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Rosemary M Hall, Amber Parry Strong, Jeremy D KrebsCentre for Endocrine, Diabetes and Obesity Research, Capital and Coast District Health Board, Wellington, New Zealand Abstract: Dietary strategies are fundamental in the management of diabetes. Historically, strict dietary control with a low carbohydrate diet was the only treatment option. With increasingly effective medications, the importance of dietary change decreased. Recommendations focused on reducing dietary fat to prevent atherosclerotic disease, with decreasing emphasis on the amount and quality of carbohydrate. As the prevalence of obesity and diabetes escalates, attention has returned to the macronutrient composition of the diet. Very low carbohydrate diets (VLCD's) have demonstrated effective initial weight loss and improvement in glycemic control, but difficult long-term acceptability and worsening lipid profile. Modifications to the very low carbohydrate (VLC) have included limiting saturated fat and increasing carbohydrate (CHO) and protein. Reducing saturated fat appears pivotal in reducing low-density lipoprotein (LDL) cholesterol and may mitigate adverse effects of traditional VLCD's. Increased dietary protein enhances satiety, reduces energy intake, and improves glycemic homeostasis, but without sustained improvements in glycemic control or cardiovascular risk over and above the effect of weight loss. Additionally, recent studies in type 1 diabetes mellitus suggest promising benefits to diabetes control with low carbohydrate diets, without concerning effects on ketosis or hypoglycemia. Dietary patterns may highlight pertinent associations. For example, Mediterranean-style and paleolithic-type diets, low in fat and carbohydrate, are associated with reduced body weight and improved glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM). A feature of these dietary patterns is low refined CHO and sugar and higher fiber, and it is possible that increasing sugar consumption is having a substantial effect on global escalations in obesity and T2DM. Dietary recommendations in type 1 diabetes and T2DM are changing. Dietary CHO is unquestionably important, but long-term acceptability of any diet is critical to sustain improvements in health benefits. Personalized dietary management, using a variety of dietary approaches, may be the key to optimal diabetes outcomes. Keywords: low carbohydrate diets, type 2 diabetes, dietary intervention studies, type 1 diabetes, paleo nutrition

Aims: To test if a New Zealand food-based Mediterranean diet (NZMedDiet) with behavioural intervention improves cardiometabolic health and wellbeing., Methods: A randomised controlled trial comparing 12 weeks of the NZMedDiet to usual diet in participants with increased cardiometabolic risk (metabolic syndrome severity score [MetSSS] > 0.35). The intervention group was provided with food and recipes to meet 75% of their energy requirements, supported by a behavioural intervention to improve adherence. The primary outcome measure was (MetSSS) after 12 weeks., Results: Two hundred individuals with mean (SD) age 49.9 (10.9) years of which 62% women were enrolled with their household/whānau. After 12 weeks, the mean (SD) MetSSS was 1.0 (0.7) in the control (n = 98) and 0.8 (0.5) in the intervention (n = 102) group; estimated difference (95% confidence interval [CI]) of -0.05 (-0.16 to 0.06), p = 0.35. The Mediterranean diet score (PyrMDS) was greater in the intervention group 1.6 (1.1-2.1), p < 0.001, consistent with a change to a more Mediterranean dietary pattern. Weight reduced in the NZMedDiet group compared with control (-1.9 kg [-2.0 to -0.34]), p = 0.006 and wellbeing, assessed by the SF-36 quality of life questionnaire, and improved across all domains. For example, the physical component summary score difference (95% CI) was 4.0 (2.4-5.7), p < 0.001, and the mental component summary score difference was 3.0 (0.7-5.2), p = 0.01., Conclusion: In participants with increased cardiometabolic risk, food provision with a Mediterranean dietary pattern and a behavioural intervention did not improve metabolic risk scores but was associated with reduced weight and improved quality of life., (© 2024 John Wiley & Sons Ltd.)

Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL)-like particle in which the apolipoprotein B component is covalently linked to apolipoprotein(a) (apo(a)). Lp(a) is a well-established independent risk factor for cardiovascular diseases. Plasma Lp(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 (Māori 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 apo(a)-size independent assay assessed plasma Lp(a) concentrations; all other lipid and apolipoprotein concentrations were measured using standard laboratory techniques. Quantitative real-time polymerase chain reaction was used to determine apo(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 Lp(a) concentrations. Median Lp(a) concentration was 10.60 nmol/L (IQR: 5.40-41.00) in non-carrier group, and was 7.60 nmol/L (IQR: 5.50-12.10) in variant carrier group (P<0.05). Lp(a) concentration inversely correlated with apo(a) isoform size. After correction for apo(a) isoform size, metabolic parameters and ethnicity, the association between the SLC22A3 variant and plasma Lp(a) concentration remained. The present 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., (© 2024 The Author(s).)

Aims: Postprandial hyperglycemia can be problematic for people with type 1 diabetes (T1DM) following carbohydrate-restricted diets. Bolus insulin calculated for meal protein plus carbohydrate may help. This study evaluated the effect of additional bolus insulin using an insulin-to-protein ratio (IPR) on glycaemic control., Materials and Methods: Participants with T1DM aged ≥18-years were randomly allocated (1:1) to either carbohydrate and protein-based, or carbohydrate-based insulin dosing alone for 12 weeks while following a carbohydrate-restricted diet (50-100 g/day). Measurement of HbA1c and continuous glucose monitoring occurred at baseline and 12 weeks, with assessment of participant experience at 12 weeks., Results: Thirty-four participants were randomised, 22 female, mean(SD): age 39.2 years (12.6) years; diabetes duration 20.6 years (12.9); HbA1c 7.3 % (0.8), 56.7 mmol/mol (9.2). Seven in each group used insulin pump therapy. HbA1c reduced at 12 weeks with no difference between treatments: mean (SD) control 7.2 % (1.0), 55.7 mmol/mol (10.6); intervention 6.9 % (0.7), 52.3 mmol/mol (7.2) (p = 0.65). Using additional protein-based insulin dosing compared with carbohydrate alone, there was no difference in glycaemic variability, time spent in euglycemic range (TIR), or below range. Participants using IPR reported more control of their diabetes, but varying levels of distress., Conclusions: Additional bolus insulin using an IPR did not improve glycaemic control or TIR in patients with well controlled T1DM following a carbohydrate-restricted diet. Importantly, the use of the IPR does not increase the risk of hypoglycemia and may be preferred., Competing Interests: Declaration of competing interest We, the authors, confirm that there is no financial or personal interest or belief that could affect our objectivity. We do not hold any potential competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nut-based products are a good source of high-quality plant protein in addition to mono- and polyunsaturated fatty acids, and may aid low-glycaemic dietary strategies important for the prevention of type 2 diabetes (T2D). In particular, they may be advantageous in populations susceptible to dysglycaemia, such as Asian Chinese. The present study aimed to compare effects of a higher-protein nut bar (HP-NB, also higher in total fibre and unsaturated fats, comprising mixed almonds and peanuts) vs. an isoenergetic higher-carbohydrate cereal bar (HC-CB) within the diet of 101 Chinese adults with overweight and normo- or hyperglycaemia. Ectopic pancreas and liver fat were characterised using magnetic resonance imaging and spectroscopy (MRI/S) as a secondary outcome. Participants were randomized to receive HP-NB or HC-CB daily as a 1 MJ light meal or snack replacement, in addition to healthy eating advice. Anthropometry and clinical indicators of T2D risk were assessed fasted and during an oral glucose tolerance test (OGTT), pre- and post-intervention. No significant difference was observed between diet groups for body weight, body mass index, waist or hip circumference, blood pressure, glucoregulatory markers, lipid profile or inflammatory markers over 12 weeks (all, p > 0.05). No difference was observed between glycaemic subgroups or those with normal versus high ectopic organ fat. Although HP-NB can attenuate postprandial glycaemia following a meal, no effects were observed for either fasting or glucose-mediated outcomes following longer-term inclusion in the habitual diet of Chinese adults with overweight, including at-risk subgroups.

