Skip to main content
SpringerLink
Log in

Beta-Cell Function in Polycystic Ovary Syndrome

  • Chapter
Polycystic Ovary Syndrome

Part of the book series: Serono Symposia USA ((SERONOSYMP))

  • 180 Accesses

Abstract

Women with polycystic ovary syndrome (PCOS) are at increased risk of developing impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) (1–10). Twenty percent of obese women with PCOS develop IGT or frank NIDDM by age 40 years (3, 11) and long-term follow-up of women with polycystic ovaries reveals an increased prevalence of NIDDM compared with controls (9, 10). This increased prevalence of IGT and NIDDM has been ascribed to the insulin resistance characteristic of the syndrome (1–6, 12). Because insulin resistance has been shown to antedate the onset of NIDDM in some studies (13–16) , it has been postu­lated to be the primary pathogenetic factor in NIDDM. The high preva­lence of NIDDM in women with PCOS is therefore consistent with similar findings in other populations in which insulin resistance is common (14, 16). On the other hand, this formulation of the pathophysiology of NIDDM in women with PCOS does not explain the observation that only a subset of these insulin-resistant women develop NIDDM. Defects in insulin secre­tion as well as familial and environmental factors must therefore also be considered as possible components in the predisposition to NIDDM seen in PCOS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Burghen G, Givens J, Kitabchi A. Correlation of hyperandrogenism with hyperinsulinemia in polycystic ovarian disease. J Clin Endocrinol Metab 1980; 50: 113–6.

    Article  PubMed  CAS  Google Scholar 

  2. Chang R, Laufer L, Meldrum D, Nakamura R, Judd H, Kaplan S. Steroid secretion in polycystic ovary disease after ovarian suppression by a long-acting gonadotropin-releasing hormone agonist. J Clin Endocrinol Metab 1983; 56: 897–903.

    Article  PubMed  CAS  Google Scholar 

  3. Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance and/or hyperinsulinemia. J Clin Endocrinol Metab 1987; 65: 499–507.

    Article  PubMed  CAS  Google Scholar 

  4. Jialal I, Naike R, Reddi K, Moodley J, Joubert S. Evidence for insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metab 1987; 64: 1066–9.

    Article  PubMed  CAS  Google Scholar 

  5. Dunaif A, Mandeli J, Fluhr H, Dobrjansky A. The impact of obestiy and chronic hyperinsulinemia on gonadotropin release and gonadal steroid secretion in the polycystic ovary syndrome. J Clin Endocrinol Metab 1988; 66: 131–9.

    Article  PubMed  CAS  Google Scholar 

  6. Dunaif A, Segal K, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38: 1165–74.

    Article  PubMed  CAS  Google Scholar 

  7. Moller D, Flier J. Insulin resistance—mechanisms, syndromes, and implications. N Engl J Med 1991; 325: 938–48.

    Article  PubMed  CAS  Google Scholar 

  8. O’Meara N, Blackman J, Ehrmann D, Barnes RB, Rosenfield RL, Jaspan JB, Polonsky KS. Defects in beta cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1993; 76: 1241–7.

    Article  PubMed  Google Scholar 

  9. Dahlgren E, Janson P, Johansson S, Linstedt G, Oden A, Crona N, Knutsson F, Mattson LA, Lundberg PA. Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril 1992; 57: 505–13.

    PubMed  CAS  Google Scholar 

  10. Dahlgren E, Lapidus L, Janson P, Lindstedt G, Johansson S, Tengborn L. Hemostatic and metabolic variables in women with polycystic ovary syndrome. Fertil Steril 1994; 61: 455–60.

    PubMed  CAS  Google Scholar 

  11. Dunaif A. Diabetes mellitus and polycystic ovary syndrome. In: Dunaif A, Givens J, Haseltine F, Merriam G, eds. Current issues in endocrinology and metabolism: polycystic ovary syndrome. Cambridge, MA: Blackwell Scientific, 1992: 347–58.

