Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty

Kaspar Sørensen, Lise Aksglaede, Thor Munch-Andersen, Niels Jacob Aachmann-Andersen, Joergen Holm Petersen, Linda Hilsted, Jørn Wulff Helge, Anders Juul, Kaspar Sørensen, Lise Aksglaede, Thor Munch-Andersen, Niels Jacob Aachmann-Andersen, Joergen Holm Petersen, Linda Hilsted, Jørn Wulff Helge, Anders Juul

Abstract

Objective: Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor of glucose metabolism and metabolic risk during puberty.

Research design and methods: This was a cross-sectional study on 132 healthy Caucasian children and adolescents evaluated by an oral glucose tolerance test, a dual-energy X-ray absorptiometry scan, direct oxygen uptake measurement during cycle ergometry, and fasting blood samples.

Results: SHBG levels declined with advancement of puberty in both boys (P < 0.001) and girls (P = 0.019). SHBG was significantly positively associated with insulin sensitivity in boys (P < 0.001) and girls (P < 0.001). In addition, SHBG was a strong predictor of insulin sensitivity (P = 0.001) and the only predictor of the disposition index (P = 0.031) after adjustment for puberty, fat mass, and aerobic fitness. SHBG was significantly negatively associated with metabolic risk (P = 0.032) and with hypersensitive C-reactive protein levels (P = 0.030) after adjustment for relevant confounders.

Conclusions: SHBG was a strong predictor of insulin sensitivity and metabolic risk during puberty. Thus, we hypothesize that SHBG integrates the marked changes in glucose metabolism and body composition that occur during the pubertal transition.

Figures

Figure 1
Figure 1
Insulin sensitivity (A), insulin secretion (B), disposition index (C), and metabolic Z score (D) during puberty based on OGTTs in healthy children and adolescents. For each pubertal stage, the effect of low versus high SHBG levels is illustrated by grouping all children according to the median SHBG level for pubertal stage and sex. ■, below median SHBG group; □, above median SHBG group. The whiskers represent the 90th percentiles. Insulin sensitivity (WBISI) (ref. 13) and insulin secretion (first-phase release) (ref. 14) were calculated using glucose in millimoles per liter and insulin in picomoles per liter concentrations. To convert WBISI to glucose in milligrams per deciliter and insulin in microunits per milliliter, multiply by a factor 3. To convert insulin secretion from picomoles per liter to microunits per milliliter, divide by a factor 6. Disposition index was calculated as the product of insulin sensitivity and insulin secretion. The metabolic Z score is generated by combining Z scores from fasting glucose, triglyceride levels, inverse HDL cholesterol levels, waist circumference, and mean blood pressure levels divided by 5. An increase in the combined Z score indicates an increase in metabolic risk.

