A Polynesian-specific SLC22A3 variant associates with low plasma lipoprotein(a) concentrations independent of apo(a) isoform size in men.

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle in which the apolipoprotein B component is covalently linked to apolipoprotein(a). Lp(a) is a well-established independent risk factor for cardiovascular diseases. Plasma lipoprotein(a) concentrations vary enormously between individuals and ethnic groups. Several nucleotide polymorphisms in the SLC22A3 gene associate with Lp(a) concentration in people of different ethnicities. We investigated the association of a Polynesian-specific (Maori and Pacific peoples) SLC22A3 gene coding variant  p.Thr44Met) with the plasma concentration of Lp(a) in a cohort of 302 healthy Polynesian males. An apolipoprotein(a)-size independent assay assessed plasma lipoprotein(a) concentrations, all other lipid and apolipoprotein concentrations were measured using standard laboratory techniques. Quantitative real-time polymerase chain reaction was used to determine apolipoprotein(a) isoforms. The range of metabolic (HbA1c, blood pressure and blood lipids) and blood lipid variables were similar between the non-carriers and carriers in age, ethnicity and BMI adjusted models. However, rs8187715 SLC22A3 variant was significantly associated with lower lipoprotein(a) concentrations. Median lipoprotein(a) concentration was 10.60 nmol/L (IQR 5.40 to 41.00) in non-carrier group, and was 7.60 nmol/L (IQR 5.50 to 12.10) in variant carrier group (p <0.05). Lp(a) concentration  inversely correlated with apolipoprotein(a) isoform size. After correction for apolipoprotein(a) isoform size, metabolic parameters and ethnicity, the association between the SLC22A3 variant and plasma Lp(a) concentration remained. This study is the first to identify the association of this gene variant and low plasma Lp(a) concentrations. This provides evidence for better guidance on ethnic specific cut-offs when defining "elevated" and "normal" plasma Lp(a) concentrations in clinical applications.

Medication use before and after bariatric surgery: 5-year results from a randomised controlled trial of banded Roux-en-Y gastric bypass versus sleeve gastrectomy in patients with obesity and type 2 diabetes.

AIM: Bariatric surgery is an effective tool for weight loss and for improving weight related co-morbidities. Changes in medication usage after a silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) are unknown. METHODS: This was a single-centre, double-blind, randomised controlled trial. Patients were randomised to either SR-LRYGB or LSG. A medication history was obtained at regular follow-up intervals, and mean numbers of prescribed medications were analysed over 5 years. Poisson regression and generalised estimating equations were used to test for statistically significant changes in usage. RESULTS: After eight patients were lost to follow-up, data from 52 patients in each group were available for analysis. There was no difference between the SR-LRYGB or LSG groups in the number of medications prescribed, with the exception of oral glucose-lowering medications, where there was a greater decrease after SR-LRYGB compared to LSG (79% vs 55% respectively) from baseline to 5 years. At 5 years, total medication prescribed was down 10% from pre-operative levels. Prescribed insulin decreased by 72%, and cardiovascular medication decreased by 56% compared to baseline. Prescriptions for analgesia increased by 50%, psychiatric medications by 133% and proton-pump inhibitors by 81%. CONCLUSION: Both SR-LRYGB and LSG reduced requirement for diabetic and cardiovascular medications, but increased requirement for nutritional supplementation, analgesia and psychiatric medications. There was a greater reduction in oral anti-diabetic medication prescriptions following SR-LRYGB compared to LSG, but no other difference in medication usage between surgical groups was found.

The impact of CREBRF rs373863828 Pacific-variant on infant body composition.

