Adipose Tissue-Derived Stromal/Stem Cells Transplantation with Cholecalciferol Supplementation in Recent-Onset Type 1 Diabetes Patients: Twelve Months Follow-Up.

To evaluate safety and therapeutic effect along 12 months of allogenic adipose tissue-derived stromal/stem cells (ASCs) transplantation with cholecalciferol (VITD) in patients with recent-onset type 1 diabetes (T1D). Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1xKgx106 cells) and VITD 2000UI/day for 12 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide area under the curve (CPAUC), insulin dose, HbA1c and frequency of FoxP3+ in CD4+ or CD8+ T-cells(flow cytometry) were evaluated at baseline(T0), after 3(T3), 6(T6) and 12 months(T12). Eleven patients completed follow up (7:group 1;4:group 2). Group 1 had lower insulin requirement at T3(0.24±0.18vs0.53±0.23UI/kg,p=0.04), T6(0.24±0.15vs0.66±0.33 UI/kg,p=0.04) and T12(0.39±0.15vs0.74±0.29 UI/Kg,p=0.04).HbA1c was lower at T6 (50.57±8.56vs72.25±10.34 mmol/mol,p=0.01), without differences at T12 (57.14±11.98 in group 1 vs. 73.5±14.57 mmol/min in group 2, p=0.16). CPAUC was not significantly different between groups at T0(p=0.07), higher in group 1 at T3(p=0.04) and T6(p=0.006), but similar at T12(p=0.23). IDAA1c was significantly lower in group 1 than group 2 at T3,T6 and T12 (p=0.006, 0.006 and 0.042, respectively). IDDA1c was inversely correlated to FoxP3 expression in CD4 and CD8+ T cells at T6 (p<0.001 and p=0.01, respectively). In group 1, one patient had recurrence of a benign teratoma that was surgically removed, not associated to the intervention. ASCs with VITD without immunosuppression were safe and associated lower insulin requirements, better glycemic control, and transient better pancreatic function in recent onset T1D, but the potential benefits were not sustained.

[Random C peptide measurement in adults with clinical diagnosis of type 1 diabetes]. / Dosagem do peptídeo C sérico ao acaso em adultos com diagnóstico clínico de diabetes mellitus tipo 1.

OBJECTIVE: C peptide measurement can be helpful for classification of diabetes mellitus (DM). The aim of this study was to investigate the association between clinical diagnosis of type 1 diabetes (T1D) and levels of random C peptide. METHODS: Random C peptide was measured in adults of multi-ethnic background who had been classified as having T1D according to their clinical presentation. All individuals were > 18 years old at onset. RESULTS: The study included 51 adults, 28 (54.9%) females and 23 (45.1%) males, 36 (70.6%) Caucasian and 15 (29.4%) non-Caucasian. Their mean age at onset and duration of DM mean age were 27.9 (+/- 7.5) years and 9.9 (+/-7.2) years, respectively. In 8 patients (15.7%) C peptide was > 1.5 ng/ml, indicating sustained beta cell function. In this group a higher level of body mass index (26.05 vs 23.05 kg/m(2); p=0.006) and a greater proportion of non Caucasian individuals (62.5% vs 23.3%; p=0.039)) were detected. CONCLUSION: Most patients with DM clinically classified as T1D exhibit low C peptide. However, pancreatic insulin secretion seems to be preserved in a significant proportion of those individuals, possibly representing an atypical form of DM, not yet elucidated, that combines characteristics of both T1D and T2D.

