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      Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals

      research-article
      Author(s): 1 , 1 , 1 ,   1 , 2 , 3 , 4 , 5 , 6 , 7 , (on behalf of the European Group for the Study of Insulin Resistance: Relationship between Insulin Sensitivity and Cardiovascular Disease Risk Study Group), 2 ,
      Publication date (Electronic):
      Journal: Diabetologia
      Publisher: Springer-Verlag
      Keywords: Adipocytokine, Adiponectin, Insulin resistance, Leptin

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          Abstract

          Aims/hypothesis

          Obesity is the dominant cause of insulin resistance. In adult humans it is characterised by a combination of adipocyte hypertrophy and, to a lesser extent, adipocyte hyperplasia. As hypertrophic adipocytes secrete more leptin and less adiponectin, the plasma leptin:adiponectin ratio (LAR) has been proposed as a potentially useful measure of insulin resistance and vascular risk. We sought to assess the usefulness of the LAR as a measure of insulin resistance in non-diabetic white adults.

          Methods

          Leptin and adiponectin levels were measured in 2,097 non-diabetic individuals from the Ely and European Group for the Study of Insulin Resistance (EGIR) Relationship between Insulin Sensitivity and Cardiovascular Risk (RISC) study cohorts. LAR was compared with fasting insulin and HOMA-derived insulin sensitivity (HOMA-S) in all individuals and with the insulin sensitivity index ( M/ I) from hyperinsulinaemic–euglycaemic clamp studies in 1,226 EGIR RISC participants.

          Results

          The LAR was highly correlated with HOMA-S in men ( r = −0.58, p = 4.5 × 10 −33 and r = −0.65, p = 1.1 × 10 −66 within the Ely and EGIR RISC study cohorts, respectively) and in women ( r = −0.51, p = 2.8 × 10 −36 and r = −0.61, p = 2.5 × 10 −73). The LAR was also strongly correlated with the clamp M/ I value ( r = −0.52, p = 4.5 × 10 −38 and r = −0.47, p = 6.6 × 10 −40 in men and women, respectively), similar to correlations between HOMA-S and the M/I value.

          Conclusions/interpretation

          The leptin:adiponectin ratio is a useful measure of insulin resistance in non-diabetic white adults. These data highlight the central role of adipocyte dysfunction in the pathogenesis of insulin resistance. Given that variations between fasting and postprandial leptin and adiponectin levels tend to be small, the leptin to adiponectin ratio might also have potential value in assessing insulin sensitivity in the non-fasted state.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00125-009-1508-3) contains supplementary material, which is available to authorized users.

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          Most cited references15

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          The assessment of insulin resistance in man.

          Brent D. Matthews, Nneka Wallace (2002)
          Insulin resistance exists when a normal concentration of insulin produces a less than normal biological response. The ability to measure insulin resistance is important in order to understand the aetiopathology of Type 2 diabetes, to examine the epidemiology and to assess the effects of intervention. We assess and compare methods of measurement and have undertaken a literature review from 1966 to 2001. Quantitative estimates of insulin resistance can be obtained using model assessments, clamps or insulin infusion sensitivity tests. There is considerable variation in the complexity and labour intensity of the various methods. The most well-established methods are the euglycaemic clamp, minimal model assessment and homeostatic model assessment (HOMA). No single test is appropriate under all circumstances. There are a number of well-established tests used to measure insulin resistance: the choice of method depends on the size and type of study to be undertaken. Although the so-called 'gold-standard' test, the euglycaemic clamp, is useful for intensive physiological studies on small numbers of subjects, a simpler tool such as HOMA is more appropriate for large epidemiological studies. It is important to be aware that most techniques measure stimulated insulin resistance whereas HOMA gives an estimate of basal insulin resistance. Caution should be exercised when making comparisons between studies due to variations in infusion protocols, sampling procedures and hormone assays used in different studies.
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            Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns.

            C.-K. Peng, Lawrence WC Chan, J Mietus … (2003)
            Adiponectin is an abundant serum adipokine secreted exclusively from differentiated adipocytes, which plays an important role in regulating insulin sensitivity. The dynamics of circulating adiponectin concentrations have yet to be systematically investigated. We sought to determine whether serum adiponectin levels exhibit diurnal or ultradian rhythms in healthy normal-weight men and to compare the 24-h profile of adiponectin fluctuations with those of leptin, leptin-binding protein (sOB-R), and cortisol. We collected blood samples at 15-min intervals over 24 h from six subjects receiving an isocaloric diet, and we measured adiponectin, leptin, sOB-R, and cortisol levels. Fourier and cross-correlation analyses were performed on these time series to study diurnal variations, and the Cluster7 program was used for pulsatility analysis. Circulating adiponectin and sOB-R levels exhibited ultradian pulsatility as well as a diurnal variation with a significant decline at night, reaching a nadir in the early morning. The 24-h variations of serum adiponectin and sOB-R were nearly identical and followed those of cortisol after a few hours, but were out-of-phase with leptin diurnal rhythms. These data suggest that adiponectin and sOB-R levels might be influenced by common regulatory factors and challenge the notion that cortisol may have a direct inhibitory effect on adiponectin in humans.
            Article 0 comments Cited 69 times – based on 0 reviews     Review now
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              The ratio of leptin to adiponectin can be used as an index of insulin resistance.

