Abstract
Since Wilkins first described chlorothiazide-induced glucose intolerance in 1959 [1], the literature has been replete with further reports and discussions of this phenomenon. Impairment of carbohydrate metabolism by the benzothiadizines has been found in both nondiabetic [2–11] and diabetic [8, 12–16] subjects. However, the mechanism(s) by which the thiazides induce glucose intolerance remains subject to dispute. Decreased insulin secretion by the pancreas [17–20], decreased tissue sensitivity to insulin [9, 21, 22], increased insulin output, accelerating the development of insulin depletion in the prediabetic state [8], and an effect on the enteropancreatic insulin axis [23] have all been implicated. Such physiologic alterations of carbohydrate economy may be a consequence of a direct effect of the benzothiadiazine molecule at any or all of the loci which participate in this economy or the consequence of potassium deficiency induced by the diuretic, as has been suggested by others [23, 24]. This paper reports experiments designed to examine the effect of thiazides on the carbohydrate metabolism of normal men in whom potassium depletion was prevented. The studies seek to determine if glucose intolerance is demonstrabable and to identify the locus of any observed alteration. We have utilized a negative feedback infusion protocol which creates steady state plasma glucose concentrations during experimental perturbation [25]. This “clamp technique” permits quantification of
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1.
glucose tolerance;
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beta cell sensitivity to hyperglycemia;
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endocrine gut cell sensitivity to ingested glucose;
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4.
beta cell sensitivity to gastric inhibitory polypeptide (GIP); and
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tissue sensitivity to insulin.
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References
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© 1986 Springer-Verlag Berlin Heidelberg
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Helderman, J.H. et al. (1986). Prevention of the Glucose Intolerance of Thiazide Diuretics by Maintenance of Body-Potassium. In: Krück, F., Schrey, A. (eds) Diuretika III. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71487-0_10
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DOI: https://doi.org/10.1007/978-3-642-71487-0_10
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