Long term maintenance of glucose and lipid concentrations after Roux-en-Y gastric bypass.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) reduces body weight and the comorbidities associated with obesity. The aim of this study was to evaluate whether glucose and lipid profiles were maintained during a 5-year follow-up period after RYGB. SUBJECTS AND METHODS: Anthropometric and laboratory data from 323 patients who had undergone this operation were analyzed. Differences in laboratory variables between the baseline and 12, 24, 36, 48 and 60 months postoperatively (PO) were assessed using a one-way ANOVA test to compare the three groups. Delta significance using one-way ANOVA was performed to assess anthropometric variable in the postoperative period (p < 0.05). RESULTS: 77 patients (24%) were included in Group 1 (G1), 101 (32%) in Group 2 (G2), and 141 (44%) in Group 3 (G3). The majority of patients, 71.7% in G1, 82.8% in G2, and 70% in G3, showed high triglycerides (TG) before surgery. A decrease in weight loss was observed in all groups followed by an increase in body weight in G2 and G3 at 36, 48 and 60 months. Laboratory results for G1, G2 and G3 showed no significant differences between groups at baseline and during the post-operative period. CONCLUSION: Our results suggest that weight regain after RYGB has no significant impact on the long-term evolution of the lipid profile and glycemia.

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

ABSTRACT Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

Thyroid disorders are common in first-degree relatives of individuals with type 1 diabetes mellitus.

OBJECTIVE: Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM. SUBJECTS AND METHODS: Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR. RESULTS: We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). CONCLUSIONS: Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals.

Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study).

BACKGROUND: Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. METHODS: Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6-3.9 mM/l and HDL cholesterol < or = 1.05 mM/l for women and < or = 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. RESULTS: After 4 months, plasma triglyceride concentrations were decreased by 44% (p < 0.001). HDL cholesterol concentrations were increased by 10% (p < 0.001). Non-HDL cholesterol was decreased by 19%. A greater HDL cholesterol response was observed in lean patients (body mass index < 25 kg/m2) compared to the rest of the population (8.2 vs 19.7%, p < 0.001). In contrast, cases with excess body weight had a larger decrease in non-HDL cholesterol levels (-20.8 vs -10.8%, p < 0.001). There were no significant complications resulting from treatment with ciprofibrate. CONCLUSIONS: Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated.

Zinc transporter 8 autoantibodies in patients with type 1 diabetes from a multiethnic population and their first degree relatives.

OBJECTIVE: Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms. SUBJECTS AND METHODS: ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 ± 11.4 years) of variable duration (15.7 ± 11.8 years) and their FDR (n = 78, mean age of 18.3 ± 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped. RESULTS: The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038). CONCLUSIONS: ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background.

Residual C-peptide in patients with Type 1 diabetes and multiethnic backgrounds.

OBJECTIVE: To evaluate serum C-peptide in 88 patients from a multiethnic population with Type-1 diabetes and variable disease durations. METHOD: Eighty-eight patients with a mean disease duration of 8.1 +7.6 years were included and underwent C-peptide measurement before and after glucagon stimulation. Chi-squared and Mann Whitney U-tests were used to compare the variables between groups (all two-tailed, α = 0.05). Spearmans correlation coefficient was used to test the association between the continuous variables. Logistic regression was used for the multivariate analysis. Twenty-eight (31.8%) individuals had significantly detectable C-peptide levels after stimuli, particularly those with a shorter disease duration (p<0.001). RESULTS: Patients with detectable C-peptide levels required lower insulin doses (p<0.009) and had similar HbA1C results (p = 0.182) and fewer chronic complications (p = 0.029). CONCLUSION: C-peptide detection was common in Type-1 diabetics, particularly shortly after being diagnosed. This result may have clinical implications.

Long term maintenance of glucose and lipid concentrations after Roux-en-Y gastric bypass

Abstract Objective: Roux-en-Y gastric bypass (RYGB) reduces body weight and the comorbidities associated with obesity. The aim of this study was to evaluate whether glucose and lipid profiles were maintained during a 5-year follow-up period after RYGB. Subjects and methods: Anthropometric and laboratory data from 323 patients who had undergone this operation were analyzed. Differences in laboratory variables between the baseline and 12, 24, 36, 48 and 60 months postoperatively (PO) were assessed using a one-way ANOVA test to compare the three groups. Delta significance using one-way ANOVA was performed to assess anthropometric variable in the postoperative period (p < 0.05). Results: 77 patients (24%) were included in Group 1 (G1), 101 (32%) in Group 2 (G2), and 141 (44%) in Group 3 (G3). The majority of patients, 71.7% in G1, 82.8% in G2, and 70% in G3, showed high triglycerides (TG) before surgery. A decrease in weight loss was observed in all groups followed by an increase in body weight in G2 and G3 at 36, 48 and 60 months. Laboratory results for G1, G2 and G3 showed no significant differences between groups at baseline and during the post-operative period. Conclusion: Our results suggest that weight regain after RYGB has no significant impact on the long-term evolution of the lipid profile and glycemia.

