ORCID Profile
0000-0002-0866-0973
Current Organisation
Garvan Institute of Medical Research
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Publisher: Wiley
Date: 06-2017
DOI: 10.1111/IMJ.13442
Abstract: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are an increasingly prescribed class of medication for type 2 diabetes mellitus. Euglycaemic diabetic ketoacidosis (euDKA) has been reported in association with SGLT2i use. Clinicians need to understand how to recognise and treat this complication. We describe three cases of euDKA in patients treated with SGLT2i.
Publisher: Wiley
Date: 09-2021
DOI: 10.1111/IMJ.15488
Publisher: Wiley
Date: 24-02-2016
DOI: 10.1002/OBY.21448
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.DIABRES.2016.04.006
Abstract: To evaluate the achievement of HbA1c targets in patients with type 2 diabetes mellitus in specialist practice. This audit was undertaken by members of the S4S Diabetes Informatics Group (DINGO), a consortium of Australian endocrinologists in private practice who contribute de-identified data from their electronic medical record, Audit 4 (Software 4 Specialists, S4S, Australia & New Zealand) for audit purposes. Data from patients with type 2 diabetes was extracted. Inclusion criteria were: initial age 7% (53mmol/mol), with at least another HbA1c recorded in the next 2years, and a minimum of 2years follow-up. Data was analysed using a linear mixed effects model. Of the 4796 patients in the dataset with type 2 diabetes mellitus, 1379 patients fulfilled inclusion criteria. The median age at initial consultation was 57 (49-64)years. The median baseline HbA1c was 8.7 (7.8-9.8)% (72mmol/mol). There was a 1.0% reduction in HbA1c to 7.7 (7.1-8.6)% (61mmol/mol) (p<0.0001) in the first 3-6months following referral, after which there were no further changes. The initial reduction was maintained with minimal loss of control at 4years. By 3-6months, 24% of patients achieved the target HbA1c. Referral of patients with type 2 diabetes to an endocrinologist reduces HbA1c, and the effect is sustained over the medium term however only a minority of patients reach targets.
Publisher: Public Library of Science (PLoS)
Date: 08-06-2015
Publisher: The Endocrine Society
Date: 09-11-2021
Publisher: Wiley
Date: 08-2018
DOI: 10.1111/IMJ.13963
Abstract: Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post-transplantation partly due to lack of detection protocols. To determine the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post-transplantation. We analysed patients on the St Vincent's Heart Lung database from 1 April 2014 to 30 September 2015 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non-diabetic patients to have an oral glucose tolerance test (modified for patients with cystic fibrosis (CF) to screen for CF-related hyperglycaemia (CFRH) (plasma glucose ≥8.2 mmol/L at 60 or 90 min). Study 1 included 114 patients (32 with CF and 82 without CF). Of 30 CF patients with glycaemic data, 27 (90%) had abnormal glucose metabolism: 18 had diabetes and nine had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism: eight had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF and 53 without CF). Fourteen CF patients had pre-existing diabetes and seven had pre-existing CFRH. All but one patient were diagnosed with diabetes post-transplantation. Hence, diabetes prevalence in CF patients post-transplantation was 96%. Among 53 transplanted patients without CF, seven (13%) had abnormal glucose metabolism but 30 (57%) were diagnosed with post-transplant diabetes. There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes-related morbidity and mortality further.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.CMET.2016.02.007
Abstract: High abundance of brown adipose tissue (BAT) is linked to lower glycaemia in humans, leading to the belief that BAT may protect against diabetes. The relationship between BAT glucose utilization and systemic glucose homeostasis has not been defined. In this paper we have characterized glycaemic excursions and BAT thermogenic responses in human brown adipocytes, BAT explants, and healthy adults through supraclavicular temperature profiling, revealing their circadian coupling in vivo and in vitro, orchestrated by UCP1, GLUT4, and Rev-erbα biorhythms. Extent of glycated haemoglobin also correlated positively with environmental temperature among community-dwelling patients. These data uncover potential crosstalk between BAT and glucose regulatory pathways, evident on cellular, tissue, in idual, and population levels, and provide impetus to search for BAT harnessing strategies for therapeutic purposes.
