المؤلفون: GONG, JOANNA Y.¹, WENTWORTH, JOHN M.², YATES, CHRISTOPHER J.³, DAMIEN QI, QI YANG⁴, FOURLANOS, SPIROS⁵ Spiros.Fourlanos@mh.org.au

المصدر: Journal of Clinical & Diagnostic Research. Dec2023, Vol. 17 Issue 12, p1-3. 3p.

مصطلحات موضوعية: *IRON overload, *GLUTAMATE decarboxylase, *TYPE 2 diabetes, *AUTOIMMUNE diseases, *IRON in the body, *ISLANDS

مستخلص: Iron’s role in diabetes pathophysiology is underrecognised. Authors describe three cases (two females and one male) with evidence of ‘ferro-immune’ hybrid diabetes, HFE C282Y homozygosity with islet autoimmunity. Case one describes iron overload followed by classical autoimmune diabetes. A 20-year-old female presented with non transfusion-dependent hereditary spherocytosis, contributing to hepatic iron overload. At the age of 26 years, the patient presented with diabetic ketoacidosis and elevated Glutamic Acid Decarboxylase (GAD) (50.5 U/mL) and Islet Antigen 2 (IA-2) (>4,000 U/mL) autoantibodies, and commenced insulin therapy. Two months after her diabetes diagnosis, she began iron chelation therapy. Case two describes haemochromatosis followed by adultonset diabetes. A fit 78-year-old woman was diagnosed with haemochromatosis at the age of 58 years and presumed to have Type 2 Diabetes (T2D) at the age of 66 years. However, subsequent testing revealed GAD autoantibody positivity (24 U/mL) with normal C-peptide levels (0.55 nmol/L). Her diabetes was diet-controlled, and her transferrin saturation normalised while GAD seropositivity resolved spontaneously. Case three describes slowly-progressive autoimmune diabetes preceding haemochromatosis. A lean man was diagnosed with latent autoimmune diabetes in adulthood with elevated GAD autoantibodies (11 U/mL). At the age of 81 years, he was diagnosed with haemochromatosis (transferrin saturation 61%), which was followed by a decline in glycaemic control (HbA1c 8.3% to 9.0%). A paired fasting glucose (10.8 mmol/L) and C-peptide (0.15 nmol/L) indicated insulin deficiency, and he remains dependent on insulin therapy. Reducing iron levels through venesection or iron chelation may help decrease islet inflammation and potentially, autoimmunity. A family history of haemochromatosis or an atypical diabetes presentation should prompt an investigation into iron status. Additionally, a low C-peptide level in the presence of haemochromatosis should prompt an investigation into islet autoantibody status. [ABSTRACT FROM AUTHOR]

المؤلفون: Qi, Qi Yang Damien, Playfair, Julie, Brown, Wendy A., Burton, Paul, O'Brien, Paul E., Wentworth, John M.

المصدر: Diabetes, Obesity & Metabolism; Jun2023, Vol. 25 Issue 6, p1464-1472, 9p

مصطلحات موضوعية: TYPE 2 diabetes, WEIGHT loss, GASTRIC banding, OVERWEIGHT persons, MORBID obesity, DISEASE remission

مستخلص: Aim: Randomized trials reporting 5‐year outcomes have shown bariatric surgery to induce diabetes remission and improve cardiovascular risk. However, the longer‐term effects of surgery are uncertain, with only one randomized trial reporting 10‐year diabetes outcomes in people with obesity. We aimed to compare 10‐year diabetes outcomes of people who are overweight but not obese, randomly assigned to receive either multidisciplinary diabetes care, or multidisciplinary diabetes care combined with gastric band (GB) surgery. Methods: Between 2009 and 2011, 51 adults were randomized. After 5 years, they were discharged to receive community care and reassessed after 10 years. The primary outcome was diabetes remission, defined as glycated haemoglobin (HbA1c) <6.5% (48 mmol/mol) without glucose‐lowering medication. Results: Forty‐one participants (20 medical and 21 GB) completed the 10‐year assessment. The median (Q1, Q3) weight loss in the GB group was 9.8 (6.7, 16.3)% at 10 years compared with 5.6 (3.4, 7.6)% in the medical group (median difference 4.2%; p =.008). Diabetes remission occurred in five GB participants and no medical participants (relative risk 0.76, 95% CI: 0.55‐0.93, p =.048). GB participants used fewer glucose‐lowering medications at 10 years but HbA1c, fasting glucose, calculated cardiovascular risk, quality‐of‐life and incident diabetes complications did not differ significantly between the groups. Conclusion: When compared with medical care, GB surgery achieved greater weight loss and modestly increased the likelihood of diabetes remission. However, it did not improve HbA1c, cardiovascular risk or quality of life. [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: Pathiraja, Nipuni P., Colman, Peter G., Wentworth, John M.