[GADA persistence and detectable C peptide in patients with long standing diabetes mellitus type 1]. / Implicações clínicas da persistência de anti-GAD positivo e peptídeo C detectável em pacientes com diabetes melito tipo 1 de longa duração.

OBJECTIVE: The aim of this study was to evaluate if GADA+ and detectable CP had any influence in other autoimmune diseases, glycemic control, and risks of retinopathy in diabetes mellitus type 1 (T1DM) lasting longer than 3 years of duration. SUBJECTS AND METHODS: Fifty T1DM subjects were interviewed, performed fundoscopic examination, and measured CP before and after glucagon, HbA1C, and GADA. RESULTS: GADA+ (n = 17) had a higher frequency of other autoimmune diseases when compared to GADA (p = 0.02). Detectable CP was also associated with a higher prevalence of these diseases (p = 0.03), although, retinopathy was not influenced by either one. Detectable CP had no influence in the glycemic control (mean HbA1C) (p = 0.28). However, insulin daily doses were lower in this group (0.62 vs. 0.91 U/kg/day; p = 0.004). CONCLUSION: Although not recommend as a marker of other autoimmune diseases, GADA+ seems to be not only a pancreatic autoimmunity signal. Detectable CP may also have some promising influence in detecting these diseases. Neither influenced the presence of retinopathy, but insulin daily requirements were smaller when CP was present.

Thyroid disorders are common in first-degree relatives of individuals with type 1 diabetes mellitus

Objective Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM. Subjects and methods Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR. Results We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). Conclusions Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals. .

[Prevalence of anti-thyroid peroxidase and anti-adrenal 21-hidroxylase in type 1 diabetes patients]. / Prevalência do anti-TPO e anti-21-hidroxilase no paciente diabético tipo 1.

UNLABELLED: There is still no consensus about the best strategy to screen Addison's disease (AD) in type 1 diabetes mellitus (T1DM) patients. OBJECTIVE: The aim of this study was to determine the frequency of anti-21-hydroxilase (anti-21OH) in a multiethnic T1DM population and investigate if its presence is associated with any adrenal dysfunction or thyroid autoimmunity. METHODS: Forty individuals underwent an interview and blood was drawn for anti-thyroperoxidase (anti-TPO), anti-21OH, TSH, free T4 and cortisol measurement. RESULTS: Anti-21OH was found in 7.5% (n = 3), none with adrenal dysfunction. This antibody was not exclusively seen in patients with anti-TPO (+). Anti-TPO was positive in 25% and associated with higher TSH levels (p = 0.034) and older age (p = 0.009). CONCLUSIONS: Although the frequency of anti-TPO in this sample was similar to previous studies, a higher prevalence of anti-21-OH was found. However, no coexisting adrenal dysfunction was detected, which does not support universal screening for AD in this group.

Zinc transporter 8 autoantibodies in patients with type 1 diabetes from a multiethnic population and their first degree relatives / Autoanticorpos transportadores de zinco 8 em pacientes com diabetes tipo 1 de uma população multiétnica e seus parentes de primeiro grau

Objective Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms. Subjects and methods ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 ± 11.4 years) of variable duration (15.7 ± 11.8 years) and their FDR (n = 78, mean age of 18.3 ± 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped. Results The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038). Conclusions ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background. .

