Hybrid Closed Loop in Adults With Type 1 Diabetes and Severely Impaired Hypoglycemia Awareness.

BACKGROUND: Benefits of hybrid closed-loop (HCL) systems in a high-risk group with type 1 diabetes and impaired awareness of hypoglycemia (IAH) have not been well-explored. METHODS: Adults with Edmonton HYPO scores ≥1047 were randomized to 26-weeks HCL (MiniMed™ 670G) vs standard therapy (multiple daily injections or insulin pump) without continuous glucose monitoring (CGM) (control). Primary outcome was percentage CGM time-in-range (TIR; 70-180 mg/dL) at 23 to 26 weeks post-randomization. Major secondary endpoints included magnitude of change in counter-regulatory hormones and autonomic symptom responses to hypoglycemia at 26-weeks post-randomization. A post hoc analysis evaluated glycemia risk index (GRI) comparing HCL with control groups at 26 weeks post-randomization. RESULTS: Nine participants (median [interquartile range (IQR)] age 51 [41, 59] years; 44% male; enrolment HYPO score 1183 [1058, 1308]; Clarke score 6 [6, 6]; n = 5 [HCL]; n = 4 [control]) completed the study. Time-in-range was higher using HCL vs control (70% [68, 74%] vs 48% [44, 50%], P = .014). Time <70 mg/dL did not differ (HCL 3.8% [2.7, 3.9] vs control 6.5% [4.3, 8.6], P = .14) although hypoglycemia episode duration was shorter (30 vs 50 minutes, P < .001) with HCL. Glycemia risk index was lower with HCL vs control (38.1 [30.0, 39.2] vs 70.8 [58.5, 72.4], P = .014). Following 6 months of HCL use, greater dopamine (24.0 [12.3, 27.6] vs -18.5 [-36.5, -4.8], P = .014), and growth hormone (6.3 [4.6, 16.8] vs 0.5 [-0.8, 3.0], P = .050) responses to hypoglycemia were observed. CONCLUSIONS: Six months of HCL use in high-risk adults with severe IAH increased glucose TIR and improved GRI without increased hypoglycemia, and partially restored counter-regulatory responses. CLINICAL TRIAL REGISTRATION: ACTRN12617000520336.

Not enough known about fenofibrate's kidney effects in people with Type 2 diabetes.

Globally ≈10% of adults have diabetes, with 80% in disadvantaged regions, hence low-cost renoprotective agents are desirable. Fenofibrate demonstrated microvascular benefits in several cardiovascular end-point diabetes trials, but knowledge of effects in late-stage kidney disease is limited. We report new FIELD substudy data and call for further kidney outcomes data.

Advances in Automated Insulin Delivery with the Medtronic 780G: The Australian Experience.

Aim: To assess the real-world performance of MiniMed™ 780G for Australians with type 1 diabetes (T1D) following advanced hybrid closed loop (AHCL) activation and to evaluate the effect of changing from MiniMed 670/770G to 780G. Methods: We analyzed deidentified Carelink™ continuous glucose monitoring (CGM) data from Australian users from January 2020 to December 2022, including the proportion attaining three major consensus targets: Glucose management indicator (GMI <7.0%), time in range (TIR 70-180 mg/dL >70%), and time below range (TBR 70 mg/dL <4%). Results: Comparing 670/770G users (n = 5676) for mean ± standard deviation 364 ± 244 days with 780G users (n = 3566) for 146 ± 145 days, the latter achieved a higher TIR (72.6% ± 10.6% vs. 67.3% ± 11.4%; P < 0.001), lower time above range (TAR) (25.5% ± 10.9% vs. 30.6% ± 11.7%; P < 0.001), and lower GMI (6.9% ± 0.4% vs. 7.2% ± 0.4%; P < 0.001) without compromising TBR (1.9% ± 1.8% vs. 2.0% ± 1.8%; P = 0.0015). Of 1051 670/770G users transitioning to 780G, TIR increased (70.0% ± 10.7% to 74.0% ± 10.2%; P < 0.001), TAR decreased (28.1% ± 10.9% to 24.0% ± 10.7%; P < 0.001), and TBR was unchanged. The percentage of users attaining all three CGM targets was higher in 780G users (50.1% vs. 29.5%; P < 0.001). CGM metrics were stable at 12 months post-transition. Conclusion: Real-world data from Australia shows that a higher proportion of MiniMed 780G users meet clinical targets for CGM consensus metrics compared to MiniMed 670/770G users and glucose control was sustained over 12 months.

Improved Glycemic Outcomes With Diabetes Technology Use Independent of Socioeconomic Status in Youth With Type 1 Diabetes.

OBJECTIVE: Technology use in type 1 diabetes (T1D) is impacted by socioeconomic status (SES). This analysis explored relationships between SES, glycemic outcomes, and technology use. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of HbA1c data from 2,822 Australian youth with T1D was undertaken. Residential postcodes were used to assign SES based on the Index of Relative Socio-Economic Disadvantage (IRSD). Linear regression models were used to evaluate associations among IRSD quintile, HbA1c, and management regimen. RESULTS: Insulin pump therapy, continuous glucose monitoring, and their concurrent use were associated with lower mean HbA1c across all IRSD quintiles (P < 0.001). There was no interaction between technology use and IRSD quintile on HbA1c (P = 0.624), reflecting a similar association of lower HbA1c with technology use across all IRSD quintiles. CONCLUSIONS: Technology use was associated with lower HbA1c across all socioeconomic backgrounds. Socioeconomic disadvantage does not preclude glycemic benefits of diabetes technologies, highlighting the need to remove barriers to technology access.

Improved Satisfaction While Maintaining Safety and High Time in Range (TIR) With a Medtronic Investigational Enhanced Advanced Hybrid Closed-Loop (e-AHCL) System.

OBJECTIVE: To determine feasibility and compare acceptance of an investigational Medtronic enhanced advanced hybrid closed-loop (e-AHCL) system in adults with type 1 diabetes with earlier iterations. RESEARCH DESIGN AND METHODS: This nonrandomized three-stage (12 weeks each) exploratory study compared e-AHCL (Bluetooth-enabled MiniMed 780G insulin pump with automatic data upload [780G] incorporating an updated algorithm; calibration-free all-in-one disposable sensor; 7-day infusion set) preceded by a run-in (non-Bluetooth 780G [670G V4.0 insulin pump] requiring manual data upload; Guardian Sensor 3 [GS3] requiring calibration; 3-day infusion set), stage 1 (780G; GS3; 3-day infusion set), and stage 2 (780G; calibration-free Guardian Sensor 4; 3-day infusion set). Treatment satisfaction was assessed by Diabetes Technology Questionnaire (DTQ)-current (primary outcome) and other validated treatment satisfaction tools with glucose outcomes by continuous glucose monitoring metrics. RESULTS: Twenty-one of 22 (11 women) participants (baseline HbA1c 6.7%/50 mmol/mol) completed the study. DTQ-current scores favored e-AHCL (123.1 [17.8]) versus run-in (101.6 [24.2]) and versus stage 1 (110.6 [20.8]) (both P < 0.001) but did not differ from stage 2 (119.4 [16.0]; P = 0.271). Diabetes Medication System Rating Questionnaire short-form scores for "Convenience and Efficacy" favored e-AHCL over run-in and all stages. Percent time in range 70-180 mg/dL was greater with e-AHCL versus run-in and stage 2 (+2.9% and +3.6%, respectively; both P < 0.001). Percent times of <70 mg/dL for e-AHCL were significantly lower than run-in, stage 1, and stage 2 (-0.9%, -0.6%, and -0.5%, respectively; all P < 0.01). CONCLUSIONS: e-AHCL was feasible. User satisfaction increased compared with earlier Medtronic HCL iterations without compromising glucose control.

Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank.

AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers. METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts. RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts. CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.

Increased Diabetes Complications in a Mouse Model of Oxidative Stress Due to 'Mismatched' Mitochondrial DNA.

Associations between chronic diabetes complications and mitochondrial dysfunction represent a subject of major importance, given the diabetes pandemic and high personal and socioeconomic costs of diabetes and its complications. Modelling diabetes complications in inbred laboratory animals is challenging due to incomplete recapitulation of human features, but offer mechanistic insights and preclinical testing. As mitochondrial-based oxidative stress is implicated in human diabetic complications, herein we evaluate diabetes in a unique mouse model that harbors a mitochondrial DNA from a divergent mouse species (the 'xenomitochondrial mouse'), which has mild mitochondrial dysfunction and increased oxidative stress. We use the streptozotocin-induced diabetes model with insulin supplementation, with 20-weeks diabetes. We compare C57BL/6 mice and the 'xenomitochondrial' mouse, with measures of heart and kidney function, histology, and skin oxidative stress markers. Compared to C57BL/6 mice, the xenomitochondrial mouse has increased diabetic heart and kidney damage, with cardiac dysfunction, and increased cardiac and renal fibrosis. Our results show that mitochondrial oxidative stress consequent to divergent mtDNA can worsen diabetes complications. This has implications for novel therapeutics to counter diabetes complications, and for genetic studies of risk, as mtDNA genotypes may contribute to clinical outcomes.

Association of circulating fibroblast growth factor 21 levels with all-cause and cardiovascular mortality: The multi-ethnic study of atherosclerosis.

BACKGROUND: Fibroblast growth factor 21 (FGF21) levels are often elevated in cardiovascular disease (CVD). However, no study has assessed its association with cardiovascular and all-cause mortality in a population free of clinically evident CVD. METHODS: A total of 5543 Multi-Ethnic Study of Atherosclerosis (MESA) participants (mean age 62.7 years, 47.5 % male), free of clinically evident CVD at baseline, were studied. From baseline (2000-2002), 1606 deaths (including 387 CVD deaths) were observed over a median follow-up of 17.7 years. Multivariable Cox regression analysis was performed to assess the association of plasma FGF21 levels with mortality. RESULTS: FGF21 levels at baseline were associated with all-cause mortality, even after adjustment for traditional risk factors, including demographic, socioeconomic and cardiovascular risk factors (adjusted hazard ratio 1.08 [95% confidence interval 1.01, 1.16] per 1 SD increase in ln-transformed levels; 1.27 for the highest vs, lowest quartile). Baseline FGF21 levels were significantly associated with both CVD and non-CVD mortality in unadjusted models. However, the association with non-CVD mortality, but not CVD mortality, remained statistically significant after adjusting for covariates. Similar results were obtained in FGF21 quartile analyses and also when using competing risk regression or matched case-control cohort in sensitivity analyses. CONCLUSIONS: In subjects without clinically-evident CVD at baseline, over 17.7 years follow-up there is a modest association of baseline FGF21 levels with all-cause mortality. The finding that this is driven primarily by a significant association with non-CVD mortality over almost two decades merits further investigation.

Interactive calculator to estimate insulin sensitivity in type 1 diabetes.

The gold standard for measuring insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp, a time, costly, and labor-intensive research tool. A low insulin sensitivity is associated with a complication-risk in type 1 diabetes. Various formulae using clinical data have been developed and correlated with measured IS in type 1 diabetes. We consolidated multiple formulae into an online calculator (bit.ly/estimated-GDR), enabling comparison of IS and its probability of IS <4.45 mg/kg/min (low) or >6.50 mg/kg/min (high), as measured in a validation set of clamps in 104 adults with type 1 diabetes. Insulin sensitivity calculations using different formulae varied significantly, with correlations (R2 ) ranging 0.005-0.87 with agreement in detecting low and high glucose disposal rates in the range 49-93% and 89-100%, respectively. We demonstrate that although the calculated IS varies between formulae, their interpretation remains consistent. Our free online calculator offers a user-friendly tool for individual IS calculations and also offers efficient batch processing of data for research.

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.

Does insulin pump therapy offer benefits for behaviour, mood, cognition and HbA1c in children and adolescents with type 1 diabetes? A randomised controlled trial with observational follow-up.

AIMS: Improved behaviour, mood, cognition and HbA1c have been reported with short-term use of continuous subcutaneous insulin infusion (CSII) in youth with type 1 diabetes (T1D). We sought to re-examine these findings in a randomised controlled trial (RCT), with longitudinal follow-up. METHODS: RCT of youth aged 7-15 years with T1D, at two tertiary paediatric centres. Participants were randomised to commence CSII or continue multiple daily injections (MDI). Behaviour, mood, cognition and HbA1c were assessed. Primary outcome was difference in parent-reported behaviour (BASC-2) at 4 months. After the 4-month RCT, MDI participants commenced CSII; outcomes were reassessed at +2 years. RESULTS: Participating youth (n=101) were randomised to CSII (n=56) or MDI (n=45). Significant differences favouring CSII were found at 4 months in parent-reported behaviour problems (Cohen's d 0.41 (95% CI 0.004 to 0.795); p=0.048) and HbA1c (mean (95% CI) difference: 7 (2.3 to 11.7) mmol/mol (0.6% (0.2 to 1.0%); p=0.001)). Improvements from baseline were documented in mood and cognitive outcomes in both study groups over the 4-month RCT; however, no between-group differences were evident at 4 months. Sixteen of 76 (21%) participants completing assessments at +2 years had discontinued CSII. In n=60 still using CSII, measurements of behaviour, mood and HbA1c were comparable to baseline. CONCLUSIONS: Parent-reported behaviour problems and HbA1c, but not mood or neurocognitive outcomes, were clinically significantly lower with CSII, relative to MDI, after 4 months. Observational follow-up indicated no impact of treatment modality at +2 years, relative to baseline levels. Taken together, these data indicate that use of CSII alone does not comprehensively benefit neuropsychological outcomes in childhood T1D.

