[Diabetes mellitus--epidemiologic and clinical statistics in Japan].
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Biomedical subjects
Publications and source records attributed to Y Omori.
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Insulin autoimmune syndrome is characterised by spontaneous hypoglycaemia without evidence of exogenous insulin administration, a high serum concentration of total immunoreactive insulin, and the presence of insulin autoantibodies in high titre. HLA typing of 27 patients with insulin autoimmune syndrome showed that all had DR4, which was present in only 43% of 51 healthy controls (odds ratio 72.1, p less than 2 x 10(-6), and 19 (70%) of the patients were positive for the allelic combination, Cw4, Bw62, and DR4. Analysis of the nucleotide sequences of the DRB1, DQA1, and DQB1 genes showed that all the patients had DRB1*0406, DQA1*0301, and DQB1*0302, compared with only 14% of the controls (odds ratio 281, p less than 1 x 10(-10). We conclude that the development of insulin autoimmune syndrome is associated with a strong genetic predisposition.
Twenty-three patients with minute hepatocellular carcinoma, defined as a solitary lesion less than or equal to 2 cm, underwent hepatectomy at our institute during the 10 years between January, 1979 and December, 1988. Hepatitis B surface antigen was positive in 4 patients and the preoperative serum alpha-fetoprotein level was within the normal range in 7 patients and slightly elevated (20-200 ng/mL) in 14 patients. Liver cirrhosis was present in 16 patients and chronic hepatitis in 6 patients. The diagnosis was first suspected from the results of periodic examinations, including echography and the measurement of alpha-fetoprotein, in all except one patient. Minor hepatic resection was performed in 22 patients, and lobectomy in one patient in whom the tumor was located centrally in the liver. Three patients died of hepatic failure in hospital following surgery, and the survival rates of the other 20 patients at 1, 3, and 5 years were 90, 79, and 61 percent, respectively. The prognostic factors that influenced long-term survival were investigated by comparing the survival curves. The only factor associated with a significant difference in survival was the severity of concomitant liver disease. Thus, severe cirrhosis is the main obstacle against the long-term survival of patients with minute hepatocellular carcinoma.
Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or beta-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIB1) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl-benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N-nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians.
Transient extreme insulin resistance was encountered during an episode of diabetic ketoacidosis (DKA) in an insulin-treated diabetic patient. On admission, the plasma glucose level was 1241 mg dl-1 and arterial blood pH 6.895 with HCO3- 4.7 mEql-1. An intravenous bolus injection of 20 units, followed by continuous infusion of 20 units h-1 of short-acting regular human insulin, was instituted. Ischemic myocardial changes were noted on the initial electrocardiogram, therefore fluid replacement was limited to 1,000 ml of 0.9% saline solution in the first hour. As the plasma glucose level declined by only 203 mg dl-1 (41 mg dl-1 h-1) in the first 5 h, the insulin dose was doubled every 2 h. At hour 4, the patient developed circulatory shock which required vasopressor support and respiratory assistance. A plasma glucose level of 300 mg dl-1 was not achieved until the total dosage of insulin amounted to 91,580 units at hour 25. Insulin resistance was not observed from that point on. The patient had neither insulin antibodies nor anti-insulin receptor antibodies in serologic testing. The insulin binding characteristics of the patient's erythrocytes were similar to those from healthy controls both with and without experimental acidosis and with a high level of beta-hydroxybutyrate. Among multiple potential factors, the severe shock associated with DKA has been considered as a primary cause of the transient severe insulin resistance in this case.
The structure of the terminal villi was observed in placentae from non-diabetic mothers and mothers with diabetes mellitus using scanning and transmission electron microscopy. The metabolic condition of maternal diabetes was tightly controlled. In the diabetic group, the diameter of the terminal villi was significantly smaller than in the control group. The ramification pattern of villi, classified into hypo-, moderate- and hyper-ramifications, was shown to be mostly moderate in the non-diabetics whereas most of the diabetic placentae had either hypo- or hyper-ramifications. Mothers with a longer duration of diabetes and complicated with retinopathy tended to have hypo-ramification; in these mothers, the weight of the neonates was significantly less than normal. Moreover, in the diabetic placentae, syncytial knots were found more frequently, the percentage of vasculo-syncytial membranes tended to be lower, and the trophoblastic basement membrane was significantly thicker than in the control. These abnormalities in the diabetic placentae were independent of the methods of delivery; they seem to be related with fetal growth retardation and poor neonatal outcome, which are commonly seen in diabetic pregnancy.