Objetivo Os autoanticorpos transportadores de zinco 8 (ZnT8A) foram pouco estudados em indivíduos não caucasianos. Nosso objetivo foi investigar a prevalência de autoanticorpos ZnT8 em pacientes com T1D e seus parentes de primeiro grau (PPG) em uma população multiétnica, assim como a sua relação com os polimorfismos genéticos da insulina (INS) ou proteína tirosina fosfatase não receptora tipo 22 (PTPN22). Sujeitos e métodos ZnT8A foram analisados no soro de pacientes com T1D (n = 72, idade média de 30,3 ± 11,4 anos) de duração variável (15,7 ± 11,8 anos) e seus PPG (n = 72, idade média de 30,3 ± 11,4 anos) usando-se um ensaio de competição com radioligantes (RBA) para variantes dos autoanticorpos ZnT8 (ZnT8-RWQ). Os polimorfismos de nucleotídeo único para a INS e PTPN22 foram genotipados. Resultados A prevalência de ZnT8A foi mais alta em pacientes T1D do que nos PPG, para ZnT8TriploA (24% contra 4%, p = 0,001), ZnT8RA (24% contra 4%, p < 0,001) e ZnT8QA (15% contra 3%, p = 0,004). Todos os PPG com ZnT8A (n = 3) apresentaram positividade para pelo menos outro anticorpo. A heterozigose para PTPN22 foi associada a uma frequência mais alta de ZnT8TriploA (p = 0,039) e de ZnT8RA (p = 0,038). Conclusões Os ZnT8A foram observados em pacientes não caucasianos com T1D, mesmo depois de anos do início da doença, assim como em seus PPG. Nos parentes, houve uma sobreposição entre os ZnT8A e outros anticorpos para T1D. Os ZnT8A mostraram-se associados aos polimorfismos PTPN22. São necessários outros estudos longitudinais para se elucidar a importância desses achados na história natural de pacientes com T1D com antecedentes étnicos variados. .

[C-peptide residual secretion makes difference on type 1 diabetes management?]. / A secreção residual do peptídeo C faz diferença no tratamento do diabetes melito tipo 1?

Type 1 diabetes is a chronic disease characterized by progressive destruction of the pancreatic beta cells, what leads to insulin deficiency and hyperglycemia. However, a significant secretory function may persist for long periods in a few patients, what is clinically evident through the detection of serum C peptide. This phenomenon might reduce the risk of chronic complications, severe hypoglycemias and allow easier metabolic control. It is possible that these advantages are caused, at least partially, by C peptide itself, acting directly in its target tissues.

Força muscular respiratória de mulheres obesas mórbidas e eutróficas / Respiratory muscle strength in morbidly obese and eutrophic women

A obesidade mórbida é uma condição clínica que afeta a capacidade funcional, sendo a musculatura respiratória igualmente comprometida. Objetivou-se avaliar a força muscular inspiratória e expiratória de mulheres obesas mórbidas (MO) e eutróficas (ME). Estudo transversal com amostra composta por 21 mulheres (14 MO e 7 ME), pareadas pela idade e altura. A avaliação da força muscular inspiratória e expiratória foi realizada por meio da verificação das pressões inspiratória e expiratória por manovacuometria. Quando comparadas as pressões respiratórias estáticas máximas obtidas com os valores preditos para ME e MO, constata-se que as do primeiro grupo apresentam valores de PImáx=119,14±1,9 cmH2O (152% do predito) e PEmáx=141,1±10,2 cmH2O (98,5% do predito) dentro dos limites de normalidade ou acima, enquanto no grupo de obesas mórbidas os valores de PImáx=66±18,7 cmH2O (84,3% do predito) e PEmáx=78,4±14,2 cmH2O (54,3% do predito) foram inferiores aos preditos. Comparando-se as pressões respiratórias estáticas máximas obtidas de MO com ME, observa-se diferença significativa tanto para os valores de PImáx (66±18,7 versus 119±1,9 cmH2O) como PEmáx (78,4±14,2 versus 141,14±10,20) com significância estatística de 0,001. Conclui-se que a força muscular respiratória é marcadamente diminuída em MO, quando comparadas a ME.