    Google Scholar 

  12. Holte J, Bergh T, Berne C, Berglund L, Lithell H. Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab 1994; 78: 1052–8.

    Article  PubMed  CAS  Google Scholar 

  13. Martin B, Warram J, Krolewski A, Bergman R, Soeldner J, Kahn C. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 1992; 340: 925–9.

    Article  PubMed  CAS  Google Scholar 

  14. Lillioja S, Mott D, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 1993; 329: 1988–92.

    Article  PubMed  CAS  Google Scholar 

  15. Schumacher M, Hasstedt S, Hunt S, Williams R, Elbein S. Major gene effect for insulin levels in familial NIDDM pedigrees. Diabetes 1992; 41: 416–23.

    Article  PubMed  CAS  Google Scholar 

  16. Warram J, Martin B, Krolewski A, Soeldner J, Kahn C. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 1990; 113: 909–15.

    PubMed  CAS  Google Scholar 

  17. Sturis J, Van Cauter E, Blackman J, Polonsky K. Entrainment of pulsatile insulin secretion by oscillatory glucose infusion. J Clin Invest 1991; 87: 439–45.

    Article  PubMed  CAS  Google Scholar 

  18. Lang D, Matthews D, Peto J, Turner R. Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. N Engl J Med 1979; 301: 1023–7.

    Article  PubMed  CAS  Google Scholar 

  19. Lang D, Matthews D, Burnett M, Ward G, Turner R. Pulsatile, synchronous basal insulin and glucagon secretion in man. Diabetes 1982; 31: 22–6.

    Article  PubMed  CAS  Google Scholar 

  20. Hansen B, Jen K, Pek S, Wolfe R. Rapid oscillations in plasma insulin, glucagon, and glucose in obese and normal weight humans. J Clin Endocrinol Metab 1982; 54: 785–92.

    Article  PubMed  CAS  Google Scholar 

  21. Matthews D, Lang D, Burnett M, Turner R. Control of pulsatile insulin secretion in man. Diabetologia 1983; 24: 231–7.

    Article  PubMed  CAS  Google Scholar 

  22. Simon C, Brandenberger G, Follenius M. Ultradian oscillations of plasma glucose, insulin and C-peptide in man during continuous enteral nutrition. J Clin Endocrinol Metab 1987; 64: 669–74.

    Article  PubMed  CAS  Google Scholar 

  23. Polonsky K, Given B, Van Cauter E. Twenty-four hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 1988; 81: 442–8.

    Article  PubMed  CAS  Google Scholar 

  24. Shapiro E, Tillil H, Polonsky K, Rubenstein A, Van Cauter E. Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose. J Clin Endocrinol Metab 1988; 67: 307–14.

    Article  PubMed  CAS  Google Scholar 

  25. Sturis J, Polonsky K, Shapiro E, Blackman J, O’Meara N, Van Cauter E. Abnormalities in the ultradian oscillations of insulin secretion and glucose levels in type 2 (non-insulin-dependent) diabetic patients. Diabetalogia 1992; 35: 681–9.

    Article  CAS  Google Scholar 

  26. Polonsky K, Given B, Hirsch L, Beebe C, Rue P, Pugh W, Frank BH, Galloway JA, Van Cauter E. Abnormal patterns of insulin secretion in non-insulin dependent diabetes. N Engl J Med 1988; 318: 1231–9.

    Article  PubMed  CAS  Google Scholar 

  27. O’Meara N, Sturis J, Van Cauter E, Polonsky K. Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in noninsulin-dependent diabetes mellitus. J Clin Invest 1993; 92: 262–71.

    Article  PubMed  Google Scholar 

  28. Perley M, Kipnis D. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967; 46: 1954–62.

    Article  PubMed  CAS  Google Scholar 

  29. Seltzer H, Allen E, Herron AJ, Brennan M. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 1967; 46: 323–35.

    Article  PubMed  CAS  Google Scholar 

  30. Bergstrom R, Wahl P, Leonetti D, Fujimoto W. Association of fasting glucose levels with a delayed secretion of insulin after oral glucose in subjects with glucose intolerance. J Clin Endocrinol Metab 1990; 71: 1447–53.

