Biomedical subjects
Publications and source records attributed to D Cheţa.
The classification, the mechanisms of action and the main side effects of sulfonylureic derivatives and biguanides are discussed. Emphasis is laid on the present controversy concerning the assumed adverse effect of these drugs on the cardiovascular system. The authors' opinion in this problem and their practical conclusions are based on their experience at the Center of Nutrition and Metabolic Diseases, Bucharest.
The first part of the work reviews some general data regarding the HLA system and emphasizes the principal implications of this system in diabetes mellitus and other metabolic diseases. Part two discusses pathoimmunological mechanisms in metabolic pathology (on the one hand those linked to autoimmunity, on the other those linked to immunologic deficiency of enzymatic origin). Finally, some immunologic aspects in the treatment of metabolic diseases are outlined.
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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.
For a preliminary estimation of the prevalence and significance of HLA antigens, tests were carried out on the A and B loci in an unselected group of 107 patients with type 1 diabetes in Bucharest. Monospecific antisera furnished by NIH, Bethesda were used. For HLA-A the following data were obtained: A2 (20.3% of the total specificities); A1 (18.4%); A3 (14.0%); A28 (10.1%). Provisional estimations in the healthy population also indicated HLA-A2 as being more frequent than followed by A30/31, A1, A9, A3. For HLA-B: B7 (38.2%); B5, B12 and B14 (14.0% each); B8 (11.1%). In the healthy subjects, the order was B12, B35, B5, B8 the same as B18, then B7 (which did not exceed 11%). The most frequently encountered haplotypes in the diabetic patients were: A2/B7 (8.4% of the total haplotypes); A3/B7 (6.9%); A1/B7 (6.6%); A10/B7 (3.8%); A9/B7 and A11/B7 (3.6% each). An unexpectedly high frequency of the HLA-B7 antigen was found in group of diabetic patients investigated, contrasting with its assumed "protector" role in the Caucasian population. The frequency of antigen HLA-A3 and haplotype HLA-A3/B7 infringes their listing in the "resistance axis" to diabetes.
Clinical heterogeneity of diabetic peripheral neuropathy could express a neurophysiological and electrophysiological heterogeneity possibly related with the dissociated metabolic susceptibility of the difference types of nerve fibres and endings. To evaluate the functional status of the skin autonomous nervous system and of the deep pain sensitivity system in diabetics we studied two electrophysiological parameters skin electrical potential (using Digital Multimeter 3466 Hewlet Packard, USA) and the perception threshold (microA) at an electrical stimulus (spike wave, 0.5 m sec duration) 1 cm deeply applied through 2 acupuncture needles placed 30 cm distance each other, in 3 groups: Ia-18 diabetic patients with clinical signs of neuropathy (12 M, 6 F, aged 55 +/- 17 yrs); Ib - 17 diabetic patients without clinical signs of diabetic neuropathy (12 M, 5 F, aged 57 +/- 16 yrs); I1 - 10 age and sex matched non-diabetic controls. Our data show: a higher mean value of the potential in the acupuncture points as against neighbour areas, both in non-diabetic control (- 111 +/- 25 mV v.s. -81 +/- 29 mV, p less than 0.05) and in diabetics (-85 +/- 43 mV v.s. -58 +/- 25 mV, p less than 0.01); a lower mean value of the electrical potentials in diabetic with clinical signs of neuropathy as against in those without clinical signs of neuropathy (-66 +/- 29 mV v.s. -108 +/- 43 mV, p less than 0.01): a higher mean value of the perception threshold in diabetics with clinical signs of neuropathy as against in diabetics without clinical signs of neuropathy (213 +/- 82 microA. v.s. 102 +/- 40 microA, p less than 0.01); a significant correlation (r = -0.81) between the perception threshold and the electrical potentials of the studied points.
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Cytochemical study of peripheral lymphocytes in 78 diabetic patients and 22 controls included the determination of glycogen (with calculation of the "glycogen score"), lipids and nucleolar RNA (with calculation of the so-called "lymphocyte nucleologram"). All three metabolic components showed marked differences between the diabetes and the controls. Further analysis in terms of sex, patient's age, duration of disease, basic treatment and main complications of diabetes, also showed certain variations of the above parameters but of lesser amplitude. Metabolic alterations of lymphocytes in diabetes mellitus reflect the pathogenic particularities of the disease, and might probably be used as a basis for further practical purposes.
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The present report discusses the immunogenic properties of insulin: the factors upon which immunogenicity depends, the characteristics of insulin antibodies, clinical aspects (insulin allergy, immunologic insulin resistance, lipodystrophy, etc.), as well as the significance of highly purified insulin products. The authors then review the role of autoimmunity in the etiopathogenesis of the diabetic disease as results from the association of diabetes with other autoimmune diseases, lymphocytic islet cell infiltration, phenomena of cell mediated and humoral mediated autoimmunity (islet cell antibodies). The present pathogenetic model of insulin-dependent diabetes (type 1) is marked by the predominance of these aspects. The last part of the report concerns immunologic functions in diabetics and the question of immune complexes.