The prevalence of ICA, thyroid-microsomal antibodies and gastric parietal cell antibodies was studied in 149 Japanese IDD, and the data were compared with the prevalence of the same antibodies in 150 Caucasians.
ICA were detected in 6 of 37 Japanese IDD (16.2%) during the first year after diagnosis and in 5.2% between 1 and 2 years after the onset of the disease. The prevalence of ICA decreased to 2.8% at 2 to 5 years and to 0% at 5-10 years and 10-20 years. This prevalence of ICA in Japanese was very low compared to that of Caucasians. In the Caucasian IDD, ICA were present in 55% of the patients during the first year and in 39% between 1 and 2 years after the onset of the disease. No correlation existed between the HLA types and ICA in the Japanese IDD. The prevalence of antithyroid-microsomal antibodies in the 150 Caucasian IDD was 16%, which was not significantly different from that in the 149 Japanese IDD (15%). However, the prevalence of gastric parietal cell antibodies was significantly higher (p<0.05) in the Caucasians (20%) than in the Japanese (9.3%).
The lower frequencies of ICA and gastric parietal cell antibodies in the Japanese subjects suggest that the Japanese may have a lower tendency to develop organ-specific autoimmunity. The pathogenic significance of such antibodies remains unclear, although the present findings do suggest that racial background may play a very important role in the incidence of autoantibodies.

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The effects of dietary fat, cholesterol and insulin administration on the activity of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase) in rat liver microsomes, the microsomal cholesterol content and cholesteryl ester content were examined. When corn oil or coconut oil was fed, animals receiving corn oil revealed a higher enzyme activity compared to those receiving coconut oil. Microsomal analysis demonstrated an inverse relationship between the cholesteryl ester contents and activities of HMG-CoA reductase when the enzyme activity was manipulated by the dietary fat or cholesterol, whereas no such relation was observed when the activity was increased by the administration of insulin. The microsomal cholesteryl ester content also remained relatively constant at different stages of the diurnal rhythm of the enzyme. Compared to normal rats, a lower enzyme activity was observed in diabetic rats but no apparent changes in microsomal cholesteryl ester content were seen. The results of the experiments indicated that two kinds of controlling factors of HMG CoA reductase may exist; in one group there is a consistent correlation between the microsomal cholesteryl ester content and the enzyme activity, whereas no such relation is observed in the other.

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The present study was undertaken to compare sensitivities to antilipolytic action of insulin of weight-matched two groups, 43 diabetic patients and 43 healthy control subjects. The sensitivity was estimated by the ratio of decrement of serum FFA (ΔFFA) to increment of serum IRI (ΔIRI) during the first 60 min-period of 100 g OGTT. The ΔFFA was not dependent upon age but there was a negative correlation (r=-0.25) between the decrement of FFA and the degree of obesity. The ΔFFA in diabetics (422.5±257.1μEq/l)(M±SD) was not significantly different from that of the control subjects (429.7±269.5μEq/l).
Since ΔFFA was revealed to be dependent upon the fasting FFA level (F-FFA), a new parameter, ΔFFA/F-FFA was calculated as “corrected decrement of FFA”. This value in diabetics was 0.78±0.41, which was significantly lower than that of the control subjects (1.12±0.51).ΔIRI in diabetics (78.0±48.7μU/ml) was remarkably less than that of the healthy subjects (272.4±137.9 μU/ml). The sensitivity index, ΔFFA/F-FFA/ΔIRI in diabetics was 16.49×10^-3, which was highly significantly greater than that of the control group (4.84×10^-3).
These results strongly suggest that the sensitivity to anti-lipolytic action of endogenous insulin was enhanced in diabetic patients irrespective of obesity.

