help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1815
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
92/5/1886    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gavi, S.
Right arrow Articles by McNurlan, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gavi, S.
Right arrow Articles by McNurlan, M. A.
Related Collections
Right arrow Diabetes and Insulin
Right arrow Metabolism
The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 5 1886-1890
Copyright © 2007 by The Endocrine Society

Retinol-Binding Protein 4 Is Associated with Insulin Resistance and Body Fat Distribution in Nonobese Subjects without Type 2 Diabetes

Shai Gavi, Louise M. Stuart, Patricia Kelly, Mark M. Melendez, Dennis C. Mynarcik, Marie C. Gelato and Margaret A. McNurlan

Departments of Medicine (S.G., L.M.S., P.K., D.C.M., M.C.G.) and Surgery (M.M.M., M.A.M.), State University of New York at Stony Brook, Stony Brook, New York 11794

Address all correspondence and requests for reprints to: Shai Gavi, Department of Medicine, Division of General Medicine and Geriatrics, School of Medicine, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, New York 11794-8154. E-mail: sgavi{at}notes.cc.sunysb.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Background: Adipose tissue is responsible for releasing various adipokines that have been related to insulin resistance. Understanding the relationship of these adipokines to insulin resistance may foster the development of new treatments for diabetes.

Objectives: The primary objective of this study was to determine whether an association between retinol-binding protein 4 (RBP4) and insulin resistance exists in nonobese individuals without a family history or diagnosis of diabetes. The secondary objective was to determine by a dual energy x-ray absorptiometry scan which adipose tissue depot most closely relates to RBP4 levels.

Design: Cross-sectional analysis of 92 study participants ranging in age from 20 to 83 yr was performed. The range of body mass index (BMI) was from 18 to 30 kg/m2. Exclusion criteria were a BMI greater than 30 kg/m2, family history of diabetes, or a diagnosis of diabetes. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp. Body fat was measured by dual energy x-ray absorptiometry scan.

Results: RBP4 values were lower in females (35.8 ± 1.7 µg/ml) compared with males (39.9 ± 1.4 µg/ml; P = 0.06). RBP4 levels were found to correlate negatively with insulin sensitivity (r = –0.32; P = 0.002) and positively with age (r = 0.38; P < 0.001). RBP4 levels did not correlate with BMI (r = –0.13; P = 0.22), trunk fat (r = 0.16; P = 0.22), or percent body fat (r = 0.07; P = 0.65). However, RBP4 levels did correlate with percent trunk fat (r = 0.36; P = 0.001).

Conclusion: These findings indicate a relationship between RBP4, insulin sensitivity, and percent trunk fat in individuals who may not have features of insulin resistance.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
INSULIN RESISTANCE IS an early and strong determinant of type 2 diabetes (1, 2). Obesity is a major cause of insulin resistance; however, its exact mechanism is still undergoing investigation (3, 4). Adipose tissue has been demonstrated to secrete various adipokines that relate to insulin resistance (5). Such adipokines include adiponectin, leptin, and, recently, retinol-binding protein 4 (RBP4) (5, 6, 7, 8, 9, 10). Recent work has identified a relationship of RBP4 to insulin resistance (10, 11, 12). This was predominantly in a heterogeneous group composed of young lean controls, obese individuals, and individuals with type 2 diabetes (11, 12). A correlation was also identified in a small group of adult subjects with a family history of diabetes and in subjects with impaired glucose tolerance (11, 12). In adipose tissue from lean, overweight, and obese menopausal women, RBP4 mRNA was closely associated with glucose transporter 4 mRNA levels (13). However, whether a relationship between RBP4 and insulin resistance exists in nonobese individuals without a family history of type 2 diabetes or a known diagnosis of type 2 diabetes is unknown.

Increasing abdominal fat is a main predictor of insulin resistance (14, 15, 16). In a group of subjects with a range of body mass index (BMI) from lean to obese, RBP4 levels correlated with waist-to-hip ratios, suggesting a linkage to abdominal adiposity (12). However, waist-to-hip ratios are also affected by muscle mass and do not provide a quantitative measure of adipose tissue content (12, 17, 18). A relationship of RBP4 to the body fat distribution between the limbs and trunk with a dual energy x-ray absorptiometry (DEXA) scan, exclusively in nonobese subjects, has not been reported. The current study evaluates the relationship of RBP4 to insulin resistance by hyperinsulinemic euglycemic clamp in nonobese, young, and elderly subjects, without a family history or a diagnosis of diabetes. A greater understanding of an association of insulin resistance with RBP4 levels may reveal a marker of insulin resistance in individuals who are not obese before the development of diabetes. In addition, this work evaluates the relationship of RBP4 to body fat distribution between the limbs and trunk as measured by a DEXA scan. Identifying an association of RBP4 with body fat distribution between the limbs and trunk will provide insight as to which fat depots may be responsible for the elevated RBP4 and insulin resistance. This may especially be true in nonobese subjects who may have a body fat distribution between the limb and trunk that is difficult to appreciate clinically or may have waist-to-hip ratios that may not be significantly high.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

