Publications by authors named "Neale Cohen"

41 Publications

Role of the sympathetic nervous system in cardiometabolic control: implications for targeted multiorgan neuromodulation approaches.

J Hypertens 2021 Mar 3. Epub 2021 Mar 3.

Dobney Hypertension Centre, School of Medicine - Royal Perth Hospital Unit, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia, Perth, Western Australia Department of Radiology, Alfred Hospital Department of Surgery, Central Clinical School, Monash University, Melbourne, Victoria Medical School, The University of Western Australia, Perth, Western Australia Baker Heart and Diabetes Institute, Melbourne, Victoria Department of Endocrinology, Medical School, The University of Western Australia Department of Radiology, Royal Perth Hospital, Perth, Western Australia Human Neurotransmitter Lab Neurovascular Hypertension & Kidney Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria Departments of Cardiology and Nephrology, Royal Perth Hospital, Perth, Western Australia, Australia.

Sympathetic overdrive plays a key role in the perturbation of cardiometabolic homeostasis. Diet-induced and exercise-induced weight loss remains a key strategy to combat metabolic disorders, but is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication intolerance and nonadherence. A clinical need exists for complementary therapies to curb the burden of cardiometabolic diseases. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. The experience from catheter-based renal denervation studies clearly demonstrates the feasibility, safety and efficacy of such an approach. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multiorgan neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum offering a holistic approach.
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http://dx.doi.org/10.1097/HJH.0000000000002839DOI Listing
March 2021

An Interactive Web Application for the Statistical Analysis of Continuous Glucose Monitoring Data in Epidemiological Studies.

J Diabetes Sci Technol 2021 Jan 12:1932296820985570. Epub 2021 Jan 12.

Melbourne School of Population and Gllobal Health, and School of Mathematics and Statistics,The University of Melbourne, Parkville, VIC, Australia.

Motivation: Continuous glucose monitoring (CGM) systems are an essential part of novel technology in diabetes management and care. CGM studies have become increasingly popular among researchers, healthcare professionals, and people with diabetes due to the large amount of useful information that can be collected using CGM systems. The analysis of the data from these studies for research purposes, however, remains a challenge due to the characteristics and large volume of the data.

Results: Currently, there are no publicly available interactive software applications that can perform statistical analyses and visualization of data from CGM studies. With the rapidly increasing popularity of CGM studies, such an application is becoming necessary for anyone who works with these large CGM datasets, in particular for those with little background in programming or statistics. CGMStatsAnalyser is a publicly available, user-friendly, web-based application, which can be used to interactively visualize, summarize, and statistically analyze voluminous and complex CGM datasets together with the subject characteristics with ease.
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http://dx.doi.org/10.1177/1932296820985570DOI Listing
January 2021

Less Nocturnal Hypoglycemia but Equivalent Time in Range Among Adults with Type 1 Diabetes Using Insulin Pumps Versus Multiple Daily Injections.

Diabetes Technol Ther 2021 Jan 27. Epub 2021 Jan 27.

Department of Medicine, University of Melbourne, Melbourne, Australia.

This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Adults using MDIs ( = 61) versus pump ( = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump ( = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively ( = 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio [95% confidence interval] 2.48 [1.51, 4.06];  < 0.001). Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps.
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http://dx.doi.org/10.1089/dia.2020.0589DOI Listing
January 2021

Combined effects of continuous exercise and intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides in adults with obesity: a randomized crossover trial.

Int J Behav Nutr Phys Act 2020 12 14;17(1):152. Epub 2020 Dec 14.

Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia.

Background: Postprandial glucose, insulin, and triglyceride metabolism is impaired by prolonged sitting, but enhanced by exercise. The aim of this study was to assess the effects of a continuous exercise bout with and without intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides.

Methods: Sedentary adults who were overweight to obese (n = 67; mean age 67 yr SD ± 7; BMI 31.2 kg∙m SD ± 4.1), completed three conditions: SIT: uninterrupted sitting (8-h, control); EX+SIT: sitting (1-h), moderate-intensity walking (30-min), uninterrupted sitting (6.5-h); EX+BR: sitting (1-h), moderate-intensity walking (30- min), sitting interrupted every 30-min with 3-min of light-intensity walking (6.5 h). Participants consumed standardized breakfast and lunch meals and blood was sampled at 13 time-points.

Results: When compared to SIT, EX+SIT increased total area under the curve (tAUC) for glucose by 2% [0.1-4.1%] and EX+BR by 3% [0.6-4.7%] (all p < 0.05). Compared to SIT, EX+SIT reduced insulin and insulin:glucose ratio tAUC by 18% [11-22%] and 21% [8-33%], respectively; and EX+BR reduced values by 25% [19-31%] and 28% [15-38%], respectively (all p < 0.001 vs SIT, all p < 0.05 EX+SIT-vs-EX+BR). Compared to SIT, EX+BR reduced triglyceride tAUC by 6% [1-10%] (p = 0.01 vs SIT), and compared to EX+SIT, EX+BR reduced this value by 5% [0.1-8.8%] (p = 0.047 vs EX+SIT). The magnitude of reduction in insulin tAUC from SIT-to-EX+BR was greater in those with increased basal insulin resistance. No reduction in triglyceride tAUC from SIT-to-EX+BR was apparent in those with high fasting triglycerides.

Conclusions: Additional reductions in postprandial insulin-glucose dynamics and triglycerides may be achieved by combining exercise with breaks in sitting. Relative to uninterrupted sitting, this strategy may reduce postprandial insulin more in those with high basal insulin resistance, but those with high fasting triglycerides may be resistant to such intervention-induced reductions in triglycerides.

Trial Registration: Australia New Zealand Clinical Trials Registry ( ACTRN12614000737639 ).
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http://dx.doi.org/10.1186/s12966-020-01057-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734727PMC
December 2020

Acute effects of interrupting prolonged sitting on vascular function in type 2 diabetes.

Am J Physiol Heart Circ Physiol 2021 01 8;320(1):H393-H403. Epub 2020 Nov 8.

School of Sport Science, Exercise and Health, University of Western Australia, Perth, Australia.

