Differential patterns of insulin secretion and sensitivity in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease versus patients with type 2 diabetes mellitus alone

Lipids in Health and Disease

Shen Qu¹  Xiao-Yun Cheng²  Fei Li²  Yue-Ye Huang²  Ke-Xiu Song²  Xiao-Yu Pan²  Shang-Yu Chai² 

[1] Shanghai 10th People’s Hospital, Nanjing Medical University, 301 Middle Yanchang Road, Shanghai, China;Department of Endocrinology, Shanghai 10th People’s Hospital, Tongji University, Shanghai, China

关键词: Insulin resistance;    Hyperinsulinemia;    Type 2 diabetes mellitus;    Impaired glucose tolerance;    Nonalcoholic fatty liver disease;   

Others  :  814674
DOI  :  10.1186/1476-511X-13-7

 received in 2013-11-22, accepted in 2014-01-03,  发布年份 2014

【 摘 要 】

Background

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) often coexist and have adverse outcomes. The aim of our study was to elucidate metabolic abnormalities in patients with DM-NAFLD versus those with T2DM alone.

Methods

Patients were divided into two groups: 26 T2DM patients with NAFLD and 26 gender-, age-, and body mass index-matched patients with T2DM alone. Patients took a 75-g oral glucose tolerance test (OGTT), which measured serum insulin and C-peptide (C-p) levels at baseline (0 min), 30 min, 60 min, and 120 min after glucose challenge.

Results

Patients with DM-NAFLD or T2DM alone had similar blood glucose levels. β-cell hypersecretion was more obvious in patients with DM-NAFLD. In addition, fasting, early-phase, and late-phase C-peptide levels were significantly increased in patients with DM-NAFLD (ΔC-p 0–30 min, P < 0.05; Area Under the Curve (AUC) C-p/PG 30–120 min ratio, P < 0.01; and AUC C-p 30–120 min, P < 0.01). Hepatic and extrahepatic insulin resistance during the OGTT did not differ significantly between groups. Hepatic insulin sensitivity independently contributed to the early phase (0–30 min) of the OGTT in patients with T2DM and NAFLD, whereas a significant deficit in late insulin secretion independently contributed to the 30–120 min glucose status in patients with T2DM only.

Conclusions

In patients with similar levels of insulin resistance and hyperglycemia, DM-NAFLD was associated with higher serum insulin levels than T2DM alone. Hyperinsulinemia is caused mainly by β-cell hypersecretion. The present study demonstrates pathophysiological differences in mechanisms of insulin resistance in patients with DM-NAFLD versus T2DM alone.

【 授权许可】

   
2014 Chai et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Smith BW, Adams LA: Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol 2011, 7:456-465.
• [2]Semple RK, Sleigh A, Murgatroyd PR, Adams CA, Bluck L, Jackson S, Vottero A, Kanabar D, Charlton-Menys V, Durrington P, et al.: Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J Clin Invest 2009, 119:315-322.
• [3]Hegele RA, Reue K: Hoofbeats, zebras, and insights into insulin resistance. J Clin Invest 2009, 119:249-251.
• [4]Cohen JC, Horton JD, Hobbs HH: Human fatty liver disease: Old questions and New insights. Science 2011, 332:1519-1523.
• [5]Kotronen A, Vehkavaara S, Seppala-Lindroos A, Bergholm R, Yki-Jarvinen H: Effect of liver fat on insulin clearance. Am J Physiol Endocrinol Metab 2007, 293:E1709-E1715.
• [6]Kruszynska YT, Goulas S, Wollen N, McIntyre N: Insulin secretory capacity and the regulation of glucagon secretion in diabetic and non-diabetic alcoholic cirrhotic patients. J Hepatol 1998, 28:280-291.
• [7]Kaji K, Yoshiji H, Kitade M, Ikenaka Y, Noguchi R, Yoshii J, Yanase K, Namisaki T, Yamazaki M, Moriya K, et al.: Impact of insulin resistance on the progression of chronic liver diseases. Int J Mol Med 2008, 22:801-808.
• [8]Goto T, Onuma T, Takebe K, Kral JG: The influence of fatty liver on insulin clearance and insulin resistance in non-diabetic Japanese subjects. Int J Obes Relat Metab Disord 1995, 19:841-845.
• [9]Kotronen A, Juurinen L, Tiikkainen M, Vehkavaara S, Yki-Jarvinen H: Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 2008, 135:122-130.
• [10]Alibegovic AC, Hojbjerre L, Sonne MP, van Hall G, Stallknecht B, Dela F, Vaag A: Impact of 9 days of bed rest on hepatic and peripheral insulin action, insulin secretion, and whole-body lipolysis in healthy young male offspring of patients with type 2 diabetes. Diabetes 2009, 58:2749-2756.
• [11]Brons C, Jensen CB, Storgaard H, Hiscock NJ, White A, Appel JS, Jacobsen S, Nilsson E, Larsen CM, Astrup A, et al.: Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men. J Physiol-London 2009, 587:2387-2397.
• [12]Marx N, Walcher D: C-peptide and atherogenesis: C-peptide as a mediator of lesion development in patients with type 2 diabetes mellitus? Exp Diabetes Res 2008, 2008:385108.
• [13]Kim CH, Park JY, Lee KU, Kim JH, Kim HK: Association of serum gamma-glutamyltransferase and alanine aminotransferase activities with risk of type 2 diabetes mellitus independent of fatty liver. Diabetes Metabol Res Rev 2009, 25:64-69.
• [14]Bugianesi E, McCullough AJ, Marchesini G: Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 2005, 42:987-1000.
• [15]Haque M, Sanyal AJ: The metabolic abnormalities associated with non-alcoholic fatty liver disease. Best Pract Res Clin Gastroenterol 2002, 16:709-731.
• [16]Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N: Nonalcoholic fatty liver disease - a feature of the metabolic syndrome. Diabetes 2001, 50:1844-1850.
• [17]Matsuda M, DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing - comparison with the euglycemic insulin clamp. Diabetes Care 1999, 22:1462-1470.
• [18]Liou I, Kowdley KV: Natural history of nonalcoholic steatohepatitis. J Clin Gastroenterol 2006, 40:S11-S16.
• [19]Farrell GC, Larter CZ: Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006, 43:S99-S112.
• [20]Brown MS, Goldstein JL: Selective versus total insulin resistance: a pathogenic paradox. Cell Metab 2008, 7:95-96.
• [21]Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA: Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care 2007, 30:89-94.
• [22]Bacha F, Gungor N, Arslanian SA: Measures of beta-cell function during the oral glucose tolerance test, liquid mixed-meal test, and hyperglycemic clamp test. J Pediatr 2008, 152:618-621.
• [23]Potteiger JA, Jacobsen DJ, Donnelly JE: A comparison of methods for analyzing glucose and insulin areas under the curve following nine months of exercise in overweight adults. Int J Obes 2002, 26:87-89.
• [24]Greco AV, Mingrone G, Mari A, Capristo E, Manco M, Gasbarrini G: Mechanisms of hyperinsulinaemia in Child’s disease grade B liver cirrhosis investigated in free living conditions. Gut 2002, 51:870-875.