Treatment-Induced Changes in Plasma Adiponectin Do Not Reduce Urinary Albumin Excretion in the Diabetes Prevention Program Cohort

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Aug 28

PMID 26312480

Citations 1

Authors

Kieren J Mather

Qing Pan

William C Knowler

Tohru Funahashi

George A Bray

Richard Arakaki

Bonita Falkner

Kumar Sharma

Barry J Goldstein

Affiliations

Soon will be listed here.

Abstract

Background And Objectives: Molecular data suggests that adiponectin may directly regulate urinary albumin excretion. In the Diabetes Prevention Program (DPP) we measured adiponectin and albuminuria before and after intervention, and we previously reported increases in adiponectin with interventions. Here we have used the DPP dataset to test the hypothesis that treatment-related increases in adiponectin may reduce albuminuria in obesity.

Design, Setting, Participants And Methods: We evaluated cross-sectional correlations between plasma adiponectin and urinary albumin excretion at baseline, and the relationship of treatment-related changes in adiponectin and albuminuria. Baseline and follow-up urine albumin to creatinine ratios (ACR (albumin to creatinine ratio)) and plasma adiponectin concentration were available in 2553 subjects.

Results: Adjusting for age, sex and race/ethnicity, we observed a statistically significant but weak inverse relationship between adiponectin and ACR at baseline (conditional Spearman's rho = (-) 0.04, p = 0.04). Although DPP treatments significantly increased plasma adiponectin, there were no treatment effects on ACR and no differences in ACR across treatment groups. There was a weak direct (not inverse) association between change in adiponectin and change in albuminuria (adjusted Spearman's rho = (+) 0.04, p = 0.03).

Conclusions: In a large, well-characterized cohort of obese dysglycemic subjects we observed a weak inverse association between circulating adiponectin concentrations and urinary albumin excretion at baseline. Contrary to the hypothesized effect, treatment-related increases in plasma adiponectin were not associated with a reduction in ACR. The association of change in adiponectin with change in ACR should be assessed in populations with overt albuminuria before excluding a beneficial effect of increasing adiponectin to reduce ACR in obesity.

Citing Articles

Prevalence of microvascular and macrovascular disease in the Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) Study cohort.

Mather K, Bebu I, Baker C, Cohen R, Crandall J, Desouza C Diabetes Res Clin Pract. 2020; 165:108235.

PMID: 32450102 PMC: 7416515. DOI: 10.1016/j.diabres.2020.108235.

References

Miyazaki Y, Cersosimo E, Triplitt C, DeFronzo R . Rosiglitazone decreases albuminuria in type 2 diabetic patients. Kidney Int. 2007; 72(11):1367-73. DOI: 10.1038/sj.ki.5002516. View

Yokoyama H, Kannno S, Ishimura I, Node K . Miglitol increases the adiponectin level and decreases urinary albumin excretion in patients with type 2 diabetes mellitus. Metabolism. 2007; 56(11):1458-63. DOI: 10.1016/j.metabol.2007.06.010. View

Sharma K, RamachandraRao S, Qiu G, Usui H, Zhu Y, Dunn S . Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest. 2008; 118(5):1645-56. PMC: 2323186. DOI: 10.1172/JCI32691. View

Saraheimo M, Forsblom C, Thorn L, Waden J, Rosengard-Barlund M, Heikkila O . Serum adiponectin and progression of diabetic nephropathy in patients with type 1 diabetes. Diabetes Care. 2008; 31(6):1165-9. DOI: 10.2337/dc07-2306. View

Amin R, Frystyk J, Ong K, Dalton R, Flyvbjerg A, Dunger D . The development of microalbuminuria is associated with raised longitudinal adiponectin levels in female but not male adolescent patients with type 1 diabetes. Diabetologia. 2008; 51(9):1707-13. DOI: 10.1007/s00125-008-1081-1. View

Friedman A, Friedman A, Marrero D, Ma Y, Ackermann R, Narayan K . Value of urinary albumin-to-creatinine ratio as a predictor of type 2 diabetes in pre-diabetic individuals. Diabetes Care. 2008; 31(12):2344-8. PMC: 2584193. DOI: 10.2337/dc08-0148. View

Gui M, Hong J, Lu A, Chen Y, Shen W, Li X . High sensitive C-reactive protein, adiponectin, and urine albumin excretion rate in Chinese coronary artery disease patients with different glucose tolerance status. Chin Med J (Engl). 2009; 121(24):2509-16. View

. Changes in albumin excretion in the diabetes prevention program. Diabetes Care. 2009; 32(4):720-5. PMC: 2660489. DOI: 10.2337/dc08-1400. View

Levey A, Stevens L, Schmid C, Zhang Y, Castro 3rd A, Feldman H . A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150(9):604-12. PMC: 2763564. DOI: 10.7326/0003-4819-150-9-200905050-00006. View

10.

Stevens L, Schmid C, Zhang Y, Coresh J, Manzi J, Landis R . Development and validation of GFR-estimating equations using diabetes, transplant and weight. Nephrol Dial Transplant. 2009; 25(2):449-57. PMC: 2910328. DOI: 10.1093/ndt/gfp510. View

11.

Navaneethan S, Kelly K, Sabbagh F, Schauer P, Kirwan J, Kashyap S . Urinary albumin excretion, HMW adiponectin, and insulin sensitivity in type 2 diabetic patients undergoing bariatric surgery. Obes Surg. 2010; 20(3):308-15. PMC: 2891346. DOI: 10.1007/s11695-009-0026-1. View

12.

Menzaghi C, De Cosmo S, Copetti M, Salvemini L, De Bonis C, Mangiacotti D . Relationship between ADIPOQ gene, circulating high molecular weight adiponectin and albuminuria in individuals with normal kidney function: evidence from a family-based study. Diabetologia. 2011; 54(4):812-8. DOI: 10.1007/s00125-010-2037-9. View

13.

Kacso I, Lenghel A, Bondor C, Moldovan D, Rusu C, Nita C . Low plasma adiponectin levels predict increased urinary albumin/creatinine ratio in type 2 diabetes patients. Int Urol Nephrol. 2011; 44(4):1151-7. DOI: 10.1007/s11255-011-0064-1. View

14.

. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J Kidney Dis. 2012; 60(5):850-86. DOI: 10.1053/j.ajkd.2012.07.005. View

15.

Rutkowski J, Wang Z, Park A, Zhang J, Zhang D, Hu M . Adiponectin promotes functional recovery after podocyte ablation. J Am Soc Nephrol. 2013; 24(2):268-82. PMC: 3559480. DOI: 10.1681/ASN.2012040414. View

16.

Mills K, Hamm L, Alper A, Miller C, Hudaihed A, Balamuthusamy S . Circulating adipocytokines and chronic kidney disease. PLoS One. 2013; 8(10):e76902. PMC: 3792047. DOI: 10.1371/journal.pone.0076902. View

17.

Meyvis K, Verrijken A, Wouters K, Van Gaal L . Plasma adiponectin level is inversely correlated with albuminuria in overweight and obese nondiabetic individuals. Metabolism. 2013; 62(11):1570-6. DOI: 10.1016/j.metabol.2013.05.023. View

18.

Stepien M, Stepien A, Wlazel R, Paradowski M, Banach M, Rysz M . Obesity indices and adipokines in non-diabetic obese patients with early stages of chronic kidney disease. Med Sci Monit. 2013; 19:1063-72. PMC: 3852621. DOI: 10.12659/MSM.889390. View

19.

Yan M, Su B, Peng W, Li L, Li H, Zhuang J . Association of serum vaspin and adiponectin levels with renal function in patients with or without type 2 diabetes mellitus. J Diabetes Res. 2014; 2014:868732. PMC: 4123592. DOI: 10.1155/2014/868732. View

20.

Looker H, Krakoff J, Funahashi T, Matsuzawa Y, Tanaka S, Nelson R . Adiponectin concentrations are influenced by renal function and diabetes duration in Pima Indians with type 2 diabetes. J Clin Endocrinol Metab. 2004; 89(8):4010-7. DOI: 10.1210/jc.2003-031916. View