              H Kakizawa, Jun Takeda, Y Horikawa … (2008)
              The level of leptin increases with obesity, whereas that of adiponectin decreases with obesity. It is reported that the ratio of leptin to adiponectin (L/A) is associated with insulin resistance. It is difficult to evaluate insulin resistance in diabetic patients who have a dysfunction of insulin secretion. The aim of this study was to examine whether the L/A ratio is a useful marker for insulin resistance in diabetic patients. We examined L/A in the serum of a total of 139 Japanese patients with type 2 diabetes mellitus (66 women and 73 men) and 7 healthy individuals recruited in our hospital. Changes in the levels of leptin and adiponectin were observed using the oral glucose tolerance test and a hyper- and euglycemic clamp test. Twenty-one patients with type 2 diabetes mellitus were observed for more than 6 months after treatment with pioglitazone, and 31 patients with type 2 diabetes mellitus were observed for more than 6 months after the treatment with metformin. The mean value of L/A in 139 Japanese patients with type 2 diabetes mellitus was 1.22 +/- 1.41 (1.68 +/- 1.76 in women, 0.81 +/- 0.80 in men; P = .0002). In the clamp tests, L/A correlated with glucose infusion rate (GIR) (r(2) = 0.26, P = .0034). The correlation of L/A and GIR indicated a stronger correlation than either leptin (r(2) = 0.144, P = .03) or adiponectin alone (r(2) = 0.023, P = .41), or the homeostasis model assessment of insulin resistance (r(2) = 0.103, P = .08). The average hemoglobin A(1c) (HbA(1c)) improved from 10.2% +/- 1.2% to 9.2% +/- 1.6% (P = .0037) in 6 months after treatment with pioglitazone. Our results indicate pioglitazone to be effective for HbA(1c) improvement in subjects with high L/A and low L/A. The average HbA(1c) improved from 9.2% +/- 0.9% to 8.0% +/- 1.2% (P = .0002) in 6 months after treatment with metformin. Our results indicate metformin to be effective for HbA(1c) improvement in subjects with a low L/A. In conclusion, we demonstrate that L/A is different between male and female subjects. The correlation of L/A and GIR by the euglycemic hyperinsulinemic clamp test suggests that L/A is a useful indicator for the choice of drug to treat diabetes mellitus.
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                Author and article information

                Contributors
                : dbs23@medschl.cam.ac.uk
                Journal
                Journal ID (nlm-ta): Diabetologia
                Title: Diabetologia
                Publisher: Springer-Verlag (Berlin/Heidelberg )
                ISSN (Print): 0012-186X
                ISSN (Electronic): 1432-0428
                Publication date (Electronic): 12 September 2009
                Publication date PMC-release: 12 September 2009
                Publication date (Print): November 2009
                Volume: 52
                Issue: 11
                Pages: 2345-2349
                Affiliations
                [1 ]MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK
                [2 ]Metabolic Research Laboratories, Level 4, Institute of Metabolic Science, University of Cambridge, Addenbrooke’s Hospital, Box 289, Hills Road, Cambridge, CB2 0QQ UK
                [3 ]INSERM Unit 780, Université Paris-Sud, Orsay, France
                [4 ]Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
                [5 ]Department of Diabetes, School of Clinical Medical Sciences, University of Newcastle, Newcastle, UK
                [6 ]Department of Endocrinology, Odense University Hospital, Odense, Denmark
                [7 ]Metabolic Research Unit, St James’s Hospital & Trinity College Dublin, Dublin, Ireland
                Article
                Publisher ID: 1508
                DOI: 10.1007/s00125-009-1508-3
                PMC ID: 2759015
                PubMed ID: 19756488
                SO-VID: 9bf9e887-4a0e-4558-b050-3334988c89a3
                Copyright © © The Author(s) 2009
                History
                Date received : 26 June 2009
                Date accepted : 3 August 2009
                Categories
                Subject: Short Communication
                Custom metadata
                issue-copyright-statement © Springer-Verlag 2009

                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: leptin,adipocytokine,insulin resistance,adiponectin
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes
                Keywords: leptin, adipocytokine, insulin resistance, adiponectin

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