Changes in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all ...researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms.
We assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls.
We identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects (
) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression (
) and immune tolerance (
)
expression correlated negatively with islet ZnT8 antibody. The expression of
, that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these data.
Our analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.
There is a scarcity of data of zinc transporter-8 autoantibody (ZnT8A) on mixed populations such as Brazilian. Therefore, we evaluated the relevance of ZnT8A for type 1 diabetes (T1D) diagnosis and ...the role of ZnT8 coding gene (SLC30A8) in T1D predisposition. Patients with T1D (n = 629; diabetes duration = 11 (6-16) years) and 651 controls were genotyped for SLC30A8 rs16889462 and rs2466295 variants (BeadXpress platform). ZnT8 triple antibody was measured by ELISA; glutamic acid decarboxylase (GAD65A) and protein tyrosine phosphatase (IA-2A) autoantibodies by radioimmunoassay.
Znt8A was detected in 68.7% of recent-onset T1D patients and 48.9% of the entire patient cohort, similar to GAD65A (68.3% and 47.2%) and IA-2A (64.8% and 42.4%) positivities respectively. ZnT8A was the only antibody in 8.4% of patients. Znt8A and IA2A frequencies and titers were independent of gender and ethnicity, whereas GAD65A titers were greater in females. The diabetes duration-dependent decline in ZnT8A frequency was similar to GAD65A and IA-2A. The SLC30A8 rs2466293 AG + GG genotypes were associated with T1D risk in non-European descents (56.2% × 42.9%; p = 0.018), and the GG genotype with higher ZnT8A titers in recent-onset T1D: 834.5 IU/mL (711.3-2190.0) × 281 IU/mL (10.7-726.8); p = 0.027. Conclusion ZnT8A detection increases T1D diagnosis rate even in mixed populations. SLC30A8 rs2466293 was associated with T1D predisposition in non-European descents.
Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM).
rs7903146 polymorphism has been associated with decreased insulin secretion, ...reduced GLP-1 action, and possible impaired peripheral insulin sensitivity.
To evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the
variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide.
Intervention study. Patients with T2DM (
= 162) were genotyped for the
rs7903146 single nucleotide polymorphism (SNP). Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C (HbA1c), HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon before and after treatment with exenatide for 8 weeks.
Patients with genotypes CC and CT/TT presented similar glucose area under the curve (AUC) 0-180 min before treatment and a similar decrease after treatment (p < 0.001). Before exenatide, insulin levels at 30-120 min were higher in CT/TT versus CC subjects (p < 0.05). After treatment with exenatide, only CT/TT individuals demonstrated insulin reduction at 30-180 min during the meal test (p < 0.05). Patients with the CC genotype presented no differences in insulin concentrations before and after treatment. The areas under the glucagon curve between 0 and 180 min were similar before treatment and reduced after treatment in both groups (p < 0.001).
The presence of the
rs7903146 T allele in patients with T2DM was associated with increased secretion of insulin response to a mixed-meal test. Furthermore, after treatment with exenatide, only the carriers of the T allele showed significantly decreased postprandial plasma insulin peak levels comparing with non carriers.
Background
The aim is to evaluate the effects of IGB in overweight or class I obese patients, by analyzing body composition and quality of life (QOL).
Methods
Prospective study including patients ...with BMI 27–34.9 kg/m
2.
body composition analysis (BCA) was performed before IGB implantation and its removal, after 6 months of treatment. QOL was assessed by the Short Form 36 (SF-36) Health Survey at baseline and after treatment.
Results
Forty patients were included in this study, but four were excluded. The total weight decreased by 12.29 kg after 6 months of use of IGB, which corresponds to loss of 13.69% of the total weight. There was a significant reduction in body fat mass and fat area. QOL improved in all eight sections analyzed (
p
< 0.001 to 0.041): functional capacity, physical aspects, pain, general health status, vitality, social aspects, emotional aspects, and mental health.
Conclusions
IGB induces not only weight loss but changes in body composition through the reduction of body fat mass and fat area. Furthermore, it improves QOL.
Aims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progression has been described but remains elusive. Objectives. To evaluate the potential biological ...involvement of miRNA expression in the immune response and beta cell function in T1D. Methods.We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group).Results. The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls. Several miRNAs were correlated with islet autoantibodies (IA2A, GADA, and Znt8A), age, and C-peptide levels, mainly from AbP, and recent T1D groups pointing these miRNAs as relevant to T1D pathogenesis and progression. Several miRNAs were related to metabolic derangements, inflammatory pathways, and several other autoimmune diseases. Pathway analysis of putative DEM targets revealed an enrichment in pathways related to metabolic syndrome, inflammatory response, apoptosis and insulin signaling pathways, metabolic derangements, and decreased immunomodulation. One of the miRNAs’ gene targets was DYRK2 (dual-specificity tyrosine-phosphorylation-regulated kinase 2), which is an autoantigen targeted by an antibody in T1D. ROC curve analysis showed hsa-miR-16 and hsa-miR-200a-3p with AUCs greater than for glucose levels, with discriminating power for T1D prediction greater than glucose levels. Conclusions/Interpretation. Our data suggests a potential influence of DEMs on disease progression from the initial autoimmune lesion up to severe beta cell dysfunction and the role of miRNAs hsa-miR-16 and hsa-miR-200a-3p as biomarkers of T1D progression.
