Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic ß-cell demand in men

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1 Brazilian Journal of Medical and Biological Research (1998) 31: SHBG and pancreatic ß-cell secretion ISSN X 1545 Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic ß-cell demand in men A.F. Reis, W.L. Miranda and A.R. Chacra Disciplina de Endocrinologia, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brasil Correspondence A.F. Reis Rua João Pinheiro, São Paulo, SP Brasil Fax: Research supported by FAPESP (No. 96/6780-0). Received February 17, 1998 Accepted August 5, 1998 Abstract Key words Insulin Proinsulin Sex hormone-binding globulin Obesity Introduction

2 1546 A.F. Reis et al. Subjects and Methods Oral glucose tolerance test

3 SHBG and pancreatic ß-cell secretion 1547 Assays Statistical analysis Results Table 1 - Clinical and hormone characteristics of the subjects. BMI, Body mass index; DPX, dual energy X-ray absorptiometry; WHR, waist-to-hip ratio; SHBG, sex hormone-binding globulin. Mean ± SD Range BMI (kg/m 2 ) 28.8 ± DPX (%fat) 24.5 ± Waist (cm) 98 ± WHR 0.91 ± Weight (kg) 91.7 ± SHBG (nmol/l) 38.7 ± Fasting proinsulin (pmol/l) 17.5 ± min proinsulin (pmol/l) 41.3 ± Fasting C-peptide (ng/ml) 2.1 ± min C-peptide (ng/ml) 5.9 ± Proinsulin/insulin 0.2 ± Fasting glucose (mg/dl) 93 ± min glucose (mg/dl) 101 ± Fasting insulin (µu/ml) 15.9 ± min insulin (µu/ml) 62.4 ±

4 1548 A.F. Reis et al. Figure 1 - Relationship between SHBG levels and 120-min proinsulin after a glucose load test in men. Table 2 - Correlations between SHBG and other variables. *P<0.05 (Pearson or Spearman test). For abbreviations, see Table 1. BMI r = P = 0.08 DPX (%fat) r = P = 0.02* Waist r = P = 0.11 WHR r = P = 0.02* Weight r = P = 0.15 Fasting proinsulin r = P = 0.047* 120-min proinsulin r = P = 0.01* Fasting C-peptide r = P = 0.01* 120-min C-peptide r = P = 0.12 Proinsulin/insulin r = 0.10 P = 0.68 Fasting glucose r = P = min glucose r = P = 0.13 Fasting insulin r = P = 0.02* 120 min-insulin r = P = 0.06 SHBG (nmol/l) r = P< min proinsulin (pmol/l) Discussion

5 SHBG and pancreatic ß-cell secretion 1549 Table 3 - Comparisons between nonobese and obese groups. *P<0.05 compared to nonobese (Mann-Whitney rank sum test or Student t- test). For abbreviations, see Table 1. Nonobese Obese (N = 10) (N = 8) BMI (kg/m 2 ) 24.2 ± ± 5.2* Waist (cm) 85.8 ± ± 10.6* WHR 0.88 ± ± 0.03* DPX (%fat) 18.0 ± ± 5.3* Weight (kg) 76.4 ± ± 19.9* Age (year) 30.2 ± ± 2.6 SHBG (nmol/l) 44.6 ± ± 10.3* Fasting insulin (µu/ml) 11.8 ± ± min insulin (µu/ml) 25.5 ± ± 75.0* Fasting proinsulin (pmol/l) 11.6 ± ± 19.0* 120-min proinsulin (pmol/l) 27.4 ± ± 18.1* Fasting C-peptide (ng/ml) 1.7 ± ± 1.2* 120-min C-peptide (ng/ml) 4.6 ± ± 3.7 Proinsulin/insulin 0.16 ± ± 0.29 Fasting glucose (mg/dl) 94 ± 9 92 ± min glucose (mg/dl) 94 ± ± 21