المصدر: Internal Medicine Journal; Nov2020, Vol. 50 Issue 11, p1415-1418, 4p

مصطلحات موضوعية: ANTIDEPRESSANTS, GLYCOSYLATED hemoglobin, TYPE 2 diabetes, OBESITY, PATIENT compliance, GLYCEMIC control

مستخلص: We aimed to describe the glycaemic trajectory and define characteristics associated with suboptimal glycaemic control in the type 2 diabetes clinic. Higher glycosylated haemoglobin (HbA1c) at 1 year was associated with higher baseline HbA1c, concurrent anti‐depressant or antipsychotic medication, higher bodyweight and low treatment adherence. These characteristics may help identify patients unlikely to attain HbA1c treatment targets and be better served by a different model of care. [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]

المؤلفون: O'Brien, Paul E., DeWitt, Dawn E., Laurie, Cheryl E., Brennan, Leah, Wentworth, John M., Anderson, Margaret, O'Dea, Kerin, Dean, Felicia, Smith, Andrew, Dalton, David P.

مصطلحات موضوعية: type 2 diabetes, obesity, bariatric surgery, gastric banding, LAGB, indigenous Aboriginal, remission of diabetes, weight loss

الوصف: Background/Objectives: Diabetes and obesity are common and serious health challenges for indigenous people worldwide. The feasibility of achieving substantial weight loss, leading to remission of diabetes, was evaluated in a regional indigenous Australian community. Subjects/Methods: A prospective cohort study of 30 obese indigenous adults from the Rumbalara Aboriginal Co-operative in Central Victoria was performed. Inclusion criteria included aboriginality, BMI > 30 kg/m2 and diabetes diagnosed within the last 10 years. Weight loss was achieved using laparoscopic adjustable gastric banding (LAGB). Participants were treated in their community and followed for 2 years. Outcomes were compared with those of non-indigenous Australians from an earlier randomized controlled trial (RCT) using a similar protocol. Results: 30 participants (26 females, mean age 44.6 years; mean BMI 44.3) had LAGB at the regional hospital. Twenty-six participants completed diabetes assessment at 2 years follow-up. They showed diabetes remission (fasting blood glucose < 7.0 mmol/L and haemoglobin A1c (HbA1c) < 6.2 % while off all therapy except metformin) in 20 of the 26 and a mean weight loss (SD) of 26.0 (14) kilograms. Based on intention-to-treat, remission rate was 66 %. Quality of life improved. There was one early event and 12 late adverse events. The outcomes for weight loss and diabetes remission were not different from the LAGB group of the RCT. Conclusions: For obese indigenous people with diabetes, a regionalized model of care centred on the LAGB is an effective approach to a serious health problem. The model proved feasible and acceptable to the indigenous people. Trial Registration: Australian New Zealand Clinical Trials Registry (ACTRN 12609000319279).

العلاقة: https://acuresearchbank.acu.edu.au/item/8q845/the-effect-of-weight-loss-on-indigenous-australians-with-diabetes-a-study-of-feasibility-acceptability-and-effectiveness-of-laparoscopic-adjustable-gastric-bandingTest; https://doi.org/10.1007/s11695-015-1733-4Test; O'Brien, Paul E., DeWitt, Dawn E., Laurie, Cheryl E., Brennan, Leah, Wentworth, John M., Anderson, Margaret, O'Dea, Kerin, Dean, Felicia, Smith, Andrew and Dalton, David P. (2016). The effect of weight loss on Indigenous Australians with diabetes: A study of feasibility, acceptability and effectiveness of laparoscopic adjustable gastric banding. Obesity Surgery. 26(1), pp. 45 - 53. https://doi.org/10.1007/s11695-015-1733-4Test

الإتاحة: https://doi.org/10.1007/s11695-015-1733-4Test

المؤلفون: Wentworth, John M., Cheng, Chloe, Laurie, Cheryl, Skinner, Stewart, Burton, Paul R., Brown, Wendy A., O'brien, Paul E.

المصدر: Obesity Surgery; Apr2018, Vol. 28 Issue 4, p982-989, 8p

مصطلحات موضوعية: GASTRIC banding, BARIATRIC surgery, PEOPLE with diabetes, BLOOD pressure, WEIGHT loss

مستخلص: Background: Long-term outcome data are needed to define the role of bariatric surgery in type 2 diabetes (T2D). To address this, we collated diabetes outcomes more than a decade after laparoscopic adjustable gastric band (LAGB) surgery.Method: Clinical and biochemical measures from 113 obese T2D patients who underwent LAGB surgery in 2003 and 2004 were analyzed. Diabetes remission was defined as HbA1c < 6.2% (44 mmol/mol) and fasting glucose < 7.0 mmol/L.Results: Seventy-nine patients had weight data at 10 years and attained a median [Q1, Q3] weight loss of 16 [10, 21] percent. Sixty patients attended a follow-up assessment. Their baseline HbA1c of 7.8 [7.1, 9.3] percentage units (62 [54, 78] mmol/mol) had decreased to 6.6 [6.1, 8.4] (49 [43, 68] mmol/mol) despite no significant change in glucose-lowering therapy. Eleven patients (18%) were in diabetes remission and another 18 had HbA1c ≤ 6.5%. Significant improvements in physical measures of quality of life, blood pressure, and lipid profile were also observed but there was no change in the proportion of patients with albuminuria and a significant decline in estimated glomerular filtration rate. Twelve patients in the follow-up cohort (20%) required anti-reflux medication after surgery and 26 (43%) underwent gastric band revision surgery.Conclusion: Weight loss for over 10 years after LAGB surgery delivers clinically meaningful improvements in HbA1c, blood pressure, lipids, and quality of life at the cost of a high rate of revision surgery and increased use of anti-reflux medication. These findings support the use of bariatric surgery as a long-term treatment for weight loss and wellbeing in patients with T2D.Study Registration: Registered with the Australian Clinical trials registry as ACTRN12615000089538. [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: Wentworth, John M.^1,2,3 wentworth@wehi.edu.au, Dalziel, Kim M.⁴, O'Brien, Paul E.¹, Burton, Paul¹, Shaba, Frackson⁴, Clarke, Philip M.⁴, Laiteerapong, Neda⁵, Brown, Wendy A.¹, O'Brien, Paul E¹ (AUTHOR)