Abstract Objective We evaluated the effects of carbohydrate (CHO) supplementation on markers of bone turnover in elite runners. Design Twenty-four male runners were randomly assigned to two groups – ...a CHO and a control (CON) group – using a double-blind design. The participants were submitted to an overload training program (days 1–8), followed by a high-intensity intermittent running protocol (10 × 800 m) on day 9. They received a maltodextrin solution (CHO group) or a placebo solution as the CON equivalent, before, during, and after these protocols. Results After 8 days of intensive training, baseline levels of osteocalcin (OC) decreased in both CHO and CON groups (before: 28.8 ± 3.6 and 26.6 ± 2.4 ng/ml, after: 24.8 ± 3.0 and 21.9 ± 1.6 ng/ml, respectively, p < 0.01). On day 9, at 80 min of the recovery period, carboxy-terminal of telopeptide type I collagen (CTX) serum concentration was suppressed in the CHO group (0.3 ± 0.1 ng/ml) vs. 0.6 ± 0.0 ng/ml for the CON group (p < 0.01). CHO supplementation was effective in decreasing CTX levels from baseline to recovery (0.5 ± 0.1 ng/mL to 0.3 ± 0.1 ng/mL, p < 0.001), while an increase from 0.4 ± 0.0 ng/mL to 0.6 ± 0.0 ng/mL (p < 0.001) was observed in the CON group. Conclusion CHO beverage ingestion attenuated the exercise-induced increase in CTX concentration, suggesting that CHO supplementation is a potential strategy to prevent bone damage in athletes.
Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of ...creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally,
51
Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 ± 10, Post 70 ± 18 mmol/kg/wt; PL Pre 52 ± 13, Post 46 ± 13 mmol/kg/wt;
p
= 0.03; estimated difference between means 23.6; 95% confidence interval 1.42–45.8). No significant differences were observed for
51
Cr-EDTA clearance (CR Pre 90.4 ± 16.9, Post 96.1 ± 15.0 mL/min/1.73 m
2
; PL Pre 97.9 ± 21.6, Post 96.4 ± 26.8 mL/min/1.73 m
2
;
p
= 0.58; estimated difference between means −0.3; 95% confidence interval −24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.
The
rs7903146 variant is strongly associated with type 2 diabetes mellitus (T2DM). However, the mechanisms involved in this association remain unknown and may include extrapancreatic effects. The aim ...of this study was to perform a metabolic characterization of T2DM patients with and without the
rs7903146 risk T allele and analyze some influences of the
genotype on glucose metabolism.
Patients with T2DM (
= 162) were genotyped for the
rs7903146 single nucleotide polymorphism. Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C, HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon. Additional secondary assessments included determination of insulinogenic index (IGI
), and insulin sensitivity (%S) and resistance (IR) by Homeostatic model assessment (HOMA).
Patients with the CT/TT genotype showed lower baseline plasma concentrations of C-peptide when compared with those with the CC genotype. Of the 56 individuals who participated in the mixed-meal test, 26 and 30 had the CC and CT/TT genotypes, respectively. CT/TT subjects, compared with CC individuals, had higher post prandial plasma levels of insulin and C-peptide at 30-120 min (p < 0.05) and proinsulin at 45-240 min (p < 0.05). Interestingly CT/TT individuals presented at baseline higher %S (p = 0.021), and lower IR (p = 0.020) than CC individuals. No significant differences in IGI
values were observed between groups.
The T2DM individuals carrying the rs7903146 T allele of the
gene presented higher IR pattern in response to a mix-meal test, different of beta cell function at baseline assessed by C-peptide levels which was lower, and Homa-IR was lower when comparing with non-carriers.
The aim of this study was to evaluate the effect of carbohydrate supplementation on free plasma DNA and conventional markers of training and tissue damage in long-distance runners undergoing an ...overload training program. Twenty-four male runners were randomly assigned to two groups (CHO group and control group). The participants were submitted to an overload training program (days 1–8), followed by a high-intensity intermittent running protocol (10 × 800 m) on day 9. The runners received maltodextrin solution (CHO group) or zero energy placebo solution as the control equivalent before, during, and after this protocol. After 8 days of intensive training, baseline LDH levels remained constant in the CHO group (before: 449.1 ± 18.2, after: 474.3 ± 22.8 U/L) and increased in the control group (from 413.5 ± 23.0 to 501.8 ± 24.1 U/L,
p
< 0.05). On day 9, LDH concentrations were lower in the CHO group (509.2 ± 23.1 U/L) than in the control group (643.3 ± 32.9 U/L,
p
< 0.01) post-intermittent running. Carbohydrate ingestion attenuated the increase of free plasma DNA post-intermittent running (48,240.3 ± 5,431.8 alleles/mL) when compared to the control group (73,751.8 ± 11,546.6 alleles/mL,
p
< 0.01). Leukocyte counts were lower in the CHO group than in the control group post-intermittent running (9.1 ± 0.1 vs
.
12.2 ± 0.7 cells/µL;
p
< 0.01) and at 80 min of recovery (10.6 ± 0.1 vs. 13.9 ± 1.1 cells/µL;
p
< 0.01). Cortisol levels were positively correlated with free plasma DNA, leukocytes, and LDH (all
r
> 0.4 and
p
< 0.001). The results showed that ingestion of a carbohydrate beverage resulted in less DNA damage and attenuated the acute post-exercise inflammation response, providing better recovery during intense training.
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