Low Sex Hormone Binding Globulin is a Potential Marker for the Metabolic Syndrome in Different Ethnic Groups

A. H. Heald; S. G. Anderson; F. Ivison; L. Riste; I. Laing; J. K. Cruickshank; J. M. Gibson

doi:10.1055/s-2005-865807

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2005; 113(9): 522-528
DOI: 10.1055/s-2005-865807

Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Low Sex Hormone Binding Globulin is a Potential Marker for the Metabolic Syndrome in Different Ethnic Groups

A. H. Heald¹ , S. G. Anderson² , F. Ivison³ , L. Riste² , I. Laing³ , J. K. Cruickshank² , J. M. Gibson¹

¹Department of Endocrinology, University of Manchester, Salford NHS Trust, Salford, UK
²Clinical Epidemiology Group, University of Manchester Medical School, Manchester, UK
³Clinical Biochemistry Department, Manchester Royal Infirmary, Oxford Road, Manchester, UK

Abstract

Hepatic sex-hormone binding globulin (SHBG) production is down-regulated by insulin and low levels reflect insulin resistance. Because insulin resistance is closely related to the development of cardiovascular disease in different ethnic groups we examined ethnic variation in SHBG across populations with different baseline cardiovascular risk and metabolic syndrome prevalence. Participants were population-based, of European (n = 142), Pakistani (n = 130), and African-Caribbean (AfC) origin (n = 193). SHBG, fasting lipids, and glucose concentrations plus insulin sensitivity (HOMA-S) were determined. Age adjusted SHBG was significantly lower in both Pakistani men and women. Circulating SHBG levels were lower in those with impaired vs. normal glucose homeostasis. SHBG correlated positively with HOMA-S (ρ = 0.28, p < 0.001), and negatively with WHR (ρ = - 0.38, p < 0.001), BMI (r = - 0.30, p < 0.001), and diastolic blood pressure (ρ = - 0.14, p < 0.01) across all ethnic groups. In multivariate logistic regression analysis a low SHBG increased the likelihood of the metabolic syndrome (odds ratio [OR] = 0.42 [0.21 - 0.82], p = 0.01) as did higher fasting NEFA (OR 1.47 [1.04 - 2.08], p = 0.03), low IGFBP-1 concentrations (OR 0.6 [0.44 - 0.81], p = 0.001), age (OR 1.05 [1.02 - 1.09], p = 0.003), and Pakistani ethnicity (p = 0.001) in a model which also contained gender, lnCRP, IGF-I, and IGF-II. As ethnic differences in SHBG level closely parallel differences in insulin resistance. Its measurement may be useful in identifying individuals at particular risk of the metabolic syndrome, for early intervention.

