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Reduced glucose effectiveness as a feature of glucose intolerance: Evidence in elderly Type-2 diabetic subjects

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Abstract

One of the factors determining glucose tolerance is glucose disappearance independent from the dynamic insulin (glucose effectiveness); the debate on its role in the development of Type-2 diabetes is still open. The aim of the present study was to evaluate insulin delivery, insulin sensitivity (Sj), and glucose effectiveness (SG) in a group of elderly Type-2 diabetic patients (D, 4/6 F/M, age 67±2 years, 64±2 kg, BMI 23.8±0.5 kg/m2), compared to young controls (C, 4/6 F/M, 25±2 years, 72±4 kg, 23.7±1.1 kg/m2) and elderly controls (E, 2/4 F/M, 73±3 years, 63±4 kg, 23.1 ±0.5 kg/m2). We performed oral (OGTT) and intravenous (FSIGT) glucose tolerance tests. The OGTT showed that C and E were normotolerant, while D had a markedly reduced glucose tolerance. This was also confirmed in the FSIGT where the glucose tolerance index (KG) was 0.6±0.1% min−1 in D vs 1.8±0.2 in C and 1.5±0.2 in E (p<0.0002). Total insulin area of D and the overall insulin delivery were not different from those of the control groups. The early phase area was instead significantly reduced (0.19±0.02 mU min/mL vs 0.61±0.06 of C and 0.46±0.06 of E, p<0.001) given the reduction in the dynamic first-phase insulin delivery (0.86±0.17 min(μU/mL)/(mg/dL) vs 3.95±0.61 in C (p<0.005) and 2.61 ±0.66 (p<0.001) in E). S1 of D was 3.4±0.4 10−4min−1/(μU/mL), not different from that of C (4.7±0.6) and E (3.5±0.2). This study showed a marked difference between SG of D and that of both control groups [0.010±0.001 min−1 vs 0.026±0.004 (p<0.001) of C and 0.020±0.003 (p<0.002) of E], mostly due to the zero-insulin component GEZI which was 0.006±0.001 in D vs 0.021±0.004 in C and 0.016±0.003 in E (p<0.003). In the elderly groups, when taken together, SG exhibited a positive correlation with the area under insulin concentration during the early phase and with KG (r=0.69, p=0.0032 and r=0.90, p=0.0001, respectively), demonstrating the importance of the first-phase insulin delivery in modulating glucose effectiveness and glucose tolerance.

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References

  1. Fink R.I., Kolterman O.G., Griffin J., Olefsky J.M.: Mechanisms of insulin resistance in aging. J. Clin. Invest. 71: 1523–1535, 1983.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chen M., Bergman R.N., Pacini G., Porte D.Jr.: Pathogenesis of age-related glucose intolerance in man: insulin resistance and decreased beta cell function. J. Clin. Endocrinol. Metab. 60: 13–20, 1985.

    Article  CAS  PubMed  Google Scholar 

  3. Chen M., Bergman R.N., Porte D.Jr.: Insulin resistance and beta cell dysfunction in aging: the importance of dietary carbohydrate. J. Clin. Endocrinol. Metab. 67: 951–957, 1988.

    Article  CAS  PubMed  Google Scholar 

  4. Pacini G., Valerio A., Beccaro F., Nosadini R., Cobelli C., Crepaldi G.: Insulin sensitivity and beta cell responsivity are not decreased in elderly subjects with normal OGTT. J. Am. Geriatr. Soc. 36: 317–323, 1988.

    Article  CAS  PubMed  Google Scholar 

  5. Kahn S.E., Larson V.G., Beard J.C, Cain K.C., Fellingham G.W., Schwartz R.S., Veith R.C., Stratton J.R., Cerqueira M.D., Abrass I.B.: Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging. Am. J. Physiol. 258: E937–E943, 1990.

    CAS  PubMed  Google Scholar 

  6. Harris M.I., Hadden W.C., Knowler W.C., Bennett P.H.: Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in US population aged 20–74 yr. Diabetes 36: 523–534, 1987. [

    Article  CAS  PubMed  Google Scholar 

  7. Ahrén B., Pacini G.: Age-related reduction in glucose elimination is accompanied by reduced glucose effectiveness and increased hepatic insulin extraction in man. J. Clin. Endocrinol. Metab. 83: 3350–3356, 1998.

    PubMed  Google Scholar 

  8. Pacini G., Bergman R.N.: MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Comput. Methods Programs Biomed. 23: 113–122, 1986.

    Article  CAS  PubMed  Google Scholar 

  9. Bergman R.N.: Toward physiological understanding of glucose tolerance. Minimal model approach. Diabetes 38: 1512–1527, 1989.

