Study protocol for a randomised open-label clinical trial examining the safety and efficacy of the Android Artificial Pancreas System (AAPS) with advanced bolus-free features in adults with type 1 diabetes: the 'CLOSE IT' (Closed Loop Open SourcE In Type 1 diabetes) trial.

INTRODUCTION: Multiple automated insulin delivery (AID) systems have become commercially available following randomised controlled trials demonstrating benefits in people with type 1 diabetes (T1D). However, their real-world utility may be undermined by user-associated burdens, including the need to carbohydrate count and deliver manual insulin boluses. There is an important need for a 'fully automated closed loop' (FCL) AID system, without manual mealtime boluses. The (Closed Loop Open SourcE In Type 1 diabetes) trial is a randomised trial comparing an FCL AID system to the same system used as a hybrid closed loop (HCL) in people with T1D, in an outpatient setting over an extended time frame. METHODS AND ANALYSIS: Randomised, open-label, parallel, non-inferiority trial comparing the Android Artificial Pancreas System (AAPS) AID algorithm used as FCL to the same algorithm used as HCL. Seventy-five participants aged 18-70 will be randomised (1:1) to one of two treatment arms for 12 weeks: (a) FCL-participants will be advised not to bolus for meals and (b) HCL-participants will use the AAPS AID algorithm as HCL with announced meals. The primary outcome is the percentage of time in target sensor glucose range (3.9-10.0 mmol/L). Secondary outcomes include other glycaemic metrics, safety, psychosocial factors, platform performance and user dietary factors. Twenty FCL arm participants will participate in a 4-week extension phase comparing glycaemic and dietary outcomes using NovoRapid (insulin aspart) to Fiasp (insulin aspart and niacinamide). ETHICS AND DISSEMINATION: Approvals are by the Alfred Health Ethics Committee (615/22) (Australia) and Health and Disability Ethics Committees (2022 FULL 13832) (New Zealand). Each participant will provide written informed consent. Data protection and confidentiality will be ensured. Study results will be disseminated by publications, conferences and patient advocacy groups. TRIAL REGISTRATION NUMBERS: ACTRN12622001400752 and ACTRN12622001401741.

The diabetes management experiences questionnaire: Psychometric validation among adults with type 1 diabetes.

AIMS: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities. METHODS: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120). RESULTS: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: rs = -0.57) and treatment satisfaction (DTSQ; rs = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: rs = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy. CONCLUSIONS: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings.

Early Discharge to Clinic-Based Therapy of Patients Presenting With Decompensated Heart Failure (EDICT-HF): Study Protocol for a Multi-Centre Randomised Controlled Trial.

BACKGROUND: Acute decompensated heart failure involves a high rate of mortality and complications. Management typically involves a multi-day hospital admission. However, patients often lose part of their function with each successive admission, and are at a high risk for hospital-associated complications such as nosocomial infection. This study aims to determine the safety and efficacy of the management of patients presenting with acute decompensated heart failure to clinic-based therapy vs usual inpatient care using a reproducible management pathway. METHOD: An investigator-initiated, prospective, non-inferiority, 1:1 randomised-controlled trial, stratified by left ventricular ejection fraction including 460 patients with a minimum follow-up of 7 days. This is a multi-centre study to be performed in centres across Victoria, Australia. Participants will be patients with either heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF), admitted for acute decompensation of heart failure. INTERVENTION: Early discharge to an outpatient-based Heart Failure Rapid Access Clinical Review (RACER) in addition to frequent medical/nursing at-home review for patients admitted with decompensated heart failure. RESULTS: The primary endpoint will be a non-inferiority assessment of re-hospitalisation at 30 days. Secondary outcomes include superiority assessment of hospitalisation at 30 days, a composite clinical endpoint of major adverse cardiac and cerebrovascular event (MACCE), hospital re-admission or mortality at 3 months, achievement of guideline-directed medical therapy, patient assessment of symptoms (visual-analogue scale quantified as area under curve and Kansas City Cardiomyopathy Questionnaire-12 [KCCQ-12]), attendance at 3-month outpatient follow-up, number of bed stays/clinics attended, proportion of patients free from congestion, change in serum creatinine level, treatment for electrolyte disturbances, time to transition from intravenous to oral diuretics, and health economics analysis (cost-benefit analysis, cost-utility analysis, incremental cost-effectiveness ratio). CONCLUSIONS: The Early Discharge to Clinic-Based Therapy of Patients Presenting with Decompensated Heart Failure (EDICT-HF) trial will help determine whether earlier discharge to out-of-hospital care is non-inferior to the usual practice of inpatient care, in patients with heart failure admitted to hospital for acute decompensation, as an alternative model of care.

