Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online April 24, 2007
Diabetes Care 30:1898-1900, 2007
DOI: 10.2337/dc06-2345
© 2007 by the American Diabetes Association
This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc06-2345v1
30/7/1898    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sibley, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sibley, S. D.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Cardiovascular and Metabolic Risk
Brief Report

Intra-Abdominal Fat and Elevated Urine Albumin Excretion in Men With Type 1 Diabetes

Shalamar D. Sibley, MD, MPH1, Ian H. de Boer, MD, MS2, Michael W. Steffes, MD, PHD1, John D. Brunzell, MD2 the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Research Study Group

1 Department of Endocrinology and Diabetes, University of Minnesota, Minneapolis, Minnesota
2 School of Medicine, University of Washington, Seattle, Washington

Address correspondence and reprint requests to Shalamar D. Sibley, Endocrinology and Diabetes, University of Minnesota, Mayo Medical Code 101, 420 Delaware St. SE, Minneapolis, MN 55455. E-mail: sible004{at}umn.edu

Abbreviations: ACR, albumin-to-creatinine ratio • IAF, intra-abdominal fat • SQF, abdominal subcutaneous fat • WHR, waist-to-hip ratio


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 
Earlier studies documented associations between central obesity and elevated albumin excretion rate or other renal injury indicators in nondiabetic subjects (1–11). A retrospective study conducted in a Kaiser Permanente mixed diabetic-nondiabetic cohort suggested that obesity increased risk for progression to end-stage renal disease (12). Studies also identified obesity as a risk factor for renal disease in type 1 diabetes (13,14). We previously examined obesity-related factors and albumin excretion within the total Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Conducted between 1982 and 1993, the DCCT included 1,441 subjects with type 1 diabetes randomized to intensive or conventional diabetes treatment and followed for 6.5 years on average. Details of resources utilized for the DCCT/EDIC (observational follow-up) study designs were previously published (15–18). These studies demonstrate the powerful effect of intensive insulin therapy on preventing and slowing progression of micro- and macrovascular complications and established intensive therapy as the current standard of diabetes care for patients with type 1 diabetes. However, type 1 diabetic subjects, like the general population, are becoming heavier and more at risk for obesity-related complications (19). In our cross-sectional analysis 4 years after the end of the DCCT, waist-to-hip ratio (WHR), a visceral fat surrogate, was associated with elevated albumin excretion (20). In our longitudinal analysis, waist circumference was associated with subsequent development of persistent microalbuminuria (21). For this current analysis, we hypothesized that intra-abdominal fat (IAF) in particular relates more strongly to elevated albumin excretion than abdominal subcutaneous fat (SQF).


   RESEARCH DESIGN AND METHODS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
RESULTS--
 CONCLUSIONS--
 References
 
We analyzed IAF and other obesity measures in relation to urine albumin excretion in a group of men with type 1 diabetes. This study included DCCT/EDIC study participants (n = 64 men) at four participating DCCT/EDIC sites. Subjects were studied at the University of Washington (n = 32) between November 1997 and November 1999 and at the University of Minnesota (n = 32) between November 2001 and November 2003. Subjects studied at the University of Minnesota were recruited from three Minnesota DCCT/EDIC sites: the University of Minnesota (n = 20), International Diabetes Center (n = 11), and Mayo Clinic (n = 1). This analysis was restricted to men because only one woman had an elevated albumin-to-creatinine ratio (ACR). Written informed consent was obtained; the study was approved by the respective institutional review boards.

Single-slice umbilical abdominal computed tomography scans for IAF and SQF were read by one trained technician at each center, each blinded to the case/control status of study participants, utilizing well-validated software and analysis techniques (22–24). Urine was collected from second-morning voids (the mean of two different-day samples when possible). Participants with symptoms and urinary findings consistent with urinary tract infection were excluded. Urinary creatinine and microalbumin were measured at the Core DCCT/EDIC Laboratory, University of Minnesota (15). Elevated urine ACR was defined as ≥30 mg/g creatinine. A1C, history, and anthropometric measurements were assessed annually at DCCT/EDIC visits with standardized forms (25,26). Measures of obesity were compared using a two-sample t test, assuming unequal variance. Logistic regression was used to estimate the associations of obesity measurements with ACR status, with and without adjustment for potential confounders. STATA software (version 8.1; Stata, College Station, TX) was utilized for statistical analyses (27).


   RESULTS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
CONCLUSIONS--
 References
 
Of 64 men, 9 had elevated urine ACR ≥30 mg/g (6 had microalbuminuria [ACR 30–300 mg/g], and 3 had clinical albuminuria). Compared with men with normal ACR, men with ACR ≥30 mg/g were more likely to have received conventional insulin therapy during the DCCT, smoke, use ACE inhibitors, and have greater blood pressures, greater A1C, and dyslipidemia (higher LDL cholesterol [P = 0.001] and triglyceride [P = 0.002]).

