Summary
In type 2 diabetes with “secondary failure of sulfonylurea therapy” good metabolic control can seldom be achieved by insulin therapy even with high insulin doses. Hyperinsulinemia however is a possible risk factor of cardiovascular disease in type 2 diabetes. Maintaining the effects of sulfonylurea action insulin should be added in as small amounts as possible to avoid hyperinsulinemia and to ameliorate hyperglycemia.
16 type 2 diabetics with “secondary failure” were treated either with insulin alone (group A;n=8) or with 3.5 mg b.i.d glibenclamide plus small amounts of intermediate insulin (group B;n=8) in a randomised order. After the inpatient period outpatient control was performed monthly up to six months, later on four times a year up to two years.
Both groups were comparable with regard to age, duration of diabetes, body weight and metabolic control. The daily insulin dose was 14±2 IU\((\bar x \pm SEM)\) after one month and 19±2 IU after two years in group B. In contrast 30±3 IU and 43±5 IU respectively were needed in group A (p<0.001). All patients B were treated with one daily injection, all patients A needed two injections. Resulting in nearly identical metabolic control in group A basal insulin levels exceeded those in group B after two years significantly (28.6±3.7 vs. 18.6±1.6 mcU/ml;p<0.01). Endogenous C-peptide response was suppressed in group A compared to group B after inpatient period and after one month (0.12±0.01 vs. 0.49±0.15 and 0.09±0.04 vs. 0.13±0.08 pmol/ml;p<0.05). The combined therapy of insulin and sulfonylureas demonstrates the benefit of a prolonged sulfonylurea administration in the treatment of type 2 diabetes with “secondary failure”.
As compared to common insulin therapy a small amount of exogenous insulin by one daily injection additionally to glibenclamide shows similar improvement in metabolic control. Hyperinsulinemia as a risk factor of macroangiopathy is markedly reduced in patients treated with combined therapy compared to those with insulin alone.
Similar content being viewed by others
Literatur
Bachmann W, Sieger C, Haslbeck M, Lotz N (1981) Combination of insulin and glibenclamide in the treatment of adult onset diabetes (type 2). Diabetologia 21:245
Bachmann W, Sieger C, Lotz N (1983) Kombinationstherapie Insulin/Glibenclamid bei Typ-II-Diabetikern mit relativer Insulinresistenz. In: Bachmann W, Mehnert H (Hrsg) Kombinationstherapie Insulin/Sulfonylharnstoff, Karger, Basel S 145–150
Beck-Nielsen H, Pedersen O, Lindskov HO (1979) Increased insulin sensitivity and cellular insulin binding in obese diabetics following treatment with glibenclamide. Acta endocr (Kbh.) 90:451
Fabrykant M (1959) Favorable effects of supplemental orinase in insulin-treated diabetics. Metabolism 6:509
Fabrykant M, Ashe BJ (1959) Combined insulin-tolbuta-mide therapy in the management of insulin-dependent diabetes. Ann NY Acad Sci 82:585
Groop L, Harno K (1979) The combination of insulin and sulfonylureas — an approach to improved metabolic control in insulin resistant diabetics. Acta Endocrinol 91 (Suppl 227):29
Henrichs HR (1983) Kombinierte Sulfonylharnstoff-Insulin-Therapie bei Diabetes mellitus nach Tablettensekundärversagen — praktisches Vorgehen. In: Bachmann W, Mehnert H (Hrsg) Kombinationstherapie Insulin/Sulfonylharnstoff, Karger, Basel S 106–116
Hofherr C, Haslbeck M, Baldermann H, Lotz N, Mehnert H (1988) Nachuntersuchungen bei Typ-II-Diabetikern mit Sekundärversagen oraler Antidiabetika nach Umstellung auf Insulin. Akt Endokr Stoffw 9:130–131
Klein W (1983) Die Kombination Insulin/Glibenclamid bei Sekundärversagen der Sulfonylharnstofftherapie. In: Bachmann W, Mehnert H (Hrsg) Kombinationstherapie Insulin/Sulfonylharnstoff, Karger, Basel S 117–123
Lotz N, Sieger C, Bachmann W (1983) Kombinationstherapie von Glibenclamid plus Insulin bei Typ-II-Diabetes mit „Sekundärversagen“ einer Sulfonylharnstofftherapie. In: Bachmann W, Mehnert H (Hrsg) Kombinationstherapie Insulin/Sulfonylharnstoff, Karger, Basel S 124–131
Lotz N, Bachmann W, Haslbeck M, Mehnert H (1984) Haben Sulfonylharnstoffe bei Typ-II-Diabetikern im sogenannten Sekundärversagen noch einen therapeutischen Effekt? Verh Dtsch Ges Inn Med 90:475–477
Lotz N, Bachmann W, Mehnert H (1988) Die Kombination von Sulfonylharnstoff und Insulin in der Langzeittherapie des „Sekundärversagens“ bei Typ-II-Diabetes. In: Bachmann W, Lotz N, Mehnert H (Hrsg) Insulin/Sulfonylharnstoff. Karger, Basel S 137–152
Marschall M, Wiederholt R, Setiakusuma I, Henrichs HR (1981) Klinische Untersuchungen zur Sulfonylharnstoff — Insulin — Kombinationstherapie beim Diabetes nach Tablettenversagen. Akt Endokr 2:104
Olefsky JM, Reaven GM (1974) Decreased insulin binding to lymphocytes from diabetic patients. J Clin Invest 54:1323
Olefsky JM, Reaven GM (1976) Insulin binding to monocytes and total mononuclear leucocytes from normal and diabetic patients. J Clin Endocr 43:226
Olefsky JM, Reaven GM (1976) Effects of sulfonylurea therapy on insulin binding to mononuclear leukocytes of diabetic patients. Amer J Med 60:89
Olefsky JM, Reaven GM (1977) Insulin binding in diabetics. Relationship with plasma insulin levels and insulin sensitivity. Diabetes 26:680
Otto H, Mikosch M, Otto-Bendfeldt E (1966) Indikationen für die kombinierte Anwendung von Insulin und Sulfonylharnstoffen in der Diabetesbehandlung. Med Welt (Stuttg) 36:1864
Pyörälä K (1979) Relationship of glucose tolerance and plasma insulin to the incidence of coronary heart disease. Results from two population studies in Finland. Diabetes Care 2:131
Stout RW (1979) Diabetes and atherosclerosis — the role of insulin. Diabetologia 16:141
Stratmann FW: Über Spätversager bei der peroralen Diabetes-Therapie und ihre kombinierte Behandlung. Med. Klin. 52:583 (1957)
Volk BW, Lazarus SS (1959) Significance of effectiveness of combined insulin — orinase treatment in maturity — onset diabetes. Amer J med Sci 237:1
Author information
Authors and Affiliations
Additional information
Herrn Professor Dr. N. Zöllner zum 65. Geburtstag gewidmet
Rights and permissions
About this article
Cite this article
Lotz, N., Bachmann, W., Ladik, T. et al. Die Kombinationstherapie Insulin/Sulfonylharnstoff in der Langzeittherapie des Typ-II-Diabetes nach „Sekundärversagen“. Klin Wochenschr 66, 1079–1084 (1988). https://doi.org/10.1007/BF01711922
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01711922