The morbid obesity is a clinical condition that affects functional capacity, and the respiratory muscles are also impaired. This study aimed to evaluate the inspiratory and expiratory muscle strength of morbidly obese women (OW) and eutrophic women (EW). Cross-sectional study, whose sample was composed by 21 women (14 OW and 7 EW) paired by age and height. Inspiratory and expiratory muscle strength evaluation was carried out by means of maximal inspiratory and expiratory pressure recordings (MIP and MEP, respectively) using manovacuometry. When comparing the maximal static respiratory pressures with predicted values for OW and EW, we observed that EW presented values of MIP=119.14±1.9 cmH2O (152% of predicted value) and MEP=141.1±10.2 cmH2O (98.5% of predicted value) within or above normal limits, while in OW group, MIP=66±18.7 cmH2O (84.3% of predicted value) and MEP=78.4±14.2 cmH2O (54.3% of predicted value) were lower than the predicted values. When comparing maximal static respiratory pressures of OW and EW, we observed a significant difference for MIP (66±18.7 versus 119±1.9 cmH2O) and MEP=78.4±14.2 versus 141.14±10.20) with statistical significance of 0.001. We conclude that respiratory muscle strength is notably decreased in OW when compared to EW.

Implicações clínicas da persistência de anti-GAD positivo e peptídeo C detectável em pacientes com diabetes melito tipo 1 de longa duração / GADA persistence and detectable C peptide in patients with long standing diabetes mellitus type 1

OBJETIVO: Avaliar se anti-GAD positivo e PC detectável se correlacionam com a presença de outras doenças autoimunes, com controle glicêmico e com risco de retinopatia no diabetes melito tipo 1 (DMT1) > 3 anos de duração. PACIENTES E MÉTODOS: Cinquenta sujeitos com DMT1 foram entrevistados, realizaram fundoscopia e dosaram PC pré e pós-glucagon, HbA1C e anti-GAD. RESULTADOS: Pacientes anti-GAD+ (n = 17) apresentaram maior frequência de doenças autoimunes em relação aos demais (p = 0,02). PC detectável (n = 11) também foi associado ao aumento dessa prevalência (p = 0,03), porém nenhum dos dois parâmetros influenciou na presença de retinopatia diabética. PC detectável não influenciou no controle glicêmico (HbA1C média) (p = 0,28), porém as doses diárias de insulina foram mais baixas (0,62 vs. 0,91 U/kg/dia; p = 0,004) neste grupo. CONCLUSÃO: Apesar de não ser um marcador para outras doenças autoimunes, o anti-GAD+ parece ser não só um sinalizador de autoimunidade pancreática. PC detectável também parece ter papel promissor na detecção dessas comorbidades. Ambos não interferiram na presença de retinopatia, entretanto, o PC detectável se relacionou a menores necessidades de insulina.

OBJECTIVE: The aim of this study was to evaluate if GADA+ and detectable CP had any influence in other autoimmune diseases, glycemic control, and risks of retinopathy in diabetes mellitus type 1 (T1DM) lasting longer than 3 years of duration. SUBJECTS AND METHODS: Fifty T1DM subjects were interviewed, performed fundoscopic examination, and measured CP before and after glucagon, HbA1C, and GADA. RESULTS: GADA+ (n = 17) had a higher frequency of other autoimmune diseases when compared to GADA (p = 0.02). Detectable CP was also associated with a higher prevalence of these diseases (p = 0.03), although, retinopathy was not influenced by either one. Detectable CP had no influence in the glycemic control (mean HbA1C) (p = 0.28). However, insulin daily doses were lower in this group (0.62 vs. 0.91 U/kg/day; p = 0.004). CONCLUSION: Although not recommend as a marker of other autoimmune diseases, GADA+ seems to be not only a pancreatic autoimmunity signal. Detectable CP may also have some promising influence in detecting these diseases. Neither influenced the presence of retinopathy, but insulin daily requirements were smaller when CP was present.

