Urinary N-acetyl-β-D-glucosaminidase activity (U-NAG) was determined and the relationship between U-NAG levels and the laboratory findings was studied by multivariate analysis in 292 noninsulin-dependent diabetes mellitus (NIDDM) patients, 39 impaired glucose toterance (IGT) patients and 10 controls. The NIDDM patients were divided into three groups: without proteinuria (DP (-): n=203), with trace proteinuria (DP (±): n=36) and with proteinuria (DP (+): n=53). The U-NAG level in NIDDM patients was significantly higher than that in the controls. In the diabetic group the U-NAG level in the DP (+) group was significantly higher than that in the DP (-) group.
In a partial correlation analysis, U-NAG was significantly correlated with hemoglobin A₁c (HbA₁c), age, proteinuria, serum creatinine (Scr), free fatty acids (FFA) and the degree of retinopathy. In a simple correlation analysis, U-NAG was also significantly correlated with the factors stated above, except Scr.
In a multiple regression analysis the independent variables that significantly contributed to the value of U-NAG were, 1) HbA₁c, Age, Proteinuria, FFA, Scr, Retinopathy in whole subjects and hole NIDDM (multiple correlation coefficient: R=0.696, 0.665, respectively), 2) HbA₁c, FFA, Age in DP (-) and controls (R=0.511, 0.858), 3) Age, Scr, FBS, Retinopthy in DP (±)(R=0.873), 4) HbA₁c, Age, Scr in DP (+)(R=0.703). The variables are listed the order of theirt values.
The U-NAG levels in DP (-) decreased in parallel with the decrease of FBS, HbA1c and FFA, but it did not reach the normal range.
It appears that the U-NAG levels should be evaluated not only by the presence of proteinu but by the patient's age, glycemic status and the degree of retinopathy.

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The incidence of rheumatoid factor (RF) as non-organ-specific autoantibodies was studied in patients with insulin-dependent (IDDM) or with non-insulin-dependent diabetes (NIDDM) and in controls. Three of 189 patients with IDDM (1.6%), 66 of 465 with NIDDM (14.2%), 3 of 478 normal children (0.6%) and 47 of 1, 229 adult controls (3.8%) were positive for RF. The incidence in patients with NIDDM was significantly higher than with IDDM or in the controls (p<0.001). There was no age-dependency in patients with NIDDM. One hundred and eight of the patientswith NIDDM were treated with insulin and the others with diet therapy or with both diet and oral hypoglycemic agents. There was no significant difference in the incidence of RF between these two groups. The lowest RF incidence, 8.3%, was in patients with NIDDM of less than one year duration. The incidence was 13.9% at 1-5 years, 17.0% at 6-10 years and 12.2% at more than 10 years. One reason why the incidence decreased at more than 10 years may be the shortness ofthe lifespan in diabetic patients with several autoantibodies. Were if not for the dropouts due to death a significant correlation may have occurred between the incidence of RF and duration from the onset of diabetes mellitus.

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Taste sensitivity in non insulin dependent diabetic patients (male 56, female 35, ages ranging from 50 to 65 years) were studied in relation to diabetes history, blood sugar control and complications such as microangiopathy and neuropathy, using a paper disc method. Each of 5 solutions were tested: NaCl for salty taste sucrose for sweet, tartaric acid for sour and quinine hydrochloride for bitter.
The female patients had significantly lower taste thresholds compared with the male patients, when diabetes history, blood sugar control and microangiopathy were not significantly different. Smoking lowered taste sensitivity significantly. Therefore the influence of smoking and sex on taste sensitivity must not be neglected in taste perception studies. Impairment of sweet sense in female nonsmokers and sour in male nonsmokers were significantly correlated with other neuropathic data. The latter was also related significantly to the time since onset of the diabetes and microangiopathy. This suggests that the impaired taste perception, one of the diabetic neuropathies, is closely related to microangiopathy. Taste abnormalities were not related to HbAi. In two series of taste perceptions tests done 2 weeks apart, controlling blood sugar in mild diabetic patrents without complications significantly improved the taste perception in a group with significantly improved FBS. But no changes occurred in a group with no significant changes in FBS. This suggests that there may be functional and easily reversible impairment of taste perception caused by poor blood sugar control.

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We analyzed the clinical features of 25 pregnancies and the deliveries of 19 diabetic patients (4insulin-dependent, 15 non-insulin-dependent) in Jichi Medical School Hospital from January 1976 to December 1985. The total number of deliveries in our hospital during the 10 yr period were 7187, thus the incidence of diabetic delivery was 0.35%.
The mean age at onset of diabetes was 25.4 yr (range 12 to 40 yr), and the mean duration of diabetes was 4.0 yr. Their previous histories of pregnancies and deliveries were extremely poor; only 3 babies out of 18 pregnancies were born alive. Diabetic retinopathy was found in 3 cases (12%), and aggravation of retinopathy was observed in 3 cases during pregnancy (12%) and in 2 cases after delivery (8%).
During pregnancy, twenty cases (80%) were treated with insulin and 5 cases (20%) were treated with diet alone. Nineteen cases (76%) required increased insulin during pregnancy. The daily insulin requirements in 5 insulin-dependent diabetics increased from 35.6 IU (prepregnant) to 56.0 IU (at delivery). Continuous subcutaneous insulin infusion (CSII) was used in 5 insulin-dependent and 1 non-insulin-dependent cases. The mean fasting plasma glucose level after the 28th week of gestation to delivery was 101 mg/dl in 1976-1981, and 90 mg/dl in 1982-1985.
The mean term at delivery was 37.3 weeks. Caesarean sections were performed in 13 cases (52%). Eight cases had trouble during pregnancy such as toxemia of pregnancy, infection, hydroamnion and so on. Perinatal mortality was 8 %(2 cases). Congenital malformations occurred in 3 babies (12%). The mean weight of neonates born after the 37th week of gestation was 3, 214 g. The incidence of the heavy-for-dates infants (7 cases) has decreased recently (1976-1981, 5/10; 1982-1985, 2/15). Complication in newborns were: hypoglycemia in 10 cases (43%), hyperbilirubinemia in 6 (26%), polycythemia in 5 (22%), and respiratory distress in one (4%). The incidence of heavy-for-dates infant and hypoglycemia was reduced when the mean fasting plasma glucose (after 28 weeks of gestation) of their mother was lower than 100 mg/dl. These data indicate that recent improvements of diabetic control and obstetric management result in a decrease in the perinatal problems of diabetic pregnancy.