All subjects who participated in this study were approved by the Committee on Research Involving Human Subjects at the University Medical Center of the State University of New York at Stony Brook. All subjects gave their written informed consent. Younger subjects were included in the study if they were between 20 and 50 yr of age. Elderly subjects were 60 yr of age or older, healthy, and ambulatory. Exclusion criteria included an acute illness 3 months before enrollment, diagnosis of diabetes, family history of diabetes, any medications that would affect insulin resistance, or fasting glucose level equal to or greater than 126 mg/dl.

Insulin sensitivity

Insulin sensitivity was determined as the rate of infused glucose necessary to maintain euglycemia during infusion of insulin (assessed by a hyperinsulinemic euglycemic clamp) (19). Subjects were admitted to the General Clinical Research Center the night before the study, ate a uniform snack at 2200 h, and then fasted from 2400 h. At 0700 h, after basal sampling, the subjects were infused with 1.2 µU of human insulin/(kg body weight x min) (human insulin from Eli Lilly and Co., Indianapolis, IN) to elevate plasma insulin levels sufficient to suppress hepatic glucose production in insulin-resistant states. Dextrose (10%) was administered iv at variable rates to maintain the plasma level at 90 mg/dl. Plasma glucose levels were assessed in arterialized blood samples obtained by the heated hand technique. Insulin sensitivity was determined between the second and third hour of insulin infusion. To normalize for differences in body composition, insulin sensitivity was expressed as milligrams of glucose per kilogram of lean body mass (LBM). LBM was quantified by a DEXA scan.

Body composition

Body composition, including LBM and total body fat, was determined by a DEXA scan performed with a whole-body scanner (Hologic, Bedford, MA) (20). Trunk fat was the amount of fat measured by the DEXA from below the neck to the pelvis, excluding the limbs. Percent trunk fat was calculated as trunk fat divided by total body fat (total body fat includes limb fat and trunk fat).

Biochemical analysis

Plasma glucose levels were determined by the glucose oxidase method, using a Beckman Glucose Analyzer II (Beckman Coulter, Brea, CA). Serum RBP4 levels were measured by a human ELISA kit (ALPCO Diagnostics, Salem, NH) (12). The coefficient of variation within each assay was less than 5%. The coefficient of variation between assays was less than 10%.

Statistical analysis

All data are presented as mean ± SEM. Differences between groups were analyzed with the Student’s t test. Pearson correlations were used to assess bivariate associations, and multiple regression modeling was used to assess multivariate associations and to identify factors predictive of RBP4 and insulin resistance, body fat distribution, and age. Differences were considered significant if P < 0.05. All analysis was performed using SPSS version 13.0 (SPSS Inc., Chicago, IL) and SAS version 9.1 (SAS Institute Inc., Cary, NC).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Table 1Go represents the characteristics of the subjects in this study. Subjects included 59 males and 33 females. The age range for the young adults was 20 to 50 yr, and the age range for the elderly was 60 to 83 yr. The study subjects were nonobese (BMI range, 18 to 30 kg/m2). Subjects did not previously have diabetes diagnosed, and the concentration of fasting glucose ranged from 71 to 125 mg/dl. The subjects did not have first-degree relatives with diabetes. RBP4 levels ranged from 19.7 to 68.0 µg/ml. This range is similar to the range previously reported for young adult subjects with normal glucose tolerance (14.0–33.9 µg/ml). Females were found to have lower RBP4 values (35.8 ± 1.7 µg/ml) compared with males (39.9 ± 1.4 µg/ml; P = 0.06). Females were more insulin-sensitive (11.3 ± 0.6 mg/kg LBM·min) than males (8.4 ± 0.4 mg/kg LBM·min; P < 0.001). In the whole group, RBP4 levels were found to correlate negatively with insulin sensitivity (r = –0.32; P = 0.002) (Fig. 1Go). Multivariate regression analysis revealed the absence of an association between RBP4 and insulin sensitivity, when adjusted for body fat distribution and age (ß = –0.005; P = 0.22; r2 = 0.24).


