Diabetologia

, Volume 35, Issue 7, pp 681–689 | Cite as

Abnormalities in the ultradian oscillations of insulin secretion and glucose levels in Type 2 (non-insulin-dependent) diabetic patients

  • J. Sturis
  • K. S. Polonsky
  • E. T. Shapiro
  • J. D. Blackman
  • N. M. O'Meara
  • E. Van Cauter
Originals

Summary

To investigate the temporal organization of insulin secretion and glucose concentration during fasting in Type 2 (non-insulin-dependent) diabetes mellitus, we studied seven patients with Type 2 diabetes, eight obese non-diabetic control subjects and eight normal weight non-diabetic subjects. Blood sampling for glucose, insulin and C-peptide was performed at 15-min intervals during a 24-h period of fasting for the diabetic and the obese control subjects and during an 8-h fasting period for the normal subjects. Insulin secretion rates were calculated from the peripheral C-peptide concentration profiles. Ultradian oscillations of glucose levels and insulin secretion rates were evident during fasting in all subjects. An additional study with blood sampling at 2-min intervals for 8 h further indicated that this ultradian periodicity is expressed independently of rapid 10–15 min insulin oscillations. There were no differences between diabetic and nondiabetic subjects in the frequency of the ultradian oscillations of insulin secretion (which averaged 12–15 oscillations per 24 h) and in the rate of concomitancy of oscillations of insulin secretion with oscillations in glucose levels, which averaged 63–65%. The relative amplitudes of both the insulin and glucose oscillations were also similar in diabetic and nondiabetic subjects. The major abnormality in patients with Type 2 diabetes was evidenced by spectral analysis, and confirmed by calculations of the distributions of inter-pulse intervals. It consisted of a slowing of the glucose oscillations, without a similar slowing of the oscillations in insulin secretion. This slowing of the glucose oscillations in fasting Type 2 diabetic patients is consistent with our previous observations of sluggish and irregular glucose oscillations in diabetic subjects receiving mixed meals. This partial dissociation between the oscillatory patterns of insulin secretion and glucose levels could represent a sensitive quantitative marker of the breakdown of the insulin-glucose feedback loop in diabetes.

Key words

Ultradian oscillations insulin secretion glucose spectral analysis pulse temporal pattern 

References

  1. 1.
    Lang DA, Matthews DR, Phil D, Peto J, Turner RC (1979) Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. N Engl J Med 301: 1023–1027PubMedGoogle Scholar
  2. 2.
    Hansen BC, Jen KL, Pek SB, Wolfe RA (1982) Rapid oscillations in plasma insulin, glucagon, and glucose in obese and normal weight humans. J Clin Endocrinol Metab 54: 785–792PubMedGoogle Scholar
  3. 3.
    Kraegen EW, Young JD, George EP, Lazarus L (1972) Oscillations in blood glucose and insulin after oral glucose. Horm Metab Res 4: 409–413PubMedGoogle Scholar
  4. 4.
    Simon C, Brandenberger G, Follenius M (1987) Ultradian oscillations of plasma glucose, insulin, and C-peptide in man during continuous enteral nutrition. J Clin Endocrinol Metab 64: 669–674PubMedGoogle Scholar
  5. 5.
    Shapiro ET, Tillil H, Polonsky KS, Fang VS, Rubenstein AH, Van Cauter E (1988) Oscillations in insulin secretion during constant glucose infusion in normal man: relationship to changes in plasma glucose. J Clin Endocrinol Metab 67: 307–314PubMedGoogle Scholar
  6. 6.
    Polonsky KS, Given BD, Van Cauter E (1988) Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 81: 442–448PubMedGoogle Scholar
  7. 7.
    Van Cauter E, Desir D, Decoster C, Féry F, Balasse EO (1989) Nocturnal decrease of glucose tolerance during constant glucose infusion. J Clin Endocrinol Metab 69: 604–611PubMedGoogle Scholar
  8. 8.
    Simon C, Follenius M, Brandenberger G (1987) Postprandial oscillations of plasma glucose, insulin and C-peptide in man. Diabetologia 30: 769–773CrossRefPubMedGoogle Scholar
  9. 9.
    Polonsky KS, Given BD, Hirsch LJ et al. (1988) Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 318: 1231–1239PubMedGoogle Scholar
  10. 10.
    Marsh BD, Marsh DJ, Bergman RN (1986) Oscillations enhance the efficiency and stability of glucose disposal. Am J Physiol 250: E576-E582PubMedGoogle Scholar
  11. 11.
    Sturis J, Van Cauter E, Blackman JD, Polonsky KS (1991) Entrainment of pulsatile insulin secretion by oscillatory glucose infusion. J Clin Invest 87: 439–445PubMedGoogle Scholar
  12. 12.
    Sturis J, Polonsky KS, Mosekilde E, Van Cauter E (1991) Computer model for mechanisms underlying ultradian oscillations of insulin and glucose. Am J Physiol 260: E801-E809PubMedGoogle Scholar
  13. 13.
    Shapiro ET, Polonsky KS, Copinschi G et al. (1991) Nocturnal elevation of glucose levels during fasting in noninsulin-dependent diabetes. J Clin Endocrinol Metab 72: 444–454PubMedGoogle Scholar
  14. 14.
    Eaton RP, Allen RC, Schade DS, Erickson KM, Standefer J (1980) Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. J Clin Endocrinol Metab 51: 520–528PubMedGoogle Scholar
  15. 15.
    Polonsky KS, Licinio-Paixao J, Given BD et al. (1986) Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest 77: 98–105PubMedGoogle Scholar
  16. 16.
    Morgan C, Lazarow A (1963) Immunoassay of insulin: two antibody systems: plasma insulin levels of normal, subdiabetic and diabetic rats. Diabetes 12: 115–126Google Scholar
  17. 17.
    Faber OK, Binder C, Markussen J et al. (1978) Characterization of seven C-peptide antisera. Diabetes 27 [Suppl 1]: 170–177PubMedGoogle Scholar
  18. 18.
    Cleveland W (1979) Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc 74: 829–836Google Scholar
  19. 19.
    Van Cauter E (1988) Estimating false-positive and false-negative errors in analyses of hormonal pulsatility. Am J Physiol 254: E786-E794PubMedGoogle Scholar
  20. 20.
    Jenkins GM, Watts DG (1968) Spectral analysis and its application. Holden Day, San FranciscoGoogle Scholar
  21. 21.
    Simon C, Brandenberger G, Follenius M, Schlienger JL (1991) Alteration in the temporal organisation of insulin secretion in Type 2 (non-insulin-dependent) diabetic patients under continuous enteral nutrition. Diabetologia 34: 435–440PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • J. Sturis
    • 1
    • 2
  • K. S. Polonsky
    • 1
  • E. T. Shapiro
    • 1
  • J. D. Blackman
    • 1
  • N. M. O'Meara
    • 1
  • E. Van Cauter
    • 1
    • 3
  1. 1.Department of MedicineUniversity of ChicagoChicagoUSA
  2. 2.Physics Laboratory IIITechnical University of DenmarkLyngbyDenmark
  3. 3.Institute of Interdisciplinary ResearchFree University of BrusselsBrusselsBelgium

Personalised recommendations