The effects of Acarbose in the treatment of hospitalized type-II diabetics (non-insulin-dependent diabetics) were studied in 19 patients who had been poorly controlled with diet alone.
In a single-blind trial, they took placebo first and 150 or 300mg/day of acarbose for 2 weeks afterwards. Daily profiles of blood glucose, serum insulin and lipids were monitored.
Acarbose significantly reduced fasting, postprandial blood glucose levels and the area under the blood glucose curve of daily profiles in comparison to placebo. Administration of acarbose at 300mg/day was more effective in lowering the blood glucose levels than at 150mg/day. However, acarbose did not affect insulin secretion, serum lipid level or body weight.
Flatulence and/or meteorism occurred in only 3 patients who were treated with 300mg/day of acarbose. Biochemical and hematological controls indicated good objective tolerance.
Thus, acarbose appears to be useful for improving daily blood glucose profiles in type-II diabetics.

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There is little information on the involvement of cranial and central neuropathy in diabetic subjects, since useful techniques for detection of such neuropathies have not been confirmed.
Auditory evoked brainstem responses (ABSR) are measures of action potentials generated through an auditory pathway from the cochlear nerve to the midbrain by a computed averaging method. Recent reports revealed that ABSR are useful for detecting lesions in the brainstem such as tumors, degenerative diseases and demyelination. By using ABSR, we examined whether or not VIII th cranial and central neuropathies are present in diabetic subjects with and without diabetic complications. Diabetic patients were divided into two groups. Group A Consisted of 9 patients without any diabetic complications, and group B consisted 10 patients with severe diabetic complications such as proliferative retinopathy (10/10), nephropathy (8/10), peripheral neuropathy (8/10) and autonomic neuropathy (8/10). As a control, 60 healthy volunteers were also examined. ABSR were measured by either DANAC-7 E or DANAC-8 through EEG electrodes placed on Cz-RM in which 100-dB monaural clicks for 64 msec-intervas were used as stimuli.
The obtained data were as follows: 1). Statistically significant prolongations of I, III, V wave latencies and I-III, I-V interpeak latencies (IPLs) were observed only in group B. 2). No significant differences were seen among IPL of the three groups. These results suggested that diabetic patients with severe diabetic complications also suffered from VIII th cranial and brainstem involvement.

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The significance of ΔCPR_5', which represents the difference between the 5-min value of plasma C-peptide (CPR) during glucagon test (1mg i.v.) and the basal value, was investigated in relation to insulin requirement in patients with diabetes mellitus (DM).
In normal controls, ΔCPR_5' (ng/ml) was 4.22±0.84 (mean±SE). In 128 outpatients whose plasma glucose levels were stable and well controlled (FBS<200mg/dl), ΔCPR_5' was 0.23±0.08 in type I DM (n-7); 0.58±0.10 in type II DM under insulin treatment (n=29); 1.49±0.12 in those under treatment with sulfonylureas (n=34); and 1.69±0.12 in those on a diet regimen (n=58), ΔCYR_5' was significantly lower in type I and type II DM under insulin treatment than in those under treatment with sulfbnylureas and on a diet regimen.ΔCPR_5' was below 0.5 in all of the patients with type I DM and below 0.7 in 21 (72%) out of 29 patients with type II DM under insulin treatment. A sharp decrease in prevalence of insulin-treated patients was noted when ΔCPR_5' was over 0.8.
In DM patients (n=17) who were hospitalized for insulin treatment because of poor control, ΔCPR_120' during 50g-OGTT and 24-hour urine CPR excretion at the time of admission failed to distinguish those who were able to become free from insulin treatment at a later date (“insulinfree group”) from those who had to continue insulin treatment (“insulin-continued group”), whereas ΔCPR5, during glucagon test at the time of admission showed a significant difference (p<0.001) between both groups: “insulin-free group” (n=8) 1.79±0.38 and “insulin-continued group” (n=9) 0.52±0.08
The above findings indicate that ΔCPR_5' during glucagon test is useful as an index for evaluation of the insulin requirement in diabetics and suggest that less than 0.7ng/ml ΔCPR_5' could be regarded as insulin requirement.