In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D), nor whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 yr) completed three 7-h conditions: ) uninterrupted sitting (SIT), ) sitting with 3-min bouts of SRA every 30 min (SRA3), and ) sitting with 6 min bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow, and endothelin-1 were measured at 0, 1, 3.5, 4.5, and 6.5-7 h. Mean femoral artery FMD over 7 h was significantly higher in SRA3 (4.1 ± 0.3%) compared with SIT (3.7 ± 0.3%, = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased significantly for SRA3 (45.3 ± 4.1/s, < 0.001) and SRA6 (46.2 ± 4.1/s, < 0.001) relative to SIT (33.1 ± 4.1/s). Endothelin-1 concentrations were not statistically different between conditions. Interrupting sitting with activity breaks every 30 min, but not 60 min, significantly increased mean femoral artery FMD over 7 h, relative to SIT. Our findings suggest that more frequent and shorter breaks may be more beneficial than longer, less frequent breaks for vascular health in those with T2D. This is the first trial to examine both the effects of interrupting prolonged sitting on vascular function in type 2 diabetes and the effects of the frequency and duration of interruptions. Brief, simple resistance activity bouts every 30 min, but not every 60 min, increased mean femoral artery flow-mediated dilation over 7 h, relative to uninterrupted sitting. With further supporting evidence, these initial findings can have important implications for cardiovascular health in type 2 diabetes.
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http://dx.doi.org/10.1152/ajpheart.00422.2020DOI Listing
January 2021

Six Months of Hybrid Closed-Loop Versus Manual Insulin Delivery With Fingerprick Blood Glucose Monitoring in Adults With Type 1 Diabetes: A Randomized, Controlled Trial.

Diabetes Care 2020 12 14;43(12):3024-3033. Epub 2020 Oct 14.

Department of Endocrinology and Diabetes, Perth Children's Hospital, Nedlands, Western Australia, Australia.

Objective: To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes).

Research Design And Methods: Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70-180 mg/dL) during the final 3 weeks.

Results: Participants were randomized to HCL ( = 61) or control ( = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19]; < 0.0001). For HCL, HbA was lower (median [95% CI] difference -0.4% [-0.6, -0.2]; -4 mmol/mol [-7, -2]; < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9]; < 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively.

Conclusions: In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.
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http://dx.doi.org/10.2337/dc20-1447DOI Listing
December 2020

Interrupting Prolonged Sitting and Endothelial Function in Polycystic Ovary Syndrome.

Med Sci Sports Exerc 2021 03;53(3):479-486

School of Human Sciences (Exercise and Sports Science), The University of Western Australia, Perth, Western Australia, AUSTRALIA.

Purpose: In healthy adults, the impairment of vascular function associated with prolonged sitting can be mitigated with intermittent brief bouts of activity. It is unknown whether these benefits extend to women with polycystic ovary syndrome (PCOS), in whom vascular function is typically impaired and sitting time is high. We examined the acute effect of regularly interrupting sitting time with brief simple resistance activities (SRA) on vascular function in PCOS.

Methods: In a randomized crossover trial, 13 physically inactive women with PCOS (18-45 yr) completed two 3.5-h conditions: 1) uninterrupted sitting (SIT) and 2) sitting interrupted by 3-min bouts of SRA every 30 min. Femoral artery flow-mediated dilation (FMD), resting shear rate, and resting blood flow were measured at 0, 1, and 3.5 h.

Results: Mean resting femoral shear rate, averaged across the 3.5 h, significantly increased in the SRA condition relative to the SIT condition (40.1 ± 6.1 vs 62.8 ± 6.1 s-1, P < 0.0001). In addition, mean resting blood flow also significantly increased across the 3.5 h for SRA relative to SIT (45.0 ± 9.8 vs 72.8 ± 9.9 mL·min-1, P < 0.0001). There were no differences between conditions in the temporal change in femoral artery FMD across 3.5 h (Ptime-condition > 0.05 for all).

Conclusion: Frequently interrupting sitting with SRA acutely increased resting shear rate and blood flow in women with PCOS but did not alter FMD. With sedentary behavior increasing in prevalence, longer-term studies of similar interventions to reduce and break up sitting time are warranted.
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http://dx.doi.org/10.1249/MSS.0000000000002513DOI Listing
March 2021

Adults With Diabetes Distress Often Want to Talk With Their Health Professionals About It: Findings From an Audit of 4 Australian Specialist Diabetes Clinics.

Can J Diabetes 2020 Aug 16;44(6):473-480. Epub 2020 Feb 16.

School of Psychology, Deakin University, Geelong, Victoria, Australia; The Australian Centre for Behavioural Research in Diabetes, Diabetes Victoria, Melbourne, Victoria, Australia.

Objectives: In an unselected clinical sample, we aimed to: 1) investigate the willingness of adults with diabetes to talk with their health professional(s) about their feelings and experiences living with diabetes, 2) assess the prevalence of impaired general emotional well-being and severe diabetes distress and 3) examine whether willingness to talk related to general and/or diabetes-specific emotional well-being.

Methods: Unselected adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) attending 4 Australian specialist diabetes clinics completed surveys about their experiences of, and preferences for, talking with their diabetes health professional(s) about their feelings and personal experiences of diabetes. They indicated preferred topics to discuss from a list and completed validated measures of emotional well-being (World Health Organisation-5 Well-being Index) and diabetes distress (Problem Areas In Diabetes scale).

Results: Among 682 participants (T1D, n=440; T2D, n=142), one-fourth of adults with T1D and nearly half with T2D wanted to talk with their health professional about their "feelings and personal experience of living with diabetes," with >50% reported having been asked. The most commonly selected topic was "How diabetes affects my mood" (T1D, 35%; T2D, 37%). Impaired emotional well-being (T1D, 33%; T2D, 39%) and severe diabetes distress (T1D, 17%; T2D, 25%) were prevalent. Those willing to talk had greater diabetes distress.

