Milton Cesar Foss

C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus

CONTEXT In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became insulin free with normal levels of glycated hemoglobin A(1c) (HbA(1c)) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients. OBJECTIVE To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up. DESIGN, SETTING, AND PARTICIPANTS A prospective phase 1/2 study of 23 patients with type 1 DM (aged 13-31 years) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti-glutamic acid decarboxylase antibodies. Enrollment was November 2003-April 2008, with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil. Hematopoietic stem cells were mobilized via the 2007 protocol. MAIN OUTCOME MEASURES C-peptide levels measured during the mixed-meal tolerance test, before, and at different times following HSCT. Secondary end points included morbidity and mortality from transplantation, temporal changes in exogenous insulin requirements, and serum levels of HbA(1c). RESULTS During a 7- to 58-month follow-up (mean, 29.8 months; median, 30 months), 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free. Twelve patients maintained this status for a mean 31 months (range, 14-52 months) and 8 patients relapsed and resumed insulin use at low dose (0.1-0.3 IU/kg). In the continuous insulin-independent group, HbA(1c) levels were less than 7.0% and mean (SE) area under the curve (AUC) of C-peptide levels increased significantly from 225.0 (75.2) ng/mL per 2 hours pretransplantation to 785.4 (90.3) ng/mL per 2 hours at 24 months posttransplantation (P < .001) and to 728.1 (144.4) ng/mL per 2 hours at 36 months (P = .001). In the transient insulin-independent group, mean (SE) AUC of C-peptide levels also increased from 148.9 (75.2) ng/mL per 2 hours pretransplantation to 546.8 (96.9) ng/mL per 2 hours at 36 months (P = .001), which was sustained at 48 months. In this group, 2 patients regained insulin independence after treatment with sitagliptin, which was associated with increase in C-peptide levels. Two patients developed bilateral nosocomial pneumonia, 3 patients developed late endocrine dysfunction, and 9 patients developed oligospermia. There was no mortality. CONCLUSION After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00315133.

Prevalence of diabetes mellitus and impaired glucose tolerance in the urban population aged 30-69 years in Ribeirão Preto (São Paulo), Brazil

CONTEXT Diabetes mellitus prevalence has been increasing worldwide due to factors like lifestyle changes and higher life expectancy. The Brazilian Multicenter Study performed between 1986 and 1988 evaluated the prevalence of diabetes and impaired glucose tolerance. OBJECTIVE To assess the prevalence of diabetes and impaired glucose tolerance in the urban population aged 30-69 years of the city of Ribeirão Preto, SP, Brazil. TYPE OF STUDY A two-stage, cross-sectional home survey. SETTING Ribeirão Preto, São Paulo, Brazil. PARTICIPANTS A random sample of 1,473 individuals. METHODS The sample plan was drawn up using a sampling scheme of stage conglomerates according to sex, age and family head income. Subjects were first screened by fasting capillary glycemia (FCG). Those that screened positive (FCG > or = 100 mg/dl) and every seventh consecutive person who screened negative (FCG < 100 mg/dl) was submitted to a 75 g oral glucose tolerance test. The diagnosis of diabetes and impaired glucose tolerance were based on World Health Organization criteria. RESULTS The overall rates of diabetes and impaired glucose tolerance were 12.1 and 7.7%, respectively. Men and women had similar rates of diabetes (12.0 vs. 12.1%) and impaired glucose tolerance (7.9 vs. 7.3%). Differences in the rates for whites (11.6%) and nonwhites (13.3%) for diabetes were not significant, while impaired glucose tolerance was more prevalent among whites. The prevalences of diabetes and impaired glucose tolerance ranged from 3.3% and 2.6% in the 30-39 year age group to 21.7% and 11.3% in the 60-69 year age group, respectively. Obese subjects (BMI > or = 30 kg/m2) and those with a family history of diabetes (first-degree relatives) presented higher prevalences of diabetes (22.6% and 19.7%, respectively). CONCLUSIONS The prevalence of diabetes in Ribeirão Preto was found to be comparable to that occurring in developed countries. With respect to the Brazilian Multicenter Study we verified an increased prevalence of diabetes but a similar prevalence of impaired glucose tolerance. These findings may reflect modifications in environmental factors and lifestyle that have been occurring in Brazilian cities like Ribeirão Preto, especially regarding increasing rates of sedentary living and obesity.