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

  		TABLE 1. Characteristics of subjects

 

Figure 1
View larger version (12K):
[in this window]
[in a new window]

  		FIG. 1. Correlation of RBP4 and insulin sensitivity in young and elderly nonobese subjects without a family history or diagnosis of type 2 diabetes. Insulin sensitivity was assessed by the rate of glucose infusion required to maintain euglycemia during the period of 120 to 180 min of insulin infusion.

 
Age is an independent risk factor for insulin resistance. Therefore, we evaluated the interaction of RBP4 levels and age. Elderly subjects and young subjects had similar BMIs (26.0 ± 0.4 kg/m2 vs. 25.0 ± 0.4 kg/m2; P = 0.07). As expected, elderly subjects were more insulin-resistant (8.6 ± 0.4 mg/kg LBM·min) than young subjects (10.3 ± 0.5 mg/kg LBM·min; P = 0.009) (Fig. 2AGo). In addition, RBP4 levels were higher in the elderly (42.0 ± 1.7 µg/ml) compared with young subjects (34.9 ± 1.2 µg/ml; P < 0.001) (Fig. 2BGo). RBP4 levels were highly correlated to age (r = 0.38; P < 0.001). Multivariate regression analysis revealed that the relationship between RBP4 and age was independent of body fat distribution and insulin sensitivity (ß = 0.002; P = 0.004).


Figure 2
View larger version (9K):
[in this window]
[in a new window]

  		FIG. 2. A, Insulin sensitivity in nonobese young and elderly subjects. Insulin sensitivity was assessed by the rate of glucose infusion required to maintain euglycemia during the period of 120 to 180 min of insulin infusion. The data are mean values ± SEM. *, P ≤ 0.05 for the difference of RBP4 between young and elderly. B, RBP4 levels in nonobese young and elderly subjects. The data are mean values ± SEM. *, P ≤ 0.05 for the difference of RBP4 between young and elderly.

 
Previous work has identified a relationship of RBP4 to BMI in a group of lean and obese subjects. In contrast, our nonobese subjects’ RBP4 levels did not correlate to BMI (r = –0.13; P = 0.22) (Fig. 3Go). A relationship between RBP4 and waist-to-hip ratio has been identified in previous work, suggesting an association between RBP4 levels and abdominal obesity. Our trunk fat measurements from DEXA scans revealed that RBP4 levels did correlate with percent trunk fat (r = 0.36; P = 0.001) (Fig. 4Go); however, RBP4 levels did not correlate with the absolute amount of trunk fat (r = 0.16; P = 0.22), total body fat (r = 0.05; P = 0.64), or percent body fat (r = 0.07; P = 0.65). Percent trunk fat was also highly correlated to insulin sensitivity (r = 0.48; P < 0.001). Multivariate regression analysis revealed a nonstatistically significant trend of an association between RBP4 and percent trunk fat after adjusting for age and insulin sensitivity (ß = 0.30; P = 0.08)


Figure 3
View larger version (12K):
[in this window]
[in a new window]

  		FIG. 3. Correlation of RBP4 and BMI in nonobese subjects.

 

Figure 4
View larger version (12K):
[in this window]
[in a new window]

  		FIG. 4. Correlation of RBP4 and percent trunk fat. Percent trunk fat is calculated as the trunk fat divided by the total body fat. The trunk fat and total body fat were quantified using DEXA scan.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Until recently, RBP4 was considered to be solely a carrier protein for retinol (21). Its purpose was to prevent retinol from being excreted by the kidney (21). However, recent work has demonstrated an association between RBP4 levels and insulin sensitivity in a mixed group consisting of lean and obese, nondiabetic subjects, and type 2 diabetic subjects (11, 12, 22). Also, a correlation was identified in 26 males with a family history of type 2 diabetes (12). However, whether an association exists between RBP4 levels and insulin sensitivity in a group of male and female subjects, with a wide age range, and no family history of type 2 diabetes is not known. In the present study, we show, for the first time, that RBP4 levels are correlated with insulin sensitivity in 92 nondiabetic subjects with a BMI range of 18–30 kg/m2 and age range of 20–83 yr. These results indicate that RBP4 is associated with insulin resistance in individuals who are not obese and no family history of diabetes, or a diagnosis of diabetes. Furthermore, these results indicate that in this group of subjects without strong risk factors for diabetes such as obesity or family history, RBP4 may be used as an index of insulin sensitivity, where currently there are no accurate markers. However, the relationship between RBP4 and insulin sensitivity is nonsignificant when adjusting for body fat distribution and age. Interestingly, our RBP4 levels ranged from 19.7–68.0 µg/ml. This range is similar to the range previously reported for normal glucose tolerance controls (14.0–33.9), but overlaps with individuals with impaired glucose tolerance (28.9–149.0) and type 2 diabetes (29.6–129.1) (12). This may mean that RBP4 levels are associated with diabetes, but one can have diabetes with low levels of RBP4 while others can have higher levels of RBP4 without frank diabetes.