Asia-Pacific Perspectives on the Role of Continuous Glucose Monitoring in Optimizing Diabetes Management.

Diabetes is prevalent, and it imposes a substantial public health burden globally and in the Asia-Pacific (APAC) region. The cornerstone for optimizing diabetes management and treatment outcomes is glucose monitoring, the techniques of which have evolved from self-monitoring of blood glucose (SMBG) to glycated hemoglobin (HbA1c), and to continuous glucose monitoring (CGM). Contextual differences with Western populations and limited regionally generated clinical evidence warrant regional standards of diabetes care, including glucose monitoring in APAC. Hence, the APAC Diabetes Care Advisory Board convened to gather insights into clinician-reported CGM utilization for optimized glucose monitoring and diabetes management in the region. We discuss the findings from a pre-meeting survey and an expert panel meeting regarding glucose monitoring patterns and influencing factors, patient profiles for CGM initiation and continuation, CGM benefits, and CGM optimization challenges and potential solutions in APAC. While CGM is becoming the new standard of care and a useful adjunct to HbA1c and SMBG globally, glucose monitoring type, timing, and frequency should be individualized according to local and patient-specific contexts. The results of this APAC survey guide methods for the formulation of future APAC-specific consensus guidelines for the application of CGM in people living with diabetes.

Asia-Pacific consensus recommendations for application of continuous glucose monitoring in diabetes management.

Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region.

Hybrid Closed Loop Using a Do-It-Yourself Artificial Pancreas System in Adults With Type 1 Diabetes.

OBJECTIVE: There is increasing use of open-source artificial pancreas systems (APS) in the management of Type 1 diabetes. Our aim was to assess the safety and efficacy of the automated insulin delivery system AndroidAPS (AAPS), compared with stand-alone pump therapy in people with type 1 diabetes. The primary outcome was the difference in the percentage of time in range (TIR, 70-180 mg/dL). Secondary aims included mean sensor glucose value and percent continuous glucose monitor (CGM) time below range (TBR, <70 mg/dL). RESEARCH DESIGN AND METHODS: This open-label single-center randomized crossover study (ANZCTR, Australian New Zealand clinical trial registry, ANZCTR-ACTRN12620001191987) comprised 20 participants with type 1 diabetes on established pump therapy, assigned to either stand-alone insulin pump therapy or the open-source AAPS hybrid closed-loop system for four weeks, with crossover to the alternate arm for the following four weeks. The CGM outcome parameters were measured by seven-day CGM at baseline and the final week of each four-week study arm. RESULTS: Twenty participants were recruited (60% women), aged 45.8 ± 15.9 years, with mean diabetes duration of 23.9 ± 13.2 years, baseline glycated hemoglobin (HbA1c) 7.5% ± 0.5% (58 ± 6 mmol/mol) and mean TIR 62.3% ± 12.9%. The change in TIR from baseline for AAPS compared with stand-alone pump therapy was 18.6% (11.4-25.9), (P < .001), TIR 76.6% ± 11.7%, 58.0% ± 15.6%, for AAPS and stand-alone pump, respectively. Time glucose <54 mg/dL was not increased (mean = -2.0%, P = .191). No serious adverse events or episodes of severe hypoglycemia were recorded. CONCLUSIONS: This clinical trial of the open-source AAPS hybrid closed-loop system performed in an at-home setting demonstrated comparable safety to stand-alone pump therapy. The glycemic outcomes of AAPS were superior with improved TIR, and there was no significant difference in TBR compared with stand-alone pump therapy.

