We explored whether camostat mesilate, a potent protease inhibitor, could change the blood glucose level in insulin-treated diabetic patients. Administration of camostat mesilate in a dose of 800 mg for one week caused a significant decrease in the basal and maximal level of blood glucose in response to arginine infusion. Camostat mesilate also decreased the maximal level of blood glucagon in response to arginine infusion, while its basal level was not changed by the same drug. Neither the basal level nor maximal response of blood C-peptide was changed by camostat mesilate. It is concluded from the present data that camostat mesilate may be an efficient drug in decreasing the basal and amino acid-induced level of blood glucose in insulin-treated diabetic patients; the latter reaction is attributed, at least in part, to a decrease in the blood glucagon level, but not the blood insulin level, while the former does not depend on these two endocrine factors.
The purpose of this study was to analyze the cardiac function of diabetic patients. The cardiac index, using the CO2 rebreathing technique, was determined at rest and after exercise in 20 diabetic patients (NIDDM: 17 males and three females) and in five healthy volunteers as a control (five males). No abnomalities on the electrocardiogram were found in any of the patients either at rest or after exercise. The results were as follows: 1) In comparison with the control group, there was a significant reduction of the increase in the ratio of the cardiac index in diabetics. 2) This reduction of the increase in the ratio of the cardiac index was recognized in diabetics without any other diabetic complications. 3) These phenomena were in accordance with the degree of diabetic retinopathy. In conclusion, cardiac dysfunction of diabetic patients during exercise was recognized even in the early stage of diabetes mellitus. This was thought to reflect a decrease in cardiac reserve. Cardiac dysfunction is considered to occur as a result of the following factors: a) abnormalities of contractile protein of the heart muscle; b) metabolic disturbance and c) the structural abnormalities of capillaries in the human diabetic heart as we have already reported.
The Adhoc Committee on Diabetic Twins was organized in the Japan Diabetes Society in 1984 to collect data on diabetic twins in Japan. During past 3 years, the Committee collected data on 87 pairs of twins, one or both of whom had diabetes mellitus or glucose intolerance. Among them, 63 were monozygotic and 24 were dizygotic twins. Probands, who are defined as those who developed diabetes or glucose intolerance earlier, included 21 patients with IDDM, 56 with NIDDM, one case with diabetes of unknown type, and 9 with borderline glucose intolerance. Physicians in charge of diabetic twins were asked to fill out a form for detailed informations and some additional examinations when necessary. These data were gathered and analyzed by the Committee. The Committee ended the term in 1987 after 3 year's activity, and reports on main results obtained so far. (1) Concordance rate for diabetes in monozygotic twins was 45%(5/11) in IDDM and 83%(38/46) in NIDDM cases. In dizygotic twins, concordance rate was 0%(0/10) in IDDM and 40 %(4/10) in NIDDM cases. It was significantly higher in NIDDM than in IDDM, and in monozygotic than in dizygotic twins. (2) Concordance rate was higher in patients with the onset of diabetes above the age of 20 years than in those whose age of onset was below 20 years. (3) The period of diacordance was not shorter in discordant pairs than in concordant pairs. (4) In IDDM cases, about 90% lived together at the onset of diabetes, while more than 80% of twins lived separately in NIDDM pairs at the time of onset. This was independent of zygosity and whether they are concordant or discordant for diabetes. It is probably due to the difference of the age of onset of IDDM and NIDDM. (5) The frequency of positive family history and the prevalence of diabetes in parents and siblings other than co-twins were higher in NIDDM than in IDDM cases, irrespective of whether they were concordant or discordant. (6) The presence or absence of various complications agreed in 68-97% of concordant diabetic pairs. There were a few pairs discordant for the severity of retinopathy. In these pairs the difference in the duration of diabetes or in the degree of hyperglycemia would explain the difference in severity of retinopathy. (7) Glucose tolerance test in 6 co-twins of discordant pairs of IDDM revealed that 4 had normal glucose tolerance and 4 had normal insulin response. In 8 co-twins of discordant pairs of NIDDM, normal glucose tolerance was found in only 2 cases and normal insulin response also in only 2 cases. (8) The thyroid autoantibodies were more frequently positive in IDDM than in NIDDM patients, and the positive and negative tests agreed well between monozygotic twin pairs irrespective of concordance for diabetes. Data on islet cell antibody and HLA antigens were obtained in too few twin pairs to draw any substantial conclusions. All of IDDM patients who were tested for HLA antigens had HLA DR 4.