Publisher: Springer Science and Business Media LLC
Date: 27-08-2016
DOI: 10.1007/S00228-016-2117-Y
Abstract: The study aimed to (1) determine the trends in the utilisation of metformin in Australia, (2) determine the appropriateness of metformin dosing in an Australian teaching hospital and (3) gather the opinions of prescribers on the relationship between metformin dose and renal function. National prescription data between 1990 and 2012 were accessed. A retrospective audit (2008-2012) of metformin doses and patient renal function (20 % random s le of all in-patients prescribed metformin) was conducted at St Vincent's Hospital (SVH), Sydney. Prescribers of metformin were interviewed (semi-structured consultants at SVH) or surveyed (Australian endocrinologists) to gather their understanding of metformin dosing in relation to renal function. Metformin utilisation increased fivefold nationally between 1995 and 2012. Metformin tended to be under-dosed in SVH patients with normal renal function (83.5 %) and over-dosed in patients with impaired renal function (estimated glomerular filtration rate (eGFR) <30 mL/min, 50 %). Consultants indicated that metformin doses needed to be reduced in renal impairment. Most endocrinologists (61 %) were comfortable prescribing metformin down to eGFRs around 30 mL/min. The use of metformin increased greatly over the period of the study. Metformin is prescribed frequently for patients with eGFR values below the minimal level approved in the product label (60 mL/min). While prescribers expressed their understanding of the need to reduce metformin doses in patients with renal impairment, we found that metformin doses were higher than appropriate in patients with impaired renal function. Metformin may be used safely when renal function is poor provided dosage is appropriately reduced.
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/IMJ.13063
Publisher: Informa UK Limited
Date: 11-2016
DOI: 10.1080/08977194.2017.1285764
Abstract: Fibroblast growth factor-1 (FGF-1) promotes differentiation of human preadipocytes into mature adipocytes via modulation of a BMP and Activin Membrane-Bound Inhibitor (BAMBI)/Peroxisome proliferator-activated receptor (PPARγ)-dependent network. Here, we combined transcriptomic and functional investigations to identify novel downstream effectors aligned with complementary analyses of gene expression in human adipose tissue to explore relationships with insulin sensitivity. RNA-Seq and qRT-PCR analysis revealed significant down-regulation of carboxypeptidase A4 (CPA4) following FGF-1 treatment or induction of differentiation of human preadipocytes in a BAMBI/PPARγ-independent manner. siRNA-mediated knockdown of CPA4 resulted in enhanced differentiation of human preadipocytes. Furthermore, expression of CPA4 in subcutaneous adipose tissue correlated negatively with indices of local and systemic (liver and muscle) insulin sensitivity. These results identify CPA4 as a negative regulator of adipogenesis that is down-regulated by FGF-1 and a putative deleterious modulator of local and systemic insulin sensitivity. Further investigations are required to define the molecular mechanism(s) involved and potential therapeutic opportunities.
Publisher: Wiley
Date: 18-04-2022
DOI: 10.1111/DME.14850
Publisher: Elsevier BV
Date: 08-2017
Publisher: Frontiers Media SA
Date: 28-02-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
Publisher: Elsevier BV
Date: 12-2016
Publisher: Informa UK Limited
Date: 10-08-2015
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.ATHEROSCLEROSIS.2017.01.033
Abstract: Glucocorticoids could impair vascular function directly, or indirectly by reducing insulin sensitivity. The aim of this study was to determine the direct and indirect effects of acute and chronic low dose prednisolone on arterial stiffness and endothelial function. Twelve subjects with inflammatory arthritis, who had not taken oral glucocorticoids for ≥6 months, and 12 subjects with inflammatory arthritis, taking chronic (>6 months) low dose (6.3 ± 2.2 mg/day) prednisolone, were studied. Patients not on glucocorticoids underwent measurement of arterial stiffness (pulse wave velocity (PWV)) and endothelial function (reactive hyperaemia index (RHI)) before and after 7-10 days of prednisolone (6 mg/day), to assess the acute effects of prednisolone. Baseline data from patients not on glucocorticoids were compared with patients on long-term prednisolone to