Conclusions: In this study we show that many adults with T1D and T2D both need and want to talk to their diabetes health professionals about the emotional impact of diabetes. Those who were most willing to have this conversation were most in need of emotional support.
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http://dx.doi.org/10.1016/j.jcjd.2020.02.004DOI Listing
August 2020

The Clinical Role of Insulin Degludec/Insulin Aspart in Type 2 Diabetes: An Empirical Perspective from Experience in Australia.

J Clin Med 2020 Apr 11;9(4). Epub 2020 Apr 11.

Department of Diabetes, Endocrinology and Metabolism, The Royal North Shore Hospital, The University of Sydney, Reserve Road, St Leonards, NSW 2065, Australia.

Treatment intensification in people with type 2 diabetes following failure of basal insulin commonly involves the addition of a rapid-acting insulin analogue (basal plus one or more prandial doses; multiple daily injections) or by a switch to premixed insulin. Insulin degludec/insulin aspart (IDegAsp), comprising rapid-acting insulin aspart and ultra-long-acting insulin degludec in solution, enables both fasting and post-prandial glucose control, with some advantages over other treatment intensification options. These include straightforward dose titration, flexibility in dose timing, low injection burden, simplicity of switching and a lower risk of hypoglycaemia. In Australia, where insulin degludec on its own is not available, IDegAsp enables patients to still benefit from its ultra-long-acting properties. This review aims to provide guidance on where and how to use IDegAsp. Specifically, guidance is included on the initiation of IDegAsp in insulin-naïve patients, treatment intensification from basal insulin, switching from premixed or basal-bolus insulin to IDegAsp, up-titration from once- to twice-daily IDegAsp and the use of IDegAsp in special populations or situations.
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http://dx.doi.org/10.3390/jcm9041091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230791PMC
April 2020

Interrupting Sitting Time with Simple Resistance Activities Lowers Postprandial Insulinemia in Adults with Overweight or Obesity.

Obesity (Silver Spring) 2019 09;27(9):1428-1433

Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Objective: This study aimed to examine the effects on postprandial glucose and insulin responses of interrupting sitting time with brief bouts of simple resistance activities (SRAs) in adults with overweight or obesity.

Methods: Participants (n = 19) were recruited for a randomized crossover trial involving the following two 6-hour conditions: (1) uninterrupted sitting or (2) sitting with 3-minute bouts of SRAs (half-squats, calf raises, gluteal contractions, and knee raises) every 30 minutes (total duration = 27 minutes). Incremental areas under the curve (iAUC) for glucose, insulin, and insulin:glucose ratio were analyzed as prespecified secondary outcomes using mixed-effects log-linear regression adjusted for sex, BMI, treatment order, and preprandial values. Results are reported as multiplicative change (exponentiated coefficient [EC] with 95% CI) relative to the control condition.

Results: Glucose iAUC during the SRA condition was not significantly different from the prolonged sitting condition (EC = 0.92; 95% CI: 0.73-1.16; P = 0.43). However, SRAs lowered the postprandial insulin response by 26% (EC = 0.74; 95% CI: 0.64-0.85; P < 0.001), and there was a 23% lowering of the iAUC for insulin:glucose (EC = 0.77; 95% CI: 0.67-0.89; P < 0.001).

Conclusions: In adults with overweight or obesity, frequent interruptions to sitting time with SRAs lowered postprandial insulin responses and insulin:glucose. These findings may have implications for mitigating cardiometabolic risk in adults with overweight or obesity who engage in prolonged periods of sitting.
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http://dx.doi.org/10.1002/oby.22554DOI Listing
September 2019

Long-Term Effectiveness of Continuous Subcutaneous Insulin Infusion in the Prevention of Hypoglycemia in Adults with Type 1 Diabetes.

Diabetes Technol Ther 2019 08 10;21(8):423-429. Epub 2019 Jun 10.

2Clinical Diabetes, Baker Heart and Diabetes Institute, Melbourne, Australia.

Reducing hyperglycemia while avoiding hypoglycemia is the key clinical goal in managing people with type 1 diabetes. Insulin delivery techniques and regimens are constantly evolving to achieve these goals. At present, use of multiple daily injections (MDI) is the standard of care, but there is increasing interest in continuous subcutaneous insulin infusion (CSII). There is a deficit of studies comparing long-term glycemic control and hypoglycemia outcomes between these therapeutic options. This was a single-center, retrospective cohort study of adults with type 1 diabetes. Data were derived from electronic medical records and included demographic and clinical factors. Participants had all undergone intensive diabetes education, followed by CSII or continued MDI. The primary outcome was difference in hypoglycemia, defined as the percentage of self-monitoring blood glucose levels less than 3.9 mmol/L. Up to 10 years of follow-up data were available, between 2000 and 2016. There were 69 participants using CSII and 78 using MDI. Self-monitoring blood glucose data showed significantly less hypoglycemia with CSII by over 30%, occurring as early as the first year and sustained throughout the follow-up period ( < 0.001). This benefit of CSII on reducing hypoglycemia was independent of more frequent hypoglycemia and higher body weight at baseline, factors that were also independently associated with reduced hypoglycemia. In selected adults with type 1 diabetes, long-term CSII can provide long-term clinically relevant and sustained reductions in hypoglycemia, particularly in those with greater initial risk of hypoglycemia and higher body weight, and improved glycemic control compared with MDI.
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http://dx.doi.org/10.1089/dia.2019.0108DOI Listing
August 2019

Effects of empagliflozin treatment on cardiac function and structure in patients with type 2 diabetes: a cardiac magnetic resonance study.

Intern Med J 2019 08;49(8):1006-1010

Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Background: The effects of empagliflozin on cardiac structure and function are not known.

Aims: To examine the changes in cardiac structure and function following the addition of empagliflozin in patients with type 2 (T2D) diabetes using cardiac magnetic resonance (CMR) imaging.

Methods: Twenty patients attending a specialist diabetes service recommended for treatment with empagliflozin, and 8 control patients with T2D on stable glucose lowering therapy were recruited for cardiac imaging. Participants underwent CMR scans at baseline and 6 months. Inclusion criteria were established T2D, age < 75 years, estimated glomerular filtration rate ≥45 mL/min/1.73 m .