It is known that age is a strong risk factor for the development of insulin resistance and diabetes, such that 50% of the elderly have insulin resistance or type 2 diabetes (23, 24). The expanding incidence of diabetes is compounded by the rapidly expanding elderly population (23, 24). Identifying new therapeutic targets in the elderly is essential; lowering RBP4 may be a new target for treating insulin resistance and diabetes (10, 12). Previous work has not evaluated the role of RBP4 in elderly, but the current study indicates that serum RBP4 levels are associated with age and are elevated in the elderly compared with young adults (12). However, the association between RBP4 and aging does not ensure that RBP4 directly causes insulin resistance in aging. This may indicate that future therapies targeted at reducing RBP4 levels in the young may improve insulin resistance in the elderly as well (10, 12).

RBP4 is secreted by adipocytes (10). A previous study revealed a correlation of RBP4 to waist-to-hip ratio, suggesting an association between RBP4 levels and abdominal adiposity; however, there was no correlation between RBP4 levels and percent body fat (11, 12). The relationship of RBP4 to abdominal adiposity was established in subjects with a range of BMI from lean to severe obesity. A correlation in those subjects was also found between RBP4 levels and BMI (12). A subsequent study similarly identified a relationship between RBP4 levels and waist circumference, but no association to percent body fat or absolute amount of fat (11). In our study, DEXA scans were used to define body fat distribution of the limbs and trunk. DEXA scans have been validated by computed tomography and magnetic resonance imaging as a tool to assess body composition (25). In our population with an upper limit of BMI of 30 kg/m2, we did not find a correlation of RBP4 levels and BMI. Interestingly, we also did not find an association between either the total amount of trunk fat or the total amount of body fat and RBP4 levels. These results indicate that RBP4 may not uniformly be secreted from all adipose tissues, because total body fat did not correlate to RBP4 levels. More so, RBP4 is not predominantly secreted by the trunk fat, because trunk fat did not correlate to RBP4. However, we did find a correlation between RBP4 levels and percent trunk fat. The correlation of RBP4 levels to percent trunk fat suggests that RBP4 relates to the distribution of body fat between the central (trunk) and peripheral fat (limb) depots, rather than an association of RBP4 to the total fat (total body fat or percent body fat). These findings also suggest that interventions that affect the distribution of adipose tissue from the central depot to the periphery may have a greater impact on reducing RBP4 levels, than overall reduction of body fat (central and peripheral).

Interestingly, a recent study of lean and obese women did not find a difference in RBP4 levels (13). This may be due to the narrow range of insulin sensitivity between the lean and obese subjects, which may have impacted the ability to demonstrate a correlation with RBP4 levels (13). The narrow range of insulin sensitivity between the lean and obese subjects is also evident by the lack of statistical difference in the high-density lipoprotein and triglyceride values (13).

A limitation of this study is that the DEXA scan measures trunk fat and does not discriminate between visceral and sc adipose tissue in this region. Therefore, we can conclude that RBP4 levels correlate with percent trunk fat, but we cannot discern whether the RBP4 is related to visceral or sc abdominal adipose tissue. This will require future evaluations via computed tomography imaging.

In summary, we report for the first time an association between RBP4 levels and insulin sensitivity in nonobese subjects without a family history or diagnosis of diabetes. However, adjustment for body fat distribution and age results in a nonsignificant association between RBP4 levels and insulin sensitivity. In addition, we show that RBP4 levels are higher in the elderly, who are also more insulin resistant. Last, we identify that RBP4 levels correlate more strongly to the distribution of adipose tissue between the central and peripheral fat depots (expressed as percent trunk fat), rather than to the total body fat (total body fat or percent body fat).