assess the chronic effects of prednisolone. Hepatic insulin sensitivity was estimated from percentage suppression of endogenous glucose production and peripheral insulin sensitivity as glucose infusion rate (M/I) during a hyperinsulinaemic-euglycaemic cl . There were no significant changes in PWV with acute (9.2 ± 0.8 vs. 8.9 ± 0.8 m/sec, p = 0.33) or chronic (8.9 ± 0.8 vs. 9.0 ± 0.7 m/sec, p = 0.69) prednisolone. In multiple regression analysis, PWV was negatively associated with M/I during hyperinsulinemic-euglycemic cl (p = 0.02), but not with suppression of endogenous glucose production (p = 0.15) or glucocorticoid use (p = 0.70). Chronic (2.4 ± 0.2 vs. 1.9 ± 0.1, p = 0.02), but not acute (1.8 ± 0.2 vs. 1.9 ± 0.1, p = 0.24), prednisolone resulted in a higher RHI. Arterial stiffness is not affected by low dose prednisolone per se, but is negatively associated with peripheral insulin sensitivity. Patients with rheumatoid arthritis taking long-term prednisolone had better endothelial function.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.CLNU.2015.08.002
Abstract: Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy in iduals. In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic cl . Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Obsen) and insulin-resistant (Obres) based on hyperinsulinemic-euglycemic cl glucose infusion rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 in iduals participated in an overfeeding intervention (+1250 kcal/day) for 28 days and studies repeated. Obsen and Obres were matched for adiposity (BMI and fat mass, both P = 1). Fasting plasma lactate was higher in Obres (0.78 [0.63-1.14] mmol/L) compared with both lean (0.71 [0.44-0.90] mmol/L, P = 0.02) and Obsen (0.67 [0.56-0.79] mmol/L, P = 0.04) and not different between lean and Obsen (P = 0.9). Overfeeding was characterized by an increase in dietary acid load scores PRAL (P = 0.003) and NEAP (P = 0.05), a reduction in GIR necessary to maintain euglycemia (P = 0.03) and an increase in fasting plasma lactate (P = 0.02). The change in lactate was inversely associated with the change in GIR (r = -0.36, P = 0.03). Mild metabolic acidosis, measured by plasma lactate, aligns with insulin resistance independent of obesity and is induced by short-term increases in energy and dietary acid load in healthy humans. Further studies are required to determine whether buffering mild metabolic acidosis improves insulin resistance and reduces diabetes risk.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.CMET.2015.05.018
Abstract: FGF21 mimetics are a promising therapeutic tool, believed to exert their anti-obesity effect partly through browning of white fat. Véniant et al. (2015) and Samms et al. (2015) present evidence arguing against fat browning as the primary mechanism causal to weight loss following FGF21-based treatment in mice.
Publisher: Wiley
Date: 09-11-2017
DOI: 10.1111/DOM.12806
Publisher: Springer Science and Business Media LLC
Date: 13-04-2023
DOI: 10.1038/S41598-023-33317-6
Abstract: To examine an impact of three types of bariatric surgery compared with dietary intervention (DIET), on concurrent changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and appetite hormones over 3 years. Fifty-five adults were studied during phase of weight loss (0–12 months) and during weight stability (12–36 months) post intervention. Measurements of HOMA-IR, fasting and postprandial PYY and GLP1, adiponectin, CRP, RBP4, FGF21 hormones and dual-Xray absorptiometry were performed throughout the study. All surgical groups achieved significant reductions in HOMA-IR with greatest difference between Roux-en-Y gastric bypass and DIET (− 3.7 95% CI − 5.4, − 2.1 p = 0.001) at 12–36 months. Initial (0–12 months) HOMA-IR values were no different to DIET after adjustment for the lost weight. During 12–36 months, after controlling for treatment procedure and weight, for every twofold increase in postprandial PYY and adiponectin, HOMA-IR decreased by 0.91 (95% CI − 1.71, − 0.11 p = 0.030) and by 0.59 (95% CI − 1.10, − 0.10 p = 0.023) respectively. Initial, non-sustained changes in RBP4 and FGF21 were not associated with HOMA-IR values. While initial rapid weight loss reduces insulin resistance, the enhanced secretions of PYY and adiponectin may contribute to weight-independent improvements in HOMA-IR during weight stability. Clinical trial registration : Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000188730.
Publisher: Wiley
Date: 27-05-2022
DOI: 10.1111/IMJ.15727
Abstract: The global burden of chronic kidney disease (CKD) has increased significantly over the past few decades. This reflects the rising prevalence of type 2 diabetes mellitus (T2DM) and hypertension, two leading causes of CKD. Hypertension, which can also be a complication of CKD, accelerates renal disease progression and augments cardiovascular risk, especially in in iduals with diabetic kidney disease. Hence, blood pressure (BP) reduction is a vital component of CKD management. Sodium‐glucose co‐transporter 2 (SGLT2) inhibitors are a relatively novel class of medications developed to treat T2DM by inducing glycosuria and hence, lowering glycaemia. Additionally, SGLT2 inhibitors are antihypertensive, renoprotective and cardioprotective, even in in iduals without T2DM, making them effective therapeutic agents for CKD. Another therapy that has proven to be antihypertensive, renoprotective and cardioprotective is dietary sodium restriction. This review evaluates the potential combined benefits of SGLT2 inhibition and dietary sodium restriction on the BP and renal parameters of in iduals with CKD.
Publisher: MDPI AG
Date: 24-03-2015
DOI: 10.3390/NU7042101
Publisher: Wiley
Date: 05-2020
DOI: 10.1111/IMJ.14819
Publisher: Wiley
Date: 12-2018
DOI: 10.1111/IMJ.14124
Abstract: We conducted three single-day point type 2 diabetes prevalence surveys of all inpatient clinical records in November 2013, 2014 and 2016. The prevalence of diabetes was 19.7-25.3%. The majority (63.4-76%) had type 2 diabetes. Twenty-one percent (n = 21) in 2013, 12% (n = 9) in 2014 and 22.6% (n = 21) in 2016 were diagnosed with diabetes during hospital admission 41.8% (n = 41) in 2013, 46.7% (n = 35) in 2014 and 51.6% (n = 48) in 2016 required insulin. The high prevalence of diabetes among inpatients mandates active detection and specialist management of diabetes during the admission.
Publisher: Springer Science and Business Media LLC
Date: 23-10-2020
Publisher: Wiley
Date: 07-08-2023
DOI: 10.1111/IMJ.16203
Abstract: Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) are now indicated for heart failure and chronic kidney disease (CKD), irrespective of the presence of diabetes. Hence, cardiologists and nephrologists have an important role in initiating these drugs. To explore cardiologists' and nephrologists' perspectives regarding initiating SGLT2i and their safety monitoring practices when initiating SGLT2i. Purposive and snowball approaches were used to recruit participants working in erse areas in New South Wales, Australia. Semi‐structured interviews were conducted with 12 cardiologists and 12 nephrologists. Interviews were conducted until thematic saturation was reached. Emergent themes were identified from transcripts. An iterative general inductive approach was used for data analysis. There was a reluctance amongst most non‐heart‐failure subspecialist cardiologists to initiate SGLT2i. Reasons included the perception of SGLT2i as diabetes drugs, concern about side effects, lack of experience and issues with follow‐up. In contrast, nephrologists reported feeling confident to initiate SGLT2i. Nephrologists varied in their opinions about the severity of CKD at which SGLT2i initiation was reasonable and monitoring of renal function following initiation. Government subsidisation was an important factor in the decision to prescribe SGLT2i to people without diabetes. Our findings highlight the complex transition from the perception of SGLT2i as diabetes drugs to cardiometabolic and reno‐protective agents. Interdisciplinary collaboration may enable greater confidence amongst specialists to initiate SGLT2i, including in patients with CKD. Additionally, there is a need for clear and detailed guidance about SGLT2i prescription in patients with renal dysfunction and renal function monitoring following SGLT2i initiation.