Key words

SHBG - insulin resistance - metabolic syndrome

Full Text

References

1 Alberti K G, Zimmet P Z. For the WHO Consultation . Definition, diagnosis and classification of diabetes mellitus and its complications. Part I, Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med. 1998; 15 539-553
2 Balajaran R. Ethnicity and variations in the nation's health. Health Trends. 1995; 7 114-119
3 Birkeland K I, Hanssen K F, Torjesen P A, Vaaler S. Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes. J Clin Endocrinol Metab. 1993; 76 275-278
4 Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes. 1997; 46 3-10
5 Cappuccio F P, Cook D G, Atkinson R W, Strazzullo P. Prevalence, detection and management of cardiovascular risk factors in different ethnic groups in South London. Heart. 1997; 78 555-563
6 Chaturvedi N, Fuller J H. Ethnic differences in mortality from cardiovascular disease in the UK: do they persist in people with diabetes. J Epid Comm Health. 1996; 50 137-139
7 Chaturvedi N, McKeigue P M. Methods for epidemiological surveys of ethnic minority groups. J Epid Comm Health. 1994; 48 107-111
8 Chiu K C, Lee N P, Chohan P, Chuang L M. Beta cell function declines with age in glucose tolerant Caucasians. Clin Endocrinol. 2000; 53 569-575
9 Crosby S R, Anderton C D, Westwood M, Holly J MP, Cwyfan Hughes S C, Gibson J M, Morrison C A, Young R J, White A. Measurement of insulin-like growth factor-II in human plasma using a specific monoclonal antibody-based two-site immunoradiometric assay. J Endocrinol. 1993; 137 141-150
10 Cruickshank J K, Cooper J, Burnett M, Macduff J, Drubra U. Ethnic differences in fasting plasma C-peptide and insulin in relation to glucose tolerance and blood pressure. Lancet. 1991; 338 842-847
11 Cruickshank J K, Heald A H, Anderson S G, Cade J E, Sampayo J, Riste L K, Greenhalgh A, Taylor W, Fraser W, White A, Gibson J M. The Epidemiology of the Insulin-like Growth Factor system in 3 ethnic groups. Am J Epidem. 2001 a; 154 504-513
12 Cruickshank J K, Mbanya J C, Wilks R, Balkau B, Forrester T, Anderson S G, Mennen L, Forhan A, Riste L, McFarlane-Anderson N. Hypertension in 4 African-origin populations: current “Rule of Halves”, quality of blood pressure control and attributable risk (fraction) for cardiovascular disease. J Hypertension. 2001 b; 19 41-46
13 DECODE Study Group . Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001; 161 397-405
14 Gascon F, Valle M, Martos R, Ruz F J, Rios R, Montilla P, Canete R. Sex hormone-binding globulin as a marker for hyperinsulinemia and/or insulin resistance in obese children. Eur J Endocrinol. 2000; 143 85-89
15 Gill M S, Whatmore A J, Tillman V, White A, Addison G M, Price D A, Clayton P E. Urinary IGF and IGF binding protein-3 in children with disordered growth. Clin Endocrinol. 1997; 46 483-492
16 Haffner S M, Dunn J F, Katz M S. Relationship of sex hormone-binding globulin to lipid, lipoprotein, glucose, and insulin concentrations in postmenopausal women. Metabolism. 1992; 41 278-284
17 Haffner S M, Katz M S, Stern M P, Dunn J F. Association of decreased sex hormone binding globulin and cardiovascular risk factors. Arteriosclerosis. 1989; 9 136-143
18 Haffner S M, Katz M S, Stern M P, Dunn J F. The relationship of sex hormones to hyperinsulinemia and hyperglycemia. Metabolism. 1988; 37 683-688
19 Haffner S M, Valdez R A, Morales P A, Hazuda H P, Stern M P. Decreased sex hormone-binding globulin predicts non-insulin dependent diabetes mellitus in women but not in men. J Clin Endocrinol Metab. 1993; 77 56-60
20 Hanson R L, Pratley R E, Bogardus C, Narayan K M, Roumain J M, Imperatore G, Fagot-Campagna A, Pettitt D J, Bennett P H, Knowler W C. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiological studies. Am J Epidemiol. 2000; 151 190-198
21 Heald A H, Anderson S G, Ivison F, Laing I, Gibson J M, Cruickshank J K. Is the relationship between C-reactive protein and the IGF-system a link to understanding the pathogenesis of cardiovascular disease in different ethnic groups?. Atherosclerosis. 2003; 170 79-86
22 Heald A H, Cruickshank J K, Riste L K, Cade J E, Anderson S, Greenhalgh A, Sampayo J, Taylor W, Fraser W, White A, Gibson J M. Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations. Diabetologia. 2001; 44 333-339
23 Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Jarvinen H, Ferrannini E J. Independent influence of age on basal insulin secretion in non-diabetic humans. European Group for the Study of Insulin Resistance. J Clin Endocrinol Metab. 1999; 84 863-868
24 Iozzo P, Turpeinen A K, Takala T, Oikonen V, Bergman J, Grönroos T, Ferrannini E, Nuutila P, Knuuti J. Defective liver disposal of free fatty acids in patients with impaired glucose tolerance. J Clin Endocrinol Metab. 2004; 89 3496-3502