In Maori and Pacific adults, the CREBRF rs373863828 minor (A) allele is associated with increased body mass index (BMI) but reduced incidence of type-2 and gestational diabetes mellitus. In this prospective cohort study of Maori and Pacific infants, nested within a nutritional intervention trial for pregnant women with obesity and without pregestational diabetes, we investigated whether the rs373863828 A allele is associated with differences in growth and body composition from birth to 12-18 months' corrected age. Infants with and without the variant allele were compared using generalised linear models adjusted for potential confounding by gestation length, sex, ethnicity and parity, and in a secondary analysis, additionally adjusted for gestational diabetes. Carriage of the rs373863828 A allele was not associated with altered growth and body composition from birth to 6 months. At 12-18 months, infants with the rs373863828 A allele had lower whole-body fat mass [FM 1.4 (0.7) vs. 1.7 (0.7) kg, aMD -0.4, 95% CI -0.7, 0.0, P = 0.05; FM index 2.2 (1.1) vs. 2.6 (1.0) kg/m2 aMD -0.6, 95% CI -1.2,0.0, P = 0.04]. However, this association was not significant after adjustment for gestational diabetes, suggesting that it may be mediated, at least in part, by the beneficial effect of CREBRF rs373863828 A allele on maternal glycemic status.

How have services for diabetes, eye, hearing and foot health been integrated for adults? Protocol for a scoping review.

INTRODUCTION: The global population is ageing, and by 2050, there will be almost 2.1 billion people over the age of 60 years. This ageing population means conditions such as diabetes are on the increase, as well as other conditions associated with ageing (and/or diabetes), including those that cause vision impairment, hearing impairment or foot problems. The aim of this scoping review is to identify the extent of the literature describing integration of services for adults of two or more of diabetes, eye, hearing or foot services. METHODS AND ANALYSIS: The main database searches are of Medline and Embase, conducted by an information specialist, without language restrictions, for studies published from 1 January 2000 describing the integration of services for two or more of diabetes, eye, hearing and foot health in the private or public sector and at the primary or secondary level of care, primarily targeted to adults aged ≥40 years. A grey literature search will focus on websites of key organisations. Reference lists of all included articles will be reviewed to identify further studies. Screening and data extraction will be undertaken by two reviewers independently and any discrepancies will be resolved by discussion. We will use tables, maps and text to summarise the included studies and findings, including where studies were undertaken, which services tended to be integrated, in which sector and level of the health system, targeting which population groups and whether they were considered effective. ETHICS AND DISSEMINATION: As our review will be based on published data, ethical approval will not be sought. This review is part of a project in Aotearoa New Zealand that aims to improve access to services for adults with diabetes or eye, hearing or foot conditions. The findings will be published in a peer-reviewed journal and presented at relevant conferences.

Mitochondrial disease in New Zealand: a nationwide prevalence study.

BACKGROUND: The complexities of mitochondrial disease make epidemiological studies challenging, yet this information is important in understanding the healthcare burden and addressing service and educational needs. Existing studies are limited to quaternary centres or focus on a single genotype or phenotype and estimate disease prevalence at 12.5 per 100 000. New Zealand's (NZ) size and partially integrated national healthcare system make it amenable to a nationwide prevalence study. AIM: To estimate the prevalence of molecularly confirmed and suspected mitochondrial disease on 31 December 2015 in NZ. METHODS: Cases were identified from subspecialists and laboratory databases and through interrogation of the Ministry of Health National Minimum Dataset with a focus on presentations between 2000 and 2015. Patient records were reviewed, and those with a diagnosis of 'mitochondrial disease' who were alive and residing in NZ on the prevalence date were included. These were divided into molecularly confirmed and clinically suspected cases. Official NZ estimated resident population data were used to calculate prevalence. RESULTS: Seven hundred twenty-three unique national health index numbers were identified. Five hundred five were excluded. The minimum combined prevalence for mitochondrial disease was 4.7 per 100 000 (95% confidence interval (CI): 4.1-5.4). The minimum prevalence for molecularly confirmed and suspected disease was 2.9 (95% CI 2.4-3.4) and 1.8 (95% CI 1.4-2.2) cases per 100 000 respectively. CONCLUSIONS: Within the limitations of this study, comparison to similar prevalence studies performed by specialist referral centres suggests mitochondrial disease is underdiagnosed in NZ. This highlights a need for improved education and referral pathways for mitochondrial disease in NZ.