Sitting less and moving more for improved metabolic and brain health in type 2 diabetes: 'OPTIMISE your health' trial protocol.

BACKGROUND: Clinical practice guidelines recommend that adults with type 2 diabetes (T2D) sit less and move more throughout the day. The 18-month OPTIMISE Your Health Clinical Trial was developed to support desk-based workers with T2D achieve these recommendations. The two-arm protocol consists of an intervention and control arms. The intervention arm receives 6 months health coaching, a sit-stand desktop workstation and an activity tracker, followed by 6 months of text message support, then 6 months maintenance. The control arm receives a delayed modified intervention after 12 months of usual care. This paper describes the methods of a randomised controlled trial (RCT) evaluating the effectiveness and cost-effectiveness of the intervention, compared to a delayed intervention control. METHODS: This is a two-arm RCT being conducted in Melbourne, Australia. Desk-based workers (≥0.8 full-time equivalent) aged 35-65 years, ambulatory, and with T2D and managed glycaemic control (6.5-10.0% HbA1c), are randomised to the multicomponent intervention (target n = 125) or delayed-intervention control (target n = 125) conditions. All intervention participants receive 6 months of tailored health coaching assisting them to "sit less" and "move more" at work and throughout the day, supported by a sit-stand desktop workstation and an activity tracker (Fitbit). Participants receive text message-based extended care for a further 6-months (6-12 months) followed by 6-months of non-contact (12-18 months: maintenance). Delayed intervention occurs at 12-18 months for the control arm. Assessments are undertaken at baseline, 3, 6, 12, 15 and 18-months. Primary outcomes are activPAL-measured sitting time (h/16 h day), glycosylated haemoglobin (HbA1c; %, mmol/mol) and, cognitive function measures (visual learning and new memory; Paired Associates Learning Total Errors [adjusted]). Secondary, exploratory, and process outcomes will also be collected throughout the trial. DISCUSSION: The OPTIMISE Your Health trial will provide unique insights into the benefits of an intervention aimed at sitting less and moving more in desk-bound office workers with T2D, with outcomes relevant to glycaemic control, and to cardiometabolic and brain health. Findings will contribute new insights to add to the evidence base on initiating and maintaining behaviour change with clinical populations and inform practice in diabetes management. TRIAL REGISTRATION: ANZCTRN12618001159246 .

Driving with Type 1 Diabetes: Real-World Evidence to Support Starting Glucose Level and Frequency of Monitoring During Journeys.

There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years; 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%; n = 436). Thirteen drivers recorded at least one trip (total n = 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.

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

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.

Different frequencies of active interruptions to sitting have distinct effects on 22 h glycemic control in type 2 diabetes.

BACKGROUND & AIMS: Whether the frequency of interruptions to sitting time involving simple resistance activities (SRAs), compared to uninterrupted sitting, differentially affected 22 h glycemic control in adults with medication-controlled type 2 diabetes (T2D). METHODS & RESULTS: Twenty-four participants (13 men; mean ± SD age 62 ± 8 years) completed three 8 h laboratory conditions: SIT: uninterrupted sitting; SRA3: sitting interrupted with 3 min of SRAs every 30 min; and, SRA6: sitting interrupted with 6 min of SRAs every 60 min. Flash glucose monitors assessed glycemic control over a 22 h period. No differences were observed between conditions for overall 22 h glycemic control as measured by AUCtotal, mean glucose and time in hyperglycemia. During the 3.5 h post-lunch period, mean glucose was significantly lower during SRA6 (10.1 mmol·L-1, 95%CI 9.2, 11.0) compared to SIT (11.1 mmol·L-1, 95%CI 10.2, 12.0; P = 0.006). Post-lunch iAUCnet was significantly lower during SRA6 (6.2 mmol·h·L-1, 95%CI 3.3, 9.1) compared to SIT (9.9 mmol·h·L-1, 95%CI 7.0, 12.9; P = 0.003). During the post-lunch period, compared to SIT (2.2 h, 95%CI 1.7, 2.6), time in hyperglycemia was significantly lower during SRA6 (1.5 h, 95%CI 1.0, 1.9, P = 0.001). Nocturnal mean glucose was significantly lower following the SRA3 condition (7.6 mmol·L-1, 95%CI 7.1, 8.1) compared to SIT (8.1 mmol·L-1, 95%CI 7.6, 8.7, P = 0.024). CONCLUSIONS: With standardized total activity time, less-frequent active interruptions to sitting may acutely improve glycemic control; while more-frequent interruptions may be beneficial for nocturnal glucose in those with medication-controlled T2D.

