Manuel Vera

Effect of standard nicotinamide in the prevention of type 1 diabetes in first degree relatives of persons with type 1 diabetes

Background: Nicotinamide has been used with success to prevent type 1 diabetes in animal models and humans. This vitamin B3 derivative has attracting effects on β-cell protection and regeneration. Aim/hypothesis: To evaluate the effect of standard nicotinamide administration on type 1 diabetes prevention in first degree relatives of persons with type 1 diabetes as well as on the concentrations of islet-cell-related autoantibodies, insulin secretion and peripheral sensitivity. Subjects and methods: A randomized double-blind placebo controlled intervention trial was conducted in 40 first degree relatives of type 1 diabetic patients. Persistence of ICA ( ≥ 10 JDF units) was among inclusion criteria. Participants were randomly allocated oral standard nicotinamide (1.2 g/m2) or placebo for 5 years. Groups were also stratified by age. Islet associated antibodies, fasting blood glucose, fasting plasma insulin concentrations, OGTT, IVGTT and HLA-DR genotyping were performed in all participants. The main criterion to stop treatment was type 1 diabetes development as defined by WHO. Results: Type 1 diabetes development frequencies were similar between the treatment groups. ICA frequencies at the end of the study, first phase insulin release, and insulin sensitivity did not differ between groups as well. None of the participants suffered from any adverse events described for nicotinamide. Conclusions: Type 1 diabetes prevention trial using standard nicotinamide is feasible but fails to prevent or delay the disease onset at the dose we used.

Relationship of type 1 diabetes to ancestral proportions and HLA DR/DQ alleles in a sample of the admixed Cuban population.

Background: Incidence of type 1 diabetes varies widely around the world, probably due to ethnic differences across populations among other factors. Aims: To determine whether there is an association between disease and ancestry proportions; and to control disease–HLA associations for possible confounding by admixture or population stratification. Subjects and methods: 100 cases and 129 controls participated in the study. Ancestry informative markers, which have considerable differences in frequency between European, West African and Native American populations were used. Type 1 diabetes associated HLA susceptibility/protection alleles were ascertained by PCR using specific primers. Statistical analyses were conducted using STRUCTURE 2.1, ADMIXMAP 3.7, SPSS 16.0 and STRAT 1.0 packages. Results: The results of logistic regression implemented in ADMIXMAP 3.7 indicated that European ancestry was associated with type 1 diabetes mellitus with an odds ratio of 5.7 corresponding to one unit change in European admixture proportion. Association was found between HLA alleles and disease, DQA1*0501, *0301 DQB1*0201 and DRB1*0301, *0401 being susceptibility alleles and DRB1*1501, DQA1*0102/3 and DQB1*0602 being protective alleles. Conclusions: We found an association between European ancestry and type 1 diabetes in our sample, indicating the contribution of ethnicity to incidence differences. Previously reported associations of HLA DR/DQ alleles with disease are confirmed for the admixed Cuban population.

Dermatoglyphics in insulin-dependent diabetic patients with limited joint mobility

Hand and palm dermatoglyphics were studied in 158 insulin-dependent diabetic children and adolescents [85 with limited joint mobility (LJM) and 73 without]. The findings in this group were compared with those in 400 control subjects, with a similar racial distribution. The main dermatoglyphics alterations found in diabetic patients with LJM, as compared with non-LJM diabetic patients and controls, may be summarized as follows: (a) decrease in digital total ridges count (TRC); (b) higher frequency in the number of arches; (c) decrease in the sum of a line and cubital loops, particularly in the women; (d) increase in the number of t′-axial triradii. These alterations suggest a genetic aetiology of this complication. Further studies are recommended in order to provide more insight into the origin of this disorder.

A study of the respiratory function in insulin-dependent diabetic patients with and without limited joint mobility (LJM)

SummaryThe respiratory function of 51 insulin-dependent diabetic patients (31 with and 20 without LJM) was studied. The variables age, diabetes duration, height, and metabolic control were similar for both groups. Vital capacity (VC), forced expiratory volume (FEV), mean maximum expiratory flow (MMEF), and FEV/VC ratio were determined before and after the administration of a bronchodilator. VC, FEV, and MMEF showed significantly lower values (p<0.02) in patients without LJM as compared to those with LJM. It is suggested that these alterations may be due to abnormalities of collagen fibers and elasticity in the lung and are not related to reversible bronchial obstruction. We believe that LJM is an extrinsic manifestation of a systemic process, aggravating the prognosis of diabetes mellitus.