A diabetes registrar assisted workflow intervention in general practice for systematic initiation of cardiorenal medications for patients with type 2 diabetes and albuminuria in Aotearoa New Zealand.

AIMS: To evaluate whether a weekly diabetes registrar clinic and case discussions conducted over 12 weeks in primary care improves guideline management of type 2 diabetes (T2D). METHODS: A registrar-led diabetes clinic was incorporated into two primary care practices in Tamaki Makaurau Auckland for 3 months. Patients with T2D and albuminuria appearing on practice dashboards as not prescribed angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARB), or sodium-glucose cotransporter-2 inhibitor/glucagon-like peptide-1 receptor agonist (SGLT2i/GLP1RA) were booked into these clinics. Opportunistic education sessions were provided by the diabetes registrar and prescribers were surveyed to understand the challenges in management of T2D. RESULTS: Of 125 patients booked, 80 attended the registrar clinic. Of these, 68% were clinically suitable for SGLT2i/GLP1RA and 8% for ACEi/ARB. SGLT2i/GLP1RA were initiated in 92% and ACEi/ARB in 89% of eligible patients. Two patients had contraindications for SGLT2i/GLP1RA, and one patient declined both. Additional cardiorenal medications were initiated in 16% of patients. Survey responses of 12 prescribers indicated acute illness takes priority over diabetes management, and lack of time and knowledge are main barriers to optimising diabetes care. CONCLUSIONS: A visiting diabetes registrar intervention was successful in initiating guideline medications for T2D in primary care. It remains to be evaluated whether this leads to practice-wide improvements in prescribing gaps in the short or longer term.

The use of precision diagnostics for monogenic diabetes: a systematic review and expert opinion.

BACKGROUND: Monogenic diabetes presents opportunities for precision medicine but is underdiagnosed. This review systematically assessed the evidence for (1) clinical criteria and (2) methods for genetic testing for monogenic diabetes, summarized resources for (3) considering a gene or (4) variant as causal for monogenic diabetes, provided expert recommendations for (5) reporting of results; and reviewed (6) next steps after monogenic diabetes diagnosis and (7) challenges in precision medicine field. METHODS: Pubmed and Embase databases were searched (1990-2022) using inclusion/exclusion criteria for studies that sequenced one or more monogenic diabetes genes in at least 100 probands (Question 1), evaluated a non-obsolete genetic testing method to diagnose monogenic diabetes (Question 2). The risk of bias was assessed using the revised QUADAS-2 tool. Existing guidelines were summarized for questions 3-5, and review of studies for questions 6-7, supplemented by expert recommendations. Results were summarized in tables and informed recommendations for clinical practice. RESULTS: There are 100, 32, 36, and 14 studies included for questions 1, 2, 6, and 7 respectively. On this basis, four recommendations for who to test and five on how to test for monogenic diabetes are provided. Existing guidelines for variant curation and gene-disease validity curation are summarized. Reporting by gene names is recommended as an alternative to the term MODY. Key steps after making a genetic diagnosis and major gaps in our current knowledge are highlighted. CONCLUSIONS: We provide a synthesis of current evidence and expert opinion on how to use precision diagnostics to identify individuals with monogenic diabetes.

Some diabetes types, called monogenic diabetes, are caused by changes in a single gene. It is important to know who has this kind of diabetes because treatment can differ from that of other types of diabetes. Some treatments also work better than others for specific types, and some people can for example change from insulin injections to tablets. In addition, relatives can be offered a test to see if they are at risk. Genetic testing is needed to diagnose monogenic diabetes but is expensive, so it's not possible to test every person with diabetes for it. We evaluated published research on who should be tested and what test to use. Based on this, we provide recommendations for doctors and health care providers on how to implement genetic testing for monogenic diabetes.

Investigating the distribution of primary and secondary care referrals for public-funded bariatric surgery at Counties Manukau Health (CMH).