References

    1. Feng Y, Hong X, Wilker E, Li Z, Zhang W, Jin D, Liu X, Zang T, Xu X, Xu X: Effects of age at menarche, reproductive years, and menopause on metabolic risk factors for cardiovascular diseases. Atherosclerosis 2008; 196: 590– 597
    1. Remsberg KE, Demerath EW, Schubert CM, Chumlea WC, Sun SS, Siervogel RM: Early menarche and the development of cardiovascular disease risk factors in adolescent girls: the Fels Longitudinal Study. J Clin Endocrinol Metab 2005; 90: 2718– 2724
    1. Frontini MG, Srinivasan SR, Berenson GS: Longitudinal changes in risk variables underlying metabolic syndrome X from childhood to young adulthood in female subjects with a history of early menarche: the Bogalusa Heart Study. Int J Obes Relat Metab Disord 2003; 27: 1398– 1404
    1. Tchernof A, Labrie F, Belanger A, Prud'homme D, Bouchard C, Tremblay A, Nadeau A, Despres JP: Relationships between endogenous steroid hormone, sex hormone-binding globulin and lipoprotein levels in men: contribution of visceral obesity, insulin levels and other metabolic variables. Atherosclerosis 1997; 133: 235– 244
    1. Nielsen TL, Hagen C, Wraae K, Brixen K, Petersen PH, Haug E, Larsen R, Andersen M: Visceral and subcutaneous adipose tissue assessed by magnetic resonance imaging in relation to circulating androgens, sex hormone-binding globulin, and luteinizing hormone in young men. J Clin Endocrinol Metab 2007; 92: 2696– 2705
    1. Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB: Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab 2006; 91: 843– 850
    1. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT: Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004; 27: 1036– 1041
    1. Tchernof A, Toth MJ, Poehlman ET: Sex hormone-binding globulin levels in middle-aged premenopausal women: associations with visceral obesity and metabolic profile. Diabetes Care 1999; 22: 1875– 1881
    1. Onat A, Hergenc G, Karabulut A, Albayrak S, Can G, Kaya Z: Serum sex hormone-binding globulin, a determinant of cardiometabolic disorders independent of abdominal obesity and insulin resistance in elderly men and women. Metabolism 2007; 56: 1356– 1362
    1. Ding EL, Song Y, Malik VS, Liu S: Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2006; 295: 1288– 1299
    1. Holly JM, Smith CP, Dunger DB, Howell RJ, Chard T, Perry LA, Savage MO, Cianfarani S, Rees LH, Wass JA: Relationship between the pubertal fall in sex hormone binding globulin and insulin-like growth factor binding protein-I: a synchronized approach to pubertal development? Clin Endocrinol (Oxf) 1989; 31: 277– 284
    1. Sorensen K, Andersson AM, Skakkebaek NE, Juul A: Serum sex hormone-binding globulin levels in healthy children and girls with precocious puberty before and during gonadotropin-releasing hormone agonist treatment. J Clin Endocrinol Metab 2007; 92: 3189– 3196
    1. Matsuda M, DeFronzo RA: Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999; 22: 1462– 1470
    1. Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van HT, Renn W, Gerich J: Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2000; 23: 295– 301
    1. Retnakaran R, Shen S, Hanley AJ, Vuksan V, Hamilton JK, Zinman B: Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test. Obesity (Silver Spring) 2008; 16: 1901– 1907
    1. Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S: The metabolic syndrome in children and adolescents—an IDF consensus report. Pediatr Diabetes 2007; 8: 299– 306
    1. Goran MI, Gower BA: Longitudinal study on pubertal insulin resistance. Diabetes 2001; 50: 2444– 2450
    1. Kahn SE: The relative contributions of insulin resistance and β-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 2003; 46: 3– 19
    1. Spencer K, Yu CK, Rembouskos G, Bindra R, Nicolaides KH: First trimester sex hormone-binding globulin and subsequent development of preeclampsia or other adverse pregnancy outcomes. Hypertens Pregnancy 2005; 24: 303– 311
    1. Tsai EC, Matsumoto AM, Fujimoto WY, Boyko EJ: Association of bioavailable, free, and total testosterone with insulin resistance: influence of sex hormone-binding globulin and body fat. Diabetes Care 2004; 27: 861– 868
    1. Lee S, Bacha F, Gungor N, Arslanian SA: Cardiorespiratory fitness in youth: relationship to insulin sensitivity and β-cell function. Obesity (Silver Spring) 2006; 14: 1579– 1585
    1. Fernandez-Real JM, Grasa M, Casamitjana R, Pugeat M, Barret C, Ricart W: Plasma total and glycosylated corticosteroid-binding globulin levels are associated with insulin secretion. J Clin Endocrinol Metab 1999; 84: 3192– 3196
    1. Bacha F, Saad R, Gungor N, Arslanian SA: Are obesity-related metabolic risk factors modulated by the degree of insulin resistance in adolescents? Diabetes Care 2006; 29: 1599– 1604
    1. Eisenmann JC: Aerobic fitness, fatness and the metabolic syndrome in children and adolescents. Acta Paediatr 2007; 96: 1723– 1729
    1. Ford ES, Ajani UA, Mokdad AH: The metabolic syndrome and concentrations of C-reactive protein among U.S. youth. Diabetes Care 2005; 28: 878– 881

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi