Passive transfer of diabetes was attempted by the injection of bone marrow cells from diabetes-prone BB/Worcester (BB/W) rats and concanavalin A activated spleen cells from acutely diabetic BB/W rats. Recipients were both MHC-compatible young diabetes-prone BB/W, diabetes-resistant BB/W, Wistar Furth, F1 hybrid (BB x Lewis) rats and MHC-incompatible Wistar, Lewis, Nude rats. Recipients were tested for diabetes during the 6 weeks following injection. A pancreatic specimen for the examination of insulitis and sera for the assays of ICSA and CAMC were obtained either at the onset of diabetes or at the end of the protocol. ICSA was determined by an 125I-protein A method and CAMC was evaluated by a 51 Cr release assay using RINr cells as target cells. Diabetes was induced only in the MHC-compatible group, whereas insulitis, ICSA, and CAMC were detected in both the MHC-compatible and-incompatible groups. In the MHC-compatible group, the incidence of insulitis and ICSA in diabetic recipients was higher than those in non-diabetic recipients. These results suggest that ICSA can contribute to the development of diabetes induced by passive transfer in the BB/W rat.

View full abstract

To evaluate the influence of hyperinsulinemia (HI) on coronary atherosclerosis, we examined coronary angiograms and coronary risk factors in 103 euglycemic patients (pts) with coronary heart disease. The glucose areas of these pts were within mean+ 1SD of normal healthy subjects, based on the results of a epidemiological study. They were classified into 3 groups according to the IRI areas during a 75 g OGTT K-1 (normoinsulinemia), K-2 (mild HI) and K-3 (severe HI), whose IRI areas were less than mean+ 2SD, mean + 2SD to 4SD and over mean + 4SD of normals, respectively. Each coronary artery was assessed according to its severity of stenosis on a scale where 0: normal, 1:<25 %, 2: 25-50 %, 3: 50-75 %, 4: 75-90 %, 5:>90 %, and the coronary atheromatous scores (CAS) being the summation of scales and risk factors (smoking, serum lipids, blood pressure, BMI etc) were compared between the 3 groups. There was no significant difference of risk factors between the groups other than cigarette smoking in K-2. However the average total CAS value in K-3 was significantly higher than K-1, even after adjustment for smoking, BMI and age. We concluded that pts with HI compensated for insulin resistance, even in euglycemia, and had severe coronary atherosclerosis. This observation may suggest that latent glucose intolerance based on insulin resistance is a coronary risk factor.

View full abstract

Recently we have shown that non-obese NIDDM (non-insulin-dependent diabetes mellitus) model rats have an enhanced capacity for ketogenesis in the liver, and that insulin deficiency plays a major role. To apply this result to the clinical management of NIDDM patients, serum levels of ketone bodies were determined in 60 non-obese NIDDM subjects with poor glycemic control on diet or sulphonylurea therapy (HbAi levels above 10 % for more than 3 months). The IR group (Insulin-Requiring group, . 30 patients) consisted of subjects who had been treated with the maximal dose of sulphonylurea and subsequently required insulin therapy for better glycemic control, and the remaining patients formed the NIR group (Non-Insulin-Requiring group, 30 patients). There were no significant differences in HbAi, age, duration of diabetes mellitus, age of onset and Body Mass Index between IR and NIR groups. Fasting plasma glucose levels in the IR group were slightly higher than in the NIR group (214±40, 181±37 mg/dl, mean±SD). Serum total ketone body levels (acetoacetate and 3-hydroxybutyrate) were 225±199μM in the IR group and 95 × 54μM in the NIR group and the difference was statistically significant (p<0.01). Z values above 0 which might express insulin dependency as reported by Kosugi et al were observed in 5 patients in the IR group, but no member of the NIR group had a value of Z>0.
These results suggest that continuously elevated levels in serum concentrations of ketone bodies together with high levels of fasting plasma glucose are important clinical markers for the indication of insulin therapy in non-obese NIDDM subjects who have been treated with the maximal dose of sulphonylurea.

View full abstract

The percentage glycation of LDL (low-density lipoprotein) or HDL (high-density lipoprotein) in 14 patients and 16 normal subjects was determined by affinity column chromatography with aminophenyl-boronate gel. Correlations between the glycated lipoproteins and various plasma factors related to diabetic control and lipoproteins were investigated. Glycated LDL was significantly increased in diabetic patients compared to controls (8.15 ± 0.63 vs 4.39 ± 0.56, p< 0.001), while glycated HDL was not (2.15 ± 0.51 % in diabetics and 1.99 ± 0.38% in the controls). The extent of LDL glycation demonstrated significant positive correlation with hemoglobin Al c, daily mean blood glucose, fructosamine, fasting blood glucose and apolipoprotein B. In contrast, the extent of HDL glycation demonstrated significant negative correlation with apolipoprotein Al or HDL-cholesterol, but not with other indices. These results indicate that glycated LDL may be increased in association with high blood glucose levels and that glycation of HDL might be related to a decrease in serum HDL level in diabetic patients.