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To elucidate the role of apolipoprotein in the evolution of hyperlipidemia in diabetic patients, VLDL apo C and E isoforms were analyzed by isoelectric focusing. VLDL-remnant and LDL-cholesterol levels were significantly higher in diabetics than in controls. In isoelectric focusing patterns of apo VLDL, there was an increased amount of apo C 111-2 and a reduced amount of apo C III-0 in diabetic patients. The apo C 111-2: C III-1 ratio was higher in diabetics than in controls, but the differences were not statistically significant. In the distribution of apo E of VLDL, apo E 3 in untreated diabetics was significantly lower than in the controls. The apo E 2: E 3 ratio in diabetics tended to be higher than in the controls. These ratios were significantly lower after treatment, except that increased ratios were observed in diabetics treated by sulfonylureas. Limited incubation of apoVLDL in untreated diabetics with neuraminidase revealed a partial loss of sialic acid of apo C and E isoforms and resulted in a TG-rich lipoprotein with decreased apo C 111-2: C III-1 and E 2: E 3 ratios. ApoVLDL of untreated diabetics showed similar compositional changes in apo C and E isoform after insulin therapy. There were significant positive correlations between apo E2: E3 ratio and VLDL-TC/VLDL-TG and apo C 111-2: C 111-1 ratio. These results suggest that increased sialylation of apo E as well as apo C III might cause inhibition of VLDL-catabolism and contribute to the development of atherosclerosis in diabetics.

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The isolated perfused rat liver preparation was used for the study of the effect of vasopressin on normal and diabetic hepatic metabolism.
Male rats of the Wistar strain weighing appoximately 250g were used. Diabetic rats were produced by the injection of streptozotocin (60mg/kg of body weight). They were made to fast 24 hours prior to use. The initial recirculating solution used was 250 ml of Krebs-Ringer bicarbonate buffer containing 0.25% bovine albumin and 25% bovine erythrocytes prepared as reported previously. 10 mM alanine, 0.8mU of vasopressin per ml, 2.86×10^-5M glucagon and 100μU of insulin per ml were added after 30 min glucose and some metabolites in the perfusate were measured serially during the liver perfusion.
In both the normal and diabetic states, vasopressin increased gluconeogenesis from alanine by 50-70%. This stimulation of gluconeogenesis by vasopressin was more marked in diabetic rats than in normal rats. The physiological concentration of insulin suppressed glucose production by either normal or diabetic livers stimulated by vasopressin. Vasopressin also accelerated ketogenesis in the isolated livers from normal and diabetic rats. The stimulatory effect of vasopressin on ketogenesis was stronger in the diabetic state than in the normal state. However, insulin did not prevent the stimulation of ketogenesis by vasopressin. These effects of vasopressin on gluconeogenesis and ketogenesis were similar when 2.86×10^-5 M glucagon was infused.
These results suggest that vasopressin may play an important role in worsening diabetic ketoacidosis.