Identifying common and specific microRNAs expressed in peripheral blood mononuclear cell of type 1, type 2, and gestational diabetes mellitus patients

BackgroundRegardless the regulatory function of microRNAs (miRNA), their differential expression pattern has been used to define miRNA signatures and to disclose disease biomarkers. To address the question of whether patients presenting the different types of diabetes mellitus could be distinguished on the basis of their miRNA and mRNA expression profiling, we obtained peripheral blood mononuclear cell (PBMC) RNAs from 7 type 1 (T1D), 7 type 2 (T2D), and 6 gestational diabetes (GDM) patients, which were hybridized to Agilent miRNA and mRNA microarrays. Data quantification and quality control were obtained using the Feature Extraction software, and data distribution was normalized using quantile function implemented in the Aroma light package. Differentially expressed miRNAs/mRNAs were identified using Rank products, comparing T1DxGDM, T2DxGDM and T1DxT2D. Hierarchical clustering was performed using the average linkage criterion with Pearson uncentered distance as metrics.ResultsThe use of the same microarrays platform permitted the identification of sets of shared or specific miRNAs/mRNA interaction for each type of diabetes. Nine miRNAs (hsa-miR-126, hsa-miR-1307, hsa-miR-142-3p, hsa-miR-142-5p, hsa-miR-144, hsa-miR-199a-5p, hsa-miR-27a, hsa-miR-29b, and hsa-miR-342-3p) were shared among T1D, T2D and GDM, and additional specific miRNAs were identified for T1D (20 miRNAs), T2D (14) and GDM (19) patients. ROC curves allowed the identification of specific and relevant (greater AUC values) miRNAs for each type of diabetes, including: i) hsa-miR-1274a, hsa-miR-1274b and hsa-let-7f for T1D; ii) hsa-miR-222, hsa-miR-30e and hsa-miR-140-3p for T2D, and iii) hsa-miR-181a and hsa-miR-1268 for GDM. Many of these miRNAs targeted mRNAs associated with diabetes pathogenesis.ConclusionsThese results indicate that PBMC can be used as reporter cells to characterize the miRNA expression profiling disclosed by the different diabetes mellitus manifestations. Shared miRNAs may characterize diabetes as a metabolic and inflammatory disorder, whereas specific miRNAs may represent biological markers for each type of diabetes, deserving further attention.

Treatment of diabetic gastroparesis with oral clonidine

Background/Aims: Clonidine, a specific alpha‐2‐adrenergic receptor agonist, has been suggested to improve symptoms of gastroparesis in diabetics with diarrhoea. The aim of this study was to investigate the effects of clonidine on gastric emptying and symptoms suggestive of gastroparesis in patients with long‐standing diabetes mellitus and evidence of autonomic neuropathy.

Peripheral glucose metabolism in human hyperprolactinaemia

OBJECTIVE Prolactin has important biological actions in several species which include metabolic control and waterlelectrolyte balance. However, human PRL has generally been characterized as a mammotrophic hormone and it is unknown whether PRL has any important metabolic actions. This study was thus conducted to evaluate the effect of hyperprolactinaemia on peripheral muscle glucose metabolism.