Global increases in metabolic disorders such as type 2 diabetes (T2D), especially within Asian populations, highlight the need for novel approaches to dietary intervention. The Tū Ora study previously evaluated the effects on metabolic health of including a nut product into the diet of a New Zealand cohort of Chinese participants with overweight and normoglycaemia or prediabetes through a 12-week randomised, parallel-group clinical trial. In this current study, we compared the impact of this higher-protein nut bar (HP-NB) versus a higher-carbohydrate cereal bar (HC-CB) on the faecal microbiome by employing both 16S rRNA gene amplicon and shotgun metagenomic sequencing of pre- and post-intervention pairs from 84 participants. Despite the higher fibre, protein, and unsaturated fat content of nuts, there was little difference between dietary groups in gut microbiome composition or functional potential, with the bacterial phylum Firmicutes dominating irrespective of diet. The lack of observed change suggests the dietary impact of the bars may have been insufficient to affect the gut microbiome. Manipulating the interplay between the diet, microbiome, and metabolic health may require a more substantial and/or prolonged dietary perturbation to generate an impactful modification of the gut ecosystem and its functional potential to aid in T2D risk reduction.

Background and Objectives: Very-low calorie diets (VLCD) achieve weight loss and remission of Type 2 diabetes (T2DM), but efficacy and acceptability in non-European populations is less clear. This feasibility study examines the impact of 10% weight loss through VLCD on metabolic and body composition outcomes in a multi-ethnic cohort of Aotearoa New Zealand (AoNZ) men with prediabetes/early T2DM, and VLCD tolerability/cultural acceptability., Methods and Study Design: Participants followed a VLCD intervention (mean energy 3033kJ/day) until achievement of 10% weight loss. An oral glucose tolerance test (OGTT), hyperinsulinaemic isoglycaemic clamp with stable isotopes, hood calorimetry and dual-energy Xray absorptiometry (DXA) were undertaken before and after intervention. Qualitative data on VLCD tolerability/cultural acceptability were collected., Results: Fifteen participants were enrolled; nine achieved 10% weight loss. In this group, mean HbA1c reduced by 4.8mmol/mol (2.4-7.1) and reverted to normoglycaemia in n=5/9; mean body weight reduced by 12.0 kg (11.0-13.1) and whole-body glucose disposal improved by 1.5 mg kgFFM-1 min-1 (0.7-2.2). Blood pressure and fasting triglycerides improved significantly. No changes in hepatic glu-cose metabolism were found. In all participants who attended completion testing, HbA1c reduced by 3.4mmol/mol (SD 3.5) and total weight by 9.0kg (SD 5.7). The intervention was highly tolerable/culturally acceptable however challenges with fulfilment of cultural obligations were described., Conclusions: Results support VLCD use in AoNZ however further work to investigate ethnic differences in physiological response to VLCDs and to optimise protocols for multi-ethnic populations are required., Competing Interests: The authors have no conflicts of interest to declare

Background: Cardiometabolic diseases are highly prevalent in Aotearoa New Zealand. Dietary intake is a modifiable risk factor for such diseases and certain dietary patterns, specifically the Mediterranean diet (MedDiet), are associated with improved metabolic health. This study aims to test whether an intervention including a Mediterranean dietary pattern incorporating high quality New Zealand foods (NZMedDiet pattern) and behavior change science can improve the metabolic health of participants and their household/whānau., Methods and Analysis: This is a multi-center, three-stage trial with two parallel group superiority randomized controlled trials (RCTs), and a longitudinal cohort study embedded within the trial design. The first RCT (RCT 1) is a comparison of the NZMedDiet pattern compared to usual diet for 12 weeks. The Behavior Change Wheel was used to select and implement strategies to support participant adherence to the NZMedDiet, such as web-based nutrition education on healthy shopping and cooking. The second (RCT 2) compares online social support to no online social support for 12 weeks, administered to participants immediately following RCT 1. The third stage is a longitudinal cohort study where all participants are followed from the beginning of their start of the active intervention for 12 months in total. The primary outcome measure for each stage is the metabolic syndrome severity score (MetSSS). The duration of enrolment is 12-15 months. The total recruitment target is 200 index participants and their household/whānau members who participate with them, and the primary analyses will be intention to treat on index participants., Discussion: The trial will test whether the NZMedDiet pattern and behavior change support improves the cardiometabolic health of people in Aotearoa New Zealand., Clinical Trial Registration: https://www.anzctr.org.au/Default.aspx, identifier ACTRN12622000906752 and https://www.isrctn.com/, identifier ISRCTN89011056 (Spirit 2)., Competing Interests: MF was employed by Edible Research Ltd. DC was employed by the New Zealand Institute for Plant & Food Research Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lithander, Parry Strong, Braakhuis, Worthington, Foster, Rolleston, Davies, Mullaney, Ross, Conroy, Merry, Gearry, Weatherall and Krebs.)

There is increasing evidence that adherence to a Mediterranean dietary pattern reduces the incidence of diet-related diseases. To date, the habitual dietary intake of New Zealand (NZ) adults has not been examined in relation to its alignment with a Mediterranean-style dietary pattern. This study aimed to define the habitual dietary patterns, nutrient intakes, and adherence to the Mediterranean Diet in a sample of 1012 NZ adults (86% female, mean age 48 ± 16 years) who had their diabetes risk defined by the Australian Type 2 Diabetes Risk Assessment Tool (AUSDRISK). Dietary intakes were collected using a validated semi-quantitative NZ food frequency questionnaire, and dietary patterns were identified using principal component analysis. Reported intakes from the FFQ were used in conjunction with the Mediterranean-Style Dietary Pattern Score (MSDPS) to determine adherence to a Mediterranean dietary pattern. Mixed linear models were used to analyze the association between dietary patterns and MSDPS with demographics, health factors, and nutrient intakes. Two distinct dietary patterns were identified: Discretionary (positive loadings on processed meat, meat/poultry, fast food, sweet drinks, and sugar, sweets, and baked good) and Guideline (positive loadings on vegetables, eggs/beans, and fruits). Adherence to dietary patterns and diet quality was associated with age and ethnicity. Dietary patterns were also associated with sex. Adherence to a Mediterranean dietary pattern defined by the MSDPS was low, indicating that a significant shift in food choices will be required if the Mediterranean Diet is to be adopted in the NZ population.