   Acknowledgments
 
The authors thank Joyce Quick for her clinical assistance on the General Clinical Research Center, Jeanne Kidd for her help in coordinating this research, and the nursing and core laboratory staff of the General Clinical Research Center for their assistance.


   Footnotes
 
This work was supported by National Institutes of Health (NIH) Grant R01 AG17446-01A2 (to M.A.M.); NIH General Clinical Research Center Grant M01 RR10710-02; the Clinical Research Scholar Program, Center for Translational Research, School of Medicine, Health Sciences Center, State University of New York at Stony Brook (to S.G.); and the Empire Clinical Research Investigators Program (to M.M.M.).

Disclosure Summary: The authors have nothing to disclose.

First Published Online February 13, 2007

Abbreviations: BMI, Body mass index; DEXA, dual energy x-ray absorptiometry; LBM, lean body mass; RBP4, retinol-binding protein 4.

Received August 18, 2006.

Accepted February 2, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Barbieri M, Rizzo MR, Manzella D, Paolisso G 2001 Age-related insulin resistance: is it an obligatory finding? The lesson from healthy centenarians. Diabetes Metab Res Rev 17:19–26[CrossRef][Medline]
  2. Ferrannini E, Vichi S, Beck-Nielsen H, Laakso M, Paolisso G, Smith U 1996 Insulin action and age. European Group for the Study of Insulin Resistance (EGIR). Diabetes 45:947–953[Abstract]
  3. Lyon CJ, Law RE, Hsueh WA 2003 Minireview: adiposity, inflammation, and atherogenesis. Endocrinology 144:2195–2200[Abstract/Free Full Text]
  4. Goodpaster BH, Krishnaswami S, Harris TB, Katsiaras A, Kritchevsky SB, Simonsick EM, Nevitt M, Holvoet P, Newman AB 2005 Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med 165:777–783[Abstract/Free Full Text]
  5. Trayhurn P, Wood IS 2004 Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92:347–355[CrossRef][Medline]
  6. Barzilai N, Wang J, Massilon D, Vuguin P, Hawkins M, Rossetti L 1997 Leptin selectively decreases visceral adiposity and enhances insulin action. J Clin Invest 100:3105–3110[Medline]
  7. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA 2001 The hormone resistin links obesity to diabetes. Nature 409:307–312[CrossRef][Medline]
  8. Fu Y, Luo N, Klein RL, Garvey WT 2005 Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res 46:1369–1379[Abstract/Free Full Text]
  9. Haque WA, Shimomura I, Matsuzawa Y, Garg A 2002 Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab 87:2395
  10. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, Kotani K, Quadro L, Kahn BB 2005 Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436:356–362[CrossRef][Medline]
  11. Cho YM, Youn BS, Lee H, Lee N, Min SS, Kwak SH, Lee HK, Park KS 2006 Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes. Diabetes Care 29:2457–2461[Abstract/Free Full Text]
  12. Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, Wason CJ, Oberbach A, Jansson PA, Smith U, Kahn BB 2006 Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 354:2552–2563[Abstract/Free Full Text]
  13. Janke J, Engeli S, Boschmann M, Adams F, Bohnke J, Luft FC, Sharma AM, Jordan J 2006 Retinol-binding protein 4 in human obesity. Diabetes 55:2805–2810[Abstract/Free Full Text]
  14. Coon PJ, Rogus EM, Drinkwater D, Muller DC, Goldberg AP 1992 Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age. J Clin Endocrinol Metab 75:1125–1132[Abstract]
  15. El-Haschimi K, Dufresne SD, Hirshman MF, Flier JS, Goodyear LJ, Bjorbaek C 2003 Insulin resistance and lipodystrophy in mice lacking ribosomal S6 kinase 2. Diabetes 52:1340–1346[Abstract/Free Full Text]
  16. Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N 2002 Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes 51:2951–2958[Abstract/Free Full Text]
  17. Snijder MB, Dekker JM, Visser M, Bouter LM, Stehouwer CD, Yudkin JS, Heine RJ, Nijpels G, Seidell JC 2004 Trunk fat and leg fat have independent and opposite associations with fasting and postload glucose levels: the Hoorn study. Diabetes Care 27:372–377[Abstract/Free Full Text]
  18. Snijder MB, Visser M, Dekker JM, Goodpaster BH, Harris TB, Kritchevsky SB, De Rekeneire N, Kanaya AM, Newman AB, Tylavsky FA, Seidell JC 2005 Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat. The Health ABC Study. Diabetologia 48:301–308[CrossRef][Medline]