25 Jayagopal V, Kilpatrick E S, Jennings P E, Hepburn D A, Atkin S L. The biological variation of testosterone and Sex Hormone-Binding Globulin (SHBG) in polycystic ovarian syndrome: Implications for SHBG as a surrogate marker of insulin resistance. J Clin Endocrinol Metab. 2003; 88 1528-1533
26 Katsuki A, Sumida Y, Murashima S, Fujii M, Ito K, Tsuchihashi K, Murata K, Yano Y, Shima T. Acute and chronic regulation of serum sex hormone-binding globulin levels by plasma insulin concentrations in male noninsulin-dependent diabetes mellitus patients. J Clin Endocrinol Metab. 1996; 81 2515-2519
27 Laaksonen D E, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen T P, Salonen R, Rauramaa R, Salonen J T. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Journal of Endocrinology. 2003; 149 601-608
28 Lindstedt G, Lundberg P A, Lapidus L, Lundgren H, Bengtsson C, Bjorntorp P. Low sex-hormone-binding globulin concentration as independent risk factor for development of NIDDM. 12-yr follow-up of population study of women in Gothenburg, Sweden. Diabetes. 1991; 40 123-128
29 Matthews D R, Hosker J B, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28 412-419
30 Mbanya J C, Cruickshank J K, Forrester T, Balkau B, Ngogang J Y, Riste L, Forhan A, Anderson N M, Bennett F, Wilks R. Standardised comparison of glucose tolerance in west African origin populations: rural/urban Cameroon, Jamaica & Caribbean migrants to Britain. Diabetes Care. 1999; 22 434-440
31 McKeigue P M, Shah B, Marmot M G. Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet. 1991; 337 382-386
32 Miller G J, Wheeler M J, Price S G, Beckles G L, Kirkwood B R, Carson D C. Serum high density lipoprotein subclasses, testosterone and sex-hormone-binding globulin in Trinidadian men of African and Indian descent. Atherosclerosis. 1985; 55 251-258
33 Nestler J E, Powers L P, Matt D W, Steingold K A, Plymate S R, Rittmaster R S, Clore J N, Blackard W G. A direct of hyperinsulinaemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 1991; 72 83-89
34 Peiris A N, Sothman N S, Aiman E J, Kissebah A H. The relationship of insulin to sex hormone binding globulin: role of adiposity. Fertil Steril. 1989; 52 69-72
35 Preziosi P, Barrett-Connor E, Papoz L, Roger M, Saint-Paul M, Nahoul K, Simon D. Interrelation between plasma sex hormone-binding globulin and plasma insulin in healthy adult women: the telecom study. J Clin Endocrinol Metab. 1993; 76 283-287
36 Riste L, Khan F, Cruickshank K. High prevalence of type 2 diabetes in all ethnic groups, including Europeans, in a British inner city: relative poverty, history, inactivity or 21st century Europe. Diabetes Care. 2001; 24 1377-1383
37 Sandhu M, Gibson J M, Heald A H, Dunger D, Wareham N J. Low circulating IGF-II concentrations predict weight gain and obesity in humans. Diabetes. 2003; 52 1403-1408
38 Sandhu M S, Heald A H, Gibson J M, Cruickshank J K, Dunger D B, Wareham N J. Circulating concentrations of insulin-like growth factor-I and the development of glucose intolerance: a prospective observational study. Lancet. 2002; 359 1740-1745
39 Sharp P S, Kiddy D S, Reed M J, Anyaoku V, Johnston D G, Franks S. Correlation of plasma insulin and insulin-like growth factor-I with indices of androgen transport and metabolism in women with polycystic ovary syndrome. Clin Endocrinol. 1991; 35 253-257
40 Shaukat N, de Bono D P, Cruickshank J K. Clinical features, risk factors and referral delay in British patients of Indian and European origin with angina matched for age and extent of coronary atheroma. BMJ. 1993; 307 717-718
41 Tchernof A, Toth M J, Poehlman E T. Sex Hormone-Binding Globulin Levels in Middle-Aged Premenopausal Women: Associations with visceral obesity and metabolic profile. Diabetes. 1999; 22 1875-1881
42 Westwood M, Gibson J M, Davies A J, Young R J, White A. The phosphorylation pattern of insulin-like growth factor binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy. J Clin Endocrinol Metab. 1994; 79 1735-1741
43 Wild S, McKeigue P. Cross sectional analysis of mortality by country of birth in England and Wales, 1970 - 92. BMJ. 1997; 314 705-710
44 Yki-Jarvinen H, Makimattila S, Ultriainen T, Rutanen E. Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone binding globulin and insulin-like growth factor binding protein-1 in vivo. J Clin Endocrinol Metab. 1995; 80 3227-3232

Dr. A H Heald

Department of Diabetes and Endocrinology
University of Manchester
Salford Royal Hospitals University Trust
Hope Hospital

Stott Lane, Salford

Greater Manchester, M6 8 HD

U.K.

Phone: + 01612065146

Fax: + 0 16 12 06 59 89

Email: aheald@fs1.ho.man.ac.uk