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Delayed gastric empyting in diabetic patients is a symptom of diabetic autonomic neuropathy.
For the evaluation of gastric emptying time, the double sampling method and the radioisotopic method have mainly been used. These methods have several disadvantages in practice, and these disadvantages have limited the study of gastric emptying function of diabetic patients with autonomic neuropathy.
Recently we have developed a simple technique for the measurement of gastric emptying time using linear ultrasonographic equipment. Five hundred ml of water or saline divided into two equal volumes was given to a patient or a healthy subject. Immediately after the administration of the first 250ml, a cross-sectional ultrasonographic image of the stomach at a certain fixed position on the abdominal wall was recorded on film. Then the second 250ml water or saline was given immediately and cross-sectional areas of the stomach at the same scanning position were followed ultrasonographically and recorded on film over time. Gastric emptying time was derived from the plotted curve of gastric sectional areas. When the value of the gastric area on the curve fits the size of the initial 250ml, the time required to arrive at this point was designated as gastric emptying time T₂₅₀. Gastric emptying time measured by this method correlated well with the values measured by the radioisotopic method, i.e., in 8 cases of saline, r=0.977 (p<0.001) and in 5 cases of water, r=0.915 (p<0.05).
With 55 diabetic patients, the elongation of gastric emptying time had a positive correlation with heart rate deviation in deep breathing (showing parasympathetic neuropathy), r=0.564 (p<0.001) and with heart rate deviation in standing (sympathetic neuropathy), r=0.370 (p<0.01).
Gastric emptying time measured by this method was 18.1±2.2min (mean±S.D.) in healthy subjects, 22.2±5.5 min in patients with parasympathetic neuropathy and 24.2±3.5 min in patients with sympathetic and parasympathetic neuropathies. Diabetic patients without autonomic neuropathy showed a tendency to have faster gastric emptying times, 16.5±2.9 min, but the result was not statistically significant.
Thus gastric emptying time in diabetic patients looked faster in the early diabetic stage and was delayed with the development of diabetic autonomic neuropathy. Measurement of gastricemptying time by this ultrasonographic method seems very useful because of its simplicity, non-invasiveness and easy repeatability.

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The term gestational diabetes is still in dispute, and the criteria for it remain obscure. This study is aimed at elucidating the incidence of glucose intolerance among pregnant women and determining the clinical significance of glucose intolerance so as to define gestational diabetes.
In 1982, there were 630 deliveries at Saiseikai Central Hospital. Among these pregnancies, 84 cases first showed glycosuria during the pregnancy, and 75 g OGTT was done during the second or third trimester. Only one case (1.2%) showed a diabetic pattern (D). Sixty-five cases (77.4%) showed a borderline pattern, and 12 (14.3%) of them had 140mg/dl or more of 2-hour value matching IGT by WHO criteria (B-2). Fifty-three (63.1%) were borderline cases excluding IGT by the Japan Diabetic Society (JDS) criteria (B-1). The group with a normal pattern (18 cases-21.4%) was designated with N.
Second, 118 patients whose glycosuria was first revealed during pregnancy in the years between 1965 and 1980 were studied for perinatal loss, macrosomia, neonatal complications, congenital malformations, toxemia of pregnancy and/or hydramnios. They had OGTT during the second or third trimester of the pregnancy, and OGTT alterations were followed for 3-5 years after delivery.
Incidence of abnormal pregnancy, delivery as well as perinatal infant complications were found to be much higher in groups B-2 (30 cases) and D (13 cases) than in B-1 (43 cases) and N (32 cases). Especially in group D, abnormalities other than congenital malformation were more frequent than in group DM (54 cases), the cases with diagnosis of diabetes mellitus before pregnancy. It was thought that the care of cases in group D might not have been stringent enough, because they were not aware of diabetes.
Three to five years after delivery, 32 out of 43 cases (74.4%) whose 2-hour value was 140mg/dl or more (B-2, D) on 75g OGTT during pregnancy showed the diabetic pattern or were in the area of IGT (WHO), while 12 out of 75 (16.0%) in groups N and B-1 shifted to diabetic pattern or to IGT.
From the above, among the pregnant women with bordeline OGTT y JDS criteria, the cases with 2-hour values of more than 140mg/dl, corresponding to IGT by WHO criteria, have to be managed carefully as “gestational diabetes” and have to be followed by repeated OGTT.

