Mônica Andrade Lima Gabbay

Aerobic exercise capacity in normal adolescents and those with type 1 diabetes mellitus.

Objective:  To compare the aerobic exercise capacity between normal adolescents and those with type 1 diabetes mellitus (T1DM).

Effect of cholecalciferol as adjunctive therapy with insulin on protective immunologic profile and decline of residual β-cell function in new-onset type 1 diabetes mellitus.

OBJECTIVE To evaluate the effect of vitamin D3 on cytokine levels, regulatory T cells, and residual β-cell function decline when cholecalciferol (vitamin D3 administered therapeutically) is given as adjunctive therapy with insulin in new-onset type 1 diabetes mellitus (T1DM). DESIGN AND SETTING An 18-month (March 10, 2006, to October 28, 2010) randomized, double-blind, placebo-controlled trial was conducted at the Diabetes Center of São Paulo Federal University, São Paulo, Brazil. PARTICIPANTS Thirty-eight patients with new-onset T1DM with fasting serum C-peptide levels greater than or equal to 0.6 ng/mL were randomly assigned to receive daily oral therapy of cholecalciferol, 2000 IU, or placebo. MAIN OUTCOME MEASURE Levels of proinflammatory and anti-inflammatory cytokines, chemokines, regulatory T cells, hemoglobin A1c, and C-peptide; body mass index; and insulin daily dose. RESULTS Mean (SD) chemokine ligand 2 (monocyte chemoattractant protein 1) levels were significantly higher (184.6 [101.1] vs 121.4 [55.8] pg/mL) at 12 months, as well as the increase in regulatory T-cell percentage (4.55% [1.5%] vs 3.34% [1.8%]) with cholecalciferol vs placebo. The cumulative incidence of progression to undetectable (≤0.1 ng/mL) fasting C-peptide reached 18.7% in the cholecalciferol group and 62.5% in the placebo group; stimulated C-peptide reached 6.2% in the cholecalciferol group and 37.5% in the placebo group at 18 months. Body mass index, hemoglobin A1c level, and insulin requirements were similar between the 2 groups. CONCLUSIONS Cholecalciferol used as adjunctive therapy with insulin is safe and associated with a protective immunologic effect and slow decline of residual β-cell function in patients with new-onset T1DM. Cholecalciferol may be an interesting adjuvant in T1DM prevention trials.

Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation

Lipodystrophies are a group of heterogeneous disorders characterized by the loss of adipose tissue and metabolic complications. The main familial forms of lipodystrophy are Congenital Generalized Lipodystrophy and Familial Partial Lipodystrophy (FPLD). FPLD may result from mutations in the LMNA gene. Besides FPLD, mutations in LMNA have been shown to be responsible for other inherited diseases called laminopathies. Here we describe the case of a 15-year-old girl who was referred to our service due to diabetes mellitus and severe hypertriglyceridemia. Physical examination revealed generalized loss of subcutaneous fat, confirmed by DEXA (total body fat 8.6%). As the patient presented with pubertal-onset of generalized lipodystrophy and insulin resistance, molecular analysis of the LMNA gene was performed. We identified a heterozygous substitution in exon 1 (c.29C>T) predicting a p.T10I mutation. In summary, we describe an atypical phenotype of lipodistrophy associated with a de novo appearance of the p.T10I mutation in LMNA gene.

Vitamin D and diabetes mellitus: an update 2013

Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.

Early subclinical limited axial and large joint flexibility in type 1 diabetes mellitus adolescents

OBJECTIVE The objective of this study was to compare the axial and large joint mobility in adolescents with and without type 1 diabetes mellitus (DM1). PATIENT AND METHODS To check this relationship, 72 DM1 adolescents aged 9-20 years were admitted into the trial and compared with 46 healthy control subjects aged 10-18 years. The youths were compared with regard to anthropometrics (age, proportion female/male, weight, height, and BMI) data. The years from DM1 diagnosis and HbA(1c) (index) were 4.9 +/- 3.6 years and 1.40 +/- 0.39%, respectively. The values of the tests of flexibility of the movements of cervical joint, the abduction of scapular, wrist and back-lumbar joints and abduction of lame-femoral were obtained through the Fleximeter. RESULTS The DM1 patients and controls did not differ regarding age (DM1 median 16, range 9-20 years vs. controls 16, range 10-18 years) and BMI (DM1 mean+/-S.D. 21.49 +/- 3.69 kg/m(2) vs. controls 20.76 +/- 2.81 kg/m(2)). The scapular, back-lumbar, and lame-femoral flexibility were, respectively, significantly lower (P < .001) in DM1 adolescents (175 +/- 8 degrees , 107 +/- 4 degrees , 66 +/- 10 degrees) compared with controls (189 +/- 13, 116 +/- 14, 76 +/- 12), but the cervical joint mobility was the same in both groups (DM1: 98 +/- l2 degrees vs. control: 101 +/- 13 degrees). CONCLUSION Thus, the results of our study show a subclinical limited axial and large joint mobility in DM1 adolescents. Future prospective studies are needed to ascertain whether the joint limitations found in these DM1 adolescents will persist into adulthood and play a role in the development of other diabetic complications.