Aim: Very low carbohydrate/ketogenic diets (VLC/KDs) are popular but their role in managing pre-diabetes and type 2 diabetes (T2D) is uncertain. This study uses a systematic review and meta-analysis of randomized controlled trials to estimate the effect of these diets in this population., Materials and Methods: A systematic review identified randomized controlled trials of at least 6 months duration comparing efficacy and safety of VLC/KDs (≤50 g carbohydrate or ≤10% total energy from carbohydrate per day) with a control diet (carbohydrate above the VLC/KD threshold) in adults with pre-diabetes or T2D. The primary outcome variable was glycated haemoglobin (HbA1c) after 12 months. The meta-analysis method was inverse variance weighting of mean values for continuous variables., Results: Key word searches identified 2290 studies; 2221 were not in scope. A full text review of 69 studies identified eight meeting inclusion criteria; in total, it involved 606 participants. Six studies reported HbA1c (%) at 12 months; four as change from baseline with a fixed effects estimate (95% confidence interval): VLC/KD minus control of 0.01% (-0.22 to 0.25), p = .91; and two as change from baseline: -0.65% (-0.99; -0.31) [-7.1 mmol/mol (-10.8; -3.4)], p < .001. Serum triglycerides were lower with VLC/KD versus control: -0.28 mmol/L (-0.44 to -0.11), p < .001. High-density lipoprotein was higher with an estimate of 0.04 mmol/L (0.01 to 0.08), p = .03, in the five studies reporting 12-month summary data., Conclusions: A VLC/KD may cause reductions in HbA1c and triglycerides in those with pre-diabetes or T2D but evidence of an advantage over other strategies is limited. More well-designed studies are required to provide certain evidence., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To investigate the relationship of metabolic syndrome severity score (MetSSS) with glucose regulatory and cardiovascular disease (CVD) status in Aotearoa New Zealand., Methods: MetSSS and MetSSS component coefficients were calculated for participants from the cross-sectional Workforce Diabetes Study (WDS) (n = 5,806) and Diabetes, Heart and Health Survey (DHAH) (n = 4,010) and compared by ethnicity (European, Māori, Pacific and Asian), glucose regulatory status [impaired fasting glucose, impaired glucose tolerance and type 2 diabetes) and history of cardiovascular disease., Results: MetSSS positively associated with impaired glucose regulatory status and history of cardiovascular disease for all ethnic groups. Ethnicity significantly affected different coefficients of the MetSSS components, however all ethnicities had an approximately normal MetSSS distribution, with Māori and Pacific curves being right-shifted compared to European. While the MetSSS thresholds that capture 80% of participant with type 2 diabetes (T2D) were higher for Māori and Pacific, the difference in MetSSS between those participants with and without type 2 diabetes within an ethnicity group was similar across ethnicities., Conclusion: MetSSS may have utility as a tool to quantify an individual's cardiometabolic disease risk within the multi-ethnic population of Aotearoa New Zealand, however ethnic-specific categories for disease risk are likely to be required., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Māori and peoples of Polynesia), with a frequency of up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It remains unclear whether the increased BMI is driven by increased adiposity or by increased lean mass., Methods: We undertook body composition analysis using DXA in 189 young men of Māori and Pacific descent living in Aotearoa New Zealand. Further investigation was carried out in two orthologous Arg458Gln knockin mouse models on FVB/NJ and C57BL/6j backgrounds., Results: The rs373863828 A allele was associated with lower fat mass when adjusted for BMI (p < 0.05) and was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p < 0.05). Supporting the human data, significant reductions in adipose tissue mass were observed in the knockin mice. This was more significant in older mice in both backgrounds and appeared to be the result of reduced age-associated increases in fat mass. The older male knockin mice on C57BL/6j background also had increased grip strength (p < 0.01) and lower levels of myostatin (p < 0.05)., Conclusion: Overall, these results prove that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contribute to an age-dependent lowering of fat mass, at least in males., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Aim: To investigate the accuracy and acceptability of the FreeStyle Libre Flash continuous glucose monitoring system (FSL-CGM) at alternative sites during free living and under experimental conditions., Materials and Methods: Participants with type 1 diabetes were provided with three FSL-CGM sensors applied to the upper arm, the lower back, and the anterior chest. On day 2 or 3, FSL-CGM sensor glucose was compared with venous glucose following a standard meal, during and after an exercise test, and after skin cooling. Participants completed 14-day use of the sensors with concomitant sensor scanning at all sites and capillary glucose tests. The primary outcome was accuracy between sensor sites of 14-day mean glucose. Clarke's error grids, precision absolute relative deviation, and mean absolute relative deviation were calculated., Results: In the 20 participants, compared with the arm sensor, the accuracy of the back sensor and the chest sensor was 97.9% and 98%, respectively. Under experimental conditions, the arm sensor was more accurate than that of the back and chest. All the sensors recorded higher glucose concentration than venous samples during exercise. The arm and chest sites were most preferred, with the greatest sensor failures from the back., Conclusions: The FSL-CGM is clinically accurate when the sensors are applied to alternate chest or back sites. Greater variability occurs during rapid changes in glucose concentration with all sensor sites compared with venous glucose. Understanding these variabilities allows appropriate use of an economically viable continuous glucose monitor., (© 2021 John Wiley & Sons Ltd.)

Aims/hypothesis: The minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased BMI, but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand Māori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes., Methods: A mixed meal tolerance test was completed by 172 men (56 with the A allele) of Māori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled IVGTT and hyperinsulinaemic-euglycaemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation., Results: The A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins glucagon-like polypeptide-1 or gastric inhibitory polypeptide. Consistent with this point, following an i.v. infusion of a glucose bolus, participants with an A allele had higher early (p < 0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p > 0.05) in insulin sensitivity index or glucose disposal during hyperinsulinaemic-euglycaemic clamp., Conclusions/interpretation: rs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase insulin release to reduce the risk of type 2 diabetes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aims: A self-reported online survey was performed to investigate the immediate effect of COVID-19 lockdown restrictions in New Zealand on dietary intake, and lifestyle behaviours among pregnant women with diabetes., Participants/methods: The survey was sent to 82 pregnant women who had Type 1, Type 2 Diabetes, or Gestational Diabetes and attended the Diabetes in Pregnancy Clinic in Wellington, New Zealand in May 2020, while the most restrictive COVID-19 lockdown measures were in place. All women received standard pregnancy nutrition advice provided by a dietitian, were monitoring blood glucose levels with nursing support, and seeing specialist endocrinologists and obstetricians for their pregnancy care., Results: Fifty women (61%) responded to the survey. There was no evidence of differences in dietary intake during the restrictions, compared to before, for most food items. During the restriction's women consumed more bread (Odds Ratio (95% CI): 0.39 (0.18-0.83) p = 0.02); less battered fish: 3.11 (1.20-8.05) p = 0.02; and less hot chips/fries: 6.32 (2.67-14.93) p < 0.0001. During the restriction's women consumed more meals at home: 0.05 (0.14-0.15) p < 0.0001; less takeaways: 3.63 (1.54-7.34) p = 0.003; and less restaurant and café meals: 15.05 (6.03-37.59) p < 0.0001, when the services reopened., Conclusions: The nutrition of pregnant women with diabetes was not compromised during a brief COVID-19 lockdown restriction. This finding is reassuring, with countries worldwide adopting brief intermittent lockdown periods to restrict the spread of the COVID-19 virus., Competing Interests: Declaration of competing interest The authors declare they have no competing interests., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Until recently, most patients with diabetes worldwide have been diagnosed when symptomatic and have high cardiovascular risk, meaning most should be prescribed cardiovascular preventive medications. However, in New Zealand, a world-first national programme led to approximately 90% of eligible adults being screened for diabetes by 2016, up from 50% in 2012, identifying many asymptomatic patients with recent-onset diabetes. We hypothesised that cardiovascular risk prediction equations derived before widespread screening would now significantly overestimate risk in screen-detected patients., Methods: New Zealanders aged 30-74 years with type 2 diabetes and without known cardiovascular disease, heart failure, or substantial renal impairment were identified from the 400 000-person PREDICT primary care cohort study between Oct 27, 2004, and Dec 30, 2016, covering the period before and after widespread screening. Sex-specific equations estimating 5-year risk of cardiovascular disease were developed using Cox regression models, with 18 prespecified predictors, including diabetes-related and renal function measures. Equation performance was compared with an equivalent equation derived in the New Zealand Diabetes Cohort Study (NZDCS), which recruited between 2000 and 2006, before widespread screening., Findings: 46 652 participants were included in the PREDICT-1° Diabetes subcohort, of whom 4114 experienced first cardiovascular events during follow-up (median 5·2 years, IQR 3·3-7·4). 14 829 (31·8%) were not taking oral hypoglycaemic medications or insulin at baseline. Median 5-year cardiovascular risk estimated by the new equations was 4·0% (IQR 2·3-6·8) in women and 7·1% (4·5-11·2) in men. The older NZDCS equation overestimated median cardiovascular risk by three times in women (median 14·2% [9·7-20·0]) and two times in men (17·1% [4·5-20·0]). Model and discrimination performance measures for PREDICT-1° Diabetse equations were also significantly better than for the NZDCS equation (eg, for women: R 2 =32% [95% CI 29-34], Harrell's C=0·73 [0·72-0·74], Royston's D=1·410 [1·330-1·490] vs R 2 =24% [21-26], C=0·69 [0·67-0·70], and D=1·147 [1·107-1·187])., Interpretation: International treatment guidelines still consider most people with diabetes to be at high cardiovascular risk; however, we show that recent widespread diabetes screening has radically changed the cardiovascular risk profile of people with diabetes in New Zealand. Many of these patients have normal renal function, are not dispensed glucose-lowering medications, and have low cardiovascular risk. These findings have clear international implications as increased diabetes screening is inevitable due to increasing obesity, simpler screening tests, and the introduction of new-generation glucose-lowering medications that prevent cardiovascular events. Cardiovascular risk prediction equations derived from contemporary diabetes populations, with multiple diabetes-related and renal function predictors, will be required to better differentiate between low-risk and high-risk patients in this increasingly heterogeneous population and to inform appropriate non-pharmacological management and cost-effective targeting of expensive new medications., Funding: Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background & Aim: Intermittent fasting (IF) is a dietary intervention that has been investigated as an alternative weight-loss diet due to conventional approaches having poor long-term adherence. However, the macronutrient and micronutrient intake and composition of IF diets have been overlooked. The primary aim of this study was to describe the macronutrient and micronutrient intake of individuals following the 5:2 intermittent fasting diet (IF 5:2)., Methods: Thirty eight overweight and obese participants were included from two previous studies of IF 5:2. The participants selected included 27 males and 11 females, with and without Type 2 Diabetes. The dietary intervention, IF 5:2, consisted of two days per week fasting, either consecutive or non-consecutive, and five days per week of habitual intake. Prospectively completed 4-day estimated food records were used to assess macronutrient and micronutrient intake at baseline and week six. The 4-day records were weighted to give a mean daily intake during IF 5:2., Results: During IF 5:2 the median (25th, 75th quartile) daily macronutrient composition was 22 (19, 24)% from protein, 33 (29, 37)% from fat and 39 (36, 43)% from carbohydrates. The intake (g/d) of carbohydrates and fibre decreased significantly from baseline to week six (p < 0.001) as well as on fasting days compared to non-fasting days (p < 0.001). The intake of calcium, zinc, magnesium and potassium were lower than recommended guidelines. Sodium intake exceeded the suggested daily target. On fasting days, the percent of total energy from protein significantly increased from 21% to 25% (p = 0.02). Despite intake being unrestricted on non-fasting days the energy intake decreased by week six when compared with baseline., Conclusion: The composition of IF 5:2 was a high protein, moderate fat, low carbohydrate diet with a low fibre intake. Some micronutrients have lower than recommended intake. However, overall IF 5:2 is a safe acceptable weight-loss diet strategy., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Research has documented a low rate of opioid use disorder (OUD) treatment utilization among individuals involved in the criminal justice system. However, racial disparities in sources of payment for OUD treatment have not been examined in the existing literature., Aim of the Study: Although substance use disorder (SUD) treatment is relatively rare for all criminal justice system involved racial-groups, previous research has indicated that, among individuals with SUD, members of racial minority groups receive treatment at lower rates than their non-Hispanic White counterparts. Given the alarming rise of OUD in the US and the association between source of payment and utilization of health care services, this study seeks to quantify racial disparities in sources of payment for OUD treatment among individuals with criminal justice involvement., Method: Using data from the 2008-2016 National Survey of Drug Use and Health (NSDUH), this study analyzes data on non-incarcerated individuals with OUD who have had any criminal justice involvement in the previous 12 months. An extension of the Blinder-Oaxaca decomposition method for non-linear models is implemented to determine the extent that differences in OUD treatment utilization across non-Hispanic Blacks and non-Hispanic Whites are explained by observed and measurable characteristics and/or unobserved factors., Results: Results indicate that non-Hispanic Whites are more likely to have their OUD treatment paid by a court (10%) relative to non-Hispanic Blacks (4.0%). Black-White differences in measurable factors explain 87% of the disparity, while the rest is attributed to unobserved factors. Non-Hispanic Blacks are more likely to have their OUD treatment paid by public insurance (77% vs 36%) than non-Hispanic Whites and only 72% of this disparity can be explained by observed characteristics., Implications for Health Care Provision and Use: Our findings indicate racial disparities in sources of payment for OUD treatment among the criminal justice-involved population. Expansion of health insurance coverage and access to substance use disorder treatments would be beneficial for reducing health care disparities., Implications for Health Policy: Equitable treatment options in the criminal justice system that incentivize OUD treatment availability may help address racial disparities in sources of payment among the criminal justice-involved population with OUD., Implications for Further Research: Future research should focus on understanding the main factors driving the court's treatment decisions among the criminal justice system involved individuals.

