Summary
The effect of metformin on Type 1 (insulin-dependent) diabetes has been assessed with the artificial pancreas. Fourteen Type 1 diabetic patients of normal body weight received in addition to their usual insulin therapy 850 mg metformin or placebo three times a day for 4–6 weeks. The sequence was placebo-metformin in eight patients and metformin-placebo in the other six. On the last day of metformin or placebo treatment, an artificial pancreas was used for about 36 h to assess insulin requirement. There was a 25.8% reduction in insulin requirement during metformin management despite slightly lower blood glucose levels (5.25±0.20 versus 5.98±0.18 mmol/l, P<0.01). Maximum reduction (about 50%) occurred 2 h after both lunch and dinner. There was no nocturnal effect. A marked decrease in specific insulin binding before metformin was found (0.56 + 0.27% to 107 monocytes versus 2.82±0.75 of control subjects) and significant increase after metformin (1.36±0.36%, p<0.05). There were no significant changes in blood lactate, total and HDL-cholesterol, triglycerides and C-peptide levels.
These results show that insulin receptor binding is diminished in Type 1 diabetes, perhaps as a consequence of higher peripheral blood insulin levels and that metformin can improve binding, and so reduce the amount of insulin needed to reach euglycaemia. The insulin sparing effect is greatest after meals, and interference with intestinal absorption of sugars may also be important. It follows that metformin could be usefully administered to Type 1 diabetic patients with unimpaired liver and renal function to reduce their insulin requirement.
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References
Nattrass M, Alberti KGGM (1978) Biguanides. Diabetologia 14: 71–74
Cohen D, Pezzino V, Vigneri R, Avola R, D'Agata R, Polosa P (1980) Phenformin increases insulin binding to human culture breast cancer cells. Diabetes 29: 329–331
Vigneri R, Pezzino V, Wong KJ, Goldfine ID (1982) Comparison of the in vitro effect of biguanides and sulfonylureas on insulin binding to its receptors in target cells. J Clin Endocrinol Metab 54: 95–100
Kreisberg RA, Birmingham MD (1968) Glucose metabolism in normal and obese subjects. Effect of phenformin. Diabetes 17: 481–488
Czyzyk A, Tawecky J, Sadowsky J, Ponikowska I, Szczepanik Z (1968) Effect of biguanides on intestinal absorption of glucose. Diabetes 17: 492–498
Creutzfeldt W, Willms B, Caspary W (1971) The mechanism of action of the blood glucose lowering biguanides. In: Rodriguez RR, Vallance-Owen J (eds) Diabetes. Proceedings of the VII Congress of the International Diabetes Federation, Buenos Aires 1970. Excerpta Medica, Amsterdam, pp 708–719
Bloom A, Kolbe RJ (1970) Phenformin in insulin-dependent diabetes. Br Med J 1: 660–662
Gin H, Slama G, Weissbrodt P, Poyanard T, Vexiau P, Klein JC, Tchobrousky G (1982) Metformin reduces post-prandial insulin needs in Type 1 (insulin-dependent) diabetic patients: assessment by artificial pancreas. Diabetologia 23: 34–36
Noll F (1970) L-Lactat: Bestimmung mit LDH, GPT und NAD. In: Bergmayer HU (ed) Methoden der enzymatischen Analyse (2nd edn). Verlag Chemie Weinheim, New York, London pp 1433–1437
Warnick RG, Albers JJ (1978) A comprehensive evaluation of the heparin-manganese precipitation for estimating high density lipoprotein-cholesterol. J Lipid Res 19: 65–76
Eggstein M, Kuhlman E (1970) Triglyceride und Glycerine. In: Bergmayer HU (ed) Methoden der enzymatischen Analyse (2nd edn). Verlag Chemie Weinheim, New York, London pp1765–1771
Melani F, Rubenstein AH, Oyer PE, Steiner DF (1970) Identification of proinsulin and C-peptide in human serum by specific immunoassay. Proc Nat Acad Sci 67: 148–166
Böyum A (1974) Separation of blood leucocytes, granulocytes and lymphocytes. Tissue Antigens 4: 269–274
Pagano G, Cassader M, Massobrio M, Bozzo C, Trossarelli GF, Menato G, Lenti G (1980) Insulin binding to human adipocytes during late pregnancy in healthy, obese and diabetic state. Horm Metab Res 12: 177–181
Beck-Nielsen H, Pedersen O, Lindskov HO (1979) Increased insulin sensitivity and cellular insulin binding in obese diabetics following treatment with glibenclamide. Acta Endocrinologica 90: 451–462
Bar RS, Gorden P, Roth J, Kahn CR, De Meyts P (1976) Fluctuation in the affinity and concentration of insulin receptors on circulating monocytes of obese patients. Effect of starvation, refeeding and dieting. J Clin Invest 58: 1123–1135
Holle A, Mangels W, Dreyer M, Kuhnau J, Rudiger HW (1981) Biguanide treatment increases the number of insulin-receptor sites on human erythrocytes. New Engl J Med 305: 563–566
Mehnert H (1969) Pharmacokinetics of blood glucose lowering biguanides derivatives. Act Diabet Lat 6 (Suppl 1): 137–142
Luft D, Schmulling RM, Eggstein M (1978) Lactic acidosis in biguanide-treated diabetics. Diabetologia 14: 75–87
Owen WC, Kreisberg RA, Siegal AM (1971) Carbohydrate-induced hypertriglyceridemia: inhibition by phenformin. Diabetes 20: 739–744
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Pagano, G., Tagliaferro, V., Carta, Q. et al. Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes. Diabetologia 24, 351–354 (1983). https://doi.org/10.1007/BF00251823
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DOI: https://doi.org/10.1007/BF00251823