No relationship between insulin antibodies and transient remission in type 1 diabetic patients.

It has been speculated that the insulin antibodies may contribute to the prevention of the onset of the transient remission in insulin-treated diabetic patients. To address this hypothesis, we analysed the titre of insulin antibodies (determined by RIA method, using polyethylenglycol separation technique and expressed as percentage of binding of insulin) in two groups of patients: group A: 46 type 1 diabetics, 25 males and 21 females aged 24 +/- 11.2 years, mean +/- SD, who did not manifest during the first period of the disease any clinical sign of remission; group B: 21 type I diabetics, 13 males and 8 females, aged 25.3 +/- 8.0 years, who manifested in the first year either a partial (18 cases) or a total (3 cases) transient remission. Thirty-eight of cases with disease onset before 1984 were treated with conventional insulins (27 of 46 cases in A group and 11 of 21 cases in B group); the remaining cases were treated with monocomponent (MC) insulins. The binding of the insulin was significantly higher in the patients treated with conventional insulins vs those treated with MC insulins, i.e., 18 +/- 7.1% vs 10.2 +/- 5.2% (p < 0.001). However, no difference was found in the binding of insulin in A group (14.5 +/- 1.3%) compared with B group (13.7 +/- 11.1%). Moreover, in 3 cases from B group the onset of the remission was coincident with the increase of insulin antibodies.

Insulin resistance: the link between impaired glucose tolerance, body mass index and plasma lipids.

Body mass index defined as weight (Kg)/height (cm2) and plasma lipids (total lipids-TL, triglycerides-TG and cholesterol-CH) were determined in 131 patients (61 males and 70 females aged between 21 and 63 years) with impaired glucose tolerance (IGT) defined according to WHO criteria. Blood glucose (BG) values and plasma insulin (PI) levels (radioimmunological assay) were determined during 2 hours OGTT with samples obtained before and after 1 h and 2 h after the intake of 75 g glucose. The sum of blood glucose and plasma insulin levels (0 + 1h + 2h) were compared in each of the following 5 groups of subjects: A--25 cases with IGT but without obesity (BMI: 23.2 +/- 2.6) and hyperlipidaemia (PL: 627 +/- 112; TG: 102 +/- 109 and CH: 208 +/- 35 mg/dl); B--35 cases with IGT and obesity (BMI: 31.2 +/- 2.6) but without hyperlipidaemia (PL: 807 +/- 109; TG: 136 +/- 31 and CH: 254 +/- 41 mg/dl); C--23 cases with IGT and hyperlipidaemia (PL: 1013 +/- 217; TG: 214 +/- 85 and CH: 311 +/- 52 mg/dl) but without obesity (BMI: 25.4 +/- 1.9); D--48 cases with IGT and both obesity (BMI: 30.9 +/- 2.8) and hyperlipidaemia (PL: 1457 +/- 155; TG: 597 +/- 188 and CH: 483 +/- 184 mg/dl); a control group of 49 cases without IGT, obesity (BMI: 26.2 +/- 1.9) or hyperlipidaemia (PL: 726 +/- 99 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired glucose tolerance in the third trimester of pregnancy: associated factors to its persistence postpartum.

Glucose tolerance (75 g OGTT, according WHO) during the third trimester of pregnancy, in 302 women, has formerly been evaluated. Of these, 37 women were reinvestigated, with the same methodology, in absence of pregnancy and lactation, 2 years postpartum. According to oral glucose tolerance three groups were differentiated: group A (n = 14) with normal glucose tolerance (NGT) both in pregnancy and postpartum. Group B1 (n = 12) with impaired glucose tolerance (IGT) in pregnancy but NGT postpartum. Group B2 (n = 11) with IGT both in pregnancy and postpartum. B2 group had increased values (mean + SD) for age (37.0 +/- 6.6 years) versus B1 (30.2 +/- 5.5; p < 0.02) and A (29.5 +/- 5.9); p < 0.02) groups and BMI (32.5 +/- 4.2) versus 26.4 +/- 5.2; p < 0.01 and 23.3 +/- 4.4; p < 0.001 respectively). The ratio between basal insulinogenic indexes (microU IRI/mg BG) during pregnancy and 2 years postpartum has been significantly reduced in B1 (1.4 +/- 0.8) and B2 (1.5 +/- 0.6) as compared to A (2.5 +/- 1.1; p < 0.01) group suggesting, by comparison, the persistence of an increased level of insulin resistance postpartum in B1 and B2 groups. Insulinogenic index, after oral glucose was lower in B2 (34.4 +/- +/- 7.8) versus B1 (53.5 +/- 20.9; p < 0.01) group. These results suggest that, on an increased insulin resistance background, the decrease in glucose induced insulin response and increase in age and BMI are associated to deterioration of glucose tolerance early in the natural history of NIDDM.

No relationship between insulin antibodies and hypoglycemia in insulin-treated diabetic patients.

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.

Comparative study of insulin antibodies in diabetic patients with primary insulin-dependence (type I) and secondary insulin-dependence (type II).

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.

[The effect of a plant mixture on the metabolic equilibrium in patients with type-2 diabetes mellitus]. / Efectul unui amestec pe plante asupra echilibrului metabolic la bolnavii cu diabet zaharat de tip 2.

The present paper analyses the results obtained in 82 patients with diabetes mellitus of the 2nd type: 59 women and 23 men, between 41 and 74 years old (average +/- DS, 58 +/- 9 years), of which 58 had an index of the body weight higher than 26. The diabetes duration ranged between newly discovered and 11 years. Each patient was given, 3 times a day, a 150 ml cup containing an infusion of the following mixture of plants previously cut into small pieces: Phaseolus vulgaris (pod), Morus alba (leaf), and Vaccinum myrtillus (leaves). The approximate dose used was of about 15 g/day. The treatment lasted for two months. Before and after treatment, the following parameters were determined: Hb Al (Bio-Rex method) in 31 cases; the average of 3 consequent glycemias; the value of glycemia and insulinemia recorded after a standard lunch, consisting of about 40 g glucides, 14 g proteins and 6 g lipids (50 g bread, a boiled egg and a boiled apple of 100 g). Analysis of the results obtained enabled the following temporary conclusions (1). In 74 out of the 82 cases studied, the average values of glycemia, after the treatment with plants, were lower than those recorded before the treatment (the average values of the whole lot: 219 +/- 82 mg/dl before treatment and 166 +/- 76 mg/dl after treatment (2). The overall decrease recorded, of 53 mg/dl, represents 24.3% of the initial value (3).(ABSTRACT TRUNCATED AT 250 WORDS)

Correlations between insulin antibodies and the HLA system in a group of type I diabetic patients in Bucharest.

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.

Disappearance rate of insulin antibodies after discontinuing insulin treatment in 42 type 2 (non-insulin-dependent) diabetic patients.

The disappearance rate of insulin antibodies was studied after cessation of insulin treatment which had been given for 3 months to 6 years in 42 Type 2 (non-insulin-dependent) diabetic patients. Insulin antibodies were measured before and 15 days after interruption of insulin treatment, and every 30 days until the disappearance of insulin antibodies. The mean +/- SD value of insulin binding in the entire group before the interruption of insulin treatment was 32 +/- 14%. There was no relationship between the antibody level at that time and the duration of insulin treatment. However, the insulin antibody level was significantly higher in 17 diabetic patients on an insulin dose of greater than 20 U/day (p less than 0.02) than in 25 on an insulin dose of less than 20 U/day (39 +/- 13% versus 28 +/- 12%). A positive correlation was found between initial insulin binding and the time required for it to fall below 10% (r = 0.74). Antibodies were absent 60 days after discontinuing insulin treatment in eight of ten subjects presenting with initial binding of less than 20%. In contrast, in only two of 12 patients with an initial binding of greater than 40% were insulin antibodies detectable 150 days after discontinuation of insulin therapy. Disappearance of insulin antibodies sometimes took up to 1 year and occasionally even more than 2 years.

The behaviour of some biologic parameters in obese patients after short-term exercise under restrictive diets.

Seven obese female patients with a mean age of 40 have received for 3-4 days a diet of 1000 cal followed by a diet of 300 cal/day. At the end of each period of diet, the patients performed an exercise of 75 watts for 15 min on the ergometric bicycle. Some biologic parameters determined before, as well as 15 min and 60 min after exercise did not show important differences in terms of the diet applied. Glycemia was constantly low, while glucagon, lactate and free fatty acids (FFA) values rose, particularly within the 15 min following exercise. After the same interval, insulinemia was unchanged or even increased. These results support the opinion that, even under restrictive diets, the reaction of obese patients to a short-term exercise is similar to that of normal weight subjects, their sources of energy being the same. The behaviour of insulinemia, which did not change or even increased, while in normal weight subjects it decreases on exercise, might be due to a lesser epinephrine activity in obese patients and/or a lesser FFA release from the adipose tissue.

Behaviour of insulin antibodies in diabetics treated with different insulins.

Determinations of insulin antibodies in 116 insulin-dependent diabetics treated successively with various types on insulin and in a group of 55 diabetics who received a single insulin type from the onset of the disease, revealed higher titers in those under treatment with conventional insulins, particularly Insulin Novo Lente. The mean titer of insulin antibodies is considered to be related to the insulin demands and sometimes to the length of disease. The presence of antibodies was also recorded after administration of highly purified insulins, but much more seldom and with lower titers, which could be an argument for a wider utilization of such products.

RIA measurement of insulin antibodies in human sera using the polyethyleneglycol separation technique.

A radioimmunological method for the detection and measurement of insulin antibodies in human sera was developed using polyethyleneglycol (PEG) as separation agent. Studies were performed on 150 sera of nondiabetic subjects and on 27 sera collected from diabetic patients treated with insulin. The per cent binding of 125I-insulin in normal sera ranged similarly to control free-insulin serum while in sera from insulin-treated patients8 the binding was significantly greater. The technique is quick (24 hours) and the intra-assay precision (correlation coefficient for replicates) varies from 0.87 to 0.99%. The separation technique using PEG for the precipitation of the antigen-antibody complexes may be extended to the measurement of antibodies for any other substance of lo, molecular weight (under 10,000 daltons).