Published: 2018-12-26

Hypoadiponectinemia is associated with increased insulin resistance, dyslipidemia and presence of type 2 diabetes in non obese central Indian population

Anil B. Choudhury, Shankar M. Pawar, Purnima Dey Sarkar, Keerti Gopi


Background: Accumulating evidence suggests that adiponectin, a major adipocyte secretory protein, has insulin-sensitizing and anti-atherogenic properties and protects against later development of type 2 diabetes. We investigated the association of adiponectin with insulin resistance, blood lipids and type 2 diabetes in non obese central Indian population.

Methods: Anthropometric and biochemical parameters were measured in 149 (81 male and 68 female) newly diagnosed non obese type 2 diabetic patients and 157 (85 male and 72 female) age and body mass index (BMI) matched controls.

Results: Adiponectin level (p<0.0001) was significantly lower in the diabetic group than in non diabetic control. In an age, gender and BMI adjusted model, adiponectin level was significantly negatively correlated with waist circumference, waist to hip ratio, systolic blood pressure, fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) (p= 0.0034), HbA1C, total cholesterol, LDL-cholesterol, and triglycerides (p<0.0001) and positively correlated with HDL-cholesterol (p =0.0014) in non obese type 2 diabetic group. However, there was no significant correlation between adiponectin and glucose in this study. In stepwise linear regression analysis, adjusted for potential confounder, significant inverse association was observed between serum adiponectin level and HOMA-IR (p = 0.0001). In multivariate logistic regression model, adjusted for age, gender, BMI, waist circumference, and waist-hip ratio, lower adiponectin was independently associated with the presence of type 2 diabetes (p<0.0001).

Conclusions: Lower adiponectin levels in non obese type 2 diabetic patients were significantly related to the increased insulin resistance, dyslipidemia, and presence of type 2 diabetes, independently of overall and abdominal adiposity, thereby suggesting a direct link between adiponectin and carbohydrate and lipid metabolism in human.


Adiponectin, Dyslipidemia, HDL-cholesterol, Insulin resistance, Triglycerides, Type 2 diabetes

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Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103(2):137-49.

International Diabetes Federation. IDF Diabetic Atlas. 7th ed. Available at: Accessed 30 Aug 2016.

Mohan V, Rao GHR. Type 2 diabetes in South Asians. 1st ed. New Delhi: South Asian Society on Atherosclerosis and Thrombosis; 2007.

Singh S. The genetics of type 2 diabetes mellitus: A Review. J Sci Res. 2011;55:35-48.

Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab. 2009;5(3):150-9.

Kendall DM, Harmel AP. The metabolic syndrome, type 2 diabetes, and cardiovascular disease: understanding the role of insulin resistance. Am J Manag Care. 2002; 8(20):S635-53.

Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q produced exclusively in adipocytes. J Biol Chem. 1995; 270(45):26746-9.

Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript1). Biochem Biophys Res Commun. 1996;221(2):286-9.

Diwan AG, Kuvalekar AA, Dharamsi S, Vora AM, Nikam VA, Ghadge AA. Correlation of serum adiponectin and leptin levels in obesity and Type 2 diabetes mellitus. Indian J Endocrinol Metab. 2018;22(1):93-9.

Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000;20(6):1595-9.

Mohan V, Deepa R, Pradeepa R, Vimaleswaran KS, Mohan A, Velmurugan K, et al. Association of low adiponectin levels with the metabolic syndrome-the Chennai Urban Rural Epidemiology Study (CURES-4). Metabolism. 2005;54(4):476-81.

Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, et al. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type-2 diabetic subjects. Diabetes. 2002;51(10):2968-74.

Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al.Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8(7):731-7.

Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941-6.

Matsuda M, Shimomura I, Sata M, Arita Y, Nishida M, Maeda N, et al. Role of adiponectin in preventing vascular stenosis the missing link of adipo-vascular axis. J Biol Chem. 2002;277(40):37487-91.

Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001; 86(5):1930-5.

Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K, et al. Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin Sci (Lond). 2002;103(2):137-42.

Dibello JR, Baylin A, Viali S, Tuitele J, Bausserman L, McGarvey ST. Adiponectin and type 2 diabetes in Samoan adults. Am J Hum Biol. 2009;21(3):389-91.

Rao CR, Kamath VG, Shetty A, Kamath A. A cross-sectional analysis of obesity among a rural population in coastal southern Karnataka, India. Australas Med J. 2011;4(1):53-7.

Zargar AH, Khan AK, Masoodi SR, Laway BA, Wani AI, Bashir MI, et al. Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in the Kashmir Valley of the Indian subcontinent. Diabetes Res Clin Pract. 2000;47(2):135-46.

World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO Consultation. Part 1: diagnosis and classification of diabetes mellitus. Geneva, Switzerland: World Health Organization, 1999. Available at: /hq/1999/WHO_ NCD_NCS _ 99.2.pdf.

Misra A, Chowbey P, Makkar BM, Vikram NK, Wasir JS, Chadha D, et al. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India. 2009;57:163-70.

Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.

Bogan JS, Lodish HF. Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes defined by endogenous ACRP30 and GLUT4.J Cell Biol. 1999;146(3):609-20.

Smith U, Axelsen M, Carvalho E, EliassonB, Jansson PA, Wesslau C. Insulin signal-ing and action in fat cells: associations with insulin resistance and type 2 diabe-tes. Ann N Y Acad Sci. 1999;892:119-26.

Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during progression to type 2 diabetes in rhesus monkeys. Diabetes. 2001;50(5):1126-33.

Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami KI, Matsuda K, Yamaguchi M, Tanabe H, Kimura-Someya T, Shirouzu M, Ogata H. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature. 2013 Nov;503(7477):493.

Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes. 2002;51(7):2325-8.

Yaghootkar H, Lamina C, Scott RA, Dastani Z, Hivert MF, Warren LL, et al. Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes. Diabetes. 2013;62(10):3589-98.

Sharon K Davis, Samson Y Gebreab, Ruihua Xu, Pia Riestra, Rumana J Khan, Anne E Sumner, et al. Association of adiponectin with type 2 diabetes and hypertension in African American men and women: the Jackson Heart Study. BMC Cardiovasc Disord. 2015;15:13.

Yamamoto S, Matsushita Y, Nakagawa T, Hayashi T, Noda M, Mizoue T. Circulating adiponectin levels and risk of type 2 diabetes in the Japanese. Nutrition & diabetes. 2014 Aug;4(8):e130.

Renju VC, Santha K, Sethupathy S, Koshy M, Marichamy G, Kumaran NS. Serum Adiponectin and Fasting Insulin Levels in Patients with Type2 Diabetics. J Pharma Sci Res. 2012 Jul 1;4(7):1844.

Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, et al. Adiponectin stimulates glucose utilization and fatty acid oxidation by activating AMP activated protein kinase. Nat Med. 2002;8(11):1288-95.

Ceddia RB, Somwar R, Maida A, Fang X, Bikopoulos G, Sweeney G. Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia. 2005;48(1):132- 9.

Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia. 2003;46(4):459-69.

Narayan A, Kulkarni S, Kothari R, Deepak TS, Kempegowda P. Association between plasma adiponectin and risk of myocardial infarction in Asian Indian patient with diabetes. BJMP. 2014;7(4):a729.

Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002;277(29):25863-6.

Qiao L, Zou C, van der Westhuyzen DR, Shao J. Adiponectin reduces plasma triglyceride by increasing VLDL triglyceride catabolism. Diabetes. 2008;57(7):1824-33.

Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002;51(9):2734-41.