المؤلفون: Russell, William E, Bundy, Brian N, Anderson, Mark S, Cooney, Laura A, Gitelman, Stephen E, Goland, Robin S, Gottlieb, Peter A, Greenbaum, Carla J, Haller, Michael J, Krischer, Jeffrey P, Libman, Ingrid M, Linsley, Peter S, Long, S Alice, Lord, Sandra M, Moore, Daniel J, Moore, Wayne V, Moran, Antoinette M, Muir, Andrew B, Raskin, Philip, Skyler, Jay S, Wentworth, John M, Wherrett, Diane K, Wilson, Darrell M, Ziegler, Anette-Gabriele, Herold, Kevan C, Group, Type 1 Diabetes TrialNet Study

المصدر: Diabetes Care. 46(5)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Clinical Research, Clinical Trials and Supportive Activities, Nutrition, Prevention, Diabetes, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Metabolic and endocrine, Humans, Abatacept, Diabetes Mellitus, Type 1, Immunosuppressive Agents, T-Lymphocytes, Regulatory, Glucose, Type 1 Diabetes TrialNet Study Group

الوصف: ObjectivePrevious studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses.Research design and methodsWe conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests.ResultsA total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline.ConclusionsAlthough abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9mc232rqTest

المؤلفون: Joshi, Kriti, Harris, Mark, Cotterill, Andrew, Wentworth, John M., Couper, Jennifer J., Haynes, Aveni, Davis, Elizabeth A., Lomax, Kate E., Huynh, Tony

المصدر: Clinical Chemistry & Laboratory Medicine; Jan2024, Vol. 62 Issue 1, p41-49, 9p

مصطلحات موضوعية: TYPE 1 diabetes, AUTOANTIBODIES, GLUCOSE tolerance tests, GLUCOSE, DIABETIC acidosis, DEFICIENCY diseases

مستخلص: Type 1 diabetes (T1D) is well-recognised as a continuum heralded by the development of islet autoantibodies, progression to islet autoimmunity causing beta cell destruction, culminating in insulin deficiency and clinical disease. Abnormalities of glucose homeostasis are known to exist well before the onset of typical symptoms. Laboratory-based tests such as the oral glucose tolerance test (OGTT) and glycated haemoglobin (HbA1c) have been used to stage T1D and assess the risk of progression to clinical T1D. Continuous glucose monitoring (CGM) can detect early glycaemic abnormalities and can therefore be used to monitor for metabolic deterioration in pre-symptomatic, islet autoantibody positive, at-risk individuals. Early identification of these children can not only reduce the risk of presentation with diabetic ketoacidosis (DKA), but also determine eligibility for prevention trials, which aim to prevent or delay progression to clinical T1D. Here, we describe the current state with regard to the use of the OGTT, HbA1c, fructosamine and glycated albumin in pre-symptomatic T1D. Using illustrative cases, we present our clinical experience with the use of CGM, and advocate for an increased role of this diabetes technology, for monitoring metabolic deterioration and disease progression in children with pre-symptomatic T1D. [ABSTRACT FROM AUTHOR]

: Copyright of Clinical Chemistry & Laboratory Medicine is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

: Copyright of Internal Medicine Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Wentworth, John M.^1,2,3 (AUTHOR) john.wentworth@mh.org.au, Colman, Peter G.^1,2 (AUTHOR)

المصدر: Diabetes, Obesity & Metabolism. Jul2020, Vol. 22 Issue 7, p1215-1219. 5p.

مصطلحات موضوعية: *TYPE 2 diabetes, *METHIONINE, *SODIUM-glucose cotransporters, *GLUCOSE, *OBESITY, *OVERWEIGHT persons

مستخلص: The methionine aminopeptidase 2 (MetAP2) inhibitor ZGN‐1061 lowered weight and improved glucose in preclinical studies. We sought to determine its efficacy and safety by performing a multicentre, phase 2, randomized controlled trial involving overweight and obese adults with type 2 diabetes and HbA1c between 7% and 11% inclusive. Participants were randomized to receive subcutaneous treatment with placebo or 0.05, 0.3, 0.9 or 1.8 mg ZGN‐1061 every third day for 12 weeks. The primary outcome was change in HbA1c at week 12. Relative to placebo, the 0.9 and 1.8 mg doses induced clinically meaningful reductions in HbA1c of 0.6% (95% CI 0.2% to 0.9%; P = 0.0006) and 1.0% (95% CI 0.6% to 1.4%; P < 0.0001), respectively. The 1.8 mg dose also induced weight loss of 2.2% (95% CI 1.1% to 3.3%; P = 0.0002). The incidence of adverse events was balanced across the treatment groups. We conclude that MetAP2 inhibition with ZGN‐1061 for 12 weeks improved glucose control and aided weight loss in overweight and obese people with type 2 diabetes. However, given safety issues, Zafgen has discontinued MetAP2 inhibitor development. [ABSTRACT FROM AUTHOR]