Meal-time glycaemia in adults with type 1 diabetes using multiple daily injections vs insulin pump therapy following carbohydrate-counting education and bolus calculator provision.

AIMS: To compare meal-time glycaemia in adults with type 1 diabetes mellitus (T1D) managed with multiple daily injections (MDI) vs. insulin pump therapy (IPT), using self-monitoring blood glucose (SMBG), following diabetes education. METHODS: Adults with T1D received carbohydrate-counting education and a bolus calculator: MDI (Roche Aviva Expert) and IPT (pump bolus calculator). All then wore 3-weeks of masked-CGM (Enlite, Medtronic). Meal-times were assessed by two approaches: 1) Set time-blocks (breakfast 06:00-10:00hrs; lunch 11:00-15:00hrs; dinner 17:00-21:00hrs) and 2) Bolus-calculator carbohydrate entries signalling meal commencement. Post-meal masked-CGM time-in-range (TIR) 3.9-10.0 mmol/L was the primary outcome. RESULTS: MDI(n = 61) and IPT (n = 59) participants were equivalent in age, sex, diabetes duration and HbA1c. Median (IQR) education time provided did not differ (MDI: 1.1 h (0.75, 1.5) vs. IPT: 1.1 h (1.0, 2.0); p = 0.86). Overall, daytime (06:00-24:00hrs), lunch and dinner TIR did not differ for MDI vs. IPT participants but was greater for breakfast with IPT in both analyses with a mean difference of 12.8%, (95 CI 4.8, 20.9); p = 0.002 (time-block analysis). CONCLUSION: After diabetes education, MDI and IPT use were associated with similar day-time glycemia, though IPT users had significantly greater TIR during the breakfast period. With education, meal-time glucose levels are comparable with use of MDI vs. pumps.

Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review.

AIMS: To systematically review randomized controlled trials assessing effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)-derived evidence for SGLT2i efficacy mechanisms in heart failure (HF). METHODS AND RESULTS: Systematic searches of Medline and Embase were performed. In seven trials [3730-17 160 patients; low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27-39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type-2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects. Five trials (56-105 patients; low RoB) assessed the effects of 6-12 months of SGLT2i treatment on left ventricular structure/function; four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N-terminal pro B-type natriuretic peptide levels; significant reductions vs. placebo were reported after 8-12 months (two studies; 3730-4744 patients) but not ≤12 weeks (three studies; 80-263 patients). Limited available RCT-derived evidence suggests various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics (natriuresis and reduced interstitial fluid without blood volume contraction/neurohormonal activation) and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics. CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitors reduce HHF regardless of T2DM status, and reversal of adverse left ventricular remodelling likely contributes to this efficacy. Hypothesis-driven mechanistic trials remain sparse, although numerous trials are planned or ongoing.

Feasibility of once weekly exenatide-LAR and enhanced diabetes care in Indigenous Australians with type 2 diabetes (Long-acting-Once-Weekly-Exenatide laR-SUGAR, 'Lower SUGAR' study).