OBJECTIVE: To elucidate the significance of ET in diabetic microvascular disease. RESEARCH DESIGN AND METHODS: We determined plasma levels of ir-ET-1 in 25 NIDDM patients without hypertension and/or renal dysfunction. RESULTS: The plasma levels of ir-ET-1 in NIDDM patients with simple (n = 8) and proliferative (n = 8) retinopathy were 0.58 +/- 0.04 pM and 0.60 +/- 0.04 pM, respectively, which were significantly higher than those in normal, nondiabetic subjects (0.24 +/- 0.02 pM [n = 31]) and NIDDM patients without retinopathy (0.30 +/- 0.05 pM [n = 9]). CONCLUSIONS: These results suggest that plasma ET-1 is related to diabetic microvascular disease.
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Fourty two (12%: Group-I) out of 358 kidney transplant (Tx) recipients showed impaired glucose tolerance in pre-Tx O-GTT and the other 49 (14%: Group-II) showed that only after Tx. Insulin therapy was more frequently required and earlier started after Tx in Group-I than in Group-II, and total dosages of steroids before the initiation of insulin therapy were also smaller in Group-I. These trends were more markedly observed in the patients treated with ciclosporin (CsA) than in those with the conventional therapy. Poor graft survival rate of Group-I in long-term follow-up (> 5 years) was demonstrated. Thus, pre-Tx impaired glucose tolerance and the subsequent immunosuppressants, especially steroids and CsA, were the key factors for deteriorating glucose metabolism after Tx, and meticulous controls of drug doses and glucose levels are needed in diabetic patients, since diabetes could change the fate of kidney grafts.
The long-term patient and graft survivals, causes of death, complications and rehabilitation status in the second decade were analyzed in 114 patients who received living related kidney transplants and were followed up for 10 years or longer. Azathioprine and prednisolone were used for basal immunosuppressive therapy in all patients. The actual patient and graft survival rates at 10 years were 76.3 per cent and 50.9 per cent respectively, the main causes of death being serious infection (10 cases), malignant disease (5 cases), cerebral bleeding (4 cases), hepatic failure (3 cases), gastrointestinal bleeding (2 cases) and cardiovascular disorder (2 cases). Four patients died from complications after re-admission for hemodialysis. The cumulative patient and graft survival rates at 15 years in 58 patients whose graft survived for over 10 years were 87 per cent and 75 per cent, respectively. Of the 51 patients still surviving at the end of the study, the complete rehabilitation rate was 90.2 per cent, however, de novo malignant disease and hepatic disorder were significant complications which not only disturbed the patients' quality of life but also reduced their survival rate. Therefore, regular follow-up of patients and appropriate management procedures are necessary to enhance the long-term success of kidney transplantation.
Islet-like cell clusters (ICCs), formed from single cells of pig pancreas in suspension culture, were embedded in an extracellular matrix. It was recently reported that nicotinamide prevented dissolution of the extracellular matrix by the ICCs. In this experiment, various conditions for embedded culture of ICCs in an extracellular matrix were studied, in an attempt to maintain the function as well as the extracted insulin content of culture specimens. The ICCs in the matrix were refed with RPMI 1640, containing 10 mM nicotinamide, 10% fetal bovine serum (FBS), 11 mM D-glucose and with or without 0.1 mM 3-isobutyl-1-methylxanthine (IBMX) or 1.0 micrograms/ml caerulein. A comparison between the different culture media showed that embedded ICCs, maintained in RPMI 1640 with caerulein, in the presence of nicotinamide, had higher insulin content accumulation than when maintained in medium containing nicotinamide alone, but had impaired glucose-stimulated insulin secretion. In the medium containing IBMX and nicotinamide, embedded ICCs showed higher insulin accumulation but lower insulin content, compared to ICCs maintained in the presence of caerulein, and also showed impaired glucose-stimulated insulin release. Thus, the effect of nicotinamide on the survival and function of B-cells is amplified by the presence of caerulein or IBMX.
