The International Diabetes Federation estimated that in 2024, 215 million adults-more than one-third of the global diabetes population-were living with diabetes within the Western Pacific Region (WPR), which includes nations with some of the highest prevalence worldwide. Rapid urbanization and economic development have profoundly reshaped lifestyles, which interact with biological predispositions resulting in an earlier onset of type 2 diabetes. These predispositions are not uniform across the heterogeneous populations within the WPR. Asian individuals tend to have a β-cell secretory failure phenotype with type 2 diabetes arising at lower adiposity, distinct from the high-adiposity phenotype with pronounced insulin resistance common among Pacific peoples. Improvements in diabetes care in high-income countries have reduced vascular complications and improved survival, shifting the clinical profile of individuals with type 2 diabetes toward an older population characterized by multimorbidity. In contrast, low-income settings continue to face a high prevalence of type 2 diabetes, compounded by limited access to medications and diagnostic tools, shortage of trained health care professionals, and other logistical barriers to care. In this diverse region where countries are at different stages of health care development, there are considerable opportunities for sharing of best practices through collaborative and translational research. These may include social and public health policies, health care delivery, use of registers to track disease patterns and care standards, and use of technologies to support self-management. For implementation of these actions, a major shift is required, toward prevention, capacity building, and demonstrating the impact of value-based prevention and data-driven care.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known to reduce cardiovascular and all-cause mortality in people with type 2 diabetes, but there are limited data regarding mortality outcomes in different ethnic groups (including Indigenous peoples). This study reports on mortality outcomes in a population in Aotearoa New Zealand (hereafter New Zealand) with type 2 diabetes, following the funded availability of the SGLT2i empagliflozin with prioritised access for Māori and Pacific people. Data were collected from primary care records for those aged 18–75 years with type 2 diabetes (Auckland/Waikato regions of New Zealand; February 2021 to December 2023; n=59,505). These data were linked to national medication-dispensing and mortality records for 2021–2024 via national health identifier numbers. Following propensity matching and Cox modelling for ethnicity, age, gender, medication use, baseline HbA1c and cardiovascular and/or renal disease/risk (CVRD) status (yes/no), mortality rates were compared by ethnicity in those with and without CVRD and who did/did not initiate empagliflozin. This study was reported in accordance with the CONSIDER statement, used to strengthen the reporting of research involving Indigenous peoples. The study was funded by the Health Research Council of New Zealand. Following matching, two groups of 12,792 individuals were identified. Annualised crude mortality (deaths per 1000 individuals per year) was higher in those not dispensed with SGLT2i than in those receiving SGLT2i (35.2 vs 13.1 in those with CVRD and 7.7 vs 3.6 in those without CVRD, respectively). After adjustment, the greatest difference in mortality with SGLT2i use was seen in Māori (HR 0.475; 95

INTRODUCTION:Management of type 2 diabetes (T2D) occurs predominantly in primary health care in Aotearoa New Zealand. Optimising the delivery of clinical diabetes management by upskilling healthcare professionals can reduce the strain on the healthcare system and improve patient care. AIM:This study aimed to qualitatively evaluate the importance of an education programme delivered by a non-physician diabetes specialist on nurses' knowledge and confidence of T2D management in primary care. METHODS:Semi-structured interviews with nurses enrolled in the programme for at least 6 months and their nurse leads across two clinics in the Waikato region were conducted to assess their confidence and knowledge in T2D management, as well as the acceptability of the programme. Transcripts were analysed using quantitative content analysis. RESULTS:Four nurses and two nurse leads were interviewed, lasting between 15 and 60 min. Nurses reported improved knowledge of diabetes medications and interpreting clinical measures. Nurses also felt more confident in their communication skills with patients, advocating for their patients, and improved patient engagement. Further education was needed on administering diabetes medication, knowledge of medical devices such as continuous glucose monitoring, and understanding the pathophysiology of diabetes. DISCUSSION:Self-efficacy and self-reported skills of nurses in T2D management improved following the diabetes mentoring programme. Further research is needed to assess quantitative clinical measures and whether the programme is effective in improving patient health outcomes.