This randomized controlled cross-over study compared postprandial glucose concentrations and incidence of hypoglycaemia for mealtime bolus insulin calculated for both meal protein and carbohydrate content, with ordinary dosing for carbohydrate content alone, in adults with type 1 diabetes who usually follow a carbohydrate-restricted diet. All 16 participants completed three test meals under each of the two conditions. The primary outcome was the time normalized Area Under the Curve (AUC) of glucose measurements. The mean (SD) AUC glucose concentration for insulin dosing for both protein and carbohydrate was 8.3 (2.1) mmol/L compared with 10.0 (2.2) mmol/L for carbohydrate alone. The difference (95% CI) was -1.76 mmol/L (-2.87 to -0.65), P = .003. The mean (SD) glucose concentration ≥ 8.0 mmol/L was 54.8 (32.4)% for dosing for protein and carbohydrate and 73.7 (26.3)% for carbohydrate alone, rate ratio (95% CI) 0.75 (0.62 to 0.89), P = .002. For glucose concentration < 4.0 mmol/L 5.5 (15.1)% and 2.8 (11.7)%; rate ratio (95% CI): 1.97 (0.90 to 4.27), P = .087. Calculating the meal insulin requirements based on the carbohydrate and protein content may have advantages over calculations based on carbohydrate alone. Further studies are required to determine how to best optimize this., (© 2018 John Wiley & Sons Ltd.)

Aims: To establish whether the risk of hypoglycaemia is greater with 2 consecutive days of very-low-calorie diet compared with 2 non-consecutive days of very-low-calorie diet in people with Type 2 diabetes., Methods: This was a non-blinded randomized parallel group interventional trial of intermittent fasting in adults. The participants had a BMI of 30-45 kg/m 2 , Type 2 diabetes treated with metformin and/or hypoglycaemic medications and an HbA 1c concentration of 50-86 mmol/mol (6.7-10%). The participants followed a 2092-2510-kJ diet on 2 days per week for 12 weeks. A total of 41 participants were randomized 1:1 to consecutive (n=19) or non-consecutive (n=22) day fasts, of whom 37 (n=18 and n=19, respectively) were included in the final analysis. The primary outcome was difference in the rate of hypoglycaemia between the two study arms. Secondary outcomes included change in diet, quality of life, weight, lipid, glucose and HbA 1c levels, and liver function., Results: The mean hypoglycaemia rate was 1.4 events over 12 weeks. Fasting increased the rate of hypoglycaemia despite medication reduction (RR 2.05, 95% CI 1.17 to 3.52). There was no difference between fasting on consecutive days and fasting on non-consecutive days (RR 1.54, 95% CI 0.35 to 6.11). Improvements in weight, HbA 1c , fasting glucose and quality of life were experienced by participants in both arms., Conclusions: In individuals with Type 2 diabetes on hypoglycaemic medications, fasting of any type increased the rate of hypoglycaemia. With education and medication reduction, fewer than expected hypoglycaemic events occurred. Although it was not possible to determine whether fasting on consecutive days increased the risk of hypoglycaemia, an acceptable rate was observed in both arms., (© 2018 Diabetes UK.)

Aims: To determine whether an individualized body weight-based glucose treatment in adults with type 2 diabetes (T2DM) is more likely to resolve hypoglycaemia with a single treatment without excessive rebound hyperglycaemia compared to fixed doses of 12 or 30 g of glucose., Methods: Adults with T2DM were enrolled in a cross-over study. Each episode of hypoglycaemia (capillary glucose <4.0 mmol/L) was randomly assigned to 1 of 3 treatment protocols: 0.3 g glucose/kg body-weight or a fixed dose of either 12 or 30 g glucose, independent of weight. All participants received each treatment in random order for up to 15 hypoglycaemic episodes. Glucose was re-tested 10 minutes after treatment, with a repeat dose if still <4 mmol/L., Results: Mean (SD) age of the 30 participants was 68 (8.1) years, mean weight was 91.5 (16.8) kg and mean HbA1c was 58.7 (9.2) mmol/mol. Among a total of 244 episodes of hypoglycaemia, 10 participants had 15 treatment episodes and 18 participants had fewer than 10 treatment episodes. The odds ratio, adjusted for multiple comparisons, for resolution of hypoglycaemia at 10 minutes, comparing weight-based treatment and 12 g treatment was 3.2 (95% CI, 1.1-9.0), P = .009, comparing 30 g treatment and 12 g treatment was 8.9 (95% CI, 2.2-36.6), P < .001, and comparing weight-based treatment and 30 g treatment was 0.36 (95% CI, 0.08-1.67) P = .10., Conclusion: In T2DM, both a weight-based 0.3 g/kg treatment and a fixed 30 g glucose treatment result in higher blood glucose than a 12 g treatment, along with increased probability of resolution of hypoglycaemia after 10 minutes. Both treatments result in an excess of mild rebound hyperglycaemia (>8 mmol/L) at 30 minutes., (© 2018 John Wiley & Sons Ltd.)

