المؤلفون: McGorm, Kelly J., Brown, James D., Roberts, Alison G., Greenbank, Susan, Brasacchio, Daniella, Sawyer, Alyssa C. P., Oakey, Helena, Colman, Peter G., Craig, Maria E., Davis, Elizabeth A., Soldatos, Georgia, Thomson, Rebecca L., Wentworth, John M., Couper, Jennifer J., Penno, Megan A. S.

المصدر: Children; Apr2023, Vol. 10 Issue 4, p637, 12p

مصطلحات موضوعية: CAREGIVER attitudes, CHILDBIRTH, TYPE 1 diabetes, COMMUNITY support, EXPERIENCE, ISLANDS of Langerhans, SURVEYS, IMMUNITY, RESEARCH funding, BLOOD testing, LONGITUDINAL method, DISEASE risk factors, CHILDREN

مستخلص: Background: We sought research experiences of caregivers and their children were enrolled in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Methods: ENDIA is a pregnancy–birth cohort investigating early-life causes of type 1 diabetes (T1D). Surveys were sent to 1090 families between June 2021 and March 2022 with a median participation of >5 years. Caregivers completed a 12-item survey. Children ≥ 3 years completed a four-item survey. Results: The surveys were completed by 550/1090 families (50.5%) and 324/847 children (38.3%). The research experience was rated as either "excellent" or "good" by 95% of caregivers, and 81% of children were either "ok", "happy" or "very happy". The caregivers were motivated by contributing to research and monitoring their children for T1D. Relationships with the research staff influenced the experience. The children most liked virtual reality headsets, toys, and "helping". Blood tests were least liked by the children and were the foremost reason that 23.4% of the caregivers considered withdrawing. The children valued gifts more than their caregivers. Only 5.9% of responses indicated dissatisfaction with some aspects of the protocol. The self-collection of samples in regional areas, or during the COVID-19 pandemic restrictions, were accepted. Conclusions: This evaluation identified modifiable protocol elements and was conducted to further improve satisfaction. What was important to the children was distinct from their caregivers. [ABSTRACT FROM AUTHOR]

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المؤلفون: Harding, Amy L., Bediaga, Naiara, Galligan, Anna, Colman, Peter G., Fourlanos, Spiros, Wentworth, John M.

المصدر: Internal Medicine Journal; Apr2021, Vol. 51 Issue 4, p515-519, 5p

مصطلحات موضوعية: SODIUM-glucose cotransporters, GLYCOSYLATED hemoglobin, BIOMARKERS, FASTING, BLOOD pressure, ALBUMINS, GLOMERULAR filtration rate, UREA, CONFIDENCE intervals, BODY weight, CLINICAL trials, GLYCEMIC control, URINATION disorders, URINARY tract infections, INDIVIDUALIZED medicine, TYPE 2 diabetes, TREATMENT effectiveness, DESCRIPTIVE statistics, URINALYSIS, ELECTROLYTES, GLUCOSE, LONGITUDINAL method, CREATININE, OUTPATIENT services in hospitals, EVALUATION

مستخلص: Aim: To determine the clinical and biochemical variables associated with change in HbA1c in patients with type 2 diabetes who start sodium‐glucose linked transporter (SGLT) inhibitor therapy. Methods: We performed a prospective cohort study (ACTRN12616000833460) of 48 adults (30 male, 18 female) with type 2 diabetes who attended a tertiary hospital diabetes clinic. Fasting serum and urine samples, collected during clinic visits prior to and at 1, 12 and 24 weeks after commencing SGLT inhibitor treatment, were analysed for HbA1c, electrolytes, urea, creatinine and glucose. Results: After 12 weeks, SGLT inhibitor therapy was associated with respective median (97% CI) decreases in weight, blood pressure, HbA1c and urine albumin/creatinine ratio of 3.0 (1.7–3.4) kg, 8 (2–16)/4 (3–9) mmHg, 6 (3–14) mmol/mol and 0.69 (0.18–1.8) mg/mmol. These effects persisted to 24 weeks. Urinary frequency and genitourinary infection were common adverse effects. Baseline HbA1c and eGFR independently predicted ΔHbA1c at 12 weeks whereas only baseline HbA1c independently predicted ΔHbA1c at 24 weeks. Urinary fractional glucose excretion and change in fasting glucose 1 week after starting SGLT inhibitor did not contribute to prediction of glycaemic response. Conclusions: SGLT inhibitor therapy in a hospital clinic setting was associated with clinical improvements comparable to those observed in clinical trials but with higher incidence of genitourinary side‐effects. Baseline HbA1c and eGFR, but not urine fractional glucose excretion, predicted glycaemic response. [ABSTRACT FROM AUTHOR]