Publisher: The Endocrine Society
Date: 23-01-2017
DOI: 10.1210/JC.2016-3282
Abstract: The contribution of insulin resistance vs adiposity to bone mineral density (BMD), bone turnover, and fractures in humans remains unclear. To evaluate BMD and bone turnover markers (BTMs) in lean (n = 18) and overweight/obese in iduals with (n = 17) and without (n = 34, insulin-sensitive [Obsensitive, n=15] or insulin-resistant [Obresistant, n=19] by homeostasis model assessment insulin resistance) diabetes mellitus. Observational study. Insulin sensitivity was assessed using the hyperinsulinemic-euglycemic cl whole body BMD and fat mass (FM) using dual energy X-ray absorptiometry and by measurement of BTMs [osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), and collagen type 1 cross-linked C-terminal telopeptide (CTx)], with the patient fasting and during cl hyperinsulinemia. Fasting BTMs correlated with glucose infusion rate/fat-free mass (GIR/FFM) and adiponectin and, inversely, with fasting insulin and visceral fat (P ≤ 0.04 for all). Obsensitive, Obresistant, and diabetic in iduals were matched by their FM percentage. Cl GIR/FFM was similar in the lean and Obsensitive subjects (P = 1) and approximately twofold greater (P < 0.001) than in the Obresistant and diabetic subjects. BMD was greater in Obresistant than in Obsensitive (P = 0.04) and lean (P = 0.001) subjects. At baseline, compared with Obsensitive and lean subjects, Obresistant and diabetic in iduals had lower OC, P1NP, and CTx levels. This reached statistical significance for Obresistant vs lean and Obresistant vs Obsensitive for both OC and CTx and for diabetic vs lean for CTx (P ≤ 0.04 for all). During hyperinsulinemia, lean in iduals suppressed CTx more than did diabetic in iduals (P = 0.03). On multiple regression analysis, visceral adiposity explained 16.7% and 19.3% of the baseline OC and CTx variability, respectively. Increased visceral adiposity and higher fasting insulin in insulin-resistant states are associated with lower fasting OC and CTx and failure to further suppress with more insulin.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.MCE.2015.05.025
Abstract: Humans maintain core temperature through a complex neuroendocrine circuitry, coupling environmental thermal and nutritional cues to heat-producing and dissipating mechanisms. Up to 40% of resting energy expenditure contributes to thermal homeostasis maintenance. Recent re-discovery of thermogenic brown adipose tissue (BAT) has brought the relation between ambient temperature, thermogenesis and systemic energy and substrate metabolism to the forefront. In addition to well-known pituitary-thyroid-adrenal axis, new endocrine signals, such as FGF21 and irisin, orchestrate crosstalk between white adipose tissue (WAT), BAT and muscle, tuning non-shivering and shivering thermogenesis responses. Cold exposure modulates the endocrine milieu, and cold-induced hormones cause bioenergetics transformation sufficient to impact whole body metabolism. This review will appraise the nature of human BAT and the basis of BAT-centred therapeutics, highlighting how the interaction between hormones and adipose tissue impacts metabolic responses. Non-pharmacological and pharmacological strategies of BAT recruitment and/or fat browning for metabolic benefits will be discussed.
Publisher: Springer Science and Business Media LLC
Date: 20-12-2022
Publisher: The Endocrine Society
Date: 21-12-2021
Abstract: The etiological mechanism of bile acid (BA) effects on insulin resistance and obesity is unknown. This work aimed to determine whether plasma BAs are elevated in human obesity and/or insulin resistance. This observational study was conducted at an academic research center. Seventy-one adult volunteers formed 4 groups: lean insulin-sensitive (body mass index [BMI] ≤ 25 kg/m2, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] & 2.0, n = 19), overweight/obese nondiabetic who were either insulin sensitive (Obsensitive, BMI & 25 kg/m2, HOMA-IR & 1.5, n = 11) or insulin resistant (Obresistant, BMI & 25 kg/m2, HOMA-IR & 3.0, n = 20), and type 2 diabetes (T2D, n = 21). Main outcome measures included insulin sensitivity by hyperinsulinemic-euglycemic cl , body composition by dual energy x-ray absorptiometry, abdominal fat distribution, and liver density by computed tomography and plasma BA. In the Obresistant group, glucose infusion rate/fat-free mass (GIR/FFM, an inverse measure of insulin resistance) was significantly lower, and visceral and liver fat higher, compared to lean and Obsensitive in iduals, despite similar total adiposity in Obresistant and Obsensitive. Total BA concentrations were higher in Obresistant (2.62 ± 0.333 mmol/L, P = .03) and T2D (3.36 ± 0.582 mmol/L, P & .001) vs Obsensitive (1.16 ± 0.143 mmol/L), but were similar between Obsensitive and lean (2.31 ± 0.329 mmol/L) in iduals. Total BAs were positively associated with waist circumference (R = 0.245, P = .041), visceral fat (R = 0.360, P = .002), and fibroblast growth factor 21 (R = 0.341, P = .004) and negatively associated with insulin sensitivity (R = –0.395, P = .001), abdominal subcutaneous fat (R = –0.352, P = .003), adiponectin (R = –0.375, P = .001), and liver fat (Hounsfield units, an inverse marker of liver fat, R = –0.245, P = .04). Conjugated BAs were additionally elevated in T2D in iduals (P & .001). BA concentrations correlated with abdominal, visceral, and liver fat in humans, though an etiological role in insulin resistance remains to be verified.
