol Metab 87:1555-1559
115. Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A 1999 Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care 22: 920-924
116. Bonora E, Kiechl S, Oberhollenzer F, Egger G, Bonadonna RC, Muggeo M, Willeit J 2000 Impaired glucose tolerance, type II diabetes mellitus and carotid atherosclerosis: prospective results from the Bruneck Study. Diabetologia 43:156-164
117. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen MR, Groop L 2001 Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24:683-689
118. Arad Y, Newstein D, Cadet F, Roth M, Guerci AD 2001 Association of multiple risk factors and insulin resistance with increased prevalence of asymptomatic coronary artery disease by an electron-beam computed tomographic study. Arterioscler Thromb Vasc Biol 21:2051-2058
119. Boyle JP, Honeycutt AA, Narayan KMV, Hoerger TJ, Geiss LS, Chen H, Thompson TJ 2001 Projection of diabetes burden through 2050. Diabetes Care 24:1936-1940