    Article  PubMed  CAS  Google Scholar 

  31. Cerasi E, Luft R. The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus. Acta Endocrinol 1967; 55: 278–304.

    PubMed  CAS  Google Scholar 

  32. Efendic S, Luft R, Wajngot A. Aspects of the pathogenesis of type 2 diabetes. Endocr Rev 1984; 5: 395–410.

    Article  PubMed  CAS  Google Scholar 

  33. Brunzell J, Robertson R, Lerner R, Hazzard WR, Ensinck JW, Bierman E, Porte D. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J Clin Endocrinol Metab 1976; 42: 222–9.

    Article  PubMed  CAS  Google Scholar 

  34. Kosaka K, Kuzuya T, Akanuma Y, Hagura R. Increase in insulin response after treatment of overt maturity-onset diabetes is independent of the mode of treatment. Diabetalogia 1980; 18: 23–8.

    Article  CAS  Google Scholar 

  35. Vague P, Houlin J. The defective glucose-sensitivity of the B-cell in non-insulin dependent diabetes: improvement after twenty hours of normoglycemia. Metabolism 1982; 31: 139–42.

    Article  PubMed  CAS  Google Scholar 

  36. Johnston C, Ward W, Beard J, McKnight B, Porte D. Islet function and insulin sensitivity in the non-diabetic offspring of conjugal type 2 diabetic patients. Diabetic Med 1990; 7: 119–25.

    Article  PubMed  CAS  Google Scholar 

  37. Lang D, Matthews D, Burnett M, Turner R. Brief, irregular oscillations of basal plasma insulin and glucose concentrations in diabetic man. Diabetes 1981; 30: 435–9.

    Article  PubMed  CAS  Google Scholar 

  38. O’Rahilly S, Nugent Z, Rudenski A, Hosker JP, Burnett MA, Darling P, Turner RC. 13-cell dysfunction rather than insulin insensitivity is the primary defect in familial type 2 diabetes. Lancet 1986; 2: 360–3.

    Article  PubMed  Google Scholar 

  39. O’Rahilly S, Turner R, Matthews D. Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes. N Engl J Med 1988; 318: 1225–30.

    Article  PubMed  Google Scholar 

  40. Garvey W, Olefsky J, Rubenstein A, Kolterman O Day-long integrated serum insulin and C-peptide profiles in patients with NIDDM: correlation with urinary C-peptide excretion. Diabetes 1988; 37: 590–9.

    Article  PubMed  CAS  Google Scholar 

  41. Falcone T, Little A, Morris D. Impaired glucose effectiveness in patients with polycystic ovary syndrome. Hum Reprod 1992; 7: 922–5.

    PubMed  CAS  Google Scholar 

  42. Dunaif A, Green G, Finegood D. Pancreatic beta (B) cell function is normal in insulin resistant women with the polycystic ovary syndrome (PCOS). The Endocrine Society, 74th Annual Meeting, San Antonio TX, 1992.

    Google Scholar 

  43. Kahn S, Prigeon R, McCulloch D, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP, Porte D. Quantification of the relationship between insulin sensitivity and B-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993; 42: 1663–72.

    Article  PubMed  CAS  Google Scholar 

  44. Sonnenberg G, Hoffman R, Mueller R, Kissebah A. Splanchnic insulin dynamics and secretion pulsatilities in abdominal obesity. Diabetes 1994; 43: 468–77.

    Article  PubMed  CAS  Google Scholar 

  45. Kissebah A. Upper body obesity: abnormalities in the metabolic profile and the androgenic/estrogenic balance. In: Dunaif A, Givens J, Haseltine F, Merriam G, eds. Current issues in endocrinology and metabolism: polycystic ovary syndrome. Cambridge, MA: Blackwell Scientific, 1992.

