• 1
    Ludwig J, Viggiano TR, McGill DB, et al. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55: 434438.
  • 2
    Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865873.
  • 3
    Farrell GC, van ??????? RD, Gan L, et al. NASH is an inflammatory disorder: pathogenic, prognostic and therapeutic implications. Gut Liver 2012; 6: 149171.
  • 4
    Fan JG, Zhu J, Li XJ, et al. Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol 2005; 43: 508514.
  • 5
    Yun JW, Cho YK, Park JH, et al. Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver disease. Liver Int 2009; 29: 525529.
  • 6
    Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 13871395.
  • 7
    Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006; 40(Suppl 1): S5S10.
  • 8
    Wang Z, Xia B, Ma C, et al. Prevalence and risk factors of fatty liver disease in the Shuiguohu district of Wuhan city, central China. Postgrad Med J 2007; 83: 192195.
  • 9
    Fan JG, Li F, Cai XB, et al. The importance of metabolic factors for the increasing prevalence of fatty liver in Shanghai factory workers. J Gastroenterol Hepatol 2007; 22: 663668.
  • 10
    Adams LA, Sanderson S, Lindor KD, et al. The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005; 42: 132138.
  • 11
    Zhou YJ, Li YY, Nie YQ, et al. Natural course of nonalcoholic fatty liver disease in southern China: a prospective cohort study. J Dig Dis 2012; 13: 153160.
  • 12
    Dam-Larsen S, Becker U, Franzmann MB, et al. Final results of a long-term, clinical follow-up in fatty liver patients. Scand J Gastroenterol 2009; 44: 12361243.
  • 13
    Shibata M, Kihara Y, Taguchi M, et al. Nonalcoholic fatty liver disease is a risk factor for type 2 diabetes in middle-aged Japanese men. Diabetes Care 2007; 30: 29402944.
  • 14
    He S, Bao W, Shao M, et al. Risk factors for non-alcoholic fatty liver disease in a Chinese population. Acta Gastroenterol Belg 2011; 74: 503508.
  • 15
    Adams LA, Lindor KD. Nonalcoholic fatty liver disease. Ann Epidemiol 2007; 17: 863869.
  • 16
    Fan JG, Li F, Cai XB, et al. Effects of nonalcoholic fatty liver disease on the development of metabolic disorders. J Gastroenterol Hepatol 2007; 22: 10861091.
  • 17
    Chon CW, Kim BS, Cho YK, et al. Effect of nonalcoholic Fatty liver disease on the development of type 2 diabetes in nonobese, nondiabetic korean men. Gut Liver 2012; 6: 368373.
  • 18
    Younossi ZM, Gramlich T, Matteoni CA, et al. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol 2004; 2: 262265.
  • 19
    Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 2010; 52: 18361846.
  • 20
    Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50: 18441850.
  • 21
    Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998; 114: 842845.
  • 22
    Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363: 13411350.
  • 23
    Alkhouri N, Dixon LJ, Feldstein AE. Lipotoxicity in nonalcoholic fatty liver disease: not all lipids are created equal. Expert Rev Gastroenterol Hepatol 2009; 3: 445451.
  • 24
    Bugianesi E, Gastaldelli A, Vanni E, et al. Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms. Diabetologia 2005; 48: 634642.
  • 25
    Byrne CD. Dorothy Hodgkin Lecture 2012* Non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management. Diabet Med 2012; 29: 10981107.
  • 26
    Donnelly KL, Smith CI, Schwarzenberg SJ, et al. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005; 115: 13431351.
  • 27
    Hirosumi J, Tuncman G, Chang L, et al. A central role for JNK in obesity and insulin resistance. Nature 2002; 420: 333336.
  • 28
    Zhang X, Xu A, Chung SK, et al. Selective inactivation of c-Jun NH2-terminal kinase in adipose tissue protects against diet-induced obesity and improves insulin sensitivity in both liver and skeletal muscle in mice. Diabetes 2011; 60: 486495.
  • 29
    Xu A, Wang Y, Keshaw H, et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91100.
  • 30
    Hoo RL, Chow WS, Yau MH, et al. Adiponectin mediates the suppressive effect of rosiglitazone on plasminogen activator inhibitor-1 production. Arterioscler Thromb Vasc Biol 2007; 27: 27772782.
  • 31
    Tsuchida A, Yamauchi T, Takekawa S, et al. Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: comparison of activation of PPARalpha, PPARgamma, and their combination. Diabetes 2005; 54: 33583370.
  • 32
    Wang Y, Lam KS, Chan L, et al. Post-translational modifications of the four conserved lysine residues within the collagenous domain of adiponectin are required for the formation of its high molecular weight oligomeric complex. J Biol Chem 2006; 281: 1639116400.
  • 33
    Stumvoll M, Tschritter O, Fritsche A, et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 2002; 51: 3741.
  • 34
    Stefan N, Hennige AM, Staiger H, et al. Alpha2-Heremans-Schmid glycoprotein/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. Diabetes Care 2006; 29: 853857.
  • 35
    Brix JM, Stingl H, Hollerl F, et al. Elevated Fetuin-A concentrations in morbid obesity decrease after dramatic weight loss. J Clin Endocrinol Metab 2010; 95: 48774881.
  • 36
    Sun Q, Cornelis MC, Manson JE, et al. Plasma levels of fetuin-a and hepatic enzymes and risk of type 2 diabetes in women in the u.s. Diabetes 2013; 62: 4955.
  • 37
    Masaki T, Chiba S, Tatsukawa H, et al. Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice. Hepatology 2004; 40: 177184.
  • 38
    Hui JM, Hodge A, Farrell GC, et al. Beyond insulin resistance in NASH: TNF-alpha or adiponectin? Hepatology 2004; 40: 4654.
  • 39
    Polyzos SA, Toulis KA, Goulis DG, et al. Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis. Metabolism 2011; 60: 313326.
  • 40
    Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8: 12881295.
  • 41
    Awazawa M, Ueki K, Inabe K, et al. Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway. Biochem Biophys Res Commun 2009; 382: 5156.
  • 42
    Wang Y, Zhou M, Lam KS, et al. Protective roles of adiponectin in obesity-related fatty liver diseases: mechanisms and therapeutic implications. Arq Bras Endocrinol Metabol 2009; 53: 201212.
  • 43
    Pettinelli P, Videla LA. Up-regulation of PPAR-gamma mRNA expression in the liver of obese patients: an additional reinforcing lipogenic mechanism to SREBP-1c induction. J Clin Endocrinol Metab 2011; 96: 14241430.
  • 44
    Zhou M, Xu A, Tam PK, et al. Mitochondrial dysfunction contributes to the increased vulnerabilities of adiponectin knockout mice to liver injury. Hepatology 2008; 48: 10871096.
  • 45
    Tietge UJ, Boker KH, Manns MP, et al. Elevated circulating adiponectin levels in liver cirrhosis are associated with reduced liver function and altered hepatic hemodynamics. Am J Physiol Endocrinol Metab 2004; 287: E82E89.
  • 46
    Savvidou S, Hytiroglou P, Orfanou-Koumerkeridou H, et al. Low serum adiponectin levels are predictive of advanced hepatic fibrosis in patients with NAFLD. J Clin Gastroenterol 2009; 43: 765772.
  • 47
    Ikejima K, Okumura K, Kon K, et al. Role of adipocytokines in hepatic fibrogenesis. J Gastroenterol Hepatol 2007; 22(Suppl 1): S87S92.
  • 48
    Zhou M, Xu A, Lam KS, et al. Rosiglitazone promotes fatty acyl CoA accumulation and excessive glycogen storage in livers of mice without adiponectin. J Hepatol 2010; 53: 11081116.
  • 49
    Berg AH, Combs TP, Du X, et al. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001; 7: 947953.
  • 50
    Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279: 1215212162.
  • 51
    Iwabu M, Yamauchi T, Okada-Iwabu M, et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature 2010; 464: 13131319.
  • 52
    Wang CH, Wang CC, Huang HC, et al. Mitochondrial dysfunction leads to impairment of insulin sensitivity and adiponectin secretion in adipocytes. FEBS J 2012; 280: 10391050.
  • 53
    Shimada M, Kawahara H, Ozaki K, et al. Usefulness of a combined evaluation of the serum adiponectin level, HOMA-IR, and serum type IV collagen 7S level to predict the early stage of nonalcoholic steatohepatitis. Am J Gastroenterol 2007; 102: 19311938.
    Direct Link:
  • 54
    Machado MV, Coutinho J, Carepa F, et al. How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 2012; 24: 11661172.
  • 55
    Spranger J, Kroke A, Mohlig M, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet 2003; 361: 226228.
  • 56
    Tabak AG, Brunner EJ, Miller MA, et al. Low serum adiponectin predicts 10-year risk of type 2 diabetes and HbA1c independently of obesity, lipids, and inflammation: Whitehall II study. Horm Metab Res 2009; 41: 626629.
  • 57
    Woo YC, Tso AW, Xu A, et al. Combined use of serum adiponectin and tumor necrosis factor-alpha receptor 2 levels was comparable to 2-hour post-load glucose in diabetes prediction. PLoS One 2012; 7: e36868.
  • 58
    Tabak AG, Carstensen M, Witte DR, et al. Adiponectin trajectories before type 2 diabetes diagnosis: Whitehall II study. Diabetes Care 2012; 35: 25402547.