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To determine the physical stability of short-acting insulin preparations, (A, B, C, D, E), changes in percent transmittance (at 540 nm), immunoreactivity, biological activity, and morphology of insulin solutions were studied during continuous shaking at 130 cpm at 37 C for 7 days in the dark.
The following results were obtained:
1) There were no significant changes in percent transmittance, immunoreactivity or biological activity when insulin preparations were stored at 37°C as long as 7 days.
2) In 3 insulin preparations A, B, and E, significant decreases in percent transmittance, immunoreactivity and biological activity within 2 days after initiation of shaking were seen.
3) In insulin preparation C, a slower decrease in percent transmittance, immunoreactivity and biological activity than in insulin preparations A, B, and E were found.
4) In insulin preparation D, although there were no significant changes in percent transmittance and immunoreactivity, aggregated insulin and decrease in biological activity were observed after 7 days of shaking.
These results indicate that these commercially available short-acting insulin preparations were physically unstable during shaking. It was suggested that during long-term continuous insulin infusion therapy with a pump, the reservoir and the inside of the catheter should be carefully examined for the formation of insulin aggregates. Further more, the development of more stable insulin preparations would be important in the future.

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Development of diabetes in subjects with normal or impaired glucose tolerance was studied in relation to insulin response to glucose during the oral glucose tolerance test and other risk factors by means of long-term observations.
1) Insulin area (IA) was found to be increased in subjects with 2h glucose≥40mg/dl, IGT (WHO criteria) and relative body weight≥115%, and in male sbjects. Insulinogenic index (II) was low in subjects with 2h glucose≥140mg/dl, IGT and positive family history of diabetes.
2) Worsening to diabetes was observed in 8.5% of the subjects, and the worsening rates were significantly related to 211 glucose level, presence or absence of family history of diabetes and relative body weight.
3) It was observed that the worsening rate increased distinctly according to the decrease in II, but no relation was found between IA and the worsening rate. However, the subjects with elevated 2h glucose levels, and excess body weight also indicated high worsening rates despite high II level, greater than 0.5.
4) Cumulative worsening rates up to 10 years were 22.4% for the subjects with II>0.5, and 11.4 for II>0.5. It was confirmed that worsening to diabetes in the subjects with normal or impaired glucose tolerance was closely related to diminished insulin response to glucose during first 30 minutes in OGTT. In addition, its was suggested that impaired glucose tolerance, family history of diabetes and obesity were independent risk factors in the development of diabetes.

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A 14-year-old boy with Down's syndrome developed diabetic ketoacidosis, and was admitted to our hospital because of drowsiness.
He was the second child of a 32-year-old woman. He had gained weight since he was 9 years old. About 3 weeks before admission, he complained of sore throat and cough, and 2 weeks before admission, his family noticed polyuria and polydipsia. He was taken to a clinic where glycosuria was found for the first time. Two days later, his blood glucose level was 648mg/dl. He complained of loss of appetite and painful urination, and he was becomuing delirious at the day of admission to our hospital.
His blood pressure was 84/58 mmHg, pulse rate 120 per minute and regular. He weighed 80kg and his height was 164cm. He showed typical features of Down's syndrome without heart disease and chromosome analysis revealed a mosaic of 21-trisomy and 46, XY.
The urine test was (+) for protein, (++) for glucose, (++) for ketone body. Blood gas analysis revealed metabolic acidosis. The hematocrit was 38.9 percent. White blood cell count was 12, 000/mm³ with 88 percent neutrophils. The urea nitrogen was 40.9mg/dl, the blood glucose 640mg/dl.
Possible causes of the onset of his diabetes were weight gain and some infection, which overlapped with some inherent diabetic factors and obesity.

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We report a case of a Type 2 (non-insulin-dependent) diabetic patient who showed an extraordinarily high HbA_1c concentration (43.7%) in the high-performance liquid chromatographic assay. This was caused by interference with the HbAie fraction by a new hemoglobin variant, Hb Okayama [β2 (NA 2) His→Gln.].
β2 His⁺ is one of the components of the 2, 3-DPG binding site of hemoglobin. The substitution of His for Gin, therefore, may inhibit 2, 3-DPG binding to the hemoglobin and consequently may increase the oxygen affinity of blood, as observed in the present case. However, no specific clinical sign induced by the oxygen affinity increase was observed. Caution should be paid when glycohemoglobin concentration is under examination, since it has been reported that the glycohemoglobin concentration may sometimes be affected not only by a hemoglobin variant as in the present case but by several other individual factors.

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