Results: 17 of 20 in the empagliflozin group, and all of 8 in the control group completed the study. Empagliflozin therapy was associated with reduction in left ventricular end diastolic volume 155 mL (137 mL, 174 mL) at baseline to 145 mL (125 mL, 165 mL) at 6 months, P < 0.01, compared with the control group 153 mL (128 mL, 179 mL) at baseline and 158 mL (128 mL, 190 mL), not significant. There were no differences in measures of left ventricular mass, ejection fraction, heart rate or markers of cardiac fibrosis at baseline and 6 months in either group.

Conclusions: This is the first CMR study to examine the effects of empagliflozin on cardiac function and structure, showing evidence of reduced end diastolic volume. This is likely to reflect change in plasma volume, and may explain the reduced cardiovascular death and heart failure seen in the EMPA-REG OUTCOME trial.
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http://dx.doi.org/10.1111/imj.14260DOI Listing
August 2019

Glucose Control Using a Standard Versus an Enhanced Hybrid Closed Loop System: A Randomized Crossover Study.

Diabetes Technol Ther 2019 01;21(1):56-58

1 Department of Medicine, St. Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Australia.

Hybrid closed loop (HCL) insulin delivery with the Medtronic Minimed 670G system is effective and safe in people with type 1 diabetes (T1D). This study compared glucose control, closed loop (CL) exits, and alarm frequency with the standard HCL (s-HCL) versus enhanced HCL (e-HCL) Medtronic system. Pump-experienced T1D adults (n = 11; 9 female; mean [SD] age: 51 years [15 years]; HbA1c 7.5% [1.0%] or 58 mmol/mol [7.7 mmol/mol]) were assigned, in random order, s-HCL or e-HCL for 1 week each in a supervised live-in setting. e-HCL incorporated enhanced bolus reminders and iterative changes, broadening glucose and insulin delivery parameters permitting persistence in CL. For both s-HCL and e-HCL, insulin delivery was by a Medtronic pump with identical interventions (missed bolus, exercise, high-glycemic index, and high-fat meals), insulin action times, and insulin-carbohydrate ratios implemented. The primary outcome was continuous glucose monitoring time in target range. Analysis was by paired t-test for normally distributed data and Wilcoxon-signed rank test otherwise. e-HCL resulted in significantly fewer CL alerts and exits. Time in target and mean glucose favored e-HCL but did not reach statistical significance. No episodes of severe hypoglycemia or ketoacidosis occurred. Relative to s-HCL, e-HCL use significantly decreases CL exits and alerts, and tended to improve glycemia without compromising safety, despite multiple food and exercise challenges during the study. Longer term studies at home are merited.
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http://dx.doi.org/10.1089/dia.2018.0279DOI Listing
January 2019

Flash glucose monitoring-using technology to improve outcomes for patients with diabetes.

Aust J Rural Health 2018 Dec 19;26(6):453-454. Epub 2018 Nov 19.

Austin Health, Heidelberg, Victoria, Australia.

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http://dx.doi.org/10.1111/ajr.12440DOI Listing
December 2018

Continuous Subcutaneous Insulin Infusion Can Be Used Effectively and Safely in Older Patients with Type 1 Diabetes: Long-Term Follow-up.

Diabetes Technol Ther 2018 11 29;20(11):783-786. Epub 2018 Sep 29.

1 Clinical Services, Baker Heart and Diabetes Institute , Melbourne, Australia .

Use of continuous subcutaneous insulin infusion (CSII) in adults with type 1 diabetes has become increasingly popular in recent years, with recent studies examining the efficacy of CSII use in pregnancy and in type 2 diabetes. However, there is very limited information on the benefit of CSII in older patients with type 1 diabetes. Electronic medical records were retrospectively analyzed for patients with type 1 diabetes undertaking structured patient education and initiated on CSII or multiple daily injections (MDI) between 2000 and 2016. Outcomes examined related to changes in glycemic parameters and weight and utilization of healthcare resources. Data relating to 293 patients fulfilled the inclusion criteria, with up to 10 years of follow-up data available. For patients commencing CSII, glycemic and weight outcomes and utilization of healthcare resources were similar in older compared with younger patients. For older patients, use of CSII was associated with better glycemic outcomes at the cost of a small increase in healthcare resources compared with MDI. CSII can be used effectively and safely in the longer term in carefully selected older patients with type 1 diabetes, with similar outcomes as observed in younger patients using CSII, and potentially better glycemic outcomes than MDI in older patients.
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http://dx.doi.org/10.1089/dia.2018.0215DOI Listing
November 2018

Between-meal sucrose-sweetened beverage consumption impairs glycaemia and lipid metabolism during prolonged sitting: A randomized controlled trial.

Clin Nutr 2019 08 1;38(4):1536-1543. Epub 2018 Sep 1.

Baker Heart & Diabetes Institute, Melbourne, Australia; Department of Physiology, Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Australia; Central Clinical School, Faculty of Medicine, Nursing & Health Sciences, Monash University, Melbourne, Australia.

Background & Aims: Chronic overconsumption of sugar-sweetened beverages (SSBs) is associated with unfavourable health effects, including promotion of obesity. However, the acute effects of consuming SSBs on glucose and lipid metabolism remain to be characterized in a real-world, post-prandial context of prolonged sitting. We quantified the acute effects of between-meal SSB consumption compared with water, on glucose and lipid metabolism in habitual soft drink consumers during prolonged sitting.

Methods: Twenty-eight overweight or obese young adults [15 males; 23 ± 3 (mean ± SD) years, body mass index (BMI) 31.0 ± 3.6 kg/m) participated. During uninterrupted sitting and following standardized breakfast and lunch meals, each participant completed two 7-h conditions on separate days in a randomized, crossover design study. For each condition, participants consumed either a sucrose SSB or water mid-morning and mid-afternoon. Peak responses and total area under the curve (tAUC) over 7 h for blood glucose, insulin, C-peptide, triglyceride and non-esterified fatty acid (NEFA) concentrations were quantified and compared.

