The Main Determinants of Serum Resistin Level in Type 2 Diabetic Patients are Renal Function and Inflammation not Presence of Microvascular Complication, Obesity and Insulin Resistance

Abstract

Aim The association of increased resistin levels in chronic kidney disease with diabetic nephropathy has not yet been clarified. Our aim was to analyze the relationship between serum resistin levels and various diabetic microvascular complications in patients.

Methods A total of 83 patients were enrolled in this cross-sectional study. The subjects were divided into 3 groups: 27 patients with type 2 diabetes mellitus (T2DM) having no diabetic retinopathy (DRP) or microalbuminuria and having normal renal function were included in Group-1, 28 patients with T2DM having DRP and normal renal function in Group-2, and 28 patients with T2DM with DRP and microalbuminuria and an estimated glomerular filtration rate (eGFR) of<60 ml/min/1.73 m² in Group-3. Serum resistin levels were analyzed by enzyme-linked immunosorbent assay.

Results The mean age of the patients [46 female (55.4%)] was 54.8±9.1 years. The resistin level in Group-3 was significantly higher than in Group-1 and Group-2 (p<0.001).However the resistin level was not different between Group-1 (without microvascular complications) and Group-2 (with microvascular complications). The resistin level was found to be correlated negatively with eGFR (r=−0.459; p<0.001) and albumin (r=−0.402; p<0.001), and positively with high-sensitivity C-reactive protein (hs-CRP) (r=0.366; p=0.001). In multivariate analysis, it was observed that eGFR and hs-CRP were independent determinants of plasma resistin level.

Conclusion The main determinants of resistin level in patients with T2DM are the level of renal function and inflammation rather than presence of microvascular complications, obesity and insulin resistance.

Chronic renal disease - complication - diabetes mellitus - resistin

• References

• 1 Steppan CM, Bailey ST, Bhat S. et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312
• 2 Savage DB, Sewter CP, Klenk ES. et al. Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001; 50: 2199-2202
• 3 McTernan CL, McTernan PG, Harte AL. et al. Resistin, central obesity, and type 2 diabetes. Lancet 2002; 359: 46-47
• 4 Patel L, Buckels AC, Kinghorn IJ. et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 2003; 300: 472-476
• 5 Verma S, Li SH, Wang CH. et al. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 2003; 108: 736-740
• 6 Kunnari A, Ukkola O, Paivansalo M. et al. High plasma resistin level is associated with enhanced highly sensitive C-reactive protein and leukocytes. J Clin Endocrinol Metab 2006; 91: 2755-2760
• 7 Kielstein JT, Becker B, Graf S. et al. Increased resistin blood levels are not associated with insulin resistance in patients with renal disease. Am J Kidney Dis 2003; 42: 62-66
• 8 Filippidis G, Liakopoulos V, Mertens PR. et al. Resistin serum levels are increased but not correlated with insulin resistance in chronic hemodialysis patients. Blood Purif 2005; 23: 421-428
• 9 Axelsson J, Bergsten A, Qureshi AR. et al. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney Int 2006; 69: 596-604
• 10 Yaturu S, Reddy RD, Rains J. et al. Plasma and urine levels of resistin and adiponectin in chronic kidney disease. Cytokine 2007; 37: 1-5
• 11 Kawamura R, Doi Y, Osawa H. et al. Circulating resistin is increased with decreasing renal function in a general Japanese population: the Hisayama Study. Nephrol Dial Transplant 2010; 25: 3236-3240
• 12 Moreno LO, Salvemini L, Mendonca C. et al. Serum resistin and glomerular filtration rate in patients with type 2 diabetes. PLoS One 2015; 10: e0119529
• 13 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2012; 35 (Suppl. 01) S64-S71
• 14 Matthews DR, Hosker JP, Rudenski AS. et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
• 15 Levey AS, Bosch JP, Lewis JB. et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-470
• 16 Matsuda M, Kawasaki F, Yamada K. et al. Impact of adiposity and plasma adipocytokines on diabetic angiopathies in Japanese Type 2 diabetic subjects. Diabet Med 2004; 21: 881-888
• 17 Schäffler A, Büchler C, Müller-Ladner U. et al. Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus. Horm Metab Res 2004; 36: 702-707
• 18 Osawa H, Ochi M, Kato K. et al. Serum resistin is associated with the severity of microangiopathies in type 2 diabetes. Biochem Biophys Res Commun. 2007; 355: 342-346
• 19 Menzaghi C, Salvemini L, Fini G. et al. Serum resistin and kidney function: a family-based study in non-diabetic, untreated individuals. PLoS One 2012; 7: e38414
• 20 Lehrke M, Reilly MP, Millington SC. et al. An inflammatory cascade leading to hyperresistinemia in humans. PLoS Med 2004; 1: e45
• 21 Reilly MP, Lehrke M, Wolfe ML. et al. Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 2005; 111: 932-939
• 22 Shetty GK, Economides PA, Horton ES. et al. Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 2004; 27: 2450-2457
• 23 Konrad A, Lehrke M, Schachinger V. et al. Resistin is an inflammatory marker of inflammatory bowel disease in humans. Eur J Gastroenterol Hepatol 2007; 19: 1070-1074
• 24 Jain SH, Massaro JM, Hoffmann U. et al. Cross-sectional associations between abdominal and thoracic adipose tissue compartments and adiponectin and resistin in the Framingham Heart Study. Diabetes Care 2009; 32: 903-938
• 25 Azuma K, Katsukawa F, Oguchi S. et al. Correlation between serum resistin level and adiposity in obese individuals. Obes Res 2003; 11: 997-1001
• 26 Moschen AR, Molnar C, Wolf AM. et al. Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression. J Hepatol 2009; 51: 765-777
• 27 Lee JH, Chan JL, Yiannakouris N. et al. Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab 2003; 88: 4848-4856
• 28 Park HK, Ahima RS. Resistin in rodents and humans. Diabetes Metab J 2013; 37: 404-414