AIM:The aim of this study was to quantify interrupted care (delayed care and complete loss to follow-up) across the diabetes eye care pathway among people aged ≥15 years in Auckland, New Zealand, and assess disparities by age, sex, ethnicity, deprivation and diabetes duration. METHOD:We analysed data from people engaged with diabetes retinal screening in Auckland between 1 January 2008 and 31 December 2019. Follow-up continued from first appointment until death or study end. Delayed care and complete loss to follow-up were assessed at retinal screening, when referred from screening to ophthalmology with referrable diabetic retinopathy (R3 or worse), and at ophthalmology review. RESULTS:Almost one-third of people experienced delays in retinal screening care beyond 24 months (n=4,471/14,708; 30.4%) and one-fifth were completely lost to follow-up (n=2,970/14,708; 20.2%). Similar proportions were observed for a delay beyond 6 months when referred from retinal screening to ophthalmology with referrable retinopathy (n=648/1,909; 33.9%) and a delay beyond 12 months between ophthalmology review (n=366/1,136; 32.2%) or complete loss to follow-up from these two stages (n=433/1,909; 22.7% and n=188/1,136; 16.5% respectively). Younger adults were more likely to experience complete loss to follow-up from retinal screening and ophthalmology review compared to people aged 50-59 years; compared to NZ Europeans, all other ethnicity groups were more likely to be lost to follow-up from retinal screening, with Māori and Pacific peoples experiencing the greatest disparity. CONCLUSION:Loss to follow-up and delayed care were common across all stages of the diabetes care pathway assessed, with disparities by age and ethnicity.

Background:It is not known how individuals respond to liraglutide or naltrexone/bupropion following low-response to a structured meal replacement low energy diet (MR-LED) programme. Methods:This was a retrospective observational study conducted at a specialist weight management service using MR-LED with intensive behavioural therapy (IBT). Adults were considered for obesity medication if they did not lose at least 5 % body weight in the first 4 weeks of the intensive MR phase, 10 % after the total 12 week MR phase or regained >4 kg either during the stepped food reintroduction or weight maintenance phases. Eligible individuals were offered liraglutide 3.0 mg (LIRA) or naltrexone/bupropion (NB32) for 13 weeks (including dose titration). The primary outcome was the proportion of individuals achieving ≥5 % weight reduction after 13 weeks of treatment. Completers were defined as those who had a body weight measured between 10 and 16 weeks and did not discontinue the medication before this period. Results:Of 114 people offered obesity medications, 85 accepted (67 LIRA, 18 NB32). 46 individuals completed 13 weeks' treatment and 11 (24 %) achieved ≥5 % weight reduction. Among completers (54 %), the mean weight change was -4.4 kg (-2.4 %), and was -2.7 kg (-1.5 %) for the total treated cohort using last weight carried forward on missing data. Those achieving ≥5 % weight reduction were more likely to be male and had lower prevalence of diabetes, binge eating, anxiety or depressive symptoms at baseline. Conclusion:People who do not respond to a MR-LED with IBT have lower than anticipated weight reduction on subsequent treatment with first-generation obesity medications.

AIMS:Structured meal replacement low energy diets (MR-LED) are effective in obesity management, but evidence for individuals of minority ethnic groups or those with BMI >35 kg/m2 and significant comorbidities is limited. MATERIALS AND METHODS:We evaluated the early effectiveness of a weight management program delivered by a multidisciplinary team within a specialist weight management service. We enrolled three groups: those who had been declined bariatric surgery, young adults with type 2 diabetes (T2D), and people awaiting corneal transplant who had their procedure deferred due to their weight. Individuals were primarily treated with a 12-week MR-LED. Adjunctive obesity medications were available under pre-specified criteria. The present study reports outcomes following the 12-week MR-LED, which was the first phase of a 12 month programme. RESULTS:Of the 1172 people screened, 482 met inclusion criteria and 128 commenced MR-LED. Most participants (111/128, 87%) had previously been declined bariatric surgery; 11/128 (9%) were young adults with T2D and 6/128 (5%) were awaiting corneal transplant surgery. Ninety-three individuals (73%) were from Pacific or indigenous Māori ethnic groups. The cohort had mean (SD) baseline weight of 145.0 (38.6) kg (BMI 49.9 (11.3) kg/m2); 94 (73%) had T2D on treatment, with a mean HbA1c of 67.6 mmol/mol (11 young adults and 83 from the bariatric surgery declined list). Psychological distress was common with 41% and 30% having moderate depressive and anxiety symptoms, respectively. Ninety-two people (72%) completed the 12-week MR-LED, achieving a mean (SD) weight loss of 10.9 (7.8) kg. Young adults with T2D were less likely to complete the programme. Among people with diabetes, 63/94 (67%) completed the 12-week intervention, with 21/63 (33%) achieving an HbA1c <50 mmol/mol on no diabetes medication. Psychological and quality of life scores improved. CONCLUSIONS:A 12-week MR-LED intervention delivered in a specialist service achieved clinically meaningful weight loss and improved metabolic and psychological outcomes in a high-risk, multi-ethnic cohort living with higher body weight.