Adesão à dieta e ao exercício físico das pessoas com diabetes mellitus

This cross-sectional and quantitative study aimed to evaluate adherence among people with type-2 Diabetes Mellitus to self-care, regarding diet and physical exercises, as well as the relationship to socio-demographic and clinical characteristics. The sample consisted of 162 type-2 Diabetes Mellitus patients under outpatient clinic follow-up. Data was collected using the Brazilian version of the Summary of Diabetes Self-care Activities Questionnaire and patient files. Low adherence to self-care was evidenced in the studied sample. For p<0.05, correlation was inversely proportional to patient educational level, suggesting that the higher the educational level, the lower the adherence. There was no statistically significant correlation between adherence to self-care and gender, age, marital status, monthly per capita income, time of diagnosis, type of medication in treatment, and/or presence of complications/ co-morbidities. Results corroborate findings in literature that socio-demographic and clinical variables may not predict adherence to treatment among people with Diabetes Mellitus.. DESCRIPTORS: Diabetes mellitus. Patient compliance. Nursing. ADHERENCIA A LA DIETA Y A LOS EJERCICIOS FISICOS DE LAS PERSONAS CON DIABETES MELLITUS RESUMEN: Estudio transversal de enfoque cuantitativo que tuvo como objetivo evaluar la adherencia de las personas con Diabetes Mellitus tipo 2 al autocuidado, con respecto a la dieta y a los ejercicios fisicos, asi como la relacion con caracteristicas sociodemograficas y clinicas. La muestra consistio de 162 personas con Diabetes Mellitus tipo 2, en consulta externa de seguimiento. Para la recoleccion de datos se utilizo la version brasilena del instrumento Summary of Diabetes Self-care Activities Questionnaire y consulta a los archivos de los participantes. Fue encontrada baja adherencia al autocuidado. Para p<0,05, la correlacion fue inversamente proporcional a la escolaridad, lo que sugiere menor adherencia para mayor escolaridad. No se encontraron correlaciones estadisticamente significantes entre la adherencia al autocuidado y sexo, edad, estado civil, ingreso per capita mensual, tiempo de diagnostico, tipo de tratamiento con medicamentos y presencia de complicaciones/comorbilidades. Los resultados corroboran la literatura, en la cual variables sociodemograficas y clinicas pueden no predecir la adhesion al tratamiento de personas con Diabetes Mellitus. DESCRIPTORES: Diabetes mellitus. Cooperacion del paciente. Enfermeria.Estudio transversal de enfoque cuantitativo que tuvo como objetivo evaluar la adherencia de las personas con Diabetes Mellitus tipo 2 al autocuidado, con respecto a la dieta y a los ejercicios fisicos, asi como la relacion con caracteristicas sociodemograficas y clinicas. La muestra consistio de 162 personas con Diabetes Mellitus tipo 2, en consulta externa de seguimiento. Para la recoleccion de datos se utilizo la version brasilena del instrumento Summary of Diabetes Self-care Activities Questionnaire y consulta a los archivos de los participantes. Fue encontrada baja adherencia al autocuidado. Para p<0,05, la correlacion fue inversamente proporcional a la escolaridad, lo que sugiere menor adherencia para mayor escolaridad. No se encontraron correlaciones estadisticamente significantes entre la adherencia al autocuidado y sexo, edad, estado civil, ingreso per capita mensual, tiempo de diagnostico, tipo de tratamiento con medicamentos y presencia de complicaciones/comorbilidades. Los resultados corroboran la literatura, en la cual variables sociodemograficas y clinicas pueden no predecir la adhesion al tratamiento de personas con Diabetes Mellitus.

Dermatoses em pacientes com diabetes mellitus

OBJECTIVE It is yet unknown the relationship between diabetes and determinants or triggering factors of skin lesions in diabetic patients. The purpose of the present study was to investigate the presence of unreported skin lesions in diabetic patients and their relationship with metabolic control of diabetes. METHODS A total of 403 diabetic patients, 31% type 1 and 69% type 2, underwent dermatological examination in an outpatient clinic of a university hospital. The endocrine-metabolic evaluation was carried out by an endocrinologist followed by the dermatological evaluation by a dermatologist. The metabolic control of 136 patients was evaluated using glycated hemoglobin. RESULTS High number of dermophytosis (82.6%) followed by different types of skin lesions such as acne and actinic degeneration (66.7%), pyoderma (5%), cutaneous tumors (3%) and necrobiosis lipoidic (1%) were found. Among the most common skin lesions in diabetic patients, confirmed by histopathology, there were seen necrobiosis lipoidic (2 cases, 0.4%), diabetic dermopathy (5 cases, 1.2%) and foot ulcerations (3 cases, 0.7%). Glycated hemoglobin was 7.2% in both type 1 and 2 patients with adequate metabolic control and 11.9% and 12.7% in type 1 and 2 diabetic patients, respectively, with inadequate metabolic controls. A higher prevalence of dermatophytoses was seen in the both groups with inadequate metabolic control. CONCLUSIONS The results showed a high prevalence of skin lesions in diabetic patients, especially dermatophytoses. Thus, poor metabolic control of diabetes increases patients susceptibility to skin infections.