Results: Compared to water, SSB consumption significantly increased the peak responses for blood glucose (20 ± 4% (mean ± SEM)), insulin (43 ± 15%) and C-peptide (21 ± 6%) concentrations. The tAUC for all these parameters was also increased by SSB consumption. The tAUC for triglycerides was 15 ± 5% lower after SSBs and this was driven by males (P < 0.05), as females showed no difference between conditions. The tAUC for NEFAs was 13 ± 5% lower after the SSB condition (P < 0.05).

Conclusions: Between-meal SSB consumption significantly elevated plasma glucose responses, associated with a sustained elevation in plasma insulin throughout a day of prolonged sitting. The SSB-induced reduction in circulating triglycerides and NEFAs indicates significant modulation of lipid metabolism, particularly in males. These metabolic effects may contribute to the development of metabolic disease when SSB consumption is habitual and co-occurring with prolonged sitting. Clinical Trial Registry number: ACTRN12616000840482, https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12616000840482.
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http://dx.doi.org/10.1016/j.clnu.2018.08.021DOI Listing
August 2019

SIMPLE INTERMITTENT RESISTANCE ACTIVITY MITIGATES THE DETRIMENTAL EFFECT OF PROLONGED UNBROKEN SITTING ON ARTERIAL FUNCTION IN OVERWEIGHT AND OBESE ADULTS.

J Appl Physiol (1985) 2018 Sep 6. Epub 2018 Sep 6.

School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Australia.

Prolonged sitting contributes to cardiovascular disease (CVD) risk. The underlying mechanisms are unknown, but may include changes in arterial function and vasoactive mediators. We examined the effects of prolonged unbroken sitting, relative to regular active interruptions to sitting time, on arterial function in adults at increased CVD risk. In a randomized crossover trial, 19 sedentary overweight/obese adults (mean±SD 57±12 yrs), completed two laboratory-based conditions: five hours uninterrupted sitting (SIT) and; five hours sitting interrupted every 30 minutes by three minutes of simple resistance activities (SRA). Femoral artery function (flow mediated dilation; FMD), blood flow and shear rate were measured at zero hour, 30 minutes, one, two and five hours. Brachial FMD was assessed at zero and five hours. Plasma was collected hourly for measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). There was a significant decline in femoral artery FMD, averaged over five hours in the SIT condition, relative to SRA (p<0.001). Plasma ET-1 total AUC over five hours increased in the SIT condition compared to SRA (p=0.006). There was no significant difference between conditions in femoral or brachial shear rate, brachial FMD, nitrates/nitrites, VCAM-1 or ICAM-1 (p>0.05 for all). Five hours of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating ET-1 in overweight/obese adults. There is the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.
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http://dx.doi.org/10.1152/japplphysiol.00544.2018DOI Listing
September 2018

Endothelial function and dysfunction: Impact of metformin.

Pharmacol Ther 2018 12 27;192:150-162. Epub 2018 Jul 27.

School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, QLD, Australia; Xinhua College of Sun Yat-sen University, Tianhe District, Guangzhou, China. Electronic address:

Cardiovascular and metabolic diseases remain the leading cause of morbidity and mortality worldwide. Endothelial dysfunction is a key player in the initiation and progression of cardiovascular and metabolic diseases. Current evidence suggests that the anti-diabetic drug metformin improves insulin resistance and protects against endothelial dysfunction in the vasculature. Hereby, we provide a timely review on the protective effects and molecular mechanisms of metformin in preventing endothelial dysfunction and cardiovascular and metabolic diseases.
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http://dx.doi.org/10.1016/j.pharmthera.2018.07.007DOI Listing
December 2018

Efficacy and safety of methionine aminopeptidase 2 inhibition in type 2 diabetes: a randomised, placebo-controlled clinical trial.

Diabetologia 2018 09 11;61(9):1918-1922. Epub 2018 Jul 11.

Zafgen, Inc., 175 Portland St, 4th Floor, Boston, MA, 02114, USA.

Aims/hypothesis: This multicentre randomised double-blind placebo-controlled clinical trial assessed the efficacy and safety of a methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib, in individuals with obesity (BMI ≥30 kg/m) and type 2 diabetes (HbA 53-97 mmol/mol [7-11%] and fasting glucose <15.6 mmol/l).

Methods: Participants were randomised (via a centralised interactive web response system) to placebo, 1.2 or 1.8 mg beloranib s.c. twice weekly for 26 weeks. Participants, investigators and the sponsor were blinded to group assignment. The primary endpoint was the change in weight from baseline to week 26. The trial was terminated early when beloranib development was stopped because of an imbalance of venous thromboembolism events in beloranib-treated individuals vs placebo that became evident during late-stage development of the drug.

Results: In total, 153 participants were randomised, 51 to placebo, 52 to 1.2 mg beloranib and 50 to 1.8 mg beloranib. In participants who completed week 26, the least squares mean ± SE weight change (baseline 111 kg) was -3.1 ± 1.2% with placebo (n = 22) vs -13.5 ± 1.1% and -12.7 ± 1.3% with 1.2 and 1.8 mg beloranib, respectively (n = 25; n = 19; p < 0.0001). The change in HbA (baseline 67 mmol/mol [8.3%]) was -6.6 ± 2.2 mmol/mol (-0.6 ± 0.2%) with placebo vs -21.9 ± 2.2 mmol/mol (-2.0 ± 0.2%) or -21.9 ± 3.3 mmol/mol (-2.0 ± 0.3%) with 1.2 or 1.8 mg beloranib (p < 0.0001), respectively. The most common beloranib adverse events were sleep related. One beloranib-treated participant experienced a non-fatal pulmonary embolism.

Conclusions/interpretation: MetAP2 inhibitors represent a novel mechanism for producing meaningful weight loss and improvement in HbA.

Trial Registration: ClinicalTrials.gov NCT02324491 FUNDING: The study was funded by Zafgen, Inc.
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http://dx.doi.org/10.1007/s00125-018-4677-0DOI Listing
September 2018

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol.

BMJ Open 2018 06 9;8(6):e020274. Epub 2018 Jun 9.

Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.

Introduction: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes.

Methods And Analysis: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users.

Ethics And Dissemination: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications.