AIM:To describe the clinical characteristics of patients with Wolfram syndrome (WFS) and diabetes mellitus (DM) in Aotearoa, New Zealand. Review of response to therapy in those treated with glucagon-like peptide-1 receptor agonists (GLP1RA). METHODS:This retrospective cohort study describes 7 patients with WFS1 genetic variants (1 patient with WFS-like syndrome), and DM from 5 New Zealand families (age range 5-33 years, 4 females, 3 males). All are receiving insulin. In 5 patients receiving GLP1RA therapy, we described their pre- and post-treatment biometric parameters, glycaemic control and visual acuity. RESULTS:Genetic testing identified compound heterozygous variants in the WFS1 gene (inherited from each parent) in five patients. Another two were heterozygous carriers of a single WFS1 missense variant, one of which was associated with uniparental disomy. Among patients receiving GLP1RA therapy, reductions were seen in HbA1c (mean 11.6 mmol/mol) and total daily insulin dose (mean 0.25 units/kg/day). CONCLUSIONS:We report genotypic and phenotypic variability in association with clinical features, including age of onset and severity. GLP1RA therapy was associated with improvements in diabetic control. Longer-term follow-up is required to monitor for sustained benefit and for progression or improvement in other WFS clinical features.

BACKGROUND:Mitochondrial proteins are encoded by both mitochondrial- and nuclear-encoded genes. Because mitochondrial DNA (mtDNA) is maternally inherited, admixed individuals may have different ancestral sources for their nuclear and mitochondrial genomes. The potential incompatibility between these genomic components may cause suboptimal mitochondrial function and result in energy-related pathologies. This incompatibility, or 'mitonuclear discordance', is defined as the proportion of the nuclear genome not derived from the same ancestral source as the mtDNA. METHODS:Based on this understanding, we hypothesized that increased mitonuclear discordance would be associated with lower mitochondrial copy number and increased risk of gout, type 2 diabetes and chronic kidney disease. We tested this prediction using genomic data from a cohort of 2301 New Zealanders with Polynesian ancestry (Indigenous Māori and Pacific peoples living in Aotearoa New Zealand). RESULTS:We observed that increased mitonuclear discordance was correlated with a decreased chance of gout (p = 5.08 × 10-5) and a decreased chance of diagnosis with type 2 diabetes, specifically in individuals having haplogroup B4a1a (p = 4.20 × 10-9), which was present in 86.0% of the Polynesian study cohort. No significant association was found between mitonuclear discordance and mitochondrial copy number (p = 0.93), risk of chronic kidney disease (p = 0.084) or gout flare frequency (p = 0.53). CONCLUSION:Overall, while these results contradicted our hypothesis, they can potentially be explained by a higher prevalence of disease-associated alleles for gout and type 2 diabetes in Polynesian genomes.

Obesity impacts physical, physiological and psychological domains of life. The long-term effects of metabolic bariatric surgery (MBS) on patient-centred outcomes such as mental health and quality of life (QOL) may enhance the management of obesity and the application of MBS. A prospective, blinded, double arm, parallel, randomised trial was carried out at a single bariatric centre in Waitemata, New Zealand. Adults with type 2 diabetes mellitus and obesity were randomised 1:1 to undergo laparoscopic sleeve gastrectomy (SG) or silastic ring Roux-en-Y gastric bypass (SR-RYGB). After unblinding at 5 years, patients were followed up at 10 years. This analysis focuses on secondary outcomes: Hospital Anxiety and Depression Scale (HADS) scores and RAND-36 QOL scores. Of 114 patients randomised, 80 patients (70.2