BACKGROUND: Diabetes is 3-4 times more prevalent in Indigenous Australians with blood glucose levels often above target range. Once weekly formulations of exenatide(exenatide-LAR) have demonstrated significantly greater improvements in glycaemic management with no increased risk of hypoglycaemia and with reductions in bodyweight but have not been studied in Indigenous Australians. AIMS: To assess the feasibility and metabolic effects of once weekly supervised injection of exenatide-LAR in addition to standard care in Indigenous Australians with type 2 diabetes. METHODS: Two communities in Central Australia with longstanding specialist clinical outreach services were allocated by random coin toss to receive once-weekly exenatide-LAR injection with weekly nurse review and adjustment of medication for 20 weeks (community with exenatide-LAR) or to weekly nurse review in addition to standard care over 20 weeks (community without exenatide-LAR). The primary outcome was the feasibility of an intensive diabetes management model of care with and without weekly supervised exenatide-LAR. Secondary outcomes included change in HbA1c. RESULTS: Thirteen participants from the community with exenatide-LAR and nine participants from the community without exenatide-LAR were analysed. Eighty-five percent of individuals in the community with exenatide-LAR and 67% in the community without exenatide-LAR attended more than half of clinic visits. Median difference in the change in HbA1c from baseline to final visit, adjusted for baseline HbA1c, between the community with exenatide-LAR and the community without exenatide-LAR was -3.1%, 95% CI (-5.80%, -0.38%; P = 0.03). CONCLUSIONS: Weekly exenatide-LAR combined with weekly nurse review demonstrated greater improvements in HbA1c, highlighting its potential for use in remote communities.

Frequency of Interruptions to Sitting Time: Benefits for Postprandial Metabolism in Type 2 Diabetes.

OBJECTIVE: To determine whether interrupting sitting with brief bouts of simple resistance activities (SRAs) at different frequencies improves postprandial glucose, insulin, and triglycerides in adults with medication-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Participants (n = 23, 10 of whom were female, with mean ± SD age 62 ± 8 years and BMI 32.7 ± 3.5 kg · m-2) completed a three-armed randomized crossover trial (6- to 14-day washout): sitting uninterrupted for 7 h (SIT), sitting with 3-min SRAs (half squats, calf raises, gluteal contractions, and knee raises) every 30 min (SRA3), and sitting with 6-min SRAs every 60 min (SRA6). Net incremental areas under the curve (iAUCnet) for glucose, insulin, and triglycerides were compared between conditions. RESULTS: Glucose and insulin 7-h iAUCnet were attenuated significantly during SRA6 (glucose 17.0 mmol · h · L-1, 95% CI 12.5, 21.4; insulin 1,229 pmol · h · L-1, 95% CI 982, 1,538) in comparison with SIT (glucose 21.4 mmol · h · L-1, 95% CI 16.9, 25.8; insulin 1,411 pmol · h · L-1, 95% CI 1,128, 1,767; P < 0.05) and in comparison with SRA3 (for glucose only) (22.1 mmol · h · L-1, 95% CI 17.7, 26.6; P = 0.01) No significant differences in glucose or insulin iAUCnet were observed in comparison of SRA3 and SIT. There was no statistically significant effect of condition on triglyceride iAUCnet. CONCLUSIONS: In adults with medication-controlled T2D, interrupting prolonged sitting with 6-min SRAs every 60 min reduced postprandial glucose and insulin responses. Other frequencies of interruptions and potential longer-term benefits require examination to clarify clinical relevance.

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

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.

Interrupting Prolonged Sitting and Endothelial Function in Polycystic Ovary Syndrome.

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.

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

Background: 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). Methods: 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 Results: Adults using MDIs (n = 61) versus pump (n = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA1c 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 (P = 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 (P = 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]; P < 0.001). Conclusions: 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.

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

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: 1) uninterrupted sitting (SIT), 2) sitting with 3-min bouts of SRA every 30 min (SRA3), and 3) 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%, P = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased significantly for SRA3 (45.3 ± 4.1/s, P < 0.001) and SRA6 (46.2 ± 4.1/s, P < 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.NEW & NOTEWORTHY 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.

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.

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- 2 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 ).

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.

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 (n = 61) or control (n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c 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]; P < 0.0001). For HCL, HbA1c was lower (median [95% CI] difference -0.4% [-0.6, -0.2]; -4 mmol/mol [-7, -2]; P < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9]; P < 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, HbA1c, 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.