Trial Registration Number: ACTRN12617000520336; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2017-020274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6009467PMC
June 2018

Impact of an integrated diabetes service involving specialist outreach and primary health care on risk factors for micro- and macrovascular diabetes complications in remote Indigenous communities in Australia.

Aust J Rural Health 2018 Dec 4;26(6):394-399. Epub 2018 Jun 4.

Baker Heart & Diabetes Institute, Melbourne, Victoria, Australia.

Objective: To determine the impact of an integrated diabetes service involving specialist outreach and primary health care teams on risk factors for micro- and macrovascular diabetes complications in three remote Indigenous Australian communities over a 12-month period.

Design: Quantitative, retrospective evaluation.

Setting: Primary health care clinics in remote Indigenous communities in Australia.

Participants: One-hundred-and-twenty-four adults (including 123 Indigenous Australians; 76.6% female) with diabetes living in remote communities.

Main Outcome Measures: Glycosylated haemoglobin, lipid profile, estimated glomerular filtration rate, urinary albumin : creatinine ratio and blood pressure.

Results: Diabetes prevalence in the three communities was high, at 32.8%. A total of 124 patients reviewed by the outreach service had a median consultation rate of 1.0 by an endocrinologist and 0.9 by a diabetes nurse educator over the 12-month period. Diabetes care plans were made in collaboration with local primary health care services, which also provided patients with diabetes care between outreach team visits. A significant reduction was seen in median (interquartile range) glycosylated haemoglobin from baseline to 12 months. Median (interquartile range) total cholesterol was also reduced. The number of patients prescribed glucagon-like peptide-1 analogues and dipeptidyl peptidase-4 inhibitors increased over the 12 months and an increase in the number of patients prescribed insulin trended towards statistical significance.

Conclusion: A collaborative health care approach to deliver diabetes care to remote Indigenous Australian communities was associated with an improvement in glycosylated haemoglobin and total cholesterol, both important risk factors, respectively, for micro- and macrovascular diabetes complications.
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http://dx.doi.org/10.1111/ajr.12426DOI Listing
December 2018

Changing environment of hyperglycemia in pregnancy: Gestational diabetes and diabetes mellitus in pregnancy.

J Diabetes 2018 Aug 26;10(8):633-640. Epub 2018 Apr 26.

School of Pharmacy, The University of Queensland, Woolloongabba, Queensland, Australia.

The diagnosis and treatment of gestational diabetes mellitus (GDM) have been in a state of flux since the World Health Organization accepted and endorsed the International Diabetes and Pregnancy Study Group's diagnostic pathway and criteria in 2013. These new diagnostic criteria identify an increasing number of women at risk of hyperglycemia in pregnancy (HGiP). Maternal hyperglycemia represents a significant risk to the mother and fetus, in both the short and long term. Controversially, metformin use for the treatment of GDM is increasing in Australia. This article identifies the multiple and varied presentations of HGiP, of which GDM is the most commonly encountered. The degree of maternal hyperglycemia experienced affects the outcomes for both the mother and neonate, and specific diagnosis determines the appropriate treatment for the pregnancy. Given the increasing incidence of women with dysglycemia and those developing HGiP, this is an important area for research and clinical attention for all health professionals.
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http://dx.doi.org/10.1111/1753-0407.12660DOI Listing
August 2018

Compression force sensing regulates integrin αβ adhesive function on diabetic platelets.

Nat Commun 2018 03 14;9(1):1087. Epub 2018 Mar 14.

Heart Research Institute, Thrombosis Group, Newtown, New South Wales, 2042, Australia.

Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin αβ on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion. Analysis of discoid platelet aggregation in the mesenteric circulation of mice confirmed that diabetes leads to a marked enhancement in the formation and stability of discoid platelet aggregates, via a mechanism that is not inhibited by therapeutic doses of aspirin and clopidogrel, but is eliminated by PI 3-kinase inhibition. These studies demonstrate the existence of a compression force sensing mechanism linked to αβ adhesive function that leads to a distinct prothrombotic phenotype in diabetes.
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http://dx.doi.org/10.1038/s41467-018-03430-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852038PMC
March 2018

Correction to: Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans.

Diabetologia 2018 02;61(2):504-505

Metabolic and Vascular Physiology Laboratory, Baker Heart and Diabetes Institute, P. O. Box 6492, Melbourne, VIC, 3004, Australia.

The baseline insulin data given in Table 1 for the placebo group were incorrectly reported as 51 ± 10 pmol/l instead of 48 ± 10 pmol/l. This mistake also impacts on data reported in Table 4.
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http://dx.doi.org/10.1007/s00125-017-4514-xDOI Listing
February 2018

Pioglitazone reduces cold-induced brown fat glucose uptake despite induction of browning in cultured human adipocytes: a randomised, controlled trial in humans.

Diabetologia 2018 01 18;61(1):220-230. Epub 2017 Oct 18.

Metabolic and Vascular Physiology Laboratory, Baker Heart and Diabetes Institute, P. O. Box 6492, Melbourne, VIC, 3004, Australia.

Aims/hypothesis: Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans.

Methods: We first examined whether pioglitazone treatment of cultured human primary subacromioclavicular-derived adipocytes induced browning. Then, in a blinded, placebo-controlled, parallel trial, conducted within the Baker Institute clinical research laboratories, 14 lean male participants who were free of cardiometabolic disease were randomised to receive either placebo (lactose; n = 7, age 22 ± 1 years) or pioglitazone (45 mg/day, n = 7, age 21 ± 1 years) for 28 days. Participants were allocated to treatments by Alfred Hospital staff independent from the study via electronic generation of a random number sequence. Researchers conducting trials and analysing data were blind to treatment allocation. The change in cold-stimulated BAT activity, assessed before and after the intervention by [F]fluorodeoxyglucose uptake via positron emission tomography/computed tomography in upper thoracic and cervical adipose tissue, was the primary outcome measure. Energy expenditure, cardiovascular responses, core temperature, blood metabolites and hormones were measured in response to acute cold exposure along with body composition before and after the intervention.

