Serum immunoreactive insulin (IRI) responses to an oral administration of 100g glucose were studied in 14 patients with liver cirrhosis and 6 patients with chronic hepatitis. Hyperresponses of serum IRI were demonstrated in the patients with liver cirrhosis, including the patients with normal glucose tolerance. Hyperresponses of serum IRI were also showed in the patients with chronic hepatitis. Serum free fatty acids (FFA) and growth hormone (HGH) responses to intravenous administration of regular insulin (0.1 u/kg) were studied in 14 patients with liver cirrhosis and 7 patients with adult-onset diabetes mellitus with low degree impairment of GTT. After insulin administration, the decrease of serum FFA was more marked in the cirrhotic patients compared with the normal subjects and the diabetic patients. Fasting HGH levels were significantly high in the patients with liver cirrhosis. After insulin administration, hyperresponses of serum HGH were demonstrated in most of the patients with liver cirrhosis, but the very low responses were shown in two cirrhotic patients with diabetic GTT. These results suggest that the high frequency of glucose intolerance and hyperresponses of serumIRI in the patients with liver cirrhosis may be related at least in part to the high levels of serum HGH and hyperresponses of HGH.
In order to investigate pancreatic islet cell function under long-term treatment with oral hypoglycemic drugs used for maturity-onset diabetics glucose tolerance and immunoreactive insulin (IRI) after a restricted diet were traced in 28 maturity-onset diabetics before and during the 3rd to 42nd months of therapy. In 31 patients with maturity-onset diabetics under long-term treatment hypoglycemic drugs, the functional reverse of insulin secretion was evaluated by the glucose-glucagon-tolbutamide stimulation test proposed by Ryan. The secretory response of insulin to the initial load of 100 g of glucose (reaction A) as a physiological stimulus was compared with that to the successive stimulus by the intravenous administration of glucagon and tolbutamide (reaction B). The concomitant changes in the levels of free fatty acid (NEFA) and human growth hormone (HGH) following the test were also evaluated. The results were as follows. 1) In the groups treated with tolbutamide and acetohexamide plus dietary measures, the insulin glucose index (I/G) at the peak levels slightly increased by the month and thereafter decreased to approach pretreatment levels in the 3rd or 4th year. 2) In the groups receiving N (p-chlorobenzensulfonyl)-N'-pyrrolidinourea (CBPU) and chlorpropamide (p 607) no significant changes in I/G were observed during therapy. 3) A gradual increase in JIG was observed in the group treated with sulfonylurea plus biguanide, though the ratio was less than that of any of the other groups. 4) In 3 patients treated with biguanide plus dietary measures the levels of IRI decreased after therapy, despite the improvement of glucose tolerance. 5) The diabetics who had an improvement or no change in GTT after long-term treatment with hypoglycemic drugs, showed a normal functional reserve of insulin secretion. 6) The insulin levels in reaction B had no correlation with those in reaction A. Good responses of IRI to the intravenous administration of glucagon and tolbutamide were observed in one out of 3 patients who showed lowered IRI responses to the glucose load during long-term therapy with p607. 7) The diabetics with angiopathy, especially retinopathy, showed lowered response of IRI and HGH to the glucose-glucagon-tolbutamide stimulation test. 8) In the obese diabetics the responses of IRI to the test increased, while the responses of HGH decreased. From these results it was suggested that sulfonylurea therapy for periods up to at least 3 years does not appear to induce an exhaustion of insulin secretory activity.
Following ingestion of the caffeinated beverages, such as coffee, tea or green tea, with either sodium cyclamate or sucrose (20g) as a sweetening, changes in blood glucose, serum cholesterol, triglyceride and free fatty acid levels were studied in diabetics, and following results were obtained: 1. The caffeine content ingested in this study was 370 mg/ 8 g of instant coffee, 150 mg/ 4g of instant tea and 110 mg/ 4g of green tea, respectively. 2. Blood glucose levels did not change after ingestion of the caffeinated beverages with sodium cyclamate. With sucrose, a slight increase in blood glucose levels was observed in normal and diabetic subjects. 3. A significant increase in free fatty acid levels was observed when the caffeinated beverages were ingested with sodium cyclamate. With sucrose, on the other hand, the increase in free fatty acid levels was suppressed during the first 2 hours after ingestion. 4. The lipolytic effect was the greatest after coffee and the least after green tea among the three caffeinated beverages. The positive relationship between the lipolytic effect and the caffeine content in these beverages was found. 5. There were no significant changes in serum cholesterol and triglyceride levels after ingestion of the caffeinated beverages. As judged by the change in free fatty acid levels, sucrose is recommended as a sweetening for the caffeinated beverages in mild diabetics.