IAF was greater in men with elevated ACR compared with men with normal ACR (P = 0.048); SQF was not (Table 1). Waist circumference (P = 0.048) and WHR (P = 0.006) were greater in men with elevated ACR, and BMI showed a similar trend (P = 0.077).


View this table:
[in this window]
[in a new window]

  		Table 1— Comparison (t test) and regression analyses of obesity measures in relation to urine ACR

 
In logistic regression, elevated ACR was associated (P < 0.05) with greater levels of each obesity measure, except SQF (Table 1). When IAF and SQF were included as dependent variables simultaneously, magnitude of association for IAF did not change (ß = 0.98 vs. ß = 0.99) and retained statistical significance (P = 0.035), and SQF was not associated with elevated ACR (ß = 0.02, P = 0.965). After adjustment for age, A1C, and smoking status, magnitudes of association with elevated ACR were similar for IAF, BMI, waist circumference, and WHR, with the association for BMI strongest (ß = 1.28). Diabetes duration and DCCT treatment group status were not related to obesity measures or ACR status and did not lead to meaningful changes in the associations of obesity measures with ACR status in the full models (data not shown).


   CONCLUSIONS—
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
References
 
In this study, we find urine ACR more strongly associated with IAF than with SQF in middle-aged males with type 1 diabetes, suggesting that metabolic factors associated with visceral rather than subcutaneous adiposity may contribute to renal injury in this population.

There are some limitations to this cross-sectional study, conducted in a small group of people. On its own, it cannot demonstrate causality. However, our prior study in this population suggested causality by demonstrating temporality between obesity and abnormal albumin excretion. Only men were analyzed; we cannot necessarily generalize these findings to women. However, our prior studies (20,21) in this population suggest that the association between central obesity and elevated albumin excretion is at least as strong in women as in men. Given sex-related anthropometric measurement differences, however, specific strengths of associations between particular obesity measures and ACR may differ somewhat in women.

In summary, this study utilizes accurate assessments of adipose distribution in a small group of individuals, more firmly substantiating the conclusion from our earlier larger cross-sectional and longitudinal epidemiologic studies (20,21) that IAF is a more important contributor to renal injury than SQF in men with type 1 diabetes. Additionally, we find that the easiest measurements to obtain in clinical settings, BMI and waist circumference, are each strong predictors of elevated ACR in these subjects. Future studies are needed to elucidate mechanisms underlying the IAF–albumin excretion link.


   Acknowledgments
 
This study was supported by the National Institutes of Health (NIH) Program Project DPPG DK-02456, NIH Clinical Research Training in Renal Diseases Fellowship (to S.D.S.), Minnesota Medical Foundation Faculty Research Grant 3055-9205 (S.D.S.), the NIH K23 Mentored Patient-Oriented Career Development Award (DK-59445 to S.D.S.), NIH Grant DK007247 (to I.D.B.), NIH K30 Grant RR-022293 (to I.D.B.), the University of Washington General Clinical Research Center (GCRC) (MO1-RR00037), and the University of Minnesota GCRC (MO1-RR00400).


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 24 April 2007. DOI: 10.2337/dc06-2345.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

Received for publication November 15, 2006. Accepted for publication April 11, 2007.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS--
 RESULTS--
 CONCLUSIONS--
 References
 