Results: Pioglitazone significantly increased in vitro browning and adipogenesis of adipocytes. In the clinical trial, cold-induced BAT maximum standardised uptake value was significantly reduced after pioglitazone compared with placebo (-57 ± 6% vs -12 ± 18%, respectively; p < 0.05). BAT total glucose uptake followed a similar but non-significant trend (-50 ± 10% vs -6 ± 24%, respectively; p = 0.097). Pioglitazone increased total and lean body mass compared with placebo (p < 0.05). No other changes between groups were detected.

Conclusions/interpretation: The disparity in the actions of pioglitazone on BAT between preclinical experimental models and our in vivo human trial highlight the imperative to conduct human proof-of-concept studies as early as possible in BAT research programmes aimed at therapeutic development. Our clinical trial findings suggest that reduced BAT activity may contribute to weight gain associated with pioglitazone and other TZDs.

Trial Registration: ClinicalTrials.gov NCT02236962 FUNDING: This work was supported by the Diabetes Australia Research Program and OIS scheme from the Victorian State Government.
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http://dx.doi.org/10.1007/s00125-017-4479-9DOI Listing
January 2018

Blood glucose levels and glycaemic burden in 76,341 patients attending primary care: Bittersweet findings from a 9-year cohort study.

Diabetes Res Clin Pract 2017 May 27;127:89-96. Epub 2017 Feb 27.

Centre for Primary Care and Prevention, MacKillop Institute for Health Research, Australian Catholic University, Level 5, 215 Spring St, Melbourne, VIC 3000, Australia; Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Wellington Rd, Clayton, VIC 3800, Australia. Electronic address:

Aims: Diabetes care is principally applied in the primary care setting whereby we examined trends in glycaemic levels and goals and estimated avoidable glycaemic burden.

Methods: We retrieved glycated haemoglobin (HbA) results and glucose-lowering prescription records from a patient-based medical database during 2005-2013. There were 275,480 available HbA measurements from 76,341 individuals managed by 960 general practitioners from 321 clinics across Australia. Change in mean levels and glycaemic control over time were assessed according to sex, age and glucose-lowering therapy. The time that HbA levels exceeded 7% (53mmol/mol) in untreated (n=4888), non-insulin (n=11,534) and insulin treated (n=4049) patients was calculated as area under the curve (AUC) and months above threshold.

Results: Average age of patients was 62.1±15.1years (47.1% women). HbA levels decreased from 7.1% (54mmol/mol) in 2005 to 6.6% (49mmol/mol) in 2013 and the proportion of patients who achieved a HbA target of <7% improved by 16% in men (53-69%) and 21% in women (55-76%). HbA levels decreased with advancing age in men and increased with insulin treatment; correspondingly, HbA goal attainment increased and decreased, respectively. Avoidable glycaemic burden was 9.3±17.7months in untreated, 16.2±25.2months in non-insulin, and 26.8±34.6months in insulin-treated patients.

Conclusions: Amid considerable improvements, many treated patients still do not attain HbA levels ≤7% and time spent above this threshold was delayed. Earlier and more vigorously intensified management may reduce lengthy periods of uncontrolled hyperglycaemia in primary care.
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http://dx.doi.org/10.1016/j.diabres.2017.02.030DOI Listing
May 2017

The emerging role of metformin in gestational diabetes mellitus.

Diabetes Obes Metab 2017 06 24;19(6):765-772. Epub 2017 Mar 24.

School of Pharmacy, The University of Queensland, Brisbane, Australia.

Metformin use during pregnancy is controversial and there is disparity in the acceptance of metformin treatment in women with gestational diabetes mellitus (GDM) in Australia. Despite short term maternal and neonatal safety measures, the placental transfer of metformin during GDM treatment and the absence of long-term safety data in offspring has regulators and prescribers cautious about its use. To determine the current role in GDM management, this literature review describes the physiological changes that occur in GDM and other forms of diabetes in pregnancy (DIP) and international changes in guidelines for GDM diagnosis. Management options are considered, with a focus on the evolving evidence for metformin, its mechanism of action, the maternal, foetal and neonatal outcomes associated with its use and benefit vs risk when compared with the current gold standard, insulin. Investigation reveals a favourable balance of evidence to support the safety and long-term benefits, to mother and child, of using metformin as an alternate to insulin for treatment of GDM. Recent findings of the gastrointestinal-directed action of metformin are at least as important as the hepatic effect and the availability of a novel delayed-release metformin dose form to exploit this new information provides a product and therapeutic strategy ideally suited to the use of metformin in GDM.
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http://dx.doi.org/10.1111/dom.12893DOI Listing
June 2017

Interrupting prolonged sitting in type 2 diabetes: nocturnal persistence of improved glycaemic control.

Diabetologia 2017 03 9;60(3):499-507. Epub 2016 Dec 9.

Baker IDI Heart and Diabetes Institute, Level 4, 99 Commercial Road, Melbourne, VIC, 3004, Australia.

Aims/hypothesis: We aimed to examine the effect of interrupting 7 h prolonged sitting with brief bouts of walking or resistance activities on 22 h glucose homeostasis (including nocturnal-to-following morning hyperglycaemia) in adults with type 2 diabetes.

Methods: This study is an extension of a previously published randomised crossover trial, which included 24 inactive overweight/obese adults with type 2 diabetes (14 men; 62 ± 6 years) who completed three 7 h laboratory conditions, separated by 6-14 day washout periods: SIT: (1) prolonged sitting (control); (2) light-intensity walking (LW): sitting plus 3 min bouts of light-intensity walking at 3.2 km/h every 30 min; (3) simple resistance activities (SRA): sitting plus 3 min bouts of simple resistance activities (alternating half-squats, calf raises, brief gluteal contractions and knee raises) every 30 min. In the present study, continuous glucose monitoring was performed for 22 h, encompassing the 7 h laboratory trial, the evening free-living period after leaving the laboratory and sleeping periods. Meals and meal times were standardised across conditions for all participants.