  19. DeFronzo RA, Tobin JD, Andres R 1979 Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–223
  20. Mynarcik DC, McNurlan MA, Steigbigel RT, Fuhrer J, Gelato MC 2000 Association of severe insulin resistance with both loss of limb fat and elevated serum tumor necrosis factor receptor levels in HIV lipodystrophy. J Acquir Immune Defic Syndr 25:312–321[CrossRef][Medline]
  21. Quadro L, Blaner WS, Salchow DJ, Vogel S, Piantedosi R, Gouras P, Freeman S, Cosma MP, Colantuoni V, Gottesman ME 1999 Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein. EMBO J 18:4633–4644[CrossRef][Medline]
  22. Abahusain MA, Wright J, Dickerson JW, de Vol EB 1999 Retinol, {alpha}-tocopherol and carotenoids in diabetes. Eur J Clin Nutr 53:630–635[CrossRef][Medline]
  23. Cree MG, Newcomer BR, Katsanos CS, Sheffield-Moore M, Chinkes D, Aarsland A, Urban R, Wolfe RR 2004 Intramuscular and liver triglycerides are increased in the elderly. J Clin Endocrinol Metab 89:3864–3871[Abstract/Free Full Text]
  24. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI 2003 Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142[Abstract/Free Full Text]
  25. Visser M, Pahor M, Tylavsky F, Kritchevsky SB, Cauley JA, Newman AB, Blunt BA, Harris TB 2003 One- and two-year change in body composition as measured by DXA in a population-based cohort of older men and women. J Appl Physiol 94:2368–2374[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
M. Mohlig, M. O Weickert, E. Ghadamgahi, A. M Arafat, J. Spranger, A. F H Pfeiffer, and C. Schofl
Retinol-binding protein 4 is associated with insulin resistance, but appears unsuited for metabolic screening in women with polycystic ovary syndrome.
Eur. J. Endocrinol., April 1, 2008; 158(4): 517 - 523.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
N. Mody, T. E. Graham, Y. Tsuji, Q. Yang, and B. B. Kahn
Decreased clearance of serum retinol-binding protein and elevated levels of transthyretin in insulin-resistant ob/ob mice
Am J Physiol Endocrinol Metab, April 1, 2008; 294(4): E785 - E793.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
Q. Qi, Z. Yu, X. Ye, F. Zhao, P. Huang, F. B. Hu, O. H. Franco, J. Wang, H. Li, Y. Liu, et al.
Elevated Retinol-Binding Protein 4 Levels Are Associated with Metabolic Syndrome in Chinese People
J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4827 - 4834.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
J. Shea, E. Randell, S. Vasdev, P. P. Wang, B. Roebothan, and G. Sun
Serum retinol-binding protein 4 concentrations in response to short-term overfeeding in normal-weight, overweight, and obese men
Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1310 - 1315.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Promintzer, M. Krebs, J. Todoric, A. Luger, M. G. Bischof, P. Nowotny, O. Wagner, H. Esterbauer, and C. Anderwald
Insulin Resistance Is Unrelated to Circulating Retinol Binding Protein and Protein C Inhibitor
J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4306 - 4312.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
M. Ziegelmeier, A. Bachmann, J. Seeger, U. Lossner, J. Kratzsch, M. Bluher, M. Stumvoll, and M. Fasshauer
Serum Levels of Adipokine Retinol-Binding Protein-4 in Relation to Renal Function
Diabetes Care, October 1, 2007; 30(10): 2588 - 2592.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
W. Jia, H. Wu, Y. Bao, C. Wang, J. Lu, J. Zhu, and K. Xiang
Association of Serum Retinol-Binding Protein 4 and Visceral Adiposity in Chinese Subjects with and without Type 2 Diabetes
J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3224 - 3229.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
M. Qatanani and M. A. Lazar
Mechanisms of obesity-associated insulin resistance: many choices on the menu
Genes & Dev., June 15, 2007; 21(12): 1443 - 1455.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
92/5/1886    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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 Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gavi, S.
Right arrow Articles by McNurlan, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gavi, S.
Right arrow Articles by McNurlan, M. A.
Related Collections
Right arrow Diabetes and Insulin
Right arrow Metabolism

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals