Br. J. clin. Pharmac. (1977), 4,455-458
EFFECT OF CLOFIBRATE ON GLUCOSE TOLERANCE IN MATURITY ONSET DIABETES D. BARNETT & J.G. CRAIG St. James's University Hospital, Leeds
D.S. ROBINSON & M. PERENNA ROGERS Department of Biochemistry, University of Leeds, Leeds
I Fourteen maturity onset diabetics showed improvement of glucose tolerance while on treatment with clofibrate. Fasting blood glucose levels were reduced by 20% after treatment for 14 and 28 days. 2 The effect was found to be independent of concurrent treatment with oral hypoglycaemic drugs. 3 Plasma insulin levels were also lower during clofibrate treatment. 4 Clofibrate may prove to be a useful adjunct to the treatment of maturity onset diabetes.
Introduction An improvement of glucose tolerance in diabetics treated with clofibrate was first reported in 1963 (Miller, 1963; Herriot, Percy-Robb, Strong & Thompson, 1963). This and subsequent evidence (Berkowitz, 1971; Danowski, Cohn, Limaye, Novak, Saul, Sunder & Moses, 1965; Danowski, Novak, Saul, Vester & Moses, 1966; Narduzzi, Danowski, Weir, Alley, Vester & Moses, 1967; Vester, Sunder, Aarons & Danowski, 1970) has not led to general use of clofibrate as a specific treatment of diabetes because the effect has not been reliably reproduced. The study reported here was designed to ascertain the effect of clofibrate on oral glucose tolerance in maturity onset diabetics. Methods
Eight female and six male maturity onset diabetics aged 45-64 years (mean 57.4 years) were studied. The known duration of diabetes ranged from 1 to 6 years and most were obese, the percentage of ideal body weight ranging from 102-154 (mean 124%). Stability of body weight and blood glucose levels for 3 months prior to the study were necessary criteria for entry. Five patients were receiving diet therapy alone (100-140 g carbohydrate daily) and in addition to diet, four received glibenclamide 5-15 mg daily; the remaining five patients received either biguanide (metformin or phenformin) alone or together with glibenclamide. No other regular medication was taken. Seven patients had evidence of diabetic retinopathy or premature arterial disease. The mean fasting * Present address: Department of Biochemistry, The University of Newcastle-upon-Tyne, Newcastle-upon-Tyne.
30
plasma triglyceride concentration was greater than 2.0 mmol/ in eight patients (range 2.3 to 4.8 mmol/l). All subjects were given a 4 week course of clofibrate (1 g twice daily) between two control periods of 2 and 4 weeks. For the duration of the study they were asked to observe their usual habits in relation to diet, exercise and consumption of hypoglycaemic drugs. A 2 h 50 g oral glucose tolerance test (GTT) was performed at the end of each period and a fasting venous blood sample was obtained 2 weeks prior to this; on these mornings all medication was omitted. Serial blood samples were taken through an indwelling venous cannula. Blood glucose was measured by a glucose oxidase method (Werner, Rey & Wielinger, 1970), plasma triglyceride by a manual modification of the acetylacetone method (Fletcher, 1968) and insulin by a double antibody precipitation technique (Hales & Randle, 1963). Significance of the differences between results was assessed using a paired Student's t-test. Results All subjects had lower mean blood glucose during the glucose tolerance test performed during clofibrate treatment (-1 to -45%) and, in all but one, a return to pre-treatment levels was seen during the second control period. Mean results of the glucose tolerance tests in fourteen subjects before, during and after clofibrate are shown in Figure 1 and Table 1. Compared with control, during clofibrate treatment the blood glucose was lower throughout the test (P
EFFECT OF CLOFIBRATE ON GLUCOSE TOLERANCE IN MATURITY ONSET DIABETES D. BARNETT & J.G. CRAIG St. James's University Hospital, Leeds
D.S. ROBINSON & M. PERENNA ROGERS Department of Biochemistry, University of Leeds, Leeds
I Fourteen maturity onset diabetics showed improvement of glucose tolerance while on treatment with clofibrate. Fasting blood glucose levels were reduced by 20% after treatment for 14 and 28 days. 2 The effect was found to be independent of concurrent treatment with oral hypoglycaemic drugs. 3 Plasma insulin levels were also lower during clofibrate treatment. 4 Clofibrate may prove to be a useful adjunct to the treatment of maturity onset diabetes.
Introduction An improvement of glucose tolerance in diabetics treated with clofibrate was first reported in 1963 (Miller, 1963; Herriot, Percy-Robb, Strong & Thompson, 1963). This and subsequent evidence (Berkowitz, 1971; Danowski, Cohn, Limaye, Novak, Saul, Sunder & Moses, 1965; Danowski, Novak, Saul, Vester & Moses, 1966; Narduzzi, Danowski, Weir, Alley, Vester & Moses, 1967; Vester, Sunder, Aarons & Danowski, 1970) has not led to general use of clofibrate as a specific treatment of diabetes because the effect has not been reliably reproduced. The study reported here was designed to ascertain the effect of clofibrate on oral glucose tolerance in maturity onset diabetics. Methods
Eight female and six male maturity onset diabetics aged 45-64 years (mean 57.4 years) were studied. The known duration of diabetes ranged from 1 to 6 years and most were obese, the percentage of ideal body weight ranging from 102-154 (mean 124%). Stability of body weight and blood glucose levels for 3 months prior to the study were necessary criteria for entry. Five patients were receiving diet therapy alone (100-140 g carbohydrate daily) and in addition to diet, four received glibenclamide 5-15 mg daily; the remaining five patients received either biguanide (metformin or phenformin) alone or together with glibenclamide. No other regular medication was taken. Seven patients had evidence of diabetic retinopathy or premature arterial disease. The mean fasting * Present address: Department of Biochemistry, The University of Newcastle-upon-Tyne, Newcastle-upon-Tyne.
30
plasma triglyceride concentration was greater than 2.0 mmol/ in eight patients (range 2.3 to 4.8 mmol/l). All subjects were given a 4 week course of clofibrate (1 g twice daily) between two control periods of 2 and 4 weeks. For the duration of the study they were asked to observe their usual habits in relation to diet, exercise and consumption of hypoglycaemic drugs. A 2 h 50 g oral glucose tolerance test (GTT) was performed at the end of each period and a fasting venous blood sample was obtained 2 weeks prior to this; on these mornings all medication was omitted. Serial blood samples were taken through an indwelling venous cannula. Blood glucose was measured by a glucose oxidase method (Werner, Rey & Wielinger, 1970), plasma triglyceride by a manual modification of the acetylacetone method (Fletcher, 1968) and insulin by a double antibody precipitation technique (Hales & Randle, 1963). Significance of the differences between results was assessed using a paired Student's t-test. Results All subjects had lower mean blood glucose during the glucose tolerance test performed during clofibrate treatment (-1 to -45%) and, in all but one, a return to pre-treatment levels was seen during the second control period. Mean results of the glucose tolerance tests in fourteen subjects before, during and after clofibrate are shown in Figure 1 and Table 1. Compared with control, during clofibrate treatment the blood glucose was lower throughout the test (P