Clinical features of arteriosclerotic heart disease (ASHD) associated with diabetes were studied. Those who were studied consisted of 1, 202 diabetics, who were subdivided into 3 groups depending on blood glucose level, seen at the Center for Adult Diseases, Osaka, and 2, 450 control subjects with normal blood glucose level. The prevalence of hypertension revealed a close relationship to aging and elevation of blood glucose level, giving excessive frequency of hypertension for diabetics. The prevalence of ASHD, however, was largely influenced by aging and elevation of blood pressure, but little by elevation of blood glucose level. Obesity and serum cholesterol level seemed to be little related to the prevalence of ASHD. To study quantitative relationship between ASHD and other related variables, the partial correlation coefficients were computed. The coefficient was significant at a 5% level between ASHD and systolic blood pressure, so was between ASHD and age. Serum cholesterol level and a two-hour blood glucose level also revealed some correlations with ASHD, although not statistically significant. The above observations led to a conclusion that the prevalence of ASHD was largely dependent on the presence of hypertension and aging. It was suggested that the clinical features of ASHD of Japanese diabetics were much different from those of diabetics in Western Countries, where carbohydrate metabolism play a more influential role in the development of ASHD. A discussion was also made on the different patterns of causes of death in diabetics between Japan and Western Countries.
Serum glucose and insulin responses to oral acetohexamide (0.5 g), oral glucose (50 g, OGTT), and oral acetohexamide followed by oral glucose (Oral acetohexamide glucose tolerance test, OAGTT) were determined in 10 normal and 24 diabetic subjects, and following results were obtained: (1) Following oral administration of acetohexamide, a slight in crease in serum insulin concentrations was observed in normal and diabetic subjects. (2) With a less increase in serum glucose, the serum insulin concentrations in response to OAGTT were greater than those to OGTT in normal subjects.In diabetic subjects, the serum insulin concentrations were also increased in response to OAGTT in the satisfactory controlled group with acetohexamide. The impaired glucose tolerance was improved markedly. In the unsatisfactory controlled group, on the other hand, the serum glucose and insulin responses to OGTT did not change significantly by prior administration of acetohexamide. (3) The improvement of impaired glucose tolerance by OAGTT was more clearly demonstrated by calculating the ratios of the increment of glucose to OAGTT (ΔGlucose-OAGTT) to that of OGTT (ΔGlucose-OGTT). The ratio was calculated to be less than 0.75 in the satisfactory controlled group and to be more than 0.75 in the unsatisfactory controlled group. (4) When applied this ratio to the newly diagnosed diabetic subjects, the prediction for acetohexamide treatment was well matched with the results of clinical evaluation after treatment for 6 or more months. These results indicate a possible mechanism of acetohexamide by increasing the sensitivity of β-cells to glucose stimulus. The oral acetohexamide glucose tolerance test might be employed as a convenient means of predicting for acetohexamide treatment in diabetic subjects.
The reliability of a “Reflectance Meter”, which was deviced for quantitative reading of the color change in Dextrostix, was tested using capillary blood samples, obtained from 51 patients attended diabetic outpatient clinic. The blood glucose levels estimated by the “Reflectance Meter” were highly correlated with those measured by Hagedorn-Jensen method (r =0.09, p<0.001). The influence of exposure time of Dextrostix to the blood samples on the estimation of blood glucose levels was also studied. It was demonstrated that the blood glucose levels were underestimated when exposure time was less than 60 seconds and overestimated when it prolonged over 60 seconds. It is concluded that this is a simple and reliable method for estimating blood glucose level if procedure was accurately performed.