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.

Incidence and trends of type 1 diabetes before and after 2000 in the Western Pacific Region: A systematic review and meta-analysis.

OBJECTIVES: To undertake a systematic review of publications describing Type 1 diabetes (T1DM) incidence, trends over time and associated factors in the Western Pacific Region (WPR). METHODS: As per the PROSPERO-registered (CRD42019122646) protocol English (MEDLINE, Embase, Global Health) and Chinese data-bases (China National Knowledge Infrastructure, VIP, Wanfang) from onset to 31/12/2019 were searched for T1DM incidence in the WPR. Country level data extracted included annual crude incidence rates by sex, number of new cases per annum (p.a.) and cumulatively, and the population at-risk. A meta-analysis for T1DM incidence was performed (by region and narrow age-bands, where possible) with subgroup analyses by time and by region. FINDINGS: Forty-five population-based studies (21 from China), published 1973-2017, estimated T1DM incidence, mostly in youth, in 11 WPR countries. After 2000, mean annual T1DM incidence/100,000 person years aged 0-14 years ranged from 0.9 (95 % confidence intervals (CI), 0.6-1.3) in Fiji to 23.2 (95 % CI, 21.3-25.2) in Australia. The mean annual increase over time ranged from 2.8 % in Australia (1990-2002) to 14.2 % in Shanghai (1997-2011). T1DM incidence increased most in China (2.7-fold over 30-years) then Thailand (2-fold over 15-years). Most studies documented increasing incidence with age, though only two studies included people aged ≥ 20 years. Many, but not all studies reported significantly higher T1DM incidence in females vs. males. CONCLUSION: T1DM incidence in the WPR is generally increasing, varying by age, sex, time and country. Results increase understanding of regional T1DM incidence and inform research and healthcare strategies.

Improving efficiency of fitting Cox proportional hazards models for time-to-event outcomes in genome-wide association studies (GWAS).

Summary: Technologies identifying single nucleotide polymorphisms (SNPs) in DNA sequencing yield an avalanche of data requiring analysis and interpretation. Standard methods may require many weeks of processing time. The use of statistical methods requiring data sorting, matrix inversions of a high-dimension and replication in subsets of the data on multiple outcomes exacerbate these times.A method which reduces the computational time in problems with time-to-event outcomes and hundreds of thousands/millions of SNPs using Cox-Snell residuals after fitting the Cox proportional hazards model (PH) to a fixed set of concomitant variables is proposed. This yields coefficients for SNP effect from a Cox-Snell adjusted Poisson model and shows a high concordance to the adjusted PH model.The method is illustrated with a sample of 10 000 SNPs from a genome-wide association study in a diabetic population. The gain in processing efficiency using the proposed method based on Poisson modelling can be as high as 62%. This could result in saving of over three weeks processing time if 5 million SNPs require analysis. The method involves only a single predictor variable (SNP), offering a simpler, computationally more stable approach to examining and identifying SNP patterns associated with the outcome(s) allowing for a faster development of genetic signatures. Use of deviance residuals from the PH model to screen SNPs demonstrates a large discordance rate at a 0.2% threshold of concordance. This rate is 15 times larger than that based on the Cox-Snell residuals from the Cox-Snell adjusted Poisson model. Availability and implementation: The method is simple to implement as the procedures are available in most statistical packges. The approach involves obtaining Cox-Snell residuals from a PH model, to a binary time-to-event outcome, for factors which need to be common when assessing each SNP. Each SNP is then fitted as a predictor to the outcome of interest using a Poisson model with the Cox-Snell as the exposure variable.

No relationship between socioeconomic status, education level and development and progression of diabetic retinopathy in type 2 diabetes: a FIELD trial substudy.

In 6002 Australian adults with type 2 diabetes and a median 5-year follow-up in the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial, baseline socioeconomic status (SES) and self-reported education level were not related to development of on-trial sight-threatening diabetic retinopathy. Similarly, in a retinal photography substudy (n = 549), two-step diabetic retinopathy progression was not related to SES or education.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

Socioeconomic status and diabetes technology use in youth with type 1 diabetes: a comparison of two funding models.