    Article  CAS  PubMed  Google Scholar 

  10. Finegood D.T.: Application of the minimal model of glucose kinetics. In: Bergman R.N., Lovejoy J.C. (Eds.), The minimal model approach and determinants of glucose tolerance. LSU Press, Baton Rouge, LA, 1997, pp. 51–122.

    Google Scholar 

  11. Best J.D., Kahn S.E., Ader M., Watanabe R.M., Ni T-.C, Bergman R.N.: Role of glucose effectiveness in the determination of glucose tolerance. Diabetes Care 19: 1018–1030, 1996.

    Article  CAS  PubMed  Google Scholar 

  12. Basu A., Caumo A., Bettini F., Gelisio A., Alzaid A., Cobelli C., Rizza R.: Impaired basal glucose effectiveness in NIDDM. Dia-betes 46: 421–432, 1997.

    CAS  Google Scholar 

  13. Kahn S.E., Klaff L.J., Schwartz M.W., Beard J.C., Bergman R.N., Taborsky G.J.Jr.: Treatment with a somatostatin analog decreases pancreatic beta cell and whole body sensitivity to glucose. J. Clin. Endocrinol. Metab. 71: 994–1002, 1990.

    Article  CAS  PubMed  Google Scholar 

  14. Meneilly G.S., Elahi D., Minaker K.L., Sclater A.L., Rowe J.W.: Impairment of noninsulin-mediated glucose disposal in the elderly. J. Clin. Endocrinol. Metab. 63: 566–571, 1989.

    Article  Google Scholar 

  15. Welch S., Gebhart S.S.P., Bergman R.N., Phillips L.S.: Minimal model analysis of intravenous glucose tolerance test-derived insulin sensitivity in diabetic subjects. J. Clin. Endocrinol. Metab. 71: 1508–1518, 1990.

    Article  CAS  PubMed  Google Scholar 

  16. Taniguchi A., Nakai Y., Fukushima M., Kawamura H., Imura H., Nagata I.: Pathogenic factors responsible for glucose intolerance in patients with NIDDM. Diabetes 41: 1540–1546, 1992.

    Article  CAS  PubMed  Google Scholar 

  17. Alzaid A.A., Dinneen S.F., Turk D.J., Caumo A., Cobelli C., Rizza R.A.: Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans. J. Clin. Invest 94: 2341–2348, 1994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Meneilly G.S., Elliott T., Tessier D., Hards L., Tildesley H.: NIDDM in the elderly. Diabetes Care 19: 1320–1325, 1996.

    Article  CAS  PubMed  Google Scholar 

  19. Pacini G., Tonolo G., Sambataro M., Maioli M., Ciccarese M., Brocco E., Avogaro A., Nosadini R.: Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT. Am. J. Physiol. 274: E592–E599, 1998.

    CAS  PubMed  Google Scholar 

  20. Ward W.K., Bolgiano D.C., McKnight B., Halter J.B., Porte D.Jr.: Diminished beta cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J. Clin. Invest. 74: 1318–1328, 1984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pacini G., Beccaro F., Valerio A., Nosadini R., Crepaldi G.: Reduced beta cell secretion and insulin hepatic extraction in healthy elderly subjects. J. Am. Geriatr. Soc. 38: 1283–1289, 1990.

    Article  CAS  PubMed  Google Scholar 

  22. Pacini G., Cobelli C.: A minimal model of C-peptide secretion and kinetics: fundamentals and clinical use. In: Cobelli C., Mariani L. (Eds.), Modelling and control in biomedical systems. Pergamon, Oxford, UK, 1989, pp. 363–369.

    Google Scholar 

  23. Thomaseth K., Pacini G.: Effects of measured glucose and insulin concentration on the accuracy of Sj and SG. In: Bergman R.N., Lovejoy J.C. (Eds.), The minimal model approach and determinants of glucose tolerance. LSU Press, Baton Rouge, LA, 1997, pp. 187–201.

    Google Scholar 

  24. Finegood D.T., Tzur D.: Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal model method. Am. J. Physiol. 271: E485–E495, 1996.

    CAS  PubMed  Google Scholar 

  25. Ader M., Ni T-C., Bergman R.N.: Glucose effectiveness assessed under dynamic and steady state conditions. Comparability of uptake versus production components. J. Clin. Invest. 99: 1187–1199, 1997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Luzi L., De Fronzo R.A.: Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans. Am. J. Physiol. 257: E241–E246, 1989.

    CAS  PubMed  Google Scholar 

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Viviani, G.L., Pacini, G. Reduced glucose effectiveness as a feature of glucose intolerance: Evidence in elderly Type-2 diabetic subjects. Aging Clin Exp Res 11, 169–175 (1999). https://doi.org/10.1007/BF03399659

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