INTRODUCTION:Monogenic diabetes accounts for 2-5% of diabetes. Although its identification has substantial therapeutic implications, more than 80% of affected individuals are undiagnosed or misdiagnosed as having type 1 or 2 diabetes. This consensus statement reviews genetic testing for monogenic diabetes in adults and provides evidence-based recommendations. With representation from the Australian Diabetes Society (ADS), Endocrine Society of Australia (ESA), Human Genetics Society of Australasia (HGSA), New Zealand Society for the Study of Diabetes (NZSSD) and Royal College of Pathologists of Australasia (RCPA), the writing group: (i) defined questions to be addressed, (ii) conducted critical literature reviews, (iii) graded the evidence, and (iv) generated recommendations that were refined until consensus was achieved. All contemporary literature was considered, with a focus on Australian and New Zealand data, where available. MAIN RECOMMENDATIONS:Indications for genetic testing for monogenic diabetes in adults include: (i) diabetes onset before 12 months of age, (ii) glucokinase (GCK)-hyperglycaemia phenotype, (iii) diabetes onset before 30 years of age without markers of type 1 or 2 diabetes, (iv) syndromic monogenic diabetes phenotype, or (v) high probability of monogenic diabetes using validated screening tools. Individuals undergoing genetic testing should be provided with comprehensive pre- and post-test counselling. Genetic testing typically involves next-generation sequencing, and should include classically syndromic genetic variants (eg, m.3243A>G, HNF1B variants) even in individuals with isolated diabetes. A molecular diagnosis facilitates gene-specific treatment, surveillance, reproductive planning and cascade testing of relatives. In pregnancies of individuals with GCK-hyperglycaemia, maternal treatment can be individualised to known or assumed fetal genotype. Individuals with monogenic diabetes variants of uncertain significance or negative results may be considered for further phenotype or genotype assessment and recruitment into research studies. CHANGES IN MANAGEMENT:This consensus statement aims to raise awareness of monogenic diabetes among clinicians involved in the care of patients with diabetes, and to improve genetic testing rates across Australia and New Zealand.

Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis. The Human Cell Atlas Adipose Bionetwork was established to support the generation of single-cell atlases of human AT as well as the development of unified approaches and consensus for cell annotation. Here, we provide a first roadmap from this bionetwork, including our suggested cell annotations for humans and mice, with the aim of describing the state of the field and providing guidelines for the production, analysis, interpretation and presentation of AT single-cell data. In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.

Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are common bariatric procedures that are effective in treating type 2 diabetes (T2D) in patients with obesity. The addition of a silastic-ring (SR) to LRYGB may increase weight loss, reduce weight regain, and improve diabetes remission. Five and seven-year results from a prospective, randomized, parallel, two-arm, clinical trial at North Shore Hospital (Auckland, Aotearoa New Zealand) found that SR-LRYGB was superior to LSG for diabetes remission and weight loss following surgery, with acceptable complication rates. Results on longer-term outcomes are still emerging in the literature. A 10-year analysis was conducted on 114 patients with T2D who underwent SR-LRYGB or LSG. The primary outcome was diabetes remission assessed at 10 years. Secondary outcomes included percentage total body weight loss (

Type 2 diabetes (T2D) is sub-optimally managed for many in Aotearoa New Zealand, and disproportionately affects Māori and Pacific peoples. In February 2021, SGLT2i/GLP1RA agents were funded for use for the first time with prioritisation for Māori, Pacific and those with cardiovascular and/or renal disease or risk (CVRD). This study evaluates the impact of health system factors on initiation of SGLT2i/GLP1RA therapy. Primary care data was collected for patients with T2D aged 18–75 years from four primary care organisations (302 general practices) in the Auckland / Waikato region of New Zealand (Feb 2021 – July 2022). Initiation of SGLT2i/GLP1RA therapy was reviewed by patient (age, gender, ethnicity, CVRD status) and health system variables (funding, provider type, staffing, patient numbers, rurality, after-hours access). Logistic regression was used to estimate the odds ratio of a patient being dispensed SGLT2i/GLP1RA. Of 57,743 patients with T2D, 22,331 were eligible for funded SGLT2i/GLP1RA access and 10,272 of those (46.0