Background: Technology use, including continuous glucose monitoring (CGM) and insulin pump therapy, is associated with improved outcomes in youth with type 1 diabetes (T1D). In 2017 CGM was universally funded for youth with T1D in Australia. In contrast, pump access is primarily accessed through private health insurance, self-funding or philanthropy. The study aim was to investigate the use of diabetes technology across different socioeconomic groups in Australian youth with T1D, in the setting of two contrasting funding models. Methods: A cross-sectional evaluation of 4957 youth with T1D aged <18 years in the national registry was performed to determine technology use. The Index of Relative Socio-Economic Disadvantage (IRSD) derived from Australian census data is an area-based measure of socioeconomic status (SES). Lower quintiles represent greater disadvantage. IRSD based on most recent postcode of residence was used as a marker of SES. A multivariable generalised linear model adjusting for age, diabetes duration, sex, remoteness classification, and location within Australia was used to determine the association between SES and device use. Results: CGM use was lower in IRSD quintile 1 in comparison to quintiles 2 to 5 (p<0.001) where uptake across the quintiles was similar. A higher percentage of pump use was observed in the least disadvantaged IRSD quintiles. Compared to the most disadvantaged quintile 1, pump use progressively increased by 16% (95% CI: 4% to 31%) in quintile 2, 19% (6% to 33%) in quintile 3, 35% (21% to 50%) in quintile 4 and 51% (36% to 67%) in the least disadvantaged quintile 5. Conclusion: In this large national dataset, use of diabetes technologies was found to differ across socioeconomic groups. For nationally subsidised CGM, use was similar across socioeconomic groups with the exception of the most disadvantaged quintile, an important finding requiring further investigation into barriers to CGM use within a nationally subsidised model. User pays funding models for pump therapy result in lower use with socioeconomic disadvantage, highlighting inequities in this funding approach. For the full benefits of diabetes technology to be realised, equitable access to pump therapy needs to be a health policy priority.

Increased intracellular miR-142 in adults with Type 1 diabetes.

microRNAs (miRs), including miR-142, modulate gene expression and processes implicated in vascular damage and may serve as therapeutic targets and agents, including in Type 1 diabetes (T1D). The project aimed to assess whether miR-142 levels differ between people with and without T1D, and to analyse miR-142 associations with cardiovascular (CVD) risk factors. Intracellular miRs were isolated from whole blood cell pellets using TRIzol-based methodology. In a cross-sectional study in 102 adults cellular miR-142 levels were significantly higher (on unadjusted and adjusted analyses) in 69 adults with T1D relative to 33 non-diabetic subjects: mean ± SD, 3.53 ± 3.66 vs. 1.25 ± 0.78, p < 0.0002, but were not related to HbA1c levels. Further miR-142 research, including longitudinal and intervention studies and basic science are of interest. miR-142 may be valuable in clinical practice for predicting health and as a treatment target.

Mitochondrial DNA copy number in adults with and without Type 1 diabetes.

AIMS: Mitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies are lacking. We related mtDNA-cn in T1D and non-diabetic adults (CON) with diabetes complications and risk factors. METHODS: Cross-sectional study: 178 T1D, 132 non-diabetic controls. Associations of whole blood mtDNA-cn (qPCR) with complications, inflammation, and C-peptide. RESULTS: mtDNA-cn (median (LQ, UQ)) was lower in: T1D vs. CON (271 (189, 348) vs. 320 (264, 410); p < 0.0001); T1D with vs. without kidney disease (238 (180, 309) vs. 294 (198, 364); p = 0.02); and insulin injection vs. pump-users (251 (180, 340) vs. 322 (263, 406); p = 0.008). Significant univariate correlates of mtDNA-cn: T1D: (positive) HDL-C; (negative) fasting glucose, white cell count (WCC), sVCAM-1, sICAM-1; CON: (negative) WHR (waist-hip-ratio). Detectable C-peptide in T1D increased with lowest-highest mtDNA-cn tertiles (54%, 69%, 79%, p = 0.02). Independent determinants of mtDNA-cn: T1D: (positive) HDL-C; (negative) age, sICAM-1; AUROC 0.71; CON: WCC (negative), never smoking, (positive) female, pulse pressure; AUROC 0.74. CONCLUSIONS: mtDNA-cn is lower in T1D vs. CON, and in T1D kidney disease. In T1D, mtDNA-cn correlates inversely with age and inflammation, and positively with HDL-C, detectable C-peptide and pump use. Further clinical and basic science studies are merited.