Fatores de risco para complicações em extremidades inferiores de pessoas com diabetes mellitus

O estudo analisou fatores de risco para complicacoes em pes de pessoas com diabetes em Unidade Ambulatorial. Os dados foram obtidos por meio de entrevista semi-estruturada, avaliacao de pes e exames laboratoriais. Os riscos tiveram a analise segundo Zavala e Braver e Sistema de Classificacao do Consenso Internacional sobre Pe Diabetico, mediante estatistica descritiva. Nos resultados, a idade media foi 53,3±13 anos, tempo da doenca 12,9±9 e 58% tinham ensino fundamental incompleto. Dentre os riscos, identificou-se complicacoes microvasculares, hipertensao arterial, nivel glicemico inadequado, sedentarismo, uso de sapatos inapropriados, somadas as alteracoes dermatologicas e estruturais. No risco para ulceras, obteve-se 19,1% entre as categorias 2 e 3. Os dados reforcaram necessidade de atendimento primario com enfase na avaliacao de riscos e educacao do paciente.

Autologous hematopoietic stem cell transplantation for type 1 diabetes.

In this review, we present (1) the scientific basis for the use of high‐dose immunosuppression followed by autologous peripheral blood hematopoietic stem cell transplantation for newly diagnosed type 1 diabetes (T1D); (2) an update of the clinical and laboratory outcome of 20 patients transplanted at the University Hospital of the Ribeirão Preto Medical School, University of São Paulo, Brazil, and followed up to January/2008, including 4 relapses among 19 patients without previous ketoacidosis; (3) a commentary on criticisms to our article that appeared in four articles from the scientific literature; and (4) a discussion of the prospectives for cellular therapy for T1D.

Abnormal Intragastric Distribution of a Liquid Nutrient Meal in Patients with Diabetes Mellitus

Disordered gastric motility and emptying arewell known complications of diabetes mellitus (DM), butthe pattern of intragastric distribution of food has notbeen extensively studied in diabetics. We examined the partition of a liquid nutrient meal betweenthe proximal and distal stomach and the relationshipsbetween intragastric distribution of food and gastricemptying (GE) and the symptoms in DM patients with and without autonomic neuropathy (AN).Fourteen healthy volunteers and 20 DM patients (13 withAN; 9 with dyspepsia symptoms) ingested a liquidnutrient meal (250 ml; 437 kcal) labeled with[99mTc]phytate. Anterior and posterior serial images of thestomach were taken for 90 min with a gamma camera.Regions of interest for the proximal and the distalhalves of the stomach and for the total gastric areawere defined. Counts from each region along timeallowed estimation of GE and the proportion of activityretained in the proximal stomach after meal ingestion(initial) and throughout GE (mean). GE half-times in controls (median; range: 66 min; 29-90 min)were not significantly different from diabetics (76 min;5->150 min, P > 0.10), but abnormal GE was foundin 11 DM patients (seven delayed and four rapid). In DM patients, initial retention inthe proximal stomach (42%; 16-79% ) was significantlylower (P < 0.02) than in controls (55%; 44-71%). Meanretention in the proximal stomach throughout emptying also was significantly lower (P <0.05) in DM patients (43%; 18-58%) than in controls(51%; 32-69%). There were no differences betweensubgroups of patients with normal, delayed, or rapid gastric emptying regarding mean meal retentionin the proximal stomach. Patients with evidence of AN orwith dyspepsia symptoms had significantly decreasedretention of food in the proximal stomach throughout gastric emptying. We concluded that patientswith diabetes mellitus have abnormally decreasedretention of gastric contents in the proximal stomachafter a liquid meal, which seems to be related to the occurrence of autonomic neuropathy anddyspepsia symptoms, but not to disordered gastricemptying.