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A specific radioimmunoassay (RIA) for glucagon-like peptide-1 (GLP-1) was established with the antibody against synthetic GLP-1 (1-37). The least detectable concentration of GLP-1 (1-37) that resulted in a response 2 SD below zero binding was 5 pg/tube. Cross-reactivity with glucagon was less than 0.001%, and cross-reactivities with other glucagon-secretin families, including GLP-2, VIP, GIP, secretin, GRF, and PHI, were negligible. The dilution test and reproducibility of this RIA were satisfactory. With this RIA, rat pancreatic extract was found to contain GLP-1 IR and a peak eluted at the same position with authentic GLP-1 in the profile of its gel chromatography. Since commercial glucagon was prepared from porcine pancreas, there could be some contamination of GLP-1 IR in the preparation. With this RIA, we have demonstrated that the commercial glucagon preparation indeed contains a small amount of GLP-1. Our results showed that this GLP-1 RIA was applicable to basic as well as clinical investigations.

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We report an autopsy case with insulin-dependent diabetes mellitus (IDDM) accompanied with severe atrophy in the exocrine pancreas. A 45-year-old woman was admitted because of acute onset diabetic symptoms including polyuria, polydipsia and general malaise. The fasting blood glucose level was 318 mg/dl and ketonuria was found on admission. Insulin therapy was started and continued thereafter. Despite the administration of insulin (24-40 U/day), her fasting blood glucose levels were unstable, ranging from 70 to 400 mg/dl, and ketonuria was frequently observed. Fifteen years after the acute onset of IDDM, she died of chronic renal failure. Pathological findings were: The pancreas was significanctly small and thin. It weighed 34.5 g. There were scattered, microscopically irregular-shaped atrophic islets although the number of the islets was almost normal.
An immunohistochemical study using the peroxidase-antiperoxidase method demonstrated that pancreatic B cells were abolished and A as well as D and P.P. cells were preserved. In the exocrine area, there was severe atrophy of the exocrine gland accompanied with mononuclear cell infiltration. These pathological changes suggest that the exocrine pancreas as well as the pancreatic islets are involved in destructive processes through the autoimmune mechanism in IDDM. Heterogeneity of pancreatic changes in IDDM is also apparent.

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A family with prevalent islet-cell surface antibodies (ICSA) and type I diabetes mellitus is reported. Four of the five members studied, mother, monozygotic male twins and sister, were positive for circulating ICSA/IgG, but none had anti-islet cell cytoplasmic antibodies (ICA). Two of them (mother and twin proband) had overt insulin-dependent diabetes mellitus. The sister showed a diabetic glucose tolerance with no fasting hyperglycemia and with substantially diminished insulin secretion in both oral and iv glucose tests. One non-diabetic twin had modest glucose intolerance and beta-cell dysfunction, when examined by a 25g iv glucose challenge test. Therefore, these non-diabetic siblings apparently are at increased risk for the development of type I diabetes mellitus. No association was found between the ICSA positivity and any types of HLA that are characteristic of Japanese type I diabetes. However, the three siblings had an identical HLA type and the mother shared 3 HLA types with them. There is no evidence for autoimmune polyendocrinopathy in any members. This family may provide interesting insight into both the genetics and pathogenesis of type I diabetes mellitus.

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The Non-obese diabetic (NOD) mouse with polyuria, glycosuria, ketonuria and weight loss with age is the animal model of human type I diabetes. To clarify which subset of T cells is responsible for the development of this type of diabetes, we analyzed the cell surface phenotypes of lymphocytes in the spleen and pancreas of NOD mice using immunofluorescent and immunohistochemical techniques. Our results indicate that T cells, especially Ly-1 and L3T4 positive helper T cells may play an essential role in the pathogenesis of autoimmunity in NOD mice. L3T4, the mouse homologue of human T cell antigen termed T 4 or Leu 3, is an antigen on mouse helper T cells that responds to antigens of the class II major histocompatibility complex (MHC). Female NOD mice were treated twice a week with injections of monoclonal antibody to L3T4. Administration of this antibody inhibited lymphocyte infiltration of the pancreatic islet (insulitis) and prevented hyperglycemia and glycosuria. These results lead to the conclusion that the autoimmune response in NOD mice is rstricted to class II MHC and is T cell dependent. Also, the manipulation of the OKT4 (Leu3)-positive subset with monoclonal antibody may provide effective therapy for type I diabetes in human.

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