AIMS: This study investigated variations in referral rates for bariatric surgery from primary and secondary care providers across the Counties Manukau district health board (CMDHB), with the aim of identifying "hot spots" for referrals so that intervention to help achieve equitable access to bariatric surgery can be implemented. METHODS: Referral data was gathered from hospital referral records from January 2017 to January 2019 (n=1,440). Referral rate per geographical location within the CMDHB catchment was calculated using 2018 census figures. RESULTS: Of the 1,195 referrals included, 1040 (87%) referrals were from primary care. The referrals came from 328 general practitioners (GPs) across 158 practices. There was considerable regional variation in referral rates per 1000 people, from a peak of 71.5/1000 to a low of 0.2/1000. Eighty-six percent of secondary care referrals were received from the public system and the remainder from private practice. The most common referral specialty was diabetes, followed by general surgery and orthopaedics. Out of these referrals, 434 (36%) proceeded to bariatric surgery. Pakeha (50%) were more likely to proceed to surgery than Maori (31%) and Pasifika (22%), despite similar referral numbers. CONCLUSION: There is significant variation in referrals for bariatric surgery across CMDHB. Systematic discussion of bariatric surgery with every patient who is likely to benefit is not occurring, given relatively low referral volumes.

The New Zealand eating behavior questionnaire - Validation study for a novel assessment tool to describe actionable eating behavior traits.

Individualised management of obesity remains challenging and, to date, most treatment is based on clinical judgement. This study aimed to develop and validate a novel questionnaire-based tool to identify three pre-defined eating behavior (EB) traits, emotional eating, reduced satiety (constant hunger) and reduced satiation (feasters) that may predict selective medication response given their targeted actions. We recruited 977 individuals from a tertiary academic diabetes clinic to participate in this two-phase validation study. Participants self-reported weight management activities and were asked to self-assess their EB characteristics. The initial questionnaire included 42 visual analogue scale questions. In Phase I, 729 participants completed the questionnaire, including Maori (11.8%) and Pacific peoples (19.3%). After random division of the study sample, Exploratory Factor Analysis (EFA) confirmed a three-factor model as the best fit. Stepwise removal of items with inadequate factor loading retained 27 of 42 items, which accounted for 96% of the variance. Confirmatory Factor Analysis (CFA), performed on the second half of the sample, demonstrated good model fit with the final 27-item questionnaire. Internal consistency was high for factor (α = 0.82-0.95) and demographic subgroups, and similar to those obtained in the EFA. Test-retest reliability in a subset of 399 participants who repeated the questionnaire after a four-week interval (Phase II) showed moderate to good reliability. Participants classified into one of three EB types based on the highest median score among the factors. Test-retest reliability was robust for emotional eaters (71.25%) and constant hunger (68.9%). The correlation between aggregate EB score (sum of three EB scores) and BMI was significant (Spearman rho = 0.314, P = .0005). The questionnaire reliably identified three distinct EB traits, which may be informative for precision medicine applications for obesity management.

Magnetic resonance study of visceral, subcutaneous, liver and pancreas fat changes after 12 weeks intermittent fasting in obese participants with prediabetes.

BACKGROUND: It is not clear whether there are differences in proportions of fat loss from visceral:subcutaneous depots by probiotic supplementation, ethnicity or sex during weight loss; or whether visceral/pancreatic fat depot changes are related to changes in HbA1c. Our objective is to investigate whether weight loss from different fat depots is related to these factors during weight loss achieved by intermittent fasting. METHOD: Prediabetes participants on 5:2 intermittent fasting were randomized 1:1 to either daily probiotic or placebo for 12 weeks. Twenty-four patients had magnetic resonance imaging data at baseline and 12 weeks. RESULTS: After 12 weeks of intermittent fasting, subcutaneous fat (%) changed from 35.9 ± 3.1 to 34.4 ± 3.2, visceral fat (%) from 15.8 ± 1.3 to 14.8 ± 1.2, liver fat (%) from 8.7 ± 0.8 to 7.5 ± 0.7 and pancreatic fat (%) from 7.7 ± 0.5 to 6.5 ± 0.5 (all p < 0.001). Changes in weight, HbA1c, SAT, VAT, LF and PF did not differ significantly between probiotic and placebo groups. CONCLUSION: Overall weight loss was correlated with fat loss from subcutaneous depots. Losses from different fat depots did not correlate with changes in HbA1c or differ by probiotic supplementation, ethnicity or sex.