6 1550 A.F. Reis et al. References 1. Rosner W (1990). The functions of corticosteroid-binding globulin and sex hormone-binding globulin; recent advances. Endocrine Reviews, 11: Plymate SR, Matej LA, Jones RE & Friedl KE (1988). Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. Journal of Clinical Endocrinology and Metabolism, 67: Preziosi P, Barrett-Connor E, Papoz L, Roger M, Saint-Paul M, Nahoul K & Simon D (1993). Interrelation between plasma sex hormone-binding globulin and plasma insulin in healthy adult women: the telecom study. Journal of Clinical Endocrinology and Metabolism, 76: Nestler JE (1993). Editorial: sex hormonebinding globulin: a marker for hyperinsulinemia and/or insulin resistance? Journal of Clinical Endocrinology and Metabolism, 76: Caprio S, Plewe G, Diamond MP, Simonson DC, Boulware SD, Sherwin RS & Tamborlane WV (1989). Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. Journal of Pediatrics, 114: Haffner SM, Valdez RA, Morales PA, Hazuda HP & Stern MP (1993). Decreased sex hormone-binding globulin predicts noninsulin-dependent diabetes mellitus in women but not in men. Journal of Clinical Endocrinology and Metabolism, 77: Andersson B, Marin P, Lissner L, Vermeulen A & Björrntorp P (1994). Testosterone concentrations in women and men with NIDDM. Diabetes Care, 17: Haffner SM, Karhapää P, Mykkänen L & Laakso M (1994). Insulin resistance, body fat distribution, and sex hormones in men. Diabetes, 43: Shimizu M, Kawazu S, Tomono S, Ohno T, Utsugi T, Kato N, Ishii C, Ito Y & Murata K (1996). Age-related alteration of pancreatic ß-cell function: Increased proinsulin and proinsulin-to-insulin molar ratio in elderly, but not in obese subjects without glucose intolerance. Diabetes Care, 19: Haffner SM, Gonzalez C, Mykkänen L & Stern M (1997). Total immunoreactive proinsulin, immunoreactive insulin and specific insulin in relation to conversion to NIDDM: the Mexico City diabetes study. Diabetologia, 40: Røder ME, Knip M, Hartling SG, Karjalainen J, Akerblom HK, Binder C & The Childhood Diabetes in Finland Study Group (1994). Disproportionately elevated proinsulin levels precede the onset of insulin-dependent diabetes mellitus in siblings with low first phase insulin responses. Journal of Clinical Endocrinology and Metabolism, 79: Kahn SE, Leonetti DL, Prigeon RL, Boyko EJ, Bergstrom RW & Fujimoto WY (1995). Proinsulin as a marker for the development of NIDDM in Japanese-American men. Diabetes, 44: Dalbosco IS, Coifman R, Moisés RCS, Vieira JGH & Russo EMK (1995). Influência da obesidade e da glicemia nos níveis de pró-insulina durante o teste oral de tolerância à glicose. Arquivos Brasileiros de Endocrinologia e Metabologia, 39: WHO - Expert Committee on Diabetes Mellitus (1980). Second Report. WHO. Technical Report Series, 646: Fendri S, Arlot S, Marcelli JM, Dubreuil A & Lalau JD (1994). Relationship between insulin sensitivity and circulating sex hormone-binding globulin levels in hyperandrogenic obese women. International Journal of Obesity, 18: Yki-Järvinen H, Mäkimattila S, Utriainen T & Rutanen EM (1995). Portal insulin concentrations rather than insulin sensitivity regulate serum sex hormone-binding globulin and insulin-like growth factor binding protein 1 in vivo. Journal of Clinical Endocrinology and Metabolism, 80: Hamilton-Fairley D, White D, Griffiths M, Anyaoku V, Koistinen R, Seppälä M & Franks S (1995). Diurnal variation of sex hormone binding globulin and insulin-like growth factor binding protein-1 in women with polycystic ovary syndrome. Clinical Endocrinology, 43:

7 SHBG and pancreatic ß-cell secretion Peiris LN, Stagner JI, Plymate SR, Vogel RL, Heck M & Samols E (1993). Relationship of insulin secretory pulses to sex hormone-binding globulin in normal men. Journal of Clinical Endocrinology and Metabolism, 76: Pasquali R, Casimirri F, De Iasio R, Mesini P, Boschi S, Chierici R, Flamia R, Biscotti M & Vicennati V (1995). Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men. Journal of Clinical Endocrinology and Metabolism, 80: Lindstedt G, Lundberg PA, Lapidus L, Lundgren H, Bengtsson C & Björntorp P (1991). 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, 40: Loukovaara M, Carson M & Adlercreutz H (1995). Regulation of sex hormone-binding globulin secretion and gene expression by cycloheximide in vitro. Journal of Steroid Biochemistry and Molecular Biology, 54: Haffner SM, Mykkänen L, Valdez RA, Stern MP, Holloway DL, Monterrosa A & Bowsher RR (1994). Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome. Journal of Clinical Endocrinology and Metabolism, 79: Yudkin JS, Denver AE, Mohamed-Ali V, Ramaiya KL, Nagi DK, Goubet S, McLarty DG & Swai A (1997). The relationship of concentration of insulin and proinsulin-like molecules with coronary heart disease prevalence and incidence. Diabetes Care, 20: Warren-Perry MG, Manley SE, Ostrega D, Polonsky K, Mussett S, Brown P & Turner RC (1997). A novel point mutation in the insulin gene giving rise to hyperproinsulinemia. Journal of Clinical Endocrinology and Metabolism, 82: Horvitz DL, Starr JI, Mako ME, Blackard WG & Rubenstein AH (1975). Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. Journal of Clinical Investigation, 55: Glauber HS, Henry RR, Wallace P, Frank BH, Gallowaw JA, Cohen RM & Olefsky JM (1987). The effects of biosynthetic human proinsulin on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. New England Journal of Medicine, 316: Robbins DC, Tager HS & Rubenstein AH (1984). Biologic and clinical importance of proinsulin. New England Journal of Medicine, 310: Haffner SM, Miettinen H & Stern MP (1997). The homeostasis model in the San Antonio heart study. Diabetes Care, 20: Ludvik B, Nolan JJ, Baloga J, Sacks D & Olefsky J (1995). Effect of obesity on insulin resistance in normal subjects and patients with NIDDM. Diabetes, 44: Banerji MA, Chaiken RL, Gordon D, Kral JG & Lebovitz HE (1995). Does intra-abdominal adipose tissue in black men determine whether NIDDM is insulin-resistant or insulin-sensitive? Diabetes, 44: Phillips GB (1993). Relationship between serum sex hormones and the glucoseinsulin-lipid defect in men with obesity. Metabolism, 42:

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Specific insulin and proinsulin in normal glucose tolerant first-degree relatives of NIDDM patients

Brazilian Journal of Medical and Biological Research (1999) 32: 67-72 Insulin and proinsulin in first-degree relatives of NIDDM ISSN 1-879X 67 Specific insulin and proinsulin in normal glucose tolerant