  1. Lokkegaard N, Haupter I, Kristensen TB: Microalbuminuria in obesity. Scand J Urol Nephrol 26:275–278, 1992[Medline]
  2. Metcalf PA, Scragg RK, Dryson E: Associations between body morphology and microalbuminuria in healthy middle-aged European, Maori, and Pacific Island New Zealanders. Int J Obes Relat Metab Disord 21:203–210, 1997[Medline]
  3. Reid M, Bennett F, Wilks R, Forrester T: Microalbuminuria, renal function, and waist:hip ratio in black hypertensive Jamaicans. J Hum Hypertens 12:221–227, 1998[Medline]
  4. Solerte SB, Fioravanti M, Pezza N, Locatelli M, Schifino N, Cerutti N, Severgnini S, Rondanelli M, Ferrari E: Hyperviscosity and microalbuminuria in central obesity: relevance to cardiovascular risk. Int J Obes Relat Metab Disord 21:417–423, 1997[Medline]
  5. Valensi P, Assayag M, Busby M, Paries L, Lormeau B, Attali JR: Microalbuminuria in obese patients with or without hypertension. Int J Obes Relat Metab Disord 20:574–579, 1996[Medline]
  6. Cirillo M, Senigalliesi L, Laurenzi M, Alfieri R, Stamler J, Stamler R, Panarelli W, De Santo NG: Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: the Gubbio Population Study. Arch Intern Med 158:1933–1939, 1998[Abstract/Free Full Text]
  7. Dingel DR, Goldberg A-P, Mayuga RS, Kairis GM, Weir MR: Insulin resistance, elevated glomerular filtration fraction, and renal injury. Hypertension 28:127–132, 1996[Abstract/Free Full Text]
  8. Ribstein J, du Cailar G, Mimran A: Combined renal effects of overweight and hypertension. Hypertension 26:610–615, 1995[Abstract/Free Full Text]
  9. Licata G, Scaglione R, Ganguzza A, Corrao S, Donatelli M, Parrinello G, Dichiara MA, Merlino G, Cecala MG: Central obesity and hypertension: relationship between fasting serum insulin, plasma renin activity, and diastolic blood pressure in young obese subjects. Am J Hypertens 7:314–320, 1994[Medline]
  10. Scaglione R, Ganguzza A, Corrao S, Parrinello G, Merlino G, Dichiara MA, Arnone S, D'Aubert MD: Central obesity and hypertension: pathophysiologic role of renal hemodynamics and function. Int J Obes Relat Metab Disord 19:403–409, 1995[Medline]
  11. Solerte SB, Rondanelli M, Giacchero R, Stabile M, Lovati E, Cravello L, Pontiggia B, Vignati G, Ferrari E, Fioravanti M: Serum glucagon concentration and hyperinsulinemia influence renal hemodynamics and urinary protein loss in normotensive patients with central obesity. Int J Obes Relat Metab Disord 23:997–1003, 1999[Medline]
  12. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS: Body mass index and risk for end-stage renal disease. Ann Intern Med 144:21–28, 2006[Abstract/Free Full Text]
  13. Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N: Factors associated with progression to macroalbuminuria in microalbuminuric type 1 diabetes patients: the EURODIAB Prospective Complications Study. Diabetologia 47:1020–1028, 2004[Medline]
  14. Stuhldreher WL, Becker DJ, Drash AL, Ellis D, Kuller LH, Wolfson SK, Orchard TJ: The association of waist/hip ratio with diabetes complications in an adult IDDM population. J Clin Epidemiol 47:447–456, 1994[Medline]
  15. DCCT Research Group: The Diabetes Control and Complications Trial (DCCT): design and methodologic considerations for the feasibility phase. Diabetes 35:530–545, 1986[Abstract]
  16. Department of Health and Human Services: The prevalence study. In The Lipid Research Clinics Population Studies Data Book. Vol. 1. Washington, DC, U.S. Govt. Printing Office, 1980, p. 1–115 (NIH publ. no. 80-1527)
  17. Metropolitan Life Insurance Company: Metropolitan height and weight tables. Stat Bull Metropolitan Life Insurance Co 64:2–9, 1983
  18. DCCT Research Group: Epidemiology of Diabetes Interventions and Complications: design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 22:99–111, 1999[Abstract/Free Full Text]
  19. Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD: Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT: Diabetes Control and Complications Trial. JAMA 280:140–146, 1998 [erratum in JAMA280:1484, 1998][Free Full Text]
  20. Sibley SD, Thomas W, de Boer I, Brunzell JD, Steffes MW: Gender and elevated albumin excretion in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort: role of central obesity. Am J Kidney Dis 47:223–232, 2006[Medline]
  21. de Boer IH, Sibley SD, Kestenbaum B, Sampson JN, Young B, Cleary PA, Steffes MW, Weiss NS, Brunzell JD, the DCCT/EDIC Research Group: Central obesity, incident microalbuminuria, and change in creatinine clearance in the Epidemiology of Diabetes Interventions and Complications Study. J Am Soc Nephrol 18:235–243, 2007[Abstract/Free Full Text]
  22. Fujimoto WY, Abbate SL, Kahn SE, Hokanson JE, Brunzell JD: The visceral adiposity syndrome in Japanese-American men. Obesity Research 2:364–371, 1994[Medline]
  23. Shuman WP, Morris LL, Leonetti DL, Wahl PW, Moceri VM, Moss AA, Fujimoto WY: Abnormal body fat distribution detected by computed tomography in diabetic men. Invest Radiol 21:483–487, 1986[Medline]
  24. Potretzke AM, Schmitz KH, Jensen MD: Preventing overestimation of pixels in computed tomography assessment of visceral fat. Obes Res 12:1698–1701, 2004[Medline]
  25. Molitch ME, Steffes M, Cleary PA, Nathan DM: Baseline analysis of renal function in the Diabetes Control and Complications Trial. Kidney Int 43:668–674, 1993[Medline]
  26. DCCT Research Group: Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial. Kidney Int 47:1703–1720, 1995[Medline]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?



This Article
Right arrow Extract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dc06-2345v1
30/7/1898    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sibley, S. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sibley, S. D.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum