Hepatic and peripheral insulin resistance: A common feature of Type 2 (non-insulin-dependent) and Type 1 (insulin-dependent) diabetes mellitus (original) (raw)

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Hepatic glucose production (3H-glucose technique) and insulin-mediated glucose uptake (insulin clamp technique) were measured in 38 Type 2 (non-insulin-dependent) and 11 Type 1 (insulin-dependent) diabetic patients. Fasting plasma glucose concentration was 8.3 ± 0.5 mmol/l in the former, and 9.6 ± 1.3 mmol/1 in the latter group; the respective fasting plasma insulin levels were 19 ± 2 mU/l (p < 0.005 versus 13 ± 1 mU/l in 33 age-matched control subjects), and 9 ± 1 mU/l (_p_ < 0.01 versus 14 ± 1 mU/l in 36 younger control subjects). In the fasting state, hepatic glucose production was slightly increased (15%, 0.1 > p > 0.05) in the Type 2 diabetic patients and markedly elevated (65%, p < 0.001) in the Type 1 patients compared with their respective control groups. In both groups of diabetic subjects, the rates of hepatic glucose production were inappropriately high for the prevailing plasma glucose and insulin levels, indicating the presence of hepatic resistance to insulin. Basal plasma glucose clearance was also significantly reduced in both the Type 2 (34%) and the Type 1 (14%) diabetic subjects. The fasting plasma glucose concentration correlated directly with hepatic glucose production, and inversely with plasma glucose clearance. During the insulin clamp, plasma insulin was maintained at approximately 100 mU/l in all groups, while plasma glucose was maintained constant at the respective fasting levels. Total glucose uptake was reduced in both the Type 2 (4.57 ± 0.31 versus 6.39 ± 0.25 mg · min–1 · kg–1 in the control subjects, p < 0.01) and the Type 1 (4.77 ± 0.48 versus 7.03 ± 0.22 mg · min–1 · kg–1, p < 0.01) diabetic patients. Insulin-stimulated glucose clearance was reduced to a similar extent in Type 2 (54%) and Type 1 (61%) diabetic subjects, and correlated directly with fasting glucose clearance. These results show that insulin resistance is a common feature of both types of diabetes and can be demonstrated in the basal as well as the insulin-stimlated state. Both hepatic and peripheral resistance to the action of insulin contribute to diabetic hyperglycaemia.

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References

  1. DeFronzo RA, Tobin J, Andres R (1979) The glucose clamp technique. A method for the quantification of beta cell sensitivity to glucose and of tissue sensitivity to insulin. Am J Physiol 237: 214–223
    Google Scholar
  2. Olefsky JM (1980) Insulin resistance and insulin action. An in vitro and in vivo perspective. Diabetes 30: 148–162
    Google Scholar
  3. Harrison LC, Martin FIR, Melick RA (1976) Correlation between insulin receptor binding in isolated fat cells and insulin sensitivity in obese human subjects. J Clin Invest 58: 1435–1441
    Google Scholar
  4. Beck-Nielsen H (1978) The pathogenic role of an insulin receptor defect in diabetes mellitus of the obese. Diabetes 27: 1175–1181
    Google Scholar
  5. Himsworth HP, Kerr RB (1939) Insulin-sensitive and insulin-insensitive types of diabetes mellitus. Clin Sci 4: 119–152
    Google Scholar
  6. Zierler KL, Rabinowitz D (1963) Roles of insulin and growth hormone, based on studies of forearm metabolism in man. Medicine 43: 385–402
    Google Scholar
  7. Jackson RA, Perry G, Rogers J, Advani V, Piklington TRE (1973) Relationship between the basal glucose concentration, glucose tolerance and forearm glucose uptake in maturity-onset diabetes. Diabetes 22: 751–761
    Google Scholar
  8. Butterfield WJH, Whichelow MJ (1965) Peripheral glucose metabolism in control subjects and diabetic patients during glucose, glucose-insulin and insulin sensitivity tests. Diabetologia 1: 43–53
    Google Scholar
  9. Ginsberg H, Kimmerling G, Olefsky JM, Reaven GM (1975) Demonstration of insulin resistance in untreated adult-onset diabetic subjects with fasting hyperglycemia. J Clin Invest 55: 454–461
    Google Scholar
  10. Harano Y, Ohgaku S, Hidaka H, Haneda K, Kikkawa R, Shigeta Y, Abe H (1977) Glucose, insulin and somatostatin infusion for the determination of insulin sensitivity. J Clin Endocrinol Metab 45: 1124–1127
    Google Scholar
  11. Forbath N, Hetenyi G (1966) Glucose dynamics in normal subjects and diabetic patients before and after a glucose load. Diabetes 15: 778–789
    Google Scholar
  12. Bowen HF, Moorhouse JA (1973) Glucose turnover and disposal in maturity-onset diabetes. J Clin Invest 52: 3033–3044
    Google Scholar
  13. Manougan E, Pollycove M, Linfoot JA, Lawrence JH (1964) 14C-glucose kinetic studies in normal, diabetic, and acromegalic subjects. J Nucl Med 5: 763–795
    Google Scholar
  14. Harano Y, Ohgaku S, Kosugi K, Yasuda H, Nakano T, Kobayashi M, Hidaka H, Izumi K, Kashiwagi A, Shigeta Y (1981) Clinical significance of altered insulin sensitivity in diabetes mellitus assessed by glucose, insulin and somatostatin infusion. J Clin Endocrinol Metab 52: 982–987
    Google Scholar
  15. Ginsberg HN (1977) Investigation of insulin sensitivity in treated subjects with ketosis-prone diabetes mellitus. Diabetes 26: 278–283
    Google Scholar
  16. DeFronzo RA (1979) Glucose intolerance and aging. Evidence for tissue insensitivity to insulin. Diabetes 28: 1095–1101
    Google Scholar
  17. DeFronzo RA, Ferrannini E (1981) Interrelationships between plasma glucose and insulin concentration and glucose uptake in man. Diabetes (in press)
  18. Cherrington AD, Williams PE, Harris MS (1978) Relationship between the plasma glucose level and glucose uptake in the conscious dog. Metabolism 27: 787–791
    Google Scholar
  19. Steele R (1959) Influence of glucose loading and of injected insulin on hepatic glucose output. Arm NY Acad Sci 82: 42CM30
    Google Scholar
  20. Rosselin GRS, Assan RS, Yalow R, Berson SA (1966) Separation of antibody-bound and unbound peptide hormones labelled with iodine131 by talcum powder and precipitated silica. Nature 194: 495–496
    Google Scholar
  21. Kuzuya H, Blix PM, Horowitz DL, Steiner D, Rubenstein AH (1977) Determination of free and total insulin and C-peptide in insulin-treated diabetics. Diabetes 26: 22–29
    CAS PubMed Google Scholar
  22. DeFronzo RA, Deibert D, Hendler R, Felig P, Soman V (1979) Insulin sensitivity and insulin binding to monocytes in maturity-onset diabetics. J Clin Invest 63: 939–946
    Google Scholar
  23. DeFronzo RA, Ferrannini E, Wahren J (1978) Regulation of hepatic glucose metabolism by IV insulin and glucose. Diabetes 28: 379 (Abstract)
    Google Scholar
  24. Berger W, Goschke H, Moppert J, Kunzli H (1973) Insulin concentrations in portal venous and peripheral venous blood in man following administration of glucose, galactose, xylitol and tolbutamide. Horm Metab Res 5: 4–8
    Google Scholar
  25. DeFronzo RA, Ferrannini E, Hendler R, Wahren J, Felig P (1978) Influence of hyperinsulinemia, hyperglycemia and the route of glucose administration on splanchnic glucose exchange. Proc Natl Acad Sci USA 75: 5173–5177
    Google Scholar

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  1. Department of Medicine, Yale University School of Medicine, New Haven, Connectitut, USA
    R. A. DeFronzo, D. Simonson & E. Ferrannini

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  1. R. A. DeFronzo
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  2. D. Simonson
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  3. E. Ferrannini
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DeFronzo, R.A., Simonson, D. & Ferrannini, E. Hepatic and peripheral insulin resistance: A common feature of Type 2 (non-insulin-dependent) and Type 1 (insulin-dependent) diabetes mellitus.Diabetologia 23, 313–319 (1982). https://doi.org/10.1007/BF00253736

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