  • 59
    Leite NC, Salles GF, Cardoso CR, et al. Serum biomarkers in type 2 diabetic patients with non-alcoholic steatohepatitis and advanced fibrosis. Hepatol Res 2012; doi: 10.1111/j.1872-034X.2012.01106.x.
  • 60
    Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 13561362.
  • 61
    Xu A, Wang Y, Xu JY, et al. Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome. Clin Chem 2006; 52: 405413.
  • 62
    Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 2008; 7: 489503.
  • 63
    Xu A, Tso AW, Cheung BM, et al. Circulating adipocyte-fatty acid binding protein levels predict the development of the metabolic syndrome: a 5-year prospective study. Circulation 2007; 115: 15371543.
  • 64
    Uysal KT, Scheja L, Wiesbrock SM, et al. Improved glucose and lipid metabolism in genetically obese mice lacking aP2. Endocrinology 2000; 141: 33883396.
  • 65
    Maeda K, Cao H, Kono K, et al. Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab 2005; 1: 107119.
  • 66
    Hui X, Li H, Zhou Z, et al. Adipocyte fatty acid-binding protein modulates inflammatory responses in macrophages through a positive feedback loop involving c-Jun NH2-terminal kinases and activator protein-1. J Biol Chem 2010; 285: 1027310280.
  • 67
    Hoo RL, Lee IP, Zhou M, et al. Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice. J Hepatol 2012; 58: 358364.
  • 68
    Kremer M, Thomas E, Milton RJ, et al. Kupffer cell and interleukin-12-dependent loss of natural killer T cells in hepatosteatosis. Hepatology 2010; 51: 130141.
  • 69
    Westerbacka J, Kolak M, Kiviluoto T, et al. Genes involved in fatty acid partitioning and binding, lipolysis, monocyte/macrophage recruitment, and inflammation are overexpressed in the human fatty liver of insulin-resistant subjects. Diabetes 2007; 56: 27592765.
  • 70
    Kim YC, Cho YK, Lee WY, et al. Serum adipocyte-specific fatty acid-binding protein is associated with nonalcoholic fatty liver disease in apparently healthy subjects. J Nutr Biochem 2011; 22: 289292.
  • 71
    Koh JH, Shin YG, Nam SM, et al. Serum adipocyte fatty acid-binding protein levels are associated with nonalcoholic fatty liver disease in type 2 diabetic patients. Diabetes Care 2009; 32: 147152.
  • 72
    Milner KL, van der Poorten D, Xu A, et al. Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease. Hepatology 2009; 49: 19261934.
  • 73
    Hotamisligil GS, Johnson RS, Distel RJ, et al. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 1996; 274: 13771379.
  • 74
    Boord JB, Maeda K, Makowski L, et al. Combined adipocyte-macrophage fatty acid-binding protein deficiency improves metabolism, atherosclerosis, and survival in apolipoprotein E-deficient mice. Circulation 2004; 110: 14921498.
  • 75
    Furuhashi M, Tuncman G, Gorgun CZ, et al. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature 2007; 447: 959965.
  • 76
    Simon I, Escote X, Vilarrasa N, et al. Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women. Obesity (Silver Spring) 2009; 17: 11241128.
  • 77
    Tuncman G, Erbay E, Hom X, et al. A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease. Proc Natl Acad Sci USA 2006; 103: 69706975.
  • 78
    Tso AW, Xu A, Sham PC, et al. Serum adipocyte fatty acid binding protein as a new biomarker predicting the development of type 2 diabetes: a 10-year prospective study in a Chinese cohort. Diabetes Care 2007; 30: 26672672.
  • 79
    Mraz M, Bartlova M, Lacinova Z, et al. Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin Endocrinol (Oxf) 2009; 71: 369375.
  • 80
    Zhang X, Yeung DC, Karpisek M, et al. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 2008; 57: 12461253.
  • 81
    Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF-21 as a novel metabolic regulator. J Clin Invest 2005; 115: 16271635.
  • 82
    Chen W, Hoo RL, Konishi M, et al. Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes. J Biol Chem 2011; 286: 3455934566.
  • 83
    Badman MK, Pissios P, Kennedy AR, et al. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab 2007; 5: 426437.
  • 84
    Xu J, Lloyd DJ, Hale C, et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 2009; 58: 250259.
  • 85
    Li H, Fang Q, Gao F, et al. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J Hepatol 2010; 53: 934940.
  • 86
    Diaz-Delfin J, Hondares E, Iglesias R, et al. TNF-alpha represses beta-Klotho expression and impairs FGF21 action in adipose cells: involvement of JNK1 in the FGF21 pathway. Endocrinology 2012; 153: 42384245.