Relationship Between Glycated Hemoglobin and Metabolic Syndrome of Type 1 and Type 2 Diabetes A factor analysis study

Glycated hemoglobin (GHb) is the best-characterized marker of glycemic control in patients with diabetes. Nevertheless, the relationship between GHb itself and aggregated cardiovascular risk factors, collectively denominated metabolic syndrome (MS), requires more studies in both type 1 and type 2 diabetes. Insulin resistance (IR) is notoriously associated with MS, but hyperglycemia, primarily resulting from insulin deficiency, might have as important a role as IR in MS of type 2 diabetes. MS is also observed in a minority of patients with type 1 diabetes, but its pathophysiology in such cases is poorly understood. Factor analyses (FAs) have described from one to five factors underlying MS in type 2 diabetes, using only variables linked to IR (1⇓–3). Factors extraneous …

Intraepithelial lymphocytes in duodenum from Brazilian adolescents with type 1 diabetes. Influence of Helicobacter pylori.

Background: An increased number of intraepithelial lymphocytes (IELs) can be the only histological feature in early stages of celiac disease (CD). This is also presented in duodenum of patients with Helicobacter pylori‐associated gastritis and in autoimmune diseases. Because CD is frequently associated with type 1 diabetes mellitus, we analyzed the density of IELs in the distal duodenum of non‐celiac diabetic patients associated or not with H.pylori infection.

Hope matters to the glycemic control of adolescents and young adults with type 1 diabetes

This study investigated the association of hope and its factors with depression and glycemic control in adolescents and young adults with type 1 diabetes. A total of 113 patients were invited to participate. Significant negative correlations were found between hope and HbA1c and also between hope and depression. Hope showed a significant association with HbA1c and depression in the stepwise regression model. Among the hope factors, “inner positive expectancy” was significantly associated with HbA1c and depression. This study supports that hope matters to glycemic control and depression. Intervention strategies focusing on hope should be further explored.

Pancreatic Agenesis due to Compound Heterozygosity for a Novel Enhancer and Truncating Mutation in the PTF1A Gene

Neonatal diabetes, defined as the onset of diabetes within the first six months of life, is very rarely caused by pancreatic agenesis. Homozygous truncating mutations in the PTF1A gene, which encodes a transcriptional factor, have been reported in patients with pancreatic and cerebellar agenesis, whilst mutations located in a distal pancreatic-specific enhancer cause isolated pancreatic agenesis. We report an infant, born to healthy non-consanguineous parents, with neonatal diabetes due to pancreatic agenesis. Initial genetic investigation included sequencing of KCNJ11, ABCC8 and INS genes, but no mutations were found. Following this, 22 neonatal diabetes associated genes were analyzed by a next generation sequencing assay. We found compound heterozygous mutations in the PTF1A gene: A frameshift mutation in exon 1 (c.437_462 del, p.Ala146Glyfs*116) and a mutation affecting a highly conserved nucleotide within the distal pancreatic enhancer (g.23508442A>G). Both mutations were confirmed by Sanger sequencing. Isolated pancreatic agenesis resulting from compound heterozygosity for truncating and enhancer mutations in the PTF1A gene has not been previously reported. This report broadens the spectrum of mutations causing pancreatic agenesis.

Comparação entre a bomba de infusão de insulina subcutânea e o esquema de múltiplas doses de insulina em adolescentes com diabetes melito do tipo 1 da rede pública de saúde na abordagem da hipoglicemia grave

OBJECTIVE: We compared the incidence of severe hypoglycemia episodes with therapy with multiple doses of insulin (MDI) and after changing to pump (CSII). PATIENTS AND METHODS: 7 T1DM patients with 14 years median and median duration of diabetes of 8 years. We analyzed insulin requirement (U/kg/day), BMI (Kg/m2), HbA1c (normal range: 3.5-6.7%) one year before and one year after changing therapy. The severe hypoglycemia episodes decreased from 1.3 to 0 episodes/patient/year; p = 0.00). The insulin requirement decreased from 1.33 ± 0.26 U/Kg/day to 0.87 ± 0.17 U/kg/day; p = 0.04 and HbA1c decreased from 8.7 ± 0.7% to 7.8 ± 0.9%; p = 0.05. CONCLUSION: CSII is efficient in decreasing severe hypoglycemia in a subgroup of T1DM using MDI also in Public Health Care System (PHCS) conditions. However, these finding should be reproduced by other Diabetes Care centers and cost studies are necessary to confirm the viability and possibility of this therapy, when necessary, to T1DM patients, which correspond to the majority of these individuals in our country, seeing in the PHCS.