المصدر: Journal of Diabetes & its Complications. Jul2017, Vol. 31 Issue 7, p1139-1144. 6p.

مصطلحات موضوعية: *TYPE 2 diabetes treatment, *OBESITY, *BARIATRIC surgery, *OBESITY treatment, *COMBINED modality therapy, *TYPE 2 diabetes, *TYPE 2 diabetes complications, *OBESITY complications, *CLINICAL trials, *COST effectiveness, *ECONOMIC aspects of diseases, *MEDICAL care costs, *QUALITY of life, *RESEARCH funding, *SURVEYS, *WEIGHT loss, *COST analysis, *BODY mass index, *STATISTICAL models, *ECONOMICS

مصطلحات جغرافية: AUSTRALIA, UNITED States

مستخلص: Aim: To determine the cost-effectiveness of gastric band surgery in overweight but not obese people who receive standard diabetes care.Method: A microsimulation model (United Kingdom Prospective Diabetes Study outcomes model) was used to project diabetes outcomes and costs from a two-year Australian randomized trial of gastric band (GB) surgery in overweight but not obese people (BMI 25 to 30kg/m2) on to a comparable population of U.S. adults from the National Health and Nutrition Examination Survey (N=254). Estimates of cost-effectiveness were calculated based on the incremental cost-effectiveness ratios (ICERs) for different treatment scenarios. Costs were inflated to 2015 U.S. dollar values and an ICER of less than $50,000 per QALY gained was considered cost-effective.Results: The incremental cost-effectiveness ratio for GB surgery at two years exceeded $90,000 per quality-adjusted life year gained but decreased to $52,000, $29,000 and $22,000 when the health benefits of surgery were assumed to endure for 5, 10 and 15 years respectively. The cost-effectiveness of GB surgery was sensitive to utility gained from weight loss and, to a lesser degree, the costs of GB surgery. However, the cost-effectiveness of GB surgery was affected minimally by improvements in HbA1c, systolic blood pressure and cholesterol.Conclusions: GB surgery for overweight but not obese people with T2D appears to be cost-effective in the U.S. setting if weight loss endures for more than five years. Health utility gained from weight loss is a critical input to cost-effectiveness estimates and therefore should be routinely measured in populations undergoing bariatric surgery. [ABSTRACT FROM AUTHOR]

المؤلفون: Wentworth, John, Playfair, Julie, Laurie, Cheryl, Brown, Wendy, Burton, Paul, Shaw, Jonathan, O'Brien, Paul

المصدر: Obesity Surgery; Dec2015, Vol. 25 Issue 12, p2400-2407, 8p

مصطلحات موضوعية: GASTRIC banding, INSULIN, TYPE 2 diabetes, OVERWEIGHT persons, PANCREATIC beta cells, WEIGHT loss

مستخلص: Background: We aimed to determine the effects of laparoscopic adjustable gastric band (LAGB) on beta-cell function in overweight people with type 2 diabetes and to assess the relationship between baseline beta-cell function and glycemic outcomes. Methods: We studied 44 overweight but not obese people with type 2 diabetes who participated in a randomized trial whose primary outcome was the rate of diabetes remission after 2 years of multidisciplinary diabetes care (MDC group) or multidisciplinary care combined with LAGB. Dynamic beta-cell function was assessed by intravenous glucose challenge, and basal beta-cell function (HOMA-B) and insulin sensitivity (HOMA-S) were determined using the homeostatic model. Results: Twelve LAGB participants and two MDC participants were in diabetes remission at 2 years. HOMA-S and the C-peptide response to intravenous glucose increased significantly in LAGB but not in MDC participants. The insulin response to glucose did not change in LAGB participants, whereas their fasting C-peptide/insulin ratio increased. Baseline measures of beta-cell function correlated with diabetes remission but not with reduction in HbA1c following LAGB. Conclusions: In overweight people with diabetes, LAGB improves endogenous beta-cell function after 2 years. Baseline beta-cell function correlated with diabetes remission, but not with HbA1c change following LAGB. [ABSTRACT FROM AUTHOR]

: Copyright of Obesity Surgery is the property of Springer Nature 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.)