Prevalência do anti-TPO e anti-21-hidroxilase no paciente diabético tipo 1 / Prevalence of anti-thyroid peroxidase and anti-adrenal 21-hidroxylase in type 1 diabetes patients

Ainda não está definida a estratégia ideal para rastrear a doença de Addison em pacientes com diabetes melito tipo 1 (DMT1). Objetivo: O objetivo deste estudo foi determinar a prevalência do anticorpo anti-21-hidroxilase (AC anti-21OH) em pacientes DMT1 de etnia diversificada e investigar sua associação à disfunção adrenal e autoimunidade tireoidiana. Métodos: Quarenta indivíduos foram avaliados, submetidos à entrevista e à dosagem de AC antitireoperoxidase (anti-TPO), anti-21OH, TSH, T4 livre e cortisol. AC anti-21OH foi encontrado em 7,5% (n = 3)dos casos, sem disfunção adrenal associada. Resultados: Positividade para anti-21OH não ocorreu exclusivamente em pacientes com anti-TPO (+). Este foi detectado em 25% dos casos e associado a níveis de TSH mais elevados (p = 0,034) e à idade mais avançada (p = 0,009). Conclusões: Embora nossa frequência de anti-TPO (+) seja similar à da literatura, a presença de anti-21OH (+) foi superior. Entretanto, esses AC não foram associados à disfunção hormonal, o que parece não justificar o rastreamento universal da doença de Addison.

There is still no consensus about the best strategy to screen Addison’s disease (AD) in type 1 diabetes mellitus (T1DM) patients. Objective: The aim of this study was to determine the frequency of anti-21-hydroxilase (anti-21OH) in a multiethnic T1DM population and investigate if its presence is associated with any adrenal dysfunction or thyroid autoimmunity. Methods: Forty individuals underwent an interview and blood was drawn for anti- thyroperoxidase (anti-TPO), anti-21OH, TSH, free T4 and cortisol measurement. Results: Anti-21OH was found in 7.5% (n = 3), none with adrenal dysfunction. This antibody was not exclusively seen in patients with anti-TPO (+). Anti-TPO was positive in 25% and associated with higher TSH levels (p = 0.034) and older age (p = 0.009). Conclusions:Although the frequency of anti-TPO in this sample was similar to previous studies, a higher prevalence of anti-21-OH was found. However, no coexisting adrenal dysfunction was detected, which does not support universal screening for AD in this group.

Dosagem do peptídeo C sérico ao acaso em adultos com diagnóstico clínico de diabetes mellitus tipo 1 / Random C peptide measurement in adults with clinical diagnosis of type 1 diabetes

OBJETIVO: A dosagem de peptídeo C (PC) pode ser útil para a classificação do Diabetes mellitus (DM). O objetivo deste estudo foi investigar a associação entre o diagnóstico clínico de DM tipo 1 e os níveis séricos de PC randômico. MÉTODOS: Foi feita dosagem de PC ao acaso em pacientes de origem multiétnica com diagnóstico clínico de DM tipo 1 na idade adulta ( > 18 anos). RESULTADOS: Estudamos 51 pacientes, sendo 28 mulheres (54,9 por cento) e 23 homens (45,1 por cento), 36 brancos (70,6 por cento) e 15 não-brancos (29,4 por cento) com idade média ao diagnóstico de 27,9 (±7,5) anos e duração média da doença de 9,9 (±7,2) anos. Oito pacientes (15,7 por cento) apresentaram PC > 1,5 ng/ml indicativo de função pancreática preservada. Neste grupo, foi detectado índice de massa corporal mais elevado (26,05 vs 23,05 kg/m²; p=0,006) e maior proporção de não-brancos (62,5 por cento vs 23,3 por cento; p=0,039) do que naqueles com PC baixo. CONCLUSÃO: A maioria dos pacientes com diagnóstico clínico de DM tipo 1 apresenta PC baixo. Entretanto, a secreção pancreática de insulina parece preservada em uma quantidade significativa de pacientes com quadro clínico indicativo de DM tipo 1. É possível que estes pacientes apresentem alguma forma atípica de DM, ainda não completamente compreendida, com características de DM tipo 1 e tipo 2 superpostas.

