Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study.
BACKGROUND
Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to provide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity.


METHODS
In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables.


RESULTS
The AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IRAR index for insulin resistance assessment were between 3.538 and 3.955.


CONCLUSIONS
The novel AR and IRAR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS.
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. lauciahin_4275@yahoo.com
Cia-Hin
CH
Lau
Sekaran
S
Muniandy
D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008296:Malaysia; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D052243:Resistin / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D055105:Waist Circumference; D049629:Waist-Hip Ratio
D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D008055:Lipids; D052243:Resistin; C499918:ADIPOQ protein, human; C499624:RETN protein, human; C517652:hemoglobin A1c protein, human
Ann Saudi Med. 2010 Jul-Aug;30(4):257-64
20622341
Lancet. 2005 Sep 24-30;366(9491):1059-62
16182882
Diabetes. 2006 Jul;55(7):1985-94
16804067
Cardiovasc Diabetol. 2010 Jun 23;9:26
20573249
FEBS Lett. 2007 Oct 16;581(25):4877-83
17889853
Diabetes Metab Res Rev. 2008 Jan-Feb;24(1):52-8
17657721
Obesity (Silver Spring). 2009 Apr;17(4):737-44
19165155
Cardiovasc Diabetol. 2010 Sep 13;9:50
20836881
Diabetologia. 2009 Jun;52(6):1061-74
19296077
Diabetologia. 2011 Apr;54(4):900-9
21181395
Diabetes Care. 2008 Jan;31 Suppl 1:S55-60
18165338
Diabetes Obes Metab. 2008 May;10(5):367-75
17645557
Diabetes. 2010 Jun;59(6):1349-57
20299466
J Hum Hypertens. 2011 Jan;25(1):38-46
20200551
Ann Hum Genet. 2010 Nov;74(6):471-8
20849430
J Obes. 2011;2011:
20871823
Curr Opin Pharmacol. 2010 Dec;10(6):676-83
20810317
Diabetes Technol Ther. 2010 May;12(5):393-8
20388049
Endocr J. 2008 Jul;55(3):549-56
18480556
Mini Rev Med Chem. 2010 Aug;10(9):856-69
20482500
J Clin Endocrinol Metab. 2006 Jul;91(7):2792-5
16670163
Med Sci Monit. 2011 Jan;17(1):CR26-32
21169907
Horm Metab Res. 2010 Aug;42(9):663-9
20560108
Clin Pharmacol Ther. 2009 Dec;86(6):592-5
19915603
Biomed Environ Sci. 2010 Feb;23(1):53-61
20486437
Biochem Biophys Res Commun. 2010 Aug 6;398(4):723-9
20621060
Int J Cardiol. 2010 Apr 1;140(1):73-81
19059660
Diabetes Res Clin Pract. 2011 Feb;91(2):239-45
21146882
Diabetes Res Clin Pract. 2007 Jul;77(1):151-4
17081646
J Atheroscler Thromb. 2010 Oct 27;17(10):1063-9
20702974
Arterioscler Thromb Vasc Biol. 2011 Apr;31(4):944-9
21212400
Metabolism. 2010 Mar;59(3):333-7
19796779
Mol Genet Metab. 2005 May;85(1):61-9
15862282
Horm Metab Res. 2010 Apr;42(4):247-53
20091459
Nat Genet. 2010 Feb;42(2):105-16
20081858
J Endocrinol Invest. 2010 Sep;33(8):514-8
20142631
Zhonghua Nei Ke Za Zhi. 2010 Jun;49(6):484-7
20979734
Obesity (Silver Spring). 2010 Sep;18(9):1781-7
20379148
Am J Cardiol. 2008 Apr 1;101(7):980-5
18359318
JAMA. 2009 Jul 8;302(2):179-88
19584347
Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1863-8
12947017
Physiol Res. 2011;60(1):139-48
20945960
Arch Dermatol Res. 2011 Aug;303(6):381-8
21170539
Heredity (Edinb). 2008 Jul;101(1):60-6
18446183
Diabetes Care. 2010 Apr;33(4):908-13
20067957
Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):624-30
16357312
Cardiovasc Diabetol. 2006 May 02;5:10
16669997
Results Probl Cell Differ. 2010;52:189-201
20865382
Metabolism. 2005 Mar;54(3):314-20
15736108
Diabetes. 2007 Mar;56(3):890-6
17327462
J Clin Hypertens (Greenwich). 2009 Feb;11(2):61-5
19222669
J Atheroscler Thromb. 2008 Apr;15(2):87-93
18385536
Atherosclerosis. 2010 Feb;208(2):412-20
20018283
Int J Biochem Cell Biol. 2010 Jun;42(6):785-8
20044026
Science. 2004 May 21;304(5674):1154-8
15155948
Nat Genet. 2010 Jul;42(7):579-89
20581827
Atherosclerosis. 2011 Jan;214(1):144-7
21075373
Nat Med. 2002 Nov;8(11):1288-95
12368907
J Hum Hypertens. 2007 Sep;21(9):709-16
17443211
Diabetes Res Clin Pract. 2010 Jan;87(1):4-14
19896746
Obesity (Silver Spring). 2008 Jul;16(7):1596-601
18421265
Diabetes Care. 2009 Feb;32(2):329-34
18957529
Diabet Med. 1998 Jul;15(7):539-53
9686693
Eur J Obstet Gynecol Reprod Biol. 2011 Jan;154(1):51-6
20889251
Hypertens Res. 2011 Jan;34(1):145-51
21107327
Mol Cell Endocrinol. 2011 Jan 30;332(1-2):261-70
21070834
Obes Res Clin Pract. 2009 May;3(2):I-II
24345560
Eur J Hum Genet. 2005 Oct;13(10):1143-53
16015283
Diabetes. 2005 Jul;54(7):1914-25
15983190
Circ Cardiovasc Genet. 2010 Oct;3(5):475-83
20923989
Diabetologia. 2010 Feb;53(2):234-46
19727657
Trends Endocrinol Metab. 2006 Jul;17(5):205-15
16766204
Int J Endocrinol. 2010;2010:515136
21113299
Mol Cell Endocrinol. 2010 Mar 25;316(2):129-39
19723556
Obesity (Silver Spring). 2008 Feb;16(2):241-56
18239630
Am J Clin Nutr. 2010 Jan;91(1):258S-261S
19906806
Obesity (Silver Spring). 2009 Jun;17(6):1189-95
19247279
J Clin Invest. 1997 Sep 1;100(5):1166-73
9303923
J Card Fail. 2011 Jan;17(1):24-30
21187261