Genetic testing for misclassified monogenic diabetes in Maori and Pacific peoples in Aotearoa New Zealand with early-onset type 2 diabetes.

Aims: Monogenic diabetes accounts for 1-2% of diabetes cases yet is often misdiagnosed as type 2 diabetes. The aim of this study was to examine in Maori and Pacific adults clinically diagnosed with type 2 diabetes within 40 years of age, (a) the prevalence of monogenic diabetes in this population (b) the prevalence of beta-cell autoantibodies and (c) the pre-test probability of monogenic diabetes. Methods: Targeted sequencing data of 38 known monogenic diabetes genes was analyzed in 199 Maori and Pacific peoples with BMI of 37.9 ± 8.6 kg/m2 who had been diagnosed with type 2 diabetes between 3 and 40 years of age. A triple-screen combined autoantibody assay was used to test for GAD, IA-2, and ZnT8. MODY probability calculator score was generated in those with sufficient clinical information (55/199). Results: No genetic variants curated as likely pathogenic or pathogenic were found. One individual (1/199) tested positive for GAD/IA-2/ZnT8 antibodies. The pre-test probability of monogenic diabetes was calculated in 55 individuals with 17/55 (31%) scoring above the 20% threshold considered for diagnostic testing referral. Discussion: Our findings suggest that monogenic diabetes is rare in Maori and Pacific people with clinical age, and the MODY probability calculator likely overestimates the likelihood of a monogenic cause for diabetes in this population.

Seven-Year Results of a Randomized Trial Comparing Banded Roux-en-Y Gastric Bypass to Sleeve Gastrectomy for Type 2 Diabetes and Weight Loss.

INTRODUCTION: 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. Limited data from randomized trials are available comparing longevity of diabetes remission directly between the two procedures beyond 5 years. METHODS: A prospective, randomized, parallel, two-arm, clinical trial comparing the outcomes of silastic ring (SR)-LRYGB versus LSG was conducted at a single (Auckland, New Zealand) center. Patients and researchers were blinded until the 5-year mark and follow-up after this was unblinded. Eligible patients had T2D of > 6 months duration with a BMI 35--65 kg/m2 and were aged 20-55 years. Randomization was 1:1 to SR-LRYGB and LSG following induction of anesthesia and was stratified by age group, BMI group, ethnicity, diabetes duration, and insulin therapy. The primary outcome was T2D remission, defined as HbA1c < 6% (42 mmol/mol), without the use of glucose-lowering medications. RESULTS: A total of 114 patients were randomized of whom 6 died before the 7-year follow-up (2 SR-LRYGB, 4 LSG). Diabetes remission, assessed in 89 (82.4%) of the remaining patients, was seen in 23/50 (46.0%) after SR-LRYGB and 12/39 (30.8%) after LSG (adjusted OR 4.64, 95% CI 1.39, 15.52, p = 0.013). Percentage total body weight loss was greater after SR-LRYGB than LSG (26.2% vs 13.4%; absolute difference 12.8%; 95% CI 7.2%, 18.2%; p < 0.001). Complication rates were similar between groups. CONCLUSION: SR-LRYGB was superior to LSG for diabetes remission and weight loss at 7 years following surgery, with acceptable complication rates.

Use of public sector diabetes eye services in New Zealand 2006-2019: Analysis of national routinely collected datasets.

