[Treatment with insulin in diabetic acidoketosis].
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Biomedical subjects
Publications and source records attributed to D Cheţa.
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The levels of serum IgD and of the circulating immune complexes (CIC) were determined in 168 diabetic patients, of whom 78 with type 1, 59 with type 2 and 31 with the so-called "intermediary" type of the disease, in comparison with 124 non-diabetic subjects for IgD and 100 for CIC. The results revealed very low IgD titres (less than 1 mg%, considered undetectable) in almost 3/4 of the cases; values over 1 mg% were recorded mostly in the cases of type 1, followed by those of "intermediary" and of type 2 diabetes. The mean CIC values of 67.13 +/- 36.53 optic density units (O.D.U.) were significantly higher than in the non-diabetic controls. Certain differences with respect to age, diabetes type, duration of the disease and of the insulin therapy were also recorded. The data are interpreted with caution, further investigations being necessary to the assertion of definite conclusions.
In a group of patients with acute myocardial infarction (AMI) an evaluation of the derangements in lipid metabolism was carried out by analysing the fat structure of the hair (closely reflecting serum lipid variations). The data obtained reflects the real incidence of dyslipidemia associated with myocardial infarction. Through hair analysis, the evaluation in time (over weeks, months) of lipids metabolism under hypolipidemic therapy can be carried out without taking repeated samples.
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To extend previous observations on the quantitative changes of IgA and other serum Ig in diabetics, additional immunochemical investigations were carried out in 96 patients, 63 males and 33 females, mean age 43.5 +/- 15.7 years, 51 with type 1 (insulin-dependent) and 45 with type 2 (non-insulin-dependent) diabetes. The immunological data were correlated with the clinical-metabolic aspects. In the whole group, the IgA level was increased (144.1 +/- 57.2 I.U.). Significant differences were recorded with respect to age for IgG, to age and diabetes type for IgA, to sex for IgM. Qualitative Ig changes, reflecting disturbances of molecular structure, mainly for IgG, seldom for IgM, but never for IgA, were observed in 20% of the patients with both types of diabetes, more seldom in cases with long disease duration. The IgG with qualitative changes were purified and their functional capacity of inhibiting the natural cytotoxic activity (NK) was tested in comparison with that induced by pretreatment of the effectory cells with normal IgG. Some of these modified IgG showed a reduced capacity of inhibiting the NK activity. These data confirm the existence of certain quantitative changes of the main serum Ig in diabetics and reveal the presence of qualitative disorders of the IgG molecules, with consequences on their functionality.
It has been speculated that insulin antibodies may contribute to the hypoglycemic attacks in insulin-treated diabetic patients. To address this hypothesis, we analyzed in a first part of the study the frequency to hypoglycemia in two groups of diabetic patients, one (Group A, 38 cases) with at least two episodes of severe hypoglycemia in the last year and another (Group B, 38 cases) without severe hypoglycemia in the last 3 years. In the second part of this study, we analyzed the frequency of severe and moderate episodes of hypoglycemia in another two groups of diabetics, one (Group C, 32 cases) with high insulin antibody titre (greater than or equal to 20% binding, mean +/- SD 31.2 +/- 8.1%) and another with low insulin antibody titre (less than 10% binding, mean +/- SD, 5.1 +/- 2.2%). No significant difference was found for bound insulin between diabetics with frequent hypoglycemic episodes (2.3 +/- 0.2/patient/year--Group A) and those without severe hypoglycemic episodes (Group B), i.e., bound insulin 4.89 +/- 3.21% in group A versus 5.32 +/- 4.5% in group B. Conversely, the frequency of severe episodes of hypoglycemia was similar in diabetic patients with high (31.2 +/- 8% binding in group C) and respectively low (5.1 +/- 2.1% binding in group D) insulin antibody titre, i.e., 0.15 episodes/patient/year in group C and 0.17 episodes/patient/year in group D.
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The genetic characteristics of the diabetic types have been assessed by following up their frequency in first degree relatives of some non-selected diabetic patients, registered at eight different centers of the country. Out of 1,003 non-diabetic controls only 46 (4.6%) had 52 diabetic relatives, 65.4% of type 2 (non-insulin-dependent). Comparatively, out of the 704 patients, 172 (24.4%) had 229 diabetic first degree relatives, 72.5 of type 2. Out of 231 type 1 (insulin-dependent) diabetic patients, 29 (12.6%) had 34 diabetic relatives, 55.9% of type 1. Out of 300 type 2 patients, 99 (33.0%) had 121 diabetic relatives, 84.0% of type 2. The other 173 diabetic patients presented an "intermediary" type of the disease (needing insulin many years after onset). Forty-four (25.4%) of them had 64 diabetic relatives, 67.2% of type 2, 20.3% of type 1 and 12.5% with "intermediary" diabetes. The five times higher frequency of diabetes in patients' relatives versus controls is pointed out. Type 2 diabetic relatives predominated. The proportion of probands with diabetic relatives increased from 4.6% in non-diabetics to 12.6% in type 1, to 25.4% in "intermediary" diabetes and to 33.0% in type 2. The heredity of type 1 prevailed in type 1 and that of type 2 in type 2 and in "intermediary" diabetes. The fact that "intermediary" diabetes tends towards type 1 (insulin-dependent) as therapy and towards type 2 (non-insulin-dependent) as heredity might be an argument supporting the controversy on the diabetic syndrome classification.