Publisher: Wiley
Date: 16-04-2021
DOI: 10.1111/DME.14564
Abstract: Insulin resistance is an under-recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes. We will study 40 adults aged 20-55 years with Type 1 diabetes (HbA1c The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an in idual's response to metformin in Type 1 diabetes. ACTRN12619001440112.
Publisher: BMJ
Date: 10-2020
DOI: 10.1136/BMJOPEN-2020-037859
Abstract: Metformin and diets aimed at promoting healthy body weight are the first line in treating type 2 diabetes mellitus (T2DM). Clinical practice, backed by clinical trials, suggests that many in iduals do not reach glycaemic targets using this approach alone. The primary aim of the Personalised Medicine in Pre-diabetes—Towards Preventing Diabetes in In iduals at Risk (PREDICT) Study is to test the efficacy of personalised diet as adjuvant to metformin in improving glycaemic control in in iduals with dysglycaemia. PREDICT is a two-arm, parallel group, single-masked randomised controlled trial in adults with pre-diabetes or early-stage T2DM (with glycated haemoglobin (HbA1c) up to 8.0% (64 mmol/mol)), not treated with glucose-lowering medication. PREDICT is conducted at the Clinical Research Facility at the Garvan Institute of Medical Research (Sydney). Enrolment of participants commenced in December 2018 and expected to complete in December 2021. Participants are commenced on metformin (Extended Release, titrated to a target dose of 1500 mg/day) and randomised with equal allocation to either (1) the Personalised Nutrition Project algorithm-based diet or (2) low-fat high-dietary fibre diet, designed to provide caloric restriction (75%) in in iduals with body mass index kg/m 2 . Treatment duration is 6 months and participants visit the Clinical Research Facility five times over approximately 7 months. The primary outcome measure is HbA1c. The secondary outcomes are (1) time of interstitial glucose .8 mmol/L and (2) glycaemic variability (continuous glucose monitoring), (3) body weight, (4) fat mass and (5) abdominal visceral fat volume (dual-energy X-ray absorptiometry), serum (6) low-density lipoprotein cholesterol (7) high-density lipoprotein cholesterol and (8) triglycerides concentrations, (9) blood pressure, and (10) liver fat (Fibroscan). The study has been approved by the St Vincent’s Hospital Human Research Ethics Committee (File 17/080, Sydney, Australia) and the Weizmann Institutional Review Board (File 528-3, Rehovot, Israel). The findings will be published in peer-reviewed open access medical journals. NCT03558867 .
Publisher: The Endocrine Society
Date: 17-06-2020
Publisher: The Endocrine Society
Date: 29-11-2022
Abstract: The efficacy of glucagon-like peptide-1 receptor agonists in type 2 diabetes is well established, but their role in type 1 diabetes (T1DM) is less clear. A 36-year-old woman with a 27-year history of T1DM and undetectable c-peptide presented for review of weight management, with body mass index 29.3 kg/m2. A previous trial of dapagliflozin led to no improvement in weight or glycemic control. Semaglutide was introduced (0.25 mg weekly increased to 0.5 mg weekly) and was well tolerated. After 6 months, weight had decreased by 16 kg and insulin dose by 36%. Despite less insulin, hemoglobin A1c improved, with reduced glycemic variability and no increase in hypoglycemia. Semaglutide may exert significant metabolic benefits in patients with established T1DM, even where c-peptide is no longer detectable. This case supports the need for a dedicated trial examining potential benefits of semaglutide in T1DM.