OBJECTIVE: To assess diabetes eye service use in New Zealand among people aged ≥15 years by estimating service attendance, biennial screening rate, and disparities in the use of screening and treatment services. METHODS: We obtained Ministry of Health data from the National Non-Admitted Patient Collection on diabetes eye service events between 1 July 2006 and 31 December 2019 and sociodemographic and mortality data from the Virtual Diabetes Register and linked these using a unique patient identifier (encrypted National Health Index). We 1) summarized attendance at retinal screening and ophthalmology services, 2) calculated biennial and triennial screening rate, 3) summarized treatment with laser and anti-VEGF and used log-binomial regression to examine associations of all of these with age group, ethnicity, and area-level deprivation. RESULTS: In total, 245,844 people aged ≥15 years had at least one diabetes eye service appointment attended or scheduled; half of these (n = 125,821, 51.2%) attended only retinal screening, one-sixth attended only ophthalmology (n = 35,883, 14.6%) and one-third attended both (n = 78,300, 31.8%). The biennial retinal screening rate was 62.1%, with large regional variation (73.9% in Southern District to 29.2% in West Coast). Compared with NZ Europeans, Maori were approximately twice as likely to never receive diabetes eye care or to access ophthalmology when referred from retinal screening, 9% relatively less likely to receive biennial screening and received the fewest anti-VEGF injections when treatment was commenced. Disparities in service access were also present for Pacific Peoples compared to NZ Europeans, younger and older age groups compared to those aged 50-59 years and those living in areas with higher deprivation. CONCLUSIONS: Access to diabetes eye care is suboptimal, with substantial disparity between age groups, ethnicity groups, area level deprivation quintile and across districts. Efforts to improve access to and quality of diabetes eye care services must include strengthening data collection and monitoring.

A Polynesian-specific missense CETP variant alters the lipid profile.

Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Maori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.

A Systematic Review of the use of Precision Diagnostics in Monogenic Diabetes.

Monogenic forms of diabetes present opportunities for precision medicine as identification of the underlying genetic cause has implications for treatment and prognosis. However, genetic testing remains inconsistent across countries and health providers, often resulting in both missed diagnosis and misclassification of diabetes type. One of the barriers to deploying genetic testing is uncertainty over whom to test as the clinical features for monogenic diabetes overlap with those for both type 1 and type 2 diabetes. In this review, we perform a systematic evaluation of the evidence for the clinical and biochemical criteria used to guide selection of individuals with diabetes for genetic testing and review the evidence for the optimal methods for variant detection in genes involved in monogenic diabetes. In parallel we revisit the current clinical guidelines for genetic testing for monogenic diabetes and provide expert opinion on the interpretation and reporting of genetic tests. We provide a series of recommendations for the field informed by our systematic review, synthesizing evidence, and expert opinion. Finally, we identify major challenges for the field and highlight areas for future research and investment to support wider implementation of precision diagnostics for monogenic diabetes.

Twelve tips for improving the quality of assessor judgements in senior medical student clinical assessments.

Assessment of senior medical students is usually calibrated at the level of achieving expected learning outcomes for graduation. Recent research reveals that clinical assessors often balance two slightly different perspectives on this benchmark. The first is the formal learning outcomes at graduation, ideally as part of a systematic, program-wide assessment approach that measures learning achievement, while the second is consideration of the candidate's contribution to safe care and readiness for practice as a junior doctor. The second is more intuitive to the workplace, based on experience working with junior doctors. This perspective may enhance authenticity in assessment decisions made in OSCEs and work-based assessments to better align judgements and feedback with professional expectations that will guide senior medical students and junior doctors' future career development. Modern assessment practices should include consideration of qualitative as well as quantitative information, overtly including perspectives of patients, employers, and regulators. This article presents 12 tips for how medical education faculty might support clinical assessors by capturing workplace expectations of first year medical graduates and develop graduate assessments based on a shared heuristic of 'work-readiness'. Peer-to-peer assessor interaction should be facilitated to achieve correct calibration that 'merges' the differing perspectives to produce a shared construct of an acceptable candidate.

Monogenic diabetes in New Zealand - An audit based revision of the monogenic diabetes genetic testing pathway in New Zealand.

Aims: To evaluate (a) the diagnostic yield of genetic testing for monogenic diabetes when using single gene and gene panel-based testing approaches in the New Zealand (NZ) population, (b) whether the MODY (Maturity Onset Diabetes of the Young) pre-test probability calculator can be used to guide referrals for testing in NZ, (c) the number of referrals for testing for Maori/Pacific ethnicities compared to NZ European, and (d) the volume of proband vs cascade tests being requested. Methods: A retrospective audit of 495 referrals, from NZ, for testing of monogenic diabetes genes was performed. Referrals sent to LabPlus (Auckland) laboratory for single gene testing or small multi-gene panel testing, or to the Exeter Genomics Laboratory, UK, for a large gene panel, received from January 2014 - December 2021 were included. Detection rates of single gene, small multi-gene and large gene panels (neonatal and non-neonatal), and cascade testing were analysed. Pre-test probability was calculated using the Exeter MODY probability calculator and ethnicity data was also collected. Results: The diagnostic detection rate varied across genes, from 32% in GCK, to 2% in HNF4A, with single gene or small gene panel testing averaging a 12% detection rate. Detection rate by type of panel was 9% for small gene panel, 23% for non-neonatal monogenic diabetes large gene panel and 40% for neonatal monogenic diabetes large gene panel. 45% (67/147) of patients aged 1-35 years at diabetes diagnosis scored <20% on MODY pre-test probability, of whom 3 had class 4/5 variants in HNF1A, HNF4A or HNF1B. Ethnicity data of those selected for genetic testing correlated with population diabetes prevalence for Maori (15% vs 16%), but Pacific People appeared under-represented (8% vs 14%). Only 1 in 6 probands generated a cascade test. Conclusions: A new monogenic diabetes testing algorithm for NZ is proposed, which directs clinicians to choose a large gene panel in patients without syndromic features who score a pre-test MODY probability of above 20%.

Association of rs9939609 in FTO with BMI among Polynesian peoples living in Aotearoa New Zealand and other Pacific nations.

The fat mass and obesity associated (FTO) locus consistently associates with higher body mass index (BMI) across diverse ancestral groups. However, previous small studies of people of Polynesian ancestries have failed to replicate the association. In this study, we used Bayesian meta-analysis to test rs9939609, the most replicated FTO variant, for association with BMI with a large sample (n = 6095) of Aotearoa New Zealanders of Polynesian (Maori and Pacific) ancestry and of Samoan people living in the Independent State of Samoa and in American Samoa. We did not observe statistically significant association within each separate Polynesian subgroup. Bayesian meta-analysis of the Aotearoa New Zealand Polynesian and Samoan samples resulted in a posterior mean effect size estimate of +0.21 kg/m2, with a 95% credible interval [+0.03 kg/m2, +0.39 kg/m2]. While the Bayes Factor (BF) of 0.77 weakly favors the null, the BF = 1.4 Bayesian support interval is [+0.04, +0.20]. These results suggest that rs9939609 in FTO may have a similar effect on mean BMI in people of Polynesian ancestries as previously observed in other ancestral groups.

Uncovering Barriers and Facilitators of Weight Loss and Weight Loss Maintenance: Insights from Qualitative Research.

Long-term weight loss maintenance is often difficult to achieve. This review analysed qualitative data on self-perceived barriers and facilitators of weight loss and weight loss maintenance among weight loss intervention participants. A literature search was conducted using electronic databases. Qualitative studies written in English and published between 2011-2021 were eligible for inclusion if they explored the perspectives and experiences of individuals who received standardised dietary and behavioural support for weight loss. Studies were excluded if weight loss was achieved through self-directed methods, only increasing physical activity, or surgical or pharmacological interventions. Fourteen studies were included, totaling 501 participants from six countries. Thematic analysis was used to identify four aggregate themes: internal factors (i.e., motivation and self-efficacy), programme-specific factors (i.e., the intervention diet), social factors (i.e., supporters and saboteurs), and environmental factors (i.e., an obesogenic environment). Our findings demonstrate that internal, social, and environmental factors all influence weight loss success, as well as the acceptability of the weight loss intervention. Future interventions may be more successful if they prioritise participant acceptability and engagement by, for example, providing tailored interventions, a structured relapse management plan, strategies to enhance autonomous motivation and emotional self-regulation, and extended contact during weight loss maintenance.