  • 87
    Kharitonenkov A, Wroblewski VJ, Koester A, et al. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 2007; 148: 774781.
  • 88
    Chavez AO, Molina-Carrion M, Abdul-Ghani MA, et al. Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care 2009; 32: 15421546.
  • 89
    Chen C, Cheung BM, Tso AW, et al. High plasma level of fibroblast growth factor 21 is an Independent predictor of type 2 diabetes: a 5.4-year population-based prospective study in Chinese subjects. Diabetes Care 2011; 34: 21132115.
  • 90
    Semba RD, Sun K, Egan JM, et al. Relationship of serum fibroblast growth factor 21 with abnormal glucose metabolism and insulin resistance: the Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2012; 97: 13751382.
  • 91
    Marchesini G, Brizi M, Bianchi G, et al. Metformin in non-alcoholic steatohepatitis. Lancet 2001; 358: 893894.
  • 92
    Lee JO, Lee SK, Kim JH, et al. Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP-activated protein kinase (AMPK)-Mediated Cbl/CAP Signaling in 3T3-L1 Preadipocyte cells. J Biol Chem 2012; 287: 4412144129.
  • 93
    Boyle JG, Logan PJ, Jones GC, et al. AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study. Diabetologia 2011; 54: 17991809.
  • 94
    Nygaard EB, Vienberg SG, Orskov C, et al. Metformin Stimulates FGF21 Expression in Primary Hepatocytes. Exp Diabetes Res 2012; 2012: 465282.
  • 95
    Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012; 55: 20052023.
  • 96
    Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 22972307.
  • 97
    Gastaldelli A, Harrison S, Belfort-Aguiar R, et al. Pioglitazone in the treatment of NASH: the role of adiponectin. Aliment Pharmacol Ther 2010; 32: 769775.
  • 98
    Oishi K, Tomita T. Thiazolidinediones are potent inducers of fibroblast growth factor 21 expression in the liver. Biol Pharm Bull 2011; 34: 11201121.
  • 99
    Dutchak PA, Katafuchi T, Bookout AL, et al. Fibroblast growth factor-21 regulates PPARgamma activity and the antidiabetic actions of thiazolidinediones. Cell 2012; 148: 556567.
  • 100
    Ben-Shlomo S, Zvibel I, Shnell M, et al. Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase. J Hepatol 2011; 54: 12141223.
  • 101
    Yang M, Zhang L, Wang C, et al. Liraglutide increases FGF-21 activity and insulin sensitivity in high fat diet and adiponectin knockdown induced insulin resistance. PLoS One 2012; 7: e48392.
  • 102
    Yilmaz Y, Yonal O, Deyneli O, et al. Effects of sitagliptin in diabetic patients with nonalcoholic steatohepatitis. Acta Gastroenterol Belg 2012; 75: 240244.
  • 103
    Iwasaki T, Yoneda M, Inamori M, et al. Sitagliptin as a novel treatment agent for non-alcoholic Fatty liver disease patients with type 2 diabetes mellitus. Hepatogastroenterology 2011; 58: 21032105.
  • 104
    Xu A, Wang H, Hoo RL, et al. Selective elevation of adiponectin production by the natural compounds derived from a medicinal herb alleviates insulin resistance and glucose intolerance in obese mice. Endocrinology 2009; 150: 625633.
  • 105
    Kasturiratne A, Weerasinghe S, Dassanayake AS, et al. Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus. J Gastroenterol Hepatol 2012; ???: ??????.
  • 106
    DeFronzo RA, Abdul-Ghani M. Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose. Am J Cardiol 2011; 108: 3B24B.
  • 107
    Ortiz-Lopez C, Lomonaco R, Orsak B, et al. Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care 2012; 35: 873878.
  • 108
    Janus ED, Watt NM, Lam KS, et al. The prevalence of diabetes, association with cardiovascular risk factors and implications of diagnostic criteria (ADA 1997 and WHO 1998) in a 1996 community-based population study in Hong Kong Chinese. Hong Kong Cardiovascular Risk Factor Steering Committee. American Diabetes Association. Diabet Med 2000; 17: 741745.
  • 109
    Wong VW, Hui AY, Tsang SW, et al. Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2006; 24: 12151222.
  • 110
    Ko GT, Chan JC, Woo J, et al. The reproducibility and usefulness of the oral glucose tolerance test in screening for diabetes and other cardiovascular risk factors. Ann Clin Biochem 1998; 35(Pt 1): 6267.
  • 111
    Bianchi C, Miccoli R, Bonadonna RC, et al. Pathogenetic mechanisms and cardiovascular risk: differences between HbA1c and oral glucose tolerance test for the diag-nosis of glucose tolerance. Diabetes Care 2012; 35: 26072612.