Background: Physiological models that are used with dynamic test data to assess insulin sensitivity (SI) assume that the metabolic target glucose concentration ( G TARGET ) is equal to fasting glucose concentration ( G 0 ). However, recent research has implied that irregularities in G 0 in diabetes may cause erroneous SI values. This study quantifies the magnitude of these errors., Methods: A clinically validated insulin/glucose model was used to calculate SI with the standard fasting assumption (SFA) G 0 = G TARGET . Then G TARGET was treated as a variable in a second analysis (VGT). The outcomes were contrasted across twelve participants with established type 2 diabetes mellitus that were recruited to take part in a 24-week dietary intervention. Participants underwent three insulin-modified intravenous glucose tolerance tests (IM-IVGTT) at 0, 12, and 24 weeks., Results: SI VGT had a median value of 3.36×10 -4 L·mU -1 ·min -1 (IQR: 2.30 - 4.95×10 -4 ) and were significantly lower ( P < .05) than the median SI SFA (6.38×10 -4 L·mU -1 ·min -1 , IQR: 4.87 - 9.39×10 -4 ). The VGT approach generally yielded lower SI values in line with expected participant physiology and more effectively tracked changes in participant state over the 24-week trial. Calculated G TARGET values were significantly lower than G 0 values (median G TARGET = 5.48 vs G 0 = 7.16 mmol·L -1 P < .001) and were notably higher in individuals with longer term diabetes., Conclusions: Typical modeling approaches can overestimate SI when G TARGET does not equal G 0 . Hence, calculating G TARGET may enable more precise SI measurements in individuals with type 2 diabetes, and could imply a dysfunction in diabetic metabolism.

Aim: To test whether weight-based treatment is more effective than usual care in people with Type 1 diabetes receiving continuous subcutaneous insulin infusion therapy with regard to both hypoglycaemia and avoiding excessive rebound hyperglycaemia., Methods: Children and adults on continuous subcutaneous insulin infusion were enrolled into a study with a crossover design. Each episode of hypoglycaemia (defined as capillary glucose <4.0 mmol/l) was randomly assigned one of two treatment protocols using glucose tablets: either 0.3 g/kg body weight or usual treatment with 15 g (adults) or 10 g (children) for capillary glucose levels 3-3.9 mmol/l or twice these doses for capillary glucose levels <3 mmol/l. All participants received each treatment in random order for up to 10 hypoglycaemic episodes. Glucose levels were re-tested 10 min after treatment, with a repeat dose if still <4 mmol/l., Results: Of the 37 participants enrolled, 35 (aged 6-68 years) completed the study. Twenty-four participants completed all treatment episodes, while 10 participants had <10 hypoglycaemic episodes and two withdrew without data. The mean glucose difference between weight-based and usual treatment after 10 min was 0.33 mmol/l (95% CI 0.005 to 0.66; P=0.047) in adults and 0.45 (95% CI 0.18 to 0.72; P=0.001) in children. The odds ratios for resolution of hypoglycaemia at 10 min with a single treatment using weight-based compared with usual treatment were 3.12 (95% CI 1.38 to 7.02; P=0.0070) in adults and 2.61 (95% CI 1.19 to 5.74; P=0.017) in children., Conclusions: Weight-based treatment using 0.3 g/kg glucose was more effective for symptomatic hypoglycaemia in children and adults with Type 1 diabetes who were using continuous subcutaneous insulin infusion than treatment based on current international recommendations., (© 2017 Diabetes UK.)

Aims: Overseas clinics specialising in management of transgender people have noted a marked increase in the numbers of people requesting therapy in the last few years. No data has been presented for New Zealand. We therefore reviewed the number of transgender people seen in the Wellington Endocrine Service to assess if the pattern was similar and assess any potential problems for service delivery., Methods: Using hospital records, we reviewed the new appointments of people who were referred for advice on gender reassignment and seen in the Wellington Endocrine Service from 1990 to 2016., Results: In total, 438 people who identified as transgender attended the clinic at least once in this period. There has been a progressive increase in number of people identifying as transgender presenting to the clinic, particularly since 2010. In addition to increasing overall numbers, there has been in particular increase in referrals for people under age 30, as well as an increasing proportion of people requesting female-to-male (FtM) therapy so that it is now approaching the number of people requesting male-to-female therapy (MtF)., Conclusion: The pattern observed is comparable to changes reported overseas. These changes have practical consequences for the delivery of both secondary and primary level healthcare, requiring an increased focus on clinical coordination between the relevant medical services and their links to the primary services sector., Competing Interests: Nil.

Aim: To develop and pilot a diabetes self-management education (DSME) program specific to the needs of New Zealanders with type 2 diabetes mellitus (T2DM)., Methods: There were two parts in the present study. The first was the development of the program. This involved a literature review, consultation with end-user groups and drafting the content of the program. In the second part, the program was tested and modified according to feedback provided by both participants and facilitators., Results: The present study achieved its primary goal of developing, piloting and modifying a DSME program specific to the New Zealand population. The DSME program was developed using concepts and content of international DSME programs. The content and concept was extensively tested via discussion groups with 71 individuals with T2DM and practice nurses to ensure the program met the unique cultural needs of New Zealanders with T2DM. Twenty-seven participants with T2DM were recruited into the pilot, of which 13 attended four of six sessions. Feedback from participants, observing nurses and facilitators was incorporated into the final program., Conclusions: DSME programs are an effective vehicle for providing individuals with T2DM the initial information and support to start self-managing their diabetes. However, to ensure DSME programs help individuals with the highest rates of diabetes and diabetes-related complications, it is important end-users participate in the development of the program. This DSME program now requires longitudinal trial to determine if in the New Zealand context it is able generate the same improvements in both clinical and qualitative outcomes as seen in similar international programs., (© 2015 Dietitians Association of Australia.)

Background: People with diabetes mellitus (DM) are using mobile phone apps to support self-management. The numerous apps available to assist with diabetes management have a variety of functions. Some functions, like insulin dose calculators, have significant potential for harm., Objectives: The study aimed to establish (1) whether people with DM in Wellington, New Zealand, use apps for DM self-management and evaluate desirable features of apps and (2) whether health professionals (HPs) in New Zealand treating people with DM recommend apps to patients, the features HPs regard as important, and their confidence with recommending apps., Methods: A survey of patients seen at a hospital diabetes clinic over 12 months (N=539) assessed current app use and desirable features. A second survey of HPs attending a diabetes conference (n=286) assessed their confidence with app recommendations and perceived usefulness., Results: Of the 189 responders (35.0% response rate) to the patient survey, 19.6% (37/189) had used a diabetes app. App users were younger and in comparison to other forms of diabetes mellitus, users prominently had type 1 DM. The most favored feature of the app users was a glucose diary (87%, 32/37), and an insulin calculator was the most desirable function for a future app (46%, 17/37). In non-app users, the most desirable feature for a future app was a glucose diary (64.4%, 98/152). Of the 115 responders (40.2% response rate) to the HPs survey, 60.1% (68/113) had recommended a diabetes app. Diaries for blood glucose levels and carbohydrate counting were considered the most useful app features and the features HPs felt most confident to recommend. HPs were least confident in recommending insulin calculation apps., Conclusions: The use of apps to record blood glucose was the most favored function in apps used by people with diabetes, with interest in insulin dose calculating function. HPs do not feel confident in recommending insulin dose calculators. There is an urgent need for an app assessment process to give confidence in the quality and safety of diabetes management apps to people with diabetes (potential app users) and HPs (potential app prescribers)., (©Leah Boyle, Rebecca Grainger, Rosemary M Hall, Jeremy D Krebs. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 30.06.2017.)

Purpose: This randomised controlled trial assessed the acute and long-term effects of daily supplementation of kanuka honey, formulated with cinnamon, chromium and magnesium on glucose metabolism, weight and lipid parameters in individuals with type 2 diabetes., Methods: Twelve individuals with type 2 diabetes received 53.5 g of a formulated honey and a control (non-formulated) kanuka honey in a random order for 40 days, using cross-over design. Fasting glucose, insulin, HbA1c, lipids and anthropometric measures were measured at baseline and end of treatment. A meal tolerance test was performed at baseline to assess acute metabolic response., Results: There was no statistically significant difference in acute glucose metabolism between treatment groups, as measured by the Matsuda index and AUC for glucose and insulin. After the 40-day intervention with honey, fasting glucose did not differ significantly between the two treatments (95 % CI -2.6 to 0.07). There was no statistically significant change in HbA1c or fasting insulin. There was a statistically significant reduction in total cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23), LDL cholesterol by -0.29 mmol/L (95 % CI -0.57 to -0.23) and weight by -2.2 kg (95 % CI -4.2 to -0.1). There was a trend towards increased HDL and reduced systolic blood pressure in the intervention treatment., Conclusion: The addition of cinnamon, chromium and magnesium supplementation to kanuka honey was not associated with a significant improvement in glucose metabolism or glycaemic control in individuals with type 2 diabetes. Use of the formulated honey was associated with a reduction in weight and improvements in lipid parameters, and should be investigated further.