A 75-g oral glucose tolerance test (OGTT) was performed in 615 nonobese pregnant women (mean +/- SD age 29.7 +/- 4.3 yr) who were referred to the Division of Internal Medicine at our diabetes center because of glycosuria. Seventy-seven cases were found to have urinary glucose at the first trimester, 185 at the second trimester, and 353 at the third trimester. With their 75-g OGTT results, the diagnostic criteria of borderline (formulated by the Japan Diabetes Society), impaired glucose tolerance (IGT; defined by the World Health Organization [WHO]), and gestational diabetes mellitus (GDM; determined by the Japan Society of Obstetrics & Gynecology standards) were compared through blood glucose (BG) curves and immunoreactive insulin (IRI) responses. Borderline (fasting BG greater than or equal to 6.1 and less than 7.8 mM and 2-h BG greater than or equal to 6.7 and less than 11.1 mM) is neither diabetes nor normal. IGT is as referred to by the WHO. GDM exceeds two points of fasting BG greater than or equal to 5.6 mM, 1-h BG greater than or equal to 10.0 mM, or 2-h BG greater than or equal to 8.3 mM. Diabetes mellitus (DM) is as referred to by the Japan Diabetes Society (same as the WHO). The prevalence of abnormal glucose tolerance among all 615 pregnant women was 54.6% in borderline, 24.5% in IGT, 7.3% in GDM, and 3.4% in DM. The 2-h BG levels in IGT during the first trimester were higher than in borderline (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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In an attempt to clarify the mechanism of lipid metabolism during pregnancy, alpha 1-acid glycoprotein (alpha 1-AG) was analyzed in normal and diabetic pregnant women. Seventy-two determinations of serum alpha 1-AG levels were performed in 18 diabetic pregnant women and 82 determinations in 82 normal pregnant women in all three trimesters and within 14 days postpartum. Serum alpha 1-AG levels in both normal and diabetic pregnant women decreased throughout pregnancy and rapidly increased postpartum. In all gestational stages, the serum alpha 1-AG levels were lower in diabetic women than in normal women, but the differences were not significant. No significant correlation was obtained between serum alpha 1-AG and hemoglobin A1 (HbA1) in diabetic patients. On the contrary, the serum triglyceride levels increased during pregnancy and decreased postpartum in both groups of subjects. These findings suggest that serum alpha 1-AG plays an important role in the activation of lipoprotein lipase during pregnancy.
Sixty-nine patients with hepatocellular carcinoma underwent curative hepatic resections as primary cases from 1981 to 1986. Seven patients died in the hospital after operation. The other 62 patients left the hospital and were closely followed for 25 to 78 months. Recurrence of carcinoma became obvious in 41 (66%) of 62 patients. The clinical and pathologic features of these 41 patients were not significantly different from those of the other patients. Recurrent tumors were found in the residual liver in 38 patients (93%), in the bone in 2 (5%), and in the lung in 1 (2%). Recurrence was diagnosed within 1 year, between 1 and 2 years, and more than 2 years after the operation in 22 (56%), 10 (26%), and 7 (18%) patients, respectively. It was difficult to determine the exact time of recurrence in two patients. There was a significant negative correlation between the size of primary tumor and time until recurrence; the larger the primary tumor, the shorter the time until recurrence. Among the 29 patients who underwent local excisions for their primary tumors, 19 recurrences were observed. Eighteen were found in the residual liver, in the same segment as the primary tumor, or in one near it. Larger hepatic resection for primary tumors is thus advocated to prevent recurrence.
Platelet prostaglandin (PG) E and plasma PGF2 alpha concentrations were measured by radioimmunoassay methods and compared in non-pregnant and pregnant, normal and diabetic subjects. The blood samples were obtained in the follicular phase in the non-pregnant women and in the third trimester and after delivery in the pregnant women. The immunoreactive platelet PGE (IRPGE) levels were significantly higher in the pregnant diabetic women than in the normal non-pregnant and pregnant women and diabetic non-pregnant women. The immunoreactive plasma PGF2 alpha (IRPGF2 alpha) concentrations were significantly higher in the non-pregnant diabetic women than in the normal non-pregnant and pregnant women. During pregnancy, the plasma IRPGF2 alpha were further increased significantly in the diabetic subjects compared to the non-pregnant diabetics. Both the platelet IRPGE and plasma IRPGF2 alpha concentrations were higher in the pregnant diabetic subjects with retinopathy than in those without retinopathy. These findings suggest that pregnancy and diabetes influence the synthesis of PGE and PGF2 alpha in the platelets and plasma, respectively. The increased production of these prostaglandins are possible exacerbating factors of diabetic retinopathy during pregnancy.
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