Objective To explore the barriers and enablers to accessing diabetes eye care services among adults in Auckland.Design This was a qualitative study that used semistructured interviews. We performed a thematic analysis and described the main barriers and enablers to accessing services using the Theoretical Domains Framework.Setting The study took place in two of the three public funding and planning agencies that provide primary and secondary health services in Auckland, the largest city in Aotearoa New Zealand.Participants Thirty people with diabetes in Auckland who had experienced interrupted diabetes eye care, having missed at least one appointment or being discharged back to their general practitioner after missing several appointments.Results We identified barriers and enablers experienced by our predominantly Pacific and Māori participants that aligned with 7 (of the 14) domains in the Theoretical Domains Framework. The most reported barriers were transport issues, lack of awareness regarding the importance of retinal screening, time constraints, limited and/or inflexible appointment times and competing family commitments. Enablers included positive interactions with healthcare providers and timely appointment notifications and reminders.Conclusions Diabetes eye services could be made more responsive by addressing systemic barriers such as service location and transport links, appointment availability and meaningful information to aid understanding.

Introduction Diabetic retinopathy is one of the leading causes of vision impairment globally. Alongside the systemic control of diabetes and timely detection of diabetic retinopathy, the prompt initiation and completion of treatment is essential to prevent vision loss. Routine monitoring of access to retinal screening services for the detection of diabetic retinopathy is common, while monitoring of coverage of subsequent treatment services is far less common. When diabetic retinopathy treatment coverage is assessed, there is great variability in how it is defined and reported. If a definition of treatment coverage could be standardised, the monitoring of the quality of diabetes eye care could more readily be compared between settings and over time. The aim of this review is to summarise how diabetic retinopathy treatment coverage has been measured in published studies and the extent to which these have been disaggregated by population groups.Methods and analysis A search will be conducted on Medline and Embase without any language restrictions, for cohort and cross-sectional studies published from 1 January 2015 that report diabetic retinopathy treatment coverage for adults with diabetic retinopathy and/or macular oedema. We will include studies from any world region reporting diabetic retinopathy treatment coverage for one or more of: (1) laser photocoagulation; (2) intravitreal injections of antivascular endothelial growth factor agents; (3) intravitreal injections of corticosteroids; (4) vitrectomy. The PROGRESS framework (place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status and social capital) will be used to assess disaggregation by population groups. Two investigators will independently screen studies and extract relevant data. Data will be synthesised descriptively to outline the full range of definitions of diabetic retinopathy treatment coverage in the literature and identify the common sources of data used.Ethics and dissemination This review will only include published data; thus, no ethical approval will be sought. The findings of this review will be published in a peer-reviewed journal and presented at relevant conferences. The findings will also be considered in conjunction with an ongoing review on retinal screening for diabetic retinopathy to develop indicators for monitoring of services along the diabetes eye care pathway, which may include an indicator of effective service coverage.Registration Open Science Framework registration 6/08/2024: https://osf.io/5b93m

AIM:To investigate the association between HbA1c and white blood cell (WBC) counts with diabetic macular edema (DME) in type 2 diabetes (T2DM). METHODS:The study was registered on PROSPERO (registration number: CRD42024523016). A comprehensive literature search was conducted on PubMed and EMBASE up to May 2024, including studies investigating HbA1c and WBC counts in patients with T2DM, with and without DME. Standardized mean differences (SMD) and odds ratios (OR) with 95 % confidence intervals (CI) were calculated. A random-effects model was used to pool data. Risk of bias was evaluated using the Newcastle-Ottawa Scale. RESULTS:Forty-eight studies involving 207,536 participants were included. Egger's test indicated a significant publication bias among studies reporting HbA1c as OR 95 %CI. Pooled results showed that higher HbA1c may increase DME risk (SMD = 0.29, 95 %CI: 0.17 to 0.41; OR = 1.32, 95 %CI: 1.19 to 1.48). Although the same cohort, subgroup analyses found no associations between HbA1c and center-involved DME (SMD = 0.3, 95 %CI: -0.08 to 0.53) or DME development in severe non-proliferative diabetic retinopathy (NPDR)/PDR (SMD = -0.14, 95 %CI: -0.37 to 0.09). In contrast, lower lymphocyte count was significantly associated with DME (SMD = -0.24, 95 %CI: -0.45 to -0.03). CONCLUSIONS:Higher HbA1c and lower lymphocyte count may increase DME risk in T2DM, suggesting potential roles of hyperglycemia and systemic inflammation in its etiology. However, substantial heterogeneity and publication bias warrant cautious interpretation. Future research should clarify the causal role of systemic inflammation through longitudinal studies and investigate DME across different DR stages and diagnostic criteria.