Background and Objectives: To determine the effect of a low carbohydrate diet and standard carbohydrate counting on glycaemic control, glucose excursions and daily insulin use compared with standard carbohydrate counting in participants with type 1 diabetes., Methods and Study Design: Participants (n=10) with type 1 diabetes using a basal; bolus insulin regimen, who attended a secondary care clinic, were randomly allocated (1:1) to either a standard carbohydrate counting course or the same course with added information on following a carbohydrate restricted diet (75 g per day). Participants attended visits at baseline and 12 weeks for measurements of weight, height, blood pressure, HbA1c, lipid profile and creatinine. They also completed a 3-day food diary and had 3 days of continuous subcutaneous glucose monitoring., Results: The carbohydrate restricted group had significant reductions in HbA1c (63 to 55 mmol/mol (8.9-8.2%), p<0.05) and daily insulin use (64.4 to 44.2 units/day, p<0.05) and non-significant reductions in body weight (83.2 to 78.0 kg). There were no changes in blood pressure, creatinine or lipid profile and all outcomes in the carbohydrate counting group were unchanged. There was no change in glycaemic variability as measured by the mean amplitude of glycaemic excursion in either group., Conclusions: A low carbohydrate diet is a feasible option for people with type 1 diabetes, and may be of benefit in reducing insulin doses and improving glycaemic control, particularly for those wishing to lose weight.

Aim: To determine whether a weight-based hypoglycaemia treatment using 0.3 g/kg (or 0.2 g/kg) glucose effectively treats adults with Type 1 diabetes mellitus compared with an internationally recommended 15-g treatment., Methods: Patients with frequent hypoglycaemia were recruited from hospital-based diabetes clinics. The treatment for each hypoglycaemic episode, defined as capillary glucose <4.0 mmol/l, was randomly assigned to one of three protocols: 0.2 g/kg, 0.3 g/kg, or 15 g, using Dextro(TM) glucose tablets (Dextro Energy, Krefeld, Germany). Each participant received each treatment in random order for up to 15 hypoglycaemic episodes. Capillary glucose was re-tested 10 min after treatment, with a repeat dose if still < 4 mmol/l., Results: The study recruited 34 participants aged 22-71 years, whose mean (sd) BMI was 25.2 (3.1) kg/m(2) and HbA1c 63 (10.4) mmol/mol [7.9 (0.9)%]. Two people withdrew because they did not like the taste of the Dextro tablets and one was excluded because they used their own glucose preparation. Unadjusted for clustering within participants, the mean (sd) capillary glucose after 10 min was 4.67 (1.25) mmol/l for 0.3 g/kg (141 episodes), 4.29 (0.94) mmol/l for 0.2 g/kg (132 episodes), and 4.37(0.99) mmol/l for 15 g (136 episodes). Capillary glucose, adjusted for clusters and baseline, was higher after 10 min for 0.3 g/kg glucose compared with 15 g glucose; a difference of 0.26 (95% CI 0.04-0.48) mmol/l (P = 0.02), but not for 0.2 g/kg; -0.07 (95% CI -0.29-0.16) mmol/l (P = 0.56). Capillary glucose for only three hypoglycaemic episodes rose above 8 mmol/l., Conclusions: A weight-based protocol of 0.3 g/kg glucose appears more effective for treating symptomatic hypoglycaemia in adults with Type 1 diabetes than either the most common current recommendation of 15 g glucose or a 0.2 g/kg glucose dose., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Background: Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, one-carbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers., Methods: Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS)., Results: Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality = 0.52) and urine (index of individuality = 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and -35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to -80% in plasma)., Conclusions: Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: The model-based dynamic insulin sensitivity and secretion test (DISST) uses fasting glucose (G 0 ) as the basal glucose (G B ) concentration when assessing insulin sensitivity (SI). However, this model was developed in a healthy, normoglycaemic cohort. We sought to determine the suitability the DISST model has for individuals with established type 2 diabetes (T2D)., Methods: 14 participants with established T2D were recruited to take part in a dietary intervention study. Insulin-modified intravenous glucose tolerance tests (IM-IVGTT) were undertaken at week 0, 12 and 24 and were used with DISST model to identify G B . A total of 36 tests were conducted across 12 participants throughout the study. Measured G 0 and identified G B values were compared using a Kolmogorov-Smirnov (KS) and signed rank (RS) test for the cohort., Results: There were significant differences between the G 0 and identified G B values in this cohort (prs and pks < 0.0001), although both values were well correlated (R = 0.70). The residual plot demonstrates that the modified model captures the behaviour of the participants more accurately than the original model., Conclusions: This analysis has shown that G B is an important variable for modelling the glycaemic behaviour in T2D. These findings suggest that the original DISST model, while appropriate for normoglycaemic cohorts, needs to model basal glucose level as a variable for assessing individuals with established T2D.

Purpose: Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes?, Methods: Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants., Results: Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy., Conclusions: Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial.

In New Zealand 28.4% of adults now classify as obese, whilst a total of 63.8% are overweight or obese (BMI >25 kg/m²). This presents an ever increasing social and economic burden to individuals, families and the healthcare system. Obesity is a major risk factor for cancer, cardiovascular, metabolic, and respiratory disorders. Preventing obesity is the optimal long-term population strategy and must be a government priority. There are many approaches which could be taken to facilitate this, however it is important not to forget those who are currently overweight or obese. This review addresses the current therapeutic options in the treatment of obesity, focusing on lifestyle changes, medications, and surgery in New Zealand. It also presents a suggested algorithm for the clinician assessing and managing obese patients in New Zealand.

Background: Group-based diabetes self-management education (DSME) programmes have been shown to be effective. A programme tailored for the unique social and ethnic environment of New Zealand (NZ) was developed using concepts from internationally developed programmes., Aim: To assess the effectiveness of a 6 week New Zealand specific DSME programme., Methods: In this observational study people with type 2 diabetes (aged 18-80 years) from diverse cultural backgrounds were recruited from primary care. Seventeen groups of six education sessions were run. Clinical data were collected from primary care at baseline, 3, 6 and 9 months. Participants also completed a self-administered questionnaire on diabetes knowledge, and self-management behaviours., Results: 107 participants, mean age 56.7±11.3 years and mean duration of diabetes 7.5±7 years (NZ European (44%), Maori (24%), Pacific (16%) and Indian (16%)), were enrolled. Confidence in self-managing diabetes, regular examination of feet, physical activity levels and smoking rates all improved. Glycaemic control improved between baseline and 6 months (HbA1C 64.9±20.0 mmol/mol to 59.9±13.9 mmol/mol (p<0.05) (baseline 8.07%±1.80, 6 months 7.62%±1.25)), but was no different to baseline at 9 months. Systolic BP reduced from 131.9±16.4 to 127.4±18.2 mmHg (p<0.05) at 6 months, but increased to baseline levels by 9 months. Diastolic BP, triglycerides and urine microalbumin:creatinine ratio were significantly reduced at 3, 6 and 9 months., Conclusion: A group-based DSME programme designed specifically for the NZ population was effective at improving aspects of diabetes care at 6 months. The attenuation of these improvements after 6 months suggests a refresher course at that time may be beneficial., (Copyright © 2013. Published by Elsevier Ltd.)

Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1) severe, non-syndromic obesity, (2) pancreatic beta cell forms of early-onset diabetes, and (3) severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.

Objective: The optimal diet for weight loss in type 2 diabetes remains controversial. This study examined a low-carbohydrate, high-fat diet with detailed physiological assessments of insulin sensitivity, glycemic control, and risk factors for cardiovascular disease., Methods: Fourteen obese patients (body mass index [BMI] 40.6 ± 4.9 kg/m(2)) with type 2 diabetes were recruited for an "Atkins"-type low-carbohydrate diet. Measurements were made at 0, 12, and 24 weeks of weight, insulin sensitivity, HbA1c, lipids, and blood pressure., Results: Twelve completers lost a mean of 9.7 ± 1.8 kg over 24 weeks attributable to a major reduction in carbohydrates and resultant reduction in total energy intake. Glycemic control significantly improved (HbA1c -1.1 ± 0.25%) with reductions in hypoglycemic medication. Fasting glucose, homeostasis model assessment (HOMA), and area under the curve (AUC) glucose (intravenous glucose tolerance test [IVGTT]) were significantly reduced by week 12 ( p < 0.05). There were nonsignificant improvements in insulin sensitivity (SI) at week 12 ( p = 0.19) and week 24 ( p = 0.31). Systolic blood pressure was reduced (mean -10.0 mmHg between weeks 0 and 24, p = 0.13). Mean high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol all increased. The ratio of total: HDL cholesterol and triglycerides was reduced., Conclusion: A low-carbohydrate diet was well tolerated and achieved weight loss over 24 weeks in subjects with diabetes. Glycemic control improved with a reduction in requirements for hypoglycemic agents.