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It has been suggested recently that high-fiber diets may be beneficial for diabetics since they reduce the postprandial blood glucose and serum lipid levels, but their exact mechanisms of action have not yet been clarified.
We have studied the treatment of diabetics with Konjac Mannan (Glucomannan). Like Guar Gum, Glucomannan has proved useful in the treatment of diabetics. We therefore compared the effects of Glucomannan and Guar Gum on the blood glucose and serum insulin levels after test meals, in particular examining the effects of their viscosity.
When 3.9 g of Glucomannan was mixed into the test meals of 6 non-insulin dependent diabetics, the mean blood glucose level was significantly below that of the control at 30 and 60 min. However, when 3.9 g of Guar Gum was given in the same way as Glucomannan, no significant reduction in mean blood glucose level was seen during the observation period.
It appeared that the viscosity of the fiber within the gastrointestinal tract might be an important factor in flattening the curves of the postprandial blood glucose levels. The viscosities of three kinds of fibers were therefore examined. The viscosity of 1 % highly purified Glucomannan solution reached 194, 800 cps, whereas those of 1 % Guar Gum and 3 % Pectin solution were only 7, 700 and 2, 429 cps, respectively, as measured with a B-type viscometer. Glucomannan's viscosity was thus the highest among the three.
The effects of differences in viscosity were examined using two types of Glucomannan. When highly purified high viscosity Glucomannan (194, 800 cps) was added to the test meals and given to 9 normal subjects, no significant rise in the mean postprandial blood glucose level was observed. On the other hand, when low viscosity Glucomannan (55, 000 cps) was given in the same way, the mean rate of postprandial rise in glucose level was almost the same as in the control. Glucomannan was thus more effective at high viscosity than at low. Xylose absorption tests showed that viscous forms of dietary fiber prolonged the time required for absorption and reduced the postprandial rise of glucose, rather than causing malabsorption. Thus, the most viscous of the dietary fibers, purified Glucomannan, was the most effective in suppressing the postprandial rise of blood glucose and this suppression appeared to be related to its very high viscosity.

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Leslie and Pyke have reported that chlorpropamide alcohol flushing (CPAF) is useful as a marker for a special type of non-insulin dependent diabetes mellitus (NIDDM), and the prevalence of diabetic retinopathy in CPAF positive diabetics is lower than that in CPAF negative diabetics.
The present study was undertaken to investigate whether a similar tendency could be recognized in Japanese patients with NIDDM. We also examined certain serum factors in the CPAF positive and negative groups, which were thought to be associated with diabetic retinopathy.
Twenty-one of the 100 NIDDM patients who flushed with alcohol alone were excluded from the study. Of the other 79 subjects, 46 (58%) were CPAF positive and 33 (42%) were CPAF negative. The incidence of diabetic retinopathy in the CPAF positive cases was significantly (p<0.05) lower than that in the CPAF negative cases at 5 years after diagnosis, while there was no difference between the CPAF positive and negative groups within 5 years of diagnosis. However, no significant differences in serum lipids, β-thromboglobulin or β-N-acetylglucosaminidase activity were noted between the two groups after 5 years. No difference was found in blood glucose and plasma insulin, or in other clinical and laboratory findings.
It is suggested therefore that the difference in prevalence of diabetic retinopathy between the CPAF positive and negative groups may be due to some other unknown factor.

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The plasma concentration of glibenclamide as used in routine clinical practice was measured by a previously reported radioimmunoassay. The glibenclamide concentration in fasting morning plasma of diabetic patients undergoing treatment with the drug for more than one month was variable and often undetectable (<5ng/ml) but roughly paralleled the dosis. The mean levels were 8.5, 12.5 and 17.2 ng/ml in patients taking 2.5 mg and 5 mg as a single dose and 5 mg as two divided doses, respectively. After a single oral administration of 2.5 mg and 5 mg in glibenclamide-treated patients, the drug level in the plasma reached peaks of 82±27ng/ml and 149 ±60 ng/ml at 90 and 120 min, respectively, and declined thereafter with half-lives of 2.7 and 2.9 hr. In normal subjects who were given a single dose of 2.5 mg orally, the peak concentration was 72±32 ng/ml and the half-life was 2.3 hr. In diabetic patients with chronic renal failure and with liver cirrhosis, the peak concentrations of the drug after an oral dose of 2.5 mg were 59±20 and 86±43ng/ml, and the half-lives were 2.8 and 3.5 hr, respectively. The half-life of the drug in patients with liver cirrhosis was prolonged. Comparison between a single dose and two divided dose schedules of 5 mg glibenclamide, revealed that the profiles of the blood glucose and plasma insulin did not differ significantly at most times of the day, although the profiles of the drug level differed between different dose schedules increasing each time after administration. The plasma of patients who were taking tolbutamide, acetohexamide and chlorpropamide interfered significantly with the binding of ³H-glibenclamide to the antiserum. This cross-reaction might be potentially useful as a means of detecting various sulfonylurea drugs in the blood, especially in such cases as factitious hypoglycemia by these drugs.

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A marked improvement of blood glucose control has recently been achieved with the use of a portable infusion pump.
To improve blood glucose control in diabetic patients by continuous subcutaneous insulin infusion (CSII), we studied 13 insulin dependent diabetic patients (including two pancreatectomized patients and one unstable diabetic patient). The basal infusion rate was adjusted so as to normalize the fasting blood glucose (FBS) levels, and thereafter a pulse dose before meals was added in six insulin dependent diabetic patients. In this manner, near-normalization of the blood glucose levels was achieved throughout the day safely, smoothly and simply. To assess the day-to-day fluctuations in basal IRI and FBS levels by CSII therapy, we compared CSII with conventional insulin injection (depot injection) by measuring the fasting IRI and FBS for 5 days. Both the fluctuations of IRI and FBS in CSII therapy were less than those in conventional insulin injection therapy. On comparison of the pulse dose, there were no significant changes in the IRI and blood glucose levels between bolus injection and square wave injection.
We also applied CSII therapy to the two total pancreatectomized patients and unstable diabetic patient. In the former, near-normalization of the blood glucose levels was achieved, but in the latter, it was not, in spite of a reduction of urine acetone bodies, urine sugar and hypoglycemic attacks.
In conclusion, it can be said the CSII system might provide a more feasible means for diabetic control than conventional insulin therapy.

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In order to evaluate the effect of thyroid stimulating hormone (TSH) on endocrine pancreatic functions, investigations were made on the dynamics of insulin and glucagon in intravenous glucose tolerance tests (IV-GTT), arginine tolerance tests (ATT) and perfusion studies of the isolated pancreas in rats treated with TSH (1 unit/day i. p. inj.) for 14 days.
Serum T₃ and T₄ levels, in TSH-treated rats, were significantly higher than those in controls. In IV-GTT, the blood sugar response was unchanged but insulin release was significantly lower than that of the controls. Insulin secretion in ATT and perfusion studies of the isolated pancreas were similar with that of the controls. Glucagon responses showed similar patterns to those of the controls in all the experiments.
These resits indicate that TSH administration, in the rat, in vivo, exerts some effect on insulin release possibly through an increase in thyroid hormones but exerts no influence on glucagon secretion.

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A few prospective follow-up studies have described the mortality and causes of death among Japanese diabetics with diabetic microangiopathies. To clarify the prognosis of Japanese diabetics, we undertook a prospective follow-up study of 1, 629 diabetic patients (898 males, 731 females) who visited our Diabetes Center in 1976. In this paper, we describe the results of a three-year follow-up study, especially regarding the mortality and causes of death among the patients with diabetic neuropathy, retinopathy and nephropathy.
During this follow-up study, only three cases dropped out within three years from the start. The deaths of 106 cases (78 males, 28 females) were confirmed at the end of the three-year follow-up. We obtained death certificates for all the deceased patients.
Although the cumulative death rate after the three-year follow-up among the 1, 629 diabetics (all cases) was 6.5%, that among 864 patients with diabetic neuropathy at registration was 8.1%. That among 139 with proliferative retinopathy and that among 139 with severe proteinuria (+++ and more) were 10.1% and 21.1%, respectively.
Whereas the cumulative death rate after the three-year follow-up among 202 diabetics with all of neuropathy, retinopathy and nephropathy (proteinuria) at registration was as high as 13.4%, that among 401 patients with none of these three diabetic microangiopathies was as low as 2.5%. The main causes of death among the patients who had had diabetic triopaties at registration were diabetic nephropathy and ischemic heart disease. On the other hand, those among patients with none of these three diabetic microangiopathies were malignant neoplasms.

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N. S. Y. mouse is a new strain of congenital diabetic mice derived from the I.C.R. strain which possesses abnormal findings on small vessels of the glomerulus and is considered to be a useful model for human diabetes. According to the osmotic theory, intracellular accumulation of sorbitol has been implicated in the initiation of the cataract and the neuropathy resulting from diabetes.
The present study was conducted to estimate the role of sorbitol on the development of renal disease in the N. S. Y. mice. In result, the concentrations of glucose and sorbitol were simillar in the kidney of N. S. Y. mice and age-matched nondiabetic controls. This result suggests that the activity of aldose reductase is low in the kidney of N. S. Y. mice and sorbitol does not play a main role in the appearance of renal disease in the N. S. Y. mice.

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In 5 cases of insulin-treated diabetics, glucose infusion tests were performed to examine the biological effect of insulin in vivo which was injected subcutaneously twice a day as usual. Intravenous infusion of 10% glucose solution was begun soon after the subcutaneous injection of insulin. The glucose infusion rate was determined according to the levels of blood glucose, which were measured every 30 min. The amounts of glucose infused to prevent falls in blood glucose reflected the insulin effect. During the test, the blood glucose was kept in a narrow range. The maximum effect of semilente insulin injected to 3 cases in the morning was detected at 4.5, 6.5, and 7hr after the injection, respectively. The maximum effect of insulin injected in the evening tended to appear earlier than that of the same kinds of insulin injected in the morning.
These results suggest that the biological effect of insulin differs from patient to patient and according to the time of injection.

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