View full abstract

Forty-three cases of pheochromocytoma were investigated to reveal the relationship of abnormal glucose metabolism with urinary catecholamine levels. Diabetes mellitus (DM) was observed in 14 cases. A urinary excretion of adrenaline (A) of more than 300 μg/day, noradrenaline (NA) of more than 1, 000 μg/day, or in particular a compound value (A + NA/3) was a good indicator of the diabetic condition. The ratios of ΣIRI (the sum of individual serum insulin values in 75-g OGTT) to ΣPG (the sum of individual plasma glucose levels in 75-g OGTT) and ΔIRI (the IRI increment in the initial 30 minutes of OGTT) to ΔPG (the PG increment in the initial 30 minutes of OGTT) showed negative correlations most strongly with log (A + NA/9) and log A, respectively, (r=-0.700 and r=-0.636). These results indicate that the suppression of insulin secretion by increased plasma A is an important cause of abnormal glucose metabolism in pheochromocytoma. On the other hand, NA exerts a diabetogenic effect through decreased insulin sensitivity or enhanced glycogenolysis in the liver.

View full abstract

We report a case of factitious hypoglycemia diagnosed by high performance liquid chromatography. A 22 year-old nurse complaining of recurrent episodes of spontaneous hypoglycemia was referred to our hospital. She did not have any abnormalities in X ray and MRI computed tomography ultrasonography and angiography examinations. Blood samples taken during a hypoglycemic attack showed elevated plasma insulin levels and comparatively depressed plasma C peptide levels. Insulin antibody and insulin receptor antibody were not detected in her plasma. Reverse phase high performance liquid chromatography analysis demonstrated animal-derived insulin peaks in her blood which enabled us to confirm the diagnosis of factitious hypoglycemia. High performance liquid chromatography analysis and measurement of plasma insulin and C peptide levels of blood samples during hypoglycemic attacks are considered to be quite useful diagnostic methods. This is the first reported case of factitious hypoglycemia found in a healthy medical person in Japan as far as we can ascertain from a survey of the literature.

View full abstract

We describe the concurrence of autoimmune thyroid disease, insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE) and Sjögren'syndrome (Sjs) in a patient.
A 21-year-old female was admitted with facial erythema, fever, polyarthralga, and xerophthalmia in July 1989. In this case the diagnostic criteria for SLE (5 of the ARA criteria occurring in 1982) and Sjs were satisfied.
There was a past history of Basedow's disease in 1975. The patient has been treated for IDDM since 1979 and for hypothyroidism since 1984.
Laboratory tests for autoantibodies including ICA and ICSA were negative except those for antinuclear antibodies and antimicrosomal antibody. HLA typing revealed A2, Bw54, B40, Cwl and DR4 types.
The association of IDDM and collagen disease is rare. To the best of our nowledge, the coexistence of these 4 autoimmune diseases in one patient has not previously been reported in Japan.
This is a useful case to aid understanding of the autoimmune nature of the pathogenesis of IDDM.

View full abstract

Insulin dependent diabetes mellitus (IDDM) with severe ketoacidosis (DKA) developed in a 47-year-old female. On admission, the blood glucose level was 850 mg/dl, urinary ketone bodies 3+, arterial blood pH 6.90, HCO₃-2.0 mmol/L, and base excess-28.5 mmol/L.
Fluid replacement and low dose insulin therapy successfully resolved the DKA within 12 hours. Serum pancreatic enzyme levels were found to be elevated on admission without any symptoms and signs indicating acute pancreatitis. Serum amylase (1013 IU/L, P-type predominant) and lipase (1660 IU/L) peaked on the 6th hospital day and trypsin, elastase 1, and pancreatic secretory trypsin inhibitor peaked on the 4th day. They then declined gradually, but did not return to normal for more than 30 days.
Nine out of 25 patients with DKA treated over five years (1982 to 1987) in our center had raised serum amylase concentrations. Among them all the 5 new-onset IDDM patients had hyperamylasemia, while only 2 of 10 preexisting IDDM patiends and 3 of 10 NIDDM patients had accompanying hyperamylasemia. These results, therefore, suggest that the elevated serum panceatic enzymes in DKA may reflect the possible immunological damage of exocrine pancreas surrounding the islets, rather than being due to the metabolic derangement of DKA.

View full abstract

A reduction in red blood cell sorbitol (RBC sorbitol) by supplementation with ascorbic acid (AA) has been reported. Since RBC sorbitol is affected by blood glucose (BG) levels, we examined the levels of BG, HbA₁c and RBC sorbitol before and after supplementation with AA 1.0 g/day for 4 weeks in 22 diabetics in order to determine how the effect of AA was influenced by simultaneously measured BG levels.
On the whole, a significant reduction in RBC sorbitol was observed after AA supplementation without any change in BG levels. The patients were classified into 3 groups from the standpoint of BG changes after supplementation, i. e., group 1; elevation above 10 mg/dl, group 2; changes less than 10 mg/dl, group 3; reduction above 10 mg/dl. RBC sorbitol in all groups decreased or tended to decrease after supplementation. It was concluded that AA decreases RBC sorbitol independent of any change in BG.

View full abstract

Insulin sensitivities and secretory responses in middle-aged (57±4yr; mean±SD) non-obese essentially hypertensive patients (HT) were measured simultaneously by means of glucose clamp tests. 75 g OGTT's showed no significant differences in plasma glucose and insulin concentrations between HT and agematched non-obese normotensive volunteers. Hyperglycemic clamps revealed no significant difference in insulin secretion between the two groups. Euglycemic-hyperinsulinemic clamps revealed a significant decrease in the rate of glucose uptake in the HT group without any change in insulin kinetics.
These data indicated that middle-aged hypertensive patients showed insulin resistance which was not compensated for by an augmentation of insulin secretion.

View full abstract