Publisher: Wiley
Date: 12-2019
DOI: 10.1111/BCP.14107
Publisher: AMPCo
Date: 11-2016
DOI: 10.5694/MJA16.00458
Abstract: Maturity onset diabetes of the young (MODY), the most common monogenic form of diabetes, accounts for 1-2% of all diabetes diagnoses. Glucokinase (GCK)-MODY (also referred to as MODY2) constitutes 10-60% of all MODY cases and is inherited as an autosomal dominant heterozygous mutation, resulting in loss of function of the GCK gene. Patients with GCK-MODY generally have mild, fasting hyperglycaemia that is present from birth, are commonly leaner and diagnosed at a younger age than patients with type 2 diabetes, and rarely develop complications from diabetes. Hence, treatment is usually unnecessary and may be ceased. Therefore, genetic screening is recommended in all young patients (< 40 years) with an autosomal dominant family history of diabetes and who lack features of the metabolic syndrome and type 1 diabetes. Further, treatment discontinuation should be discussed with the patient as part of the informed consent process, as the realisation that prior treatment may have not been necessary - or that it could have been less burdensome - may have psychological implications for the patient. This is true for other forms of MODY, such as hepatocyte nuclear factor 1A mutations (MODY3) where hyperglycaemia is managed with low dose sulfonylurea rather than insulin. Patients with GCK-MODY, in line with trends in the general population, are becoming older and more overweight and obese, and are concomitantly developing features of insulin resistance and glucose intolerance. Therefore, controversy exists as to whether such "treatment-exempt" patients should be reassessed for treatment later in life. As testing becomes more accessible, clinicians and patients are likely to embrace genetic screening earlier in the course of diabetes, which may avert the consequences of delayed testing years after diagnosis and treatment initiation.
Publisher: Springer Science and Business Media LLC
Date: 12-11-2015
Publisher: Wiley
Date: 16-06-2023
DOI: 10.1111/ANAE.16068
Publisher: Wiley
Date: 27-01-2021
DOI: 10.1111/DME.14513
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.TEM.2019.11.007
Abstract: In iduals with type 1 diabetes (T1D) frequently fail to achieve glycemic goals and have excess cardiovascular risk and premature death. Adjunctive agents may play a role in reducing morbidity, mortality, and the adverse sequelae of insulin treatment. A surge in type 2 diabetes drug development has revealed agents with benefits beyond glucose lowering, including cardiovascular risk reduction. Could these benefits translate to T1D? Specific trials for T1D demonstrate substantial hemoglobin (Hb)A1c reductions with sodium glucose cotransporter inhibitors (SGLTis) and glucagon-like peptide (GLP)1 agonists, and modest improvements with metformin, dipeptidyl peptidase-4 inhibitor (DPP4i), and pramlintide. Studies exploring cardiovascular risk reduction are warranted. This review synthesizes the emerging literature for researchers and clinicians treating people with T1D. Challenges in T1D research are discussed.
Publisher: Wiley
Date: 23-03-2015
DOI: 10.1111/BCP.12525
Publisher: Wiley
Date: 25-04-2023
DOI: 10.1111/BCP.15737
Abstract: This study investigated the safe use of metformin in patients with (1) type 2 diabetes mellitus (T2DM) and heart failure on metformin, and (2) heart failure without T2DM and metformin naïve. Two prospective studies on heart failure patients were undertaken. The first was a cross‐sectional study with two patient cohorts, one with T2DM on metformin (n = 44) and one without T2DM metformin naive (n = 47). The second was a 12‐week interventional study of patients without T2DM (n = 27) where metformin (500 mg immediate release, twice daily) was prescribed. Plasma metformin and lactate concentrations were monitored. In idual pharmacokinetics were compared between cohorts. Univariable and multivariable analysis analysed the effects of variables on plasma lactate concentrations. Plasma metformin and lactate concentrations mostly (99.9%) remained below safety thresholds (5 mg/L and 5 mmol/L, respectively). Metformin concentration had no significant relationship with lactic acidosis safety markers. In the interventional study, New York Heart Association (NYHA) II ( P .03) and III ( P .001) grading was associated with higher plasma lactate concentrations, whereas male sex was associated with 47% higher plasma lactate concentrations ( P .05). The pharmacokinetics of heart failure patients with and without T2DM were similar. We observed no unsafe plasma lactate concentrations in patients with heart failure treated with metformin. Metformin exposure did not influence plasma lactate concentrations, but NYHA class and sex did. The pharmacokinetics of metformin in heart failure patients are similar irrespective of T2DM. These findings may support the safe use of metformin in heart failure patients with and without T2DM.
No related grants have been discovered for Jerry Greenfield.