    Google Scholar 

  46. Ehrmann D, Sturis J, Byrne M, Karrison T, Rosenfield R, Polonsky K. Insulin secretory defects in polycystic ovary syndrome: relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 96: 520–7.

    Article  PubMed  CAS  Google Scholar 

  47. Ehrmann D, Rosenfield R, Barnes R, Brigell D, Sheikh Z. Detection of functional ovarian hyperandrogenism in women with androgen excess. N Engl J Med 1992; 327: 157–62.

    Article  PubMed  CAS  Google Scholar 

  48. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 28: 1039–57.

    Google Scholar 

  49. Bergman R, Phillips L, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and 13-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 1981; 68: 1456–67.

    Article  PubMed  CAS  Google Scholar 

  50. Byrne M, Sturis J, Polonsky K. Insulin secretion and clearance during low-dose graded glucose infusion. Am J Physiol 1995; 268: E21–7.

    PubMed  CAS  Google Scholar 

  51. Jenkins G, Watts D. Spectral analysis and its applications. San Francisco: Holden Day, 1968: 525.

    Google Scholar 

  52. Van Cauter E, Mestrez F, Sturis J, Polonsky K. Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 1992; 41: 368–77.

    Article  PubMed  Google Scholar 

  53. Eaton R, Allen R, Schade D, Erickson K, Standefer J. Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. J Clin Endocrinol Metab 1980; 51: 520–8.

    Article  PubMed  CAS  Google Scholar 

  54. Polonsky K, Licinio-Paixao J, Given B, Pugh W, Rue P, Galloway J, Karrison T, Frank BI. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest 1986; 77: 98–105.

    Article  PubMed  CAS  Google Scholar 

  55. Lillioja S, Mott D, Zadawadzki J, Young AA, Abbott WGH, Knowler WC, Bennett PH, Moll P, Bogardus C. In vivo insulin action is familial characteristic in nondiabetic Pima Indians. Diabetes 1987; 36: 1329–35.

    Article  PubMed  CAS  Google Scholar 

  56. Janssen R, Bogardus C, Takeda J, Knowler W, Thompson D. Linkage analysis of acute insulin secretion with GLUT-2 and glucokinase in Pima Indians and the identification of a missense mutation in GLUT-2. Diabetes 1994; 43: 558–63.

    Article  PubMed  CAS  Google Scholar 

  57. Henriksen J, Alford F, Handberg A, Vaag A, Ward GM, Kalfas A, Beck-Nielsen H. Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1994; 94: 1196–204.

    Article  PubMed  CAS  Google Scholar 

  58. O’Rahilly S, Spivey R, Holman R, Nugent Z, Clark A, Turner R. Type II diabetes of early onset: a distinct clinical and genetic syndrome? Br Med J 1987; 294: 923–8.

    Article  Google Scholar 

  59. Dunaif A, Segal K, Shelley D, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1992; 41: 1257–66.

    Article  PubMed  CAS  Google Scholar 

  60. Ciaraldi T, El-Roeiy A, Madar Z, Reichart D, Olefsky J, Yen S. Cellular mechanisms of insulin resistance in polycystic ovary syndrome. J Clin Endocrinol Metab 1992; 75: 577–83.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. David A. Ehrmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeppe Sturis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Maria M. Byrne
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert L. Rosenfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kenneth S. Polonsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis, 95816, Sacramento, CA, USA

    R. Jeffrey Chang M.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag New York, Inc.

About this chapter

Cite this chapter

Ehrmann, D.A., Sturis, J., Byrne, M.M., Rosenfield, R.L., Polonsky, K.S. (1996). Beta-Cell Function in Polycystic Ovary Syndrome. In: Chang, R.J. (eds) Polycystic Ovary Syndrome. Serono Symposia USA. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-8483-0_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-8483-0_9

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4613-8485-4

  • Online ISBN: 978-1-4613-8483-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation