Not only quantitative but also qualitative changes of serum immunoglobulins in diabetes mellitus.

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.

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.

Microalbuminuria following exercise, an early sign of diabetic nephropathy.

Microalbuminuria after physical exercise is characteristic for the preclinical stage of diabetic nephropathy, permitting an early diagnosis of this severe complication of diabetes mellitus. In 24 patients with type I diabetes, 11 women and 13 men free of clinical and biological signs of renal damage, the presence of microalbuminuria has been investigated by radial immunodiffusion in the urines collected between 3 and 7 hrs in the morning, as well as after a 20-min rest following a moderate exercise of 75 watts during 20 min at the ergometric bicycle. The patients were distributed into four groups, according to the age of disease, and microalbuminuria was expressed in micrograms/min. Compared with the mean values recorded in normal subjects by the same method (6.8 micrograms/min), the level of microalbuminuria has been significantly higher in the cases evaluating since more than two years, in keeping with the time elapsed after onset, and particularly following exercise. No relationship could be established between the quality of metabolic control of diabetes and the levels of microalbuminuria after exercise.

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.

Study of some serum protein fractions in various clinical forms of diabetes mellitus.

With a view to studying the eventual alterations of protein metabolism, some serum protein fractions such as: immunoglobulins (IgG, IgA, IgM), transferrin and ceruloplasmin were determined in 100 diabetics (52 males, 48 females) in comparison with a control group of 26 healthy subjects. Significant differences were found between IgA and transferrin values both in diabetics and in controls. IgA tended to increase with the length of disease, whereas IgG, IgM and transferrin showed a contrary trend. IgA and transferrin values were higher in the patients with juvenile and young adult diabetes, as compared to maturity onset and senile diabetes. Other immunoglobulin and transferrin changes were related to sex, age, type of treatment, degree of stability, presence of chronic complications. No significant anomalies were found for ceruloplasmin. The results confirm the presence of serum protein alterations in diabetes mellitus, whose significance may be correlated with the clinical particularities of the disease.