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المؤلفون: Harbison, Jessica E., Roth‐Schulze, Alexandra J., Giles, Lynne C., Tran, Cuong D., Ngui, Katrina M., Penno, Megan A., Thomson, Rebecca L., Wentworth, John M., Colman, Peter G., Craig, Maria E., Morahan, Grant, Papenfuss, Anthony T., Barry, Simon C., Harrison, Leonard C., Couper, Jennifer J.

المصدر: Pediatric Diabetes; Aug2019, Vol. 20 Issue 5, p574-583, 10p, 2 Charts, 2 Graphs

مصطلحات موضوعية: AUTOANTIBODY analysis, AGE factors in disease, CONFIDENCE intervals, DEOXY sugars, DISACCHARIDES, INGESTION, TYPE 1 diabetes, INTESTINAL mucosa, ISLANDS of Langerhans, LONGITUDINAL method, PEDIATRICS, PERMEABILITY, REGRESSION analysis, GUT microbiome, DISEASE progression, GRAM-negative anaerobic bacteria, SHORT-chain fatty acids

مستخلص: Aims/hypothesis: To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls. Methods: We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent‐onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2‐34) months follow‐up. Results: Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti‐inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P =.006), lower within‐sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P =.005), and lower abundance of SCFA‐producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P =.008). Conclusions/Interpretation: Children with ≥2 IA who progress to diabetes, like those with recent‐onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA‐producing bacteria, may have a role to decrease progression to diabetes in children at‐risk. [ABSTRACT FROM AUTHOR]

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المؤلفون: Redondo, Maria J., Geyer, Susan, Steck, Andrea K., Sosenko, Jay, Anderson, Mark, Antinozzi, Peter, Michels, Aaron, Wentworth, John, Ping Xu, Pugliese, Alberto, Xu, Ping, Type 1 Diabetes TrialNet Study Group

المصدر: Diabetes Care; Feb2018, Vol. 41 Issue 2, p311-317, 7p

مصطلحات موضوعية: PHENOTYPES, TYPE 1 diabetes, TRANSCRIPTION factors, SINGLE nucleotide polymorphisms, DIAGNOSIS of diabetes, ALLELES, COMPARATIVE studies, DISEASE susceptibility, GENETIC polymorphisms, GENETICS, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, PROTEINS, RESEARCH, EVALUATION research

مستخلص: Objective: The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis.Research Design and Methods: We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data (n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders.Results: The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old (n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones (n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) (P = 0.008) and lower mean glucose AUC (P = 0.0127). The results were similar for the rs7901695 SNP.Conclusions: In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

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المؤلفون: Nathan, Brandon M., Boulware, David, Geyer, Susan, Atkinson, Mark A., Colman, Peter, Goland, Robin, Russell, William, Wentworth, John M., Wilson, Darrell M., Evans-Molina, Carmella, Wherrett, Diane, Skyler, Jay S., Moran, Antoinette, Sosenko, Jay M., Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups

المصدر: Diabetes Care; Nov2017, Vol. 40 Issue 11, p1494-1499, 6p

مصطلحات موضوعية: DIAGNOSIS of diabetes, GLYCEMIC control, BLOOD sugar, BLOOD sugar monitoring, TYPE 2 diabetes, BIOLOGICAL assay, C-peptide, GLUCOSE tolerance tests, LONGITUDINAL method, TYPE 1 diabetes, RESEARCH funding, DIAGNOSIS