Histological and histochemical skin changes in insulin-dependent diabetic patients with and without limited joint mobility

SummaryWe studied 24 skin biopsies of the hand in 24 IDDM patients followed at the National Institute of Endocrinology (NIE). Biopsies of 7 healthy individuals were used as controls. The diabetics were divided into two groups, with limited joint mobility (LJM) and without LJM. We compared the different structural components of the skin, and their changes; we used quantitative, semi-quantitative and qualitative methods. We found that patients with LJM had a greater levelling, less rete pegs and dermal papillae (p<0.05), increased alteration of the mucopolysaccharides distribution (p<0.005), higher frequency of alterations of the elastic fibers (p<0.05) and collagen (p<0.005), vessel enlargement (p<0.025) acquiring cord shape, and reduction of the vessel lumen (p<0.005) in comparison with patients without LJM and controls. This could be a consequence of the chronic hyperglycemia from childhood that affects the structure, architecture and function of collagen fibers. Genetic and immunologic studies could help to elucidate the mechanisms of this alteration.

[Frequency and characteristics of metabolic syndrome and insulin resistance in the first-degree relatives of persons with type 1 diabetes].

AIM To determine the frequency of metabolic syndrome (MS) and insulin resistance (IR) in first-degree relatives of type 1 diabetic patients (FDR1) and to study the relationship between these two disorders and some clinical, biochemical and immunological characteristics. SUBJECTS AND METHODS We studied 289 persons, of which 193 were children/adolescents and 96 were adults. Weight, height, waist and hip circumference, blood pressure, blood glucose, insulin, cholesterol, triglycerides, high-density lipoprotein-cholesterol, glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies were determined. IR was assessed through the insulin resistance index (HOMA-IR). The criteria of the World Health Organization for adults and the Cuban consensus for children and adolescents were used to define MS. RESULTS The prevalence of MS in child and adolescent FDR1 was 5.7% (11/193) while IR was found in 24.9% (48/193). For adult FDR1, the frequency of MS was 6.2% (6/96) and that of IR was 14.6% (14/96). Interestingly, an association was found between IR and MS in adults but not in children and adolescents. IR was more frequent in children and adolescents than in adults (p<0.05). The presence of GADA was associated with IR but not with MS (p<0.05). CONCLUSIONS The frequency of MS in child and adolescent FDR1 was similar to that found in the general population according to studies using similar definitions of MS. In contrast, the frequency of MS in adults was lower than that reported in Cuba for the first-degree relatives of patients with type 2 diabetes. IR was not only associated with MS in first-degree relatives. The association of IR with the presence of GADA may reflect the fact that beta cell hyperactivity increases autoantigen expression.

Frecuencia y características del síndrome metabólico y de la resistencia a la insulina en familiares de primer grado de personas con diabetes mellitus tipo 1

AIM To determine the frequency of metabolic syndrome (MS) and insulin resistance (IR) in first-degree relatives of type 1 diabetic patients (FDR1) and to study the relationship between these two disorders and some clinical, biochemical and immunological characteristics. SUBJECTS AND METHODS We studied 289 persons, of which 193 were children/adolescents and 96 were adults. Weight, height, waist and hip circumference, blood pressure, blood glucose, insulin, cholesterol, triglycerides, high-density lipoprotein-cholesterol, glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies were determined. IR was assessed through the insulin resistance index (HOMA-IR). The criteria of the World Health Organization for adults and the Cuban consensus for children and adolescents were used to define MS. RESULTS The prevalence of MS in child and adolescent FDR1 was 5.7% (11/193) while IR was found in 24.9% (48/193). For adult FDR1, the frequency of MS was 6.2% (6/96) and that of IR was 14.6% (14/96). Interestingly, an association was found between IR and MS in adults but not in children and adolescents. IR was more frequent in children and adolescents than in adults (p<0.05). The presence of GADA was associated with IR but not with MS (p<0.05). CONCLUSIONS The frequency of MS in child and adolescent FDR1 was similar to that found in the general population according to studies using similar definitions of MS. In contrast, the frequency of MS in adults was lower than that reported in Cuba for the first-degree relatives of patients with type 2 diabetes. IR was not only associated with MS in first-degree relatives. The association of IR with the presence of GADA may reflect the fact that beta cell hyperactivity increases autoantigen expression.