The objective was to determine the effect of a single dose of espresso caffeinated coffee, decaffeinated coffee, or water on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus. Eighteen participants who were habitual coffee drinkers, were studied using a random-order cross-over design. After a fasting blood sample participants consumed either a double-shot black espresso coffee, decaffeinated coffee, or hot water. The main outcomes were area under the curve (AUC) glucose and insulin, and insulin sensitivity (Matsuda index) during a 75 g oral glucose tolerance test (OGTT) performed one hour later. Other outcomes were change in glucose and insulin and also the insulinogenic index (IGI) and disposition index (DI). AUC glucose was marginally different between beverages (P=.06) being greater following caffeinated coffee than water, mean difference 104 mmol/L/180 min (95% CI 0.1 to 198.1, P=.031), or decaffeinated coffee, mean difference 92.1 mmol/L/180 min (95% CI -1.9 to 186.1, P=.055). There was no difference in AUC insulin (P=.87) or insulin sensitivity (P=.47), nor in change in glucose or insulin over the hour following beverage consumption. There was a marginal difference in IGI between beverages (P=.097) with coffee having a lower incremental increase in insulin/glucose than water (P=.037) though no difference between coffee and decaffeinated coffee (P=.54) and no difference in DI (P=.23). Black espresso coffee in people with type 2 diabetes mellitus results in a marginally greater excursion of glucose during a following OGTT compared with water or decaffeinated coffee. This effect does not appear to be mediated by changes in insulin sensitivity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims/hypothesis: To compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss, using group-based interventions, among overweight people with type 2 diabetes. Study design Multicentre parallel (1:1) design, blinded randomised controlled trial., Methods: Individuals with type 2 diabetes aged 30–75 years and a BMI >27 kg/m2 were randomised, by an independent statistician using sequentially numbered sealed envelopes, to be prescribed either a low-fat high-protein (30% of energy as protein, 40% as carbohydrate, 30% as fat) or a low-fat high carbohydrate(15% of energy as protein, 55%as carbohydrate,30% as fat) diet. Participants attended 18 group sessions over 12 months. Primary outcomes were change in weight and waist circumference assessed at baseline, 6 and 12 months.Secondary outcomes were body fatness, glycaemic control,lipid profile, blood pressure and renal function. A further assessment was undertaken 12 months after the intervention.Research assessors remained blinded to group allocation throughout. Intention-to-treat analysis was performed., Results: A total of 419 participants were enrolled (mean±SDage 58±9.5 years,BMI 36.6±6.5 kg/m2 and HbA1c 8.1±1.2%(65 mmol/mol)). The study was completed by 70%(294/419).No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up. Both groups had lost weight (2–3 kg, p<0.001) and reduced their waist circumference (2–3 cm, p<0.001) by 12 months and largely maintained this weight loss for the following 12 months. By 6 months, the difference in self-reported dietary protein between groups was small (1.1%total energy; p<0.001). No significant differences between groups were found in secondary outcomes: body fatness, HbA1c, lipids, blood pressure and renal function.There were no important adverse effects., Conclusions/interpretation: In a 'real-world' setting, prescription of an energy-reduced low-fat diet, with either increased protein or carbohydrate, results in similar modest losses in weight and waist circumference over 2 years

The Maori and Pacific Islands peoples of New Zealand suffer a greater burden of type 2 diabetes mellitus (T2DM) and associated comorbidities than their European counterparts. Empirical evidence supports the clinical application of aerobic and resistance training for effective diabetes management and potential remission, but few studies have investigated the effectiveness of these interventions in specific ethnic cohorts. We recently conducted the first trial to investigate the effect of prescribed exercise training in Polynesian people with T2DM. This article presents the cultural considerations undertaken to successfully implement the study. The research procedures were accepted and approved by cultural liaisons and potential participants. The approved methodology involved a trial evaluating and comparing the effects of two, 16-week exercise regimens (i.e. aerobic training and resistance training) on glycosylated haemoglobin (HbA1c), related diabetes markers (i.e. insulin resistance, blood lipids, relevant cytokines and anthropometric and hemodynamic indices) and health-related quality of life. Future exercise-related research or implementation strategies in this cohort should focus on cultural awareness and techniques to enhance participation and compliance. Our approach to cultural consultation could be considered by researchers undertaking trials in this and other ethnic populations suffering an extreme burden of T2DM, including indigenous Australians and Americans.

Background: Adipose tissue produces a number of inflammatory mediators. Circulating concentrations of these inflammatory markers are increasingly used as markers of local or systemic inflammation. This study compares results for 3 inflammatory adipokines measured using 2 techniques, (multiplex and ELISA), and determines the relationships with C-reactive protein (CRP), obesity, and the impact of moderate weight loss., Subjects and Methods: Fasting blood samples were collected at baseline and after a 24-week weight loss intervention. Interleukin 6 (IL-6), tumour necrosis factor alpha(TNF-alpha), and monocyte chemoattractant protein 1 (MCP-1) were measured using a standard ELISA technique or a new multiplex technique. A total of 54 women with complete data were included in this analysis., Results: Multiplex showed poor correlation with ELISA results, and were not significantly correlated with CRP. Using ELISA data, IL-6 and CRP were significantly correlated with body mass index (BMI) (r = 0.42 and r = 0.55), but MCP-1 and TNF-alpha were not (r = - 0.07 and r = 0.06). Changes in MCP-1, TNF-alpha, and IL-6 were not significantly different between control and weight loss groups. CRP was significantly reduced in weight loss vs. control group (p < 0.05), and change in CRP correlated with change in BMI (r = 0.31)., Conclusion: Circulating IL-6 and CRP, but not MCP-1 and TNF-alpha, are significantly associated with indices of adiposity in obese women. This study suggests that circulating IL-6 and CRP, but not MCP-1 and TNF-alpha, are useful markers of obesity-related inflammation.

Background: Inflammation is strongly related to obesity and the risk of cardiovascular disease (CVD). The metabolic benefits of long chain (LC) n-3 polyunsaturated fatty acid (PUFA) may be attributable to its anti-inflammatory properties., Objective: To investigate whether an individual's habitual inflammatory status influences the impact of a LC n-3 PUFA intervention on CVD risk., Design: The study was a randomized crossover design. Subjects received LC n-3 PUFA capsules or a placebo for 12 weeks, with 4-week washout between phases. Thirty women, in the top and bottom tertiles of baseline sialic acid concentration, formed raised inflammatory status (top, n = 12) and reference (bottom, n = 18) groups. Baseline data were analysed using one-way anova, differences between treatment phases were calculated at each timepoint and analysed using a random effects model., Results: At baseline, the raised inflammatory status group had significantly higher body mass index and area under the curve (AUC) insulin than the reference group. With LC n-3 PUFA supplementation, both groups showed significantly higher plasma eicosapentaenoic acid and docosahexaenoic acid at 4 and 12 weeks (p < 0.001), and lower triacylglycerols (4 weeks p < 0.01 and 12 weeks p < 0.05). The difference in AUC insulin between the two treatment phases at 12 weeks was significantly greater in the raised inflammatory status group compared to the reference group (p < 0.05). Inflammatory markers were significantly lower after 12 weeks LC n-3 PUFA supplementation compared to baseline (C-reactive protein p < 0.05 and interleukin-6 p < 0.01), but there was no significant group effect., Conclusions: Habitual inflammatory status influences the impact of LC n-3 PUFA supplementation, but it is not clear whether the effect of LC n-3 PUFA on AUC insulin is mediated through inflammatory mechanisms.