OBJECTIVE: C peptide measurement can be helpful for classification of diabetes mellitus (DM). The aim of this study was to investigate the association between clinical diagnosis of type 1 diabetes (T1D) and levels of random C peptide. METHODS: Random C peptide was measured in adults of multi-ethnic background who had been classified as having T1D according to their clinical presentation. All individuals were > 18 years old at onset. RESULTS: The study included 51 adults, 28 (54.9 percent) females and 23 (45.1 percent) males, 36 (70.6 percent) Caucasian and 15 (29.4 percent) non-Caucasian. Their mean age at onset and duration of DM mean age were 27.9 (± 7.5) years and 9.9 (±7.2) years, respectively. In 8 patients (15.7 percent) C peptide was > 1.5 ng/ml, indicating sustained beta cell function. In this group a higher level of body mass index (26.05 vs 23.05 kg/m²; p=0.006) and a greater proportion of non Caucasian individuals (62.5 percent vs 23.3 percent; p=0.039)) were detected. CONCLUSION: Most patients with DM clinically classified as T1D exhibit low C peptide. However, pancreatic insulin secretion seems to be preserved in a significant proportion of those individuals, possibly representing an atypical form of DM, not yet elucidated, that combines characteristics of both T1D and T2D.

A secreção residual do peptídeo C faz diferença no tratamento do diabetes melito tipo 1?: [revisão] / C-peptide residual secretion makes difference on type 1 diabetes management?: [review]

O diabetes melito tipo 1 (DM1) é uma doença crônica causada por destruição progressiva das células-beta das ilhotas pancreáticas, o que leva à insulinopenia e à hiperglicemia. Uma proporção significativa de pacientes acometidos pode apresentar manutenção de alguma função secretora por longos períodos, identificada clinicamente por meio da detecção de peptídeo C sérico. Há evidências de que isso possa trazer alguns benefícios, como redução do risco de complicações crônicas, maior facilidade em atingir o controle metabólico adequado e menor frequência de hipoglicemias graves. É possível que o próprio peptídeo C, atuando diretamente em tecidos-alvo, contribua para esses efeitos.

Type 1 diabetes is a chronic disease characterized by progressive destruction of the pancreatic beta cells, what leads to insulin deficiency and hyperglycemia. However, a significant secretory function may persist for long periods in a few patients, what is clinically evident through the detection of serum C peptide. This phenomenon might reduce the risk of chronic complications, severe hypoglycemias and allow easier metabolic control. It is possible that these advantages are caused, at least partially, by C peptide itself, acting directly in its target tissues.

Relato de caso: diabetes Flatbush - da cetoacidose ao tratamento não-farmacológico / Case report: diabetes Flatbush - from ketoacidosis to non pharmacological treatment

Um subgrupo de pacientes, em sua maioria negros ou hispânicos e obesos, tem a cetoacidose diabética (CAD) como forma de apresentação de diabetes mellitus (DM), mas, devido à sua evolução clínica, posteriormente é classificado como DM tipo 2. Estes indivíduos têm pesquisa de auto-anticorpos anti-GAD, anti-IA2 e anti-insulina negativa, mas freqüentemente em associação com HLA classe II de risco para DM tipo 1 (DRB1*03 e/ou DRB1*04). Este subtipo peculiar de DM é denominado diabetes flatbush. Neste artigo, relatamos o caso de uma paciente de origem caucasiana com tais características, na qual foi possível retirada da insulinoterapia. Os possíveis fatores associados a esta evolução favorável serão discutidos.

A subgroup of patients presents diabetic ketoacidosis at the onset of diabetes mellitus (DM) but later is classified as type 2 DM based on the clinical follow-up. These individuals, most commonly obese of African or Hispanic origin, have negative auto-antibodies associated with type 1 DM, but frequently HLA class II DRB1*03 and/or DRB1*04 are detected. This peculiar subtype of DM is commonly referred to as diabetes flatbush. Here we report the case of a Caucasian patient that exhibited the described evolution and in whom it was possible to withdraw insulin therapy. The possible factors associated with this favorable development are also discussed.