مستخلص: Objective: We assessed dysglycemia and a T1D Diagnostic Index60 (Index60) ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants.Research Design and Methods: Two cohorts were analyzed: 1) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and 2) baseline Index60 <1.00 OGTTs with an incident Index60 ≥1.00 OGTT. Incident dysglycemic OGTTs were divided into those with (DYS/IND+) and without (DYS/IND-) concomitant Index60 ≥1.00. Incident Index60 ≥1.00 OGTTs were divided into those with (IND/DYS+) and without (IND/DYS-) concomitant dysglycemia.Results: The cumulative incidence for type 1 diabetes was greater after IND/DYS- than after DYS/IND- (P < 0.01). Within the normoglycemic cohort, the cumulative incidence of type 1 diabetes was higher after DYS/IND+ than after DYS/IND- (P < 0.001), whereas within the Index60 <1.00 cohort, the cumulative incidence after IND/DYS+ and after IND/DYS- did not differ significantly. Among nonprogressors, type 1 diabetes risk at the last OGTT was greater for IND/DYS- than for DYS/IND- (P < 0.001). Hazard ratios (HRs) of DYS/IND- with age and 30- to 0-min C-peptide were positive (P < 0.001 for both), whereas HRs of type 1 diabetes with these variables were inverse (P < 0.001 for both). In contrast, HRs of IND/DYS- and type 1 diabetes with age and 30- to 0-min C-peptide were consistent (all inverse [P < 0.01 for all]).Conclusions: The findings suggest that incident dysglycemia without Index60 ≥1.00 is a suboptimal prediagnostic end point for type 1 diabetes. Measures that include both glucose and C-peptide levels, such as Index60 ≥1.00, appear better suited as prediagnostic end points. [ABSTRACT FROM AUTHOR]

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المؤلفون: Redondo, Maria J, Steck, Andrea K, Sosenko, Jay, Anderson, Mark, Antinozzi, Peter, Michels, Aaron, Wentworth, John M, Atkinson, Mark A, Pugliese, Alberto, Geyer, Susan, Type 1 Diabetes TrialNet Study Group

المصدر: Diabetes Care; Oct2018, Vol. 41 Issue 10, pN.PAG-N.PAG, 1p

مصطلحات موضوعية: OBESITY complications, AUTOANTIBODIES, COMPARATIVE studies, DISEASE susceptibility, GENES, GENETIC polymorphisms, IMMUNITY, TYPE 1 diabetes, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, OBESITY, PROTEINS, RESEARCH, EVALUATION research, DISEASE progression, DISEASE complications

مستخلص: Objective: The type 2 diabetes-associated alleles at the TCF7L2 locus mark a type 1 diabetes phenotype characterized by single islet autoantibody positivity as well as lower glucose and higher C-peptide measures. Here, we studied whether the TCF7L2 locus influences progression of islet autoimmunity, from single to multiple (≥2) autoantibody positivity, in relatives of patients with type 1 diabetes.Research Design and Methods: We evaluated 244 participants in the Type 1 Diabetes TrialNet Pathway to Prevention study with confirmed single autoantibody positivity at screening and Immunochip single nucleotide polymorphism data (47.5% male; median age 12.8 years, range 1.2-45.9; 90.2% white). We analyzed risk allele frequency at TCF7L2 rs4506565 (in linkage disequilibrium with rs7903146). Altogether, 62.6% participants carried ≥1 risk allele. Univariate and multivariable Cox proportional hazards models and Kaplan-Meier statistical methods were used.Results: During follow-up (median 5.2 years, range 0.2-12.6), 62% of the single autoantibody-positive participants developed multiple autoantibody positivity. In the overall cohort, the TCF7L2 locus did not significantly predict progression to multiple autoantibody positivity. However, among single GAD65 autoantibody-positive participants (n = 158), those who carried ≥1 risk allele had a lower rate of progression to multiple autoantibody positivity (hazard ratio [HR] 0.65, P = 0.033) than those who did not, after adjustment for HLA risk haplotypes and age. Among subjects who were either IA-2 or insulin autoantibody positive only, carrying ≥1 TCF7L2 risk allele was not a significant factor overall, but in overweight or obese participants, it increased the risk of progression to multiple autoantibody positivity (HR 3.02, P = 0.016) even with adjustment for age.Conclusions: The type 2 diabetes-associated TCF7L2 locus influences progression of islet autoimmunity, with differential effects by autoantibody specificity and interaction by obesity/overweight. [ABSTRACT FROM AUTHOR]

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