Background: Obesity, inflammation, insulin resistance and cardiovascular disease (CVD) risk are inter-related. Both weight-loss and long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) are independently known to reduce metabolic risk, but the combined effects are unclear., Objective: This study examines whether addition of LC n-3 PUFA to a low fat/high carbohydrate weight-loss programme results in greater improvements in inflammation, insulin sensitivity and CVD risk, than weight-loss alone., Design: One hundred and sixteen overweight insulin-resistant women entered a 24-week randomised intervention study. Thirty-nine women were randomised to a weight-loss programme, with LC n-3 PUFA (WLFO), 38 to a weight-loss programme with placebo oil (WLPO), and 39 to receive placebo oil, with no weight-loss programme (control)., Results: Ninety-three women completed the study (35 WLFO, 32 WLPO and 26 control), with significant weight-loss in WLFO (10.8+/-1.0%) and WLPO (12.4+/-1.0%) compared to the control group (P<0.0001). The WLFO, but not WLPO or control group, showed significant increases in adipose tissue LC n-3 PUFA (0.34+/-0.20 vs 0.17+/-0.10 and 0.16+/-0.10 %DHA, P<0.0001). Weight-loss showed significant improvements in insulin sensitivity (P<0.001), lipid profile (triglycerides P<0.05) and inflammation (sialic acid P<0.05). Time*group effects showed significant decreases in triglycerides (P<0.05) and increases in adiponectin (P<0.01) with LC n-3 PUFA, in the WLFO vs WLPO groups., Conclusions: Weight-loss improved risk factors associated with CVD, with some additional benefits of LC n-3 PUFA on triglycerides and adiponectin. Given the current low dietary intake of LC n-3 PUFA, greater attention should be given to increase these fatty acids in the treatment of obesity.

Objective: Previous studies have demonstrated benefits of high-dose long-chain omega-3 polyunsaturated fatty acid (LC omega-3 PUFA) supplements on metabolic risk. Effects of increased dietary omega-3 PUFA, via oily fish and/or plant-derived omega-3 PUFAs, are less clear and may be modulated by the omega-6:omega-3 PUFA of the habitual diet. This study examined the effect on cardiovascular disease risk markers of reducing dietary omega-6:omega-3 PUFA by changes in linoleic acid:alpha-linolenic acid (LA:LNA) and/or increasing LC omega-3 PUFA. It tested whether decreases in LA:LNA modulate effects of LC omega-3 PUFA., Methods: One hundred forty-two subjects, recruited to a 24-wk randomized study, were assigned to a control group or one of four interventions. Intervention groups received two portions of oily fish (4.5 g eicosapentaenoic acid + docosahexanoic acid) or white fish (0.7 g eicosapentaenoic acid + docosahexanoic acid) per week, and replaced habitual household fats with ones high in sunflower (high LA:LNA) or rapeseed (low LA:LNA) oil., Results: Modest dietary manipulations of omega-6 and omega-3 PUFAs resulted in significant group x time interactions for serum triacylglycerols (TAGs; P = 0.05); at 24 wk the control and two oily fish groups showed lower TAG than did the white fish/sunflower group (P = 0.05). Reductions in TAG, associated with increased oily fish intakes, were maximized when combined with lower dietary LA:LNA. There were no significant changes in several other cardiovascular disease risk markers., Conclusions: Two portions of oily fish per week led to significant reductions in TAG relative to consumption of two portions of white fish per week. Changes in TAG were maximized when combined with lower LA:LNA.

Aims: C-reactive protein (CRP) is a predictor of many diseases including type II diabetes and cardiovascular disease. Fewer studies have similarly shown sialic acid (SA) to be a predictor of obesity-related diseases, but importantly SA shows less intra-individual variability than CRP and acts as an integrated marker of the activity of a number of acute-phase proteins. This study examines the association between both CRP and SA with individual and combined features of the metabolic syndrome., Subjects: In all, 257 women with a body mass index (BMI) ranging from 25.1 to 54.5 kg/m2 (geometric mean 33.1+/-5.8 kg/m2) and aged 19-71 y (mean 45.6+/-12.1 y) were studied. Subjects had no symptoms of intercurrent infection, known diabetes, treated dyslipidaemia, a chronic inflammatory condition, liver disease or malignancy., Results: Linear regression demonstrates that both CRP and SA were positively associated with weight, BMI, insulin resistance, dyslipidaemia and hypertension. There was a highly significant (P<0.0001) positive association of both SA and CRP with none, one, two, three or four features of the metabolic syndrome. For a 1 s.d. (4.0 mg/l) increase in CRP, there was a significant increased risk when comparing the odds of having metabolic syndrome (defined as three or more individual features) compared with the remainder of the population (odds ratio=1.7, P<0.0001), but this was not significant after adjustment for BMI. However, for a 1 s.d. (0.34 mmol/l) increase in SA, the odds of having metabolic syndrome compared with those without metabolic syndrome was 2.5 (P<0.0001), and persisted after additional adjustment for BMI (adjusted odds ratio=1.9, P<0.0001)., Conclusions: While SA and CRP are both univariately associated with individual features of the metabolic syndrome, SA, but not CRP, is significantly associated with the metabolic syndrome, independent of BMI. We conclude that SA identifies a subgroup of overweight individuals with an inflammatory phenotype, who are at the greatest risk of metabolic syndrome.

To understand the role of inflammation in chronic disease it is important to have a reliable measure of habitual inflammatory status. A number of acute-phase response markers have been used as measures of inflammatory status, but the ability of a single measure to appropriately reflect habitual inflammatory status has not been assessed. This study compares the ability of different inflammatory markers to characterize habitual inflammatory status in overweight women. A single fasting blood sample was taken from 86 overweight women (mean body mass index [BMI], 35.2 kg/m2; range, 26.2 to 47.6 kg/m2) and a number of inflammatory markers (both acute-phase response markers and cytokines) were measured. A randomly selected subpopulation of 15 women attended on 2 further occasions for further blood samples. Using the subpopulation, discrimination ratios (DRs) were calculated for each inflammatory marker to assess the within-subject variability. The DRs were then used to determine the relationship between these markers, adjusted for within-subject variability, in the whole population. In this highly controlled experimental environment, interleukin-6 (IL-6), with a DR of 3.71, was the cytokine with the greatest ability to discriminate between subjects, suggesting that it is best able to characterize habitual inflammatory status. Sialic acid was the acute-phase response marker with the highest DR (3.16), and showed stronger correlations with other inflammatory markers, including C-reactive protein (CRP), than IL-6. This study suggests that use of some inflammatory markers, such as CRP, with large within-individual variability, will underestimate the relationship between inflammation and disease, and thus relationships between inflammation and chronic disease may be stronger than previously appreciated. Future studies should consider IL-6 or sialic acid to provide a more robust measure of inflammatory status.

Background: Current guidelines for obesity management emphasize the improvements in health risks associated with weight losses of 5-10% initial weight. However, most of the data is derived from periods of acute weight loss and may not represent the true effect in the longer term or in obese but otherwise healthy individuals. This study examines the temporal changes in risk factors for cardiovascular disease with weight change over 52 weeks., Methods: In total, 57 overweight women (age 43.7 +/- 9.1 years, mean BMI of 31.7 kg/m2, range 27.2-38.5 kg/m2) with no other significant medical history, entered a milk-based, low-energy weight loss programme for 12 weeks and were then monitored without further intervention until 52 weeks. Weight, fat mass, fasting plasma insulin, lipids and blood pressure were measured at 0, 12, 24 and 52 weeks., Results: The mean weight change in sequential periods was -11.6% (p < 0.0001), +1.1% (p = 0.02) and +5.2% (p < 0.0001). The change from baseline to 1 year being -6.0% (p < 0.0001) an 11% (p < 0.0001) reduction in initial body fat mass. Initial weight loss (0-12 weeks) was positively correlated with greater longer term weight loss (0-52 weeks, r = 0.75, p < 0.0001) and not with weight regain (12-52 weeks, r = 0.14, p = 0.28). Despite significant improvements in insulin sensitivity, lipid profile and blood pressure (BP) with acute weight loss, in the group overall, only benefits in BP were maintained after 52 weeks. However, improvements in insulin sensitivity were sustained in those who maintained more than 5% weight loss, and those with higher baseline metabolic risk had greater benefits with weight loss. Change in waist circumference was better than BMI or fat mass in predicting improvements in metabolic risk in these obese women., Conclusions: This study suggests, in otherwise apparently healthy obese women, the rationale of targeting individuals most likely to benefit from weight management. Most importantly it highlights the need to focus on achieving initial weight losses of greater than 10% to maintain longer term losses of at least 5% and the associated health benefits.