Results: Compared with SIT, both LW and SRA reduced 22 h glucose [SIT: 11.6 ± 0.3 mmol/l, LW: 8.9 ± 0.3 mmol/l, SRA: 8.7 ± 0.3 mmol/l; p < 0.001] and nocturnal mean glucose concentrations [SIT: 10.6 ± 0.4 mmol/l, LW: 8.1 ± 0.4 mmol/l, SRA: 8.3 ± 0.4 mmol/l; p < 0.001]. Furthermore, mean glucose concentrations were sustained nocturnally at a lower level until the morning following the intervention for both LW and SRA (waking glucose both -2.7 ± 0.4 mmol/l compared with SIT; p < 0.001).

Conclusions/interpretation: Interrupting 7 h prolonged sitting time with either LW or SRA reduced 22 h hyperglycaemia. The glycaemic improvements persisted after these laboratory conditions and nocturnally, until waking the following morning. These findings may have implications for adults with relatively well-controlled type 2 diabetes who engage in prolonged periods of sitting, for example, highly desk-bound workers.

Trial Registration: anzctr.org.au ACTRN12613000576729 FUNDING: : This research was supported by a National Health and Medical Research Council (NHMRC) project grant (no. 1081734) and the Victorian Government Operational Infrastructure Support scheme.
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http://dx.doi.org/10.1007/s00125-016-4169-zDOI Listing
March 2017

Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes.

J Hypertens 2016 12;34(12):2376-2382

aBaker IDI Heart & Diabetes Institute bCentral Clinical School, Faculty of Medicine, Nursing & Health Sciences, Monash University cCentre of Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Victoria, Australia dSchool of Public Health, The University of Hong Kong, Hong Kong, China eMary MacKillop Institute of Health Research, Australian Catholic University, Melbourne, Victoria, Australia fSchool of Public Health, The University of Queensland, Brisbane, Queensland gSchool of Sport Science, Exercise and Health, The University of Western Australia, Perth, Western Australia hSwinburne University of Technology iSchool of Population and Global Health, The University of Melbourne jInstitute for Health and Ageing, Australian Catholic University, Melbourne, Victoria, Australia.

Objective: Prolonged sitting is increasingly recognized as a ubiquitous cardiometabolic risk factor, possibly distinct from lack of physical exercise. We examined whether interrupting prolonged sitting with brief bouts of light-intensity activity reduced blood pressure (BP) and plasma noradrenaline in type 2 diabetes (T2D).

Methods: In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men; mean ± SD; 62 ± 6 years) consumed standardized meals during 3 × 8 h conditions: uninterrupted sitting (SIT); sitting + half-hourly bouts of walking (3.2 km/h for 3-min) (light-intensity walking); and sitting + half-hourly bouts of simple resistance activities for 3 min (SRAs), each separated by 6-14 days washout. Resting seated BP was measured hourly (mean of three recordings, ≥20-min postactivity). Plasma noradrenaline was measured at 30-min intervals for the first hour after meals and hourly thereafter.

Results: Compared with SIT, mean resting SBP and DBP were significantly reduced (P < 0.001) for both light-intensity walking (mean ± SEM; -14 ± 1/-8 ± 1 mmHg) and SRA (-16 ± 1/-10 ± 1 mmHg), with a more pronounced effect for SRA (P < 0.05 versus light-intensity walking). Similarly, mean plasma noradrenaline was significantly reduced for both light-intensity walking (-0.3 ± 0.1 nmol/l) and SRA (-0.6 ± 0.1 nmol/l) versus SIT, with SRA lower than light-intensity walking (P < 0.05). Mean resting heart rate was lowered by light-intensity walking (-3 ± 1 bpm; P < 0.05), but not SRA (-1 ± 1 bpm).

Conclusion: Interrupting prolonged sitting with brief bouts of light-intensity walking or SRA reduces resting BP and plasma noradrenaline in adults with T2D, with SRA being more effective. Given the ubiquity of sedentary behaviors and poor adherence to structured exercise, this approach may have important implications for BP management in patients with T2D.
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http://dx.doi.org/10.1097/HJH.0000000000001101DOI Listing
December 2016

Benefits for Type 2 Diabetes of Interrupting Prolonged Sitting With Brief Bouts of Light Walking or Simple Resistance Activities.

Diabetes Care 2016 Jun 13;39(6):964-72. Epub 2016 Apr 13.

Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia Centre of Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria, Australia.

Objective: To determine whether interrupting prolonged sitting with brief bouts of light-intensity walking (LW) or simple resistance activities (SRA) improves postprandial cardiometabolic risk markers in adults with type 2 diabetes (T2D).

Research Design And Methods: In a randomized crossover trial, 24 inactive overweight/obese adults with T2D (14 men 62 ± 6 years old) underwent the following 8-h conditions on three separate days (with 6-14 days washout): uninterrupted sitting (control) (SIT), sitting plus 3-min bouts of LW (3.2 km · h(-1)) every 30 min, and sitting plus 3-min bouts of SRA (half-squats, calf raises, gluteal contractions, and knee raises) every 30 min. Standardized meals were consumed during each condition. Incremental areas under the curve (iAUCs) for glucose, insulin, C-peptide, and triglycerides were compared between conditions.

Results: Compared with SIT, both activity-break conditions significantly attenuated iAUCs for glucose (SIT mean 24.2 mmol · h · L(-1) [95% CI 20.4-28.0] vs. LW 14.8 [11.0-18.6] and SRA 14.7 [10.9-18.5]), insulin (SIT 3,293 pmol · h · L(-1) [2,887-3,700] vs. LW 2,104 [1,696-2,511] and SRA 2,066 [1,660-2,473]), and C-peptide (SIT 15,641 pmol · h · L(-1) [14,353-16,929] vs. LW 11,504 [10,209-12,799] and SRA 11,012 [9,723-12,301]) (all P < 0.001). The iAUC for triglycerides was significantly attenuated for SRA (P < 0.001) but not for LW (SIT 4.8 mmol · h · L(-1) [3.6-6.0] vs. LW 4.0 [2.8-5.1] and SRA 2.9 [1.7-4.1]).

Conclusions: Interrupting prolonged sitting with brief bouts of LW or SRA attenuates acute postprandial glucose, insulin, C-peptide, and triglyceride responses in adults with T2D. With poor adherence to structured exercise, this approach is potentially beneficial and practical.
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http://dx.doi.org/10.2337/dc15-2336DOI Listing
June 2016