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Contradictory results have been published on serum immunoglobulin levels in diabetes. Our study population consisted of 26 "juvenile" IDDM patients (males/females 14/12, mean age 15.8 +/- 2.4 yrs), 42 "adult-onset" IDDM patients (25/17, 45.1 +/- 15.2 yrs), 62 NIDDM patients (27/35, 59.8 +/- 7.7 yrs), 128 controls. IgM has been measured by a highly standardized endpoint radial immunodiffusion. Since age and sex significantly influence serum IgM levels, we calculated Z values using the formula: log (Xobs:Xexp): SDexp, where Xobs is the measured IgM in any individual and Xexp and SDexp are the expected (geometric) mean and standard deviation of the log IgM values for each year of age in both sexes, as previously calculated by orthogonal polynomials from a large population of "laboratory controls" (n = 755; 10-70 yrs). These Z values (+/- SD) in juvenile IDDM (-0.442 +/- 0.988) and NIDDM (-0.559 +/- 1.215) were significantly lower (P = 0.035 and P less than 10(-3)) than in "laboratory controls" (0 +/- 1). Values in adult IDDM (-0.0225 +/- 1.213; P = 0.24) and in controls (-0.018 +/- 1.04) did not differ significantly from the "laboratory controls". The prevalence of diabetes within the four quartiles of the IgM distribution differed significantly from the one expected according to the null hypothesis (chi-square = 42.2; 3df; P less than 10(-4]. This is also applied to juvenile IDDM (P less than 0.05) and NIDDM (P less than 10(-4], but not to adult-onset IDDM. These results suggest that the low IgM levels may partly contribute to the poorly explained increase in susceptibility to infections in some diabetics.
Insulin antibodies (% binding) were determined by RIA method in 404 insulin-treated diabetic patients divided into two groups: (A) primary insulin-dependent patients (Type I diabetes): 300 cases, 170 M, 130 F, mean age +/- SD 29.2 +/- 7.5 yrs, disease and insulin treatment duration 7.7 +/- 6 yrs: (B) Type II diabetic patients needing insulin (secondary insulin-dependence): 104 cases, 47 M, 57 F, aged 53.4 +/- 9.2 yrs, duration of diabetes 13.1 +/- 8.3 yrs, and of insulin treatment 3.1 +/- 2.1 yrs. Both groups of patients were with the same types of insulin preparations. In 297 cases, all belonging to group (A), fasting C-peptide was also determined. The titre of insulin antibodies was significantly (p less than 0.001) higher in patients with secondary insulin dependence than in those with primary insulin dependence (22.96 +/- 15.1% vs 10.25 +/- 9.89) in spite of the longer duration of insulin treatment in the later group; the mean C-peptide value found in 58 Type I diabetic patients with a binding capacity less than 10% was significantly lower (p less than 0.001) than that found in 11 Type I diabetic cases with a binding capacity greater than 20% (0.091 +/- 0.57 vs 0.273 +/- 0.37 pmol/ml); no correlation was found between insulin antibodies and metabolic control, insulin requirements or chronic complications.
Investigations on the activity of three erythrocytic enzymes i.e., glucose-6-phosphate dehydrogenase (G-6-PDH), catalase and lactate dehydrogenase (LDH), in 20 patients with extracorpuscular hemolytic anemias of various origins showed a general tendency to decrease of G-6-PDH and catalase, with a concomitant increase in LDH. These results are interpreted as due to metabolic disturbances induced by hemolysis in the erythroblastic series and/or to possible perturbations specific for each type of anemia.
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The presence of viral and/or inframicrobial antigens was investigated by the immunofluorescence (IF) technique in exfoliated pharyngeal cells collected from 85 children aged 0-5 years, with acute infections of the upper or lower respiratory tract. Positive IF reactions were recorded in 83% of the children with bronchopneumonia, 81.8% of those with acute pharyngitis, 77.7% of those with acute upper respiratory tract infections and 66.6% of those with acute bronchitis. In 68.75% of the IF-positive cases 2-5 different antigens were simultaneously visualized. Herpes and parainfluenza virus antigens appeared to be predominant. The proportion of positive IF reactions was much lower (20%) in a control group of 20 apparently healthy children, where a single viral antigen (parainfluenza 1) was detected.
Investigations were carried out in Bucharest in 102 patients with insulin-dependent diabetes mellitus (IDDM) in order to verify the possible existence of a relationship between the HLA system and the level of insulin antibodies. The A and B loci were tested with monospecific antisera, using PEC as a separation agent for the determination of the insulin antibody titer. Group I, without antibodies (34 cases), presented: HLA-B7 (18.89% of total specificities), A3 (11.02%), A1 and B5 (8.74% each), etc.: for haplotypes the following were found: HLA-A3/B7 (9.91% of the total haplotypes), A2/B7 (8.26%), A1/B7 (5.78%). Group II (50 cases) with low or medium titers (less than 30% binding) included: HLA-B7 (20.47%), A2 (11.88%), (A1 (9.44%), B5 (8.74%), and haplotypes: HLA-A2/B7 (8.88%), A1/B7 (7.22%), A3/B7 (6.11%). Group III (18 cases), with high antibody titers (greater than 30% binding), presented: HLA-B7 (20.28%), A1 and A2 (11.59% each), A10 (10.14%), and haplotypes: HLA-A1/B7 (10.60%), A2/B7 and A10/B7 (9.09% each), A3 B7, A2 B5 and A10/B5, (6.06% each). Irrespective of the insulin antibody titer, B7 antigen surprisingly appeared predominant in our cases. Moreover, a marked tendency of A1, and to a certain extent of A2, to increase in terms of the titer was noted in parallel with a significant decrease of A3.
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