A very-low-calorie diet (VLCD) intervention for the management of prediabetes and early Type 2 diabetes mellitus in a multi-ethnic cohort in Aotearoa New Zealand: The PROGRESS NZ feasibility study.

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.

Impact of diabetes on surgery and radiotherapy for breast cancer.

PURPOSES: This study aims to examine whether diabetes has an impact on the use of surgery and adjuvant radiotherapy in treating women with localised breast cancer. METHODS: Women diagnosed with stage I-III breast cancer between 2005 and 2020 were identified from Te Rehita Mate Utaetae-Breast Cancer Foundation New Zealand National Register, with diabetes status determined using New Zealand's Virtual Diabetes Register. The cancer treatments examined included breast conserving surgery (BCS), mastectomy, breast reconstruction after mastectomy, and adjuvant radiotherapy after BCS. Logistic regression modelling was used to estimate the adjusted odds ratio (OR) and 95% confidence interval (95% CI) of having cancer treatment and treatment delay (> 31 days) for patients with diabetes at the time of cancer diagnosis compared to patients without diabetes. RESULTS: We identified 25,557 women diagnosed with stage I-III breast cancer in 2005-2020, including 2906 (11.4%) with diabetes. After adjustment for other factors, there was no significant difference overall in risk of women with diabetes having no surgery (OR 1.12, 95% CI 0.94-1.33), although for patients with stage I disease not having surgery was more likely (OR 1.45, 95% CI 1.05-2.00) in the diabetes group. Patients with diabetes were more likely to have their surgery delayed (adjusted OR of 1.16, 95% CI 1.05-1.27) and less likely to have reconstruction after mastectomy compared to the non-diabetes group-adjusted OR 0.54 (95% CI 0.35-0.84) for stage I cancer, 0.50 (95% CI 0.34-0.75) for stage II and 0.48 (95% CI 0.24-1.00) for stage III cancer. CONCLUSIONS: Diabetes is associated with a lower likelihood of receiving surgery and a greater delay to surgery. Women with diabetes are also less likely to have breast reconstruction after mastectomy. These differences need to be taken in to account when considering factors that may impact on the outcomes of women with diabetes especially for Maori, Pacific and Asian women.

Association of diabetes and breast cancer characteristics at diagnosis.

PURPOSE: This study aims to examine the association of diabetes and breast cancer characteristics at diagnosis in Aotearoa/New Zealand. METHODS: Patients diagnosed with invasive breast cancer between 2005 and 2020 were identified from the National Breast Cancer Register. Logistic regression modeling was used to estimate the adjusted odds ratio (OR) of having stage III-IV cancer and the OR of having stage IV cancer for women with diabetes compared to those without diabetes. The adjusted OR of having screen-detected breast cancers for patients aged 45-69 years with diabetes compared to patients without diabetes was estimated. RESULTS: 26,968 women were diagnosed with breast cancer, with 3,137 (11.6%) patients having diabetes at the time of cancer diagnosis. The probability of co-occurrence of diabetes and breast cancer increased with time. Maori, Pacific and Asian women were more likely to have diabetes than European/Others. The probability of having diabetes also increased with age. For patients with diabetes, the probability of being diagnosed with stage III-IV cancer and stage IV cancer was higher than for patients without diabetes (OR 1.14, 95% CI 1.03-1.27; and 1.17, 95% CI 1.00-1.38). Women aged 45-69 years with diabetes were more likely to have screen-detected cancer than those without diabetes (OR 1.13, 95% CI 1.02-1.26). CONCLUSIONS: The co-occurrence of diabetes and breast cancer is becoming more common. Overall there is a small but significant adverse impact of having advanced disease for women with diabetes that is found at the time of breast cancer diagnosis, and this may contribute to other inequities that occur in the treatment pathway that may impact on patient outcomes.

Cardiovascular risk prediction in type 2 diabetes before and after widespread screening: a derivation and validation study.

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: R2=32% [95% CI 29-34], Harrell's C=0·73 [0·72-0·74], Royston's D=1·410 [1·330-1·490] vs R2=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.

Where can you wear your Libre? Using the FreeStyle Libre continuous glucose monitor on alternative sites.

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.

Very low carbohydrate (ketogenic) diets in type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

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.

The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Maori and Pacific ancestry.

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 Maori) 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 Maori 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.

A cannulated prolactin series reduces the need for further investigations in women with infertility and lowers the number of false positive screening prolactin measurements.

BACKGROUND: The prevalence of hyperprolactinaemia in women presenting for infertility investigation has been found to be up to 17%, and many of these women are asymptomatic. Prolactin levels may be elevated by stress, including phlebotomy and not be of clinical significance. A cannulated prolactin study may be a useful way to discriminate this. AIM: To determine the utility of a cannulated prolactin series in women presenting with infertility who have a raised prolactin measurement at referral for first fertility consultation. MATERIALS AND METHODS: All women referred to two fertility centres had a prolactin level measured prior to first appointment over a two-year period. If the level remained elevated on the second measure after macroprolactin precipitation, women were referred for a cannulated prolactin series. If the prolactin concentration fell within the reference range during the series then the result was regarded as normal. RESULTS: Forty-four (2.7%) of 1660 women seen for a first specialist appointment had persistently raised prolactin concentrations after two samples and were referred for a cannulated series. The proportion of women whose prolactin was found to be normal during the cannulated prolactin series was 61% (95% CI 47-74%). Even in patients with a referral prolactin of greater than 1000 mU/L, 45% had a normal two-hour cannulated series. CONCLUSION: A high proportion (61%) of women with raised prolactin at time of referral for first specialist appointment had a normal prolactin after a two-hour cannulated series. A cannulated prolactin study can avoid unnecessary further investigations in these women.

Impact of a comprehensive digital health programme on HbA1c and weight after 12 months for people with diabetes and prediabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this RCT was to evaluate the effectiveness of a digital health programme (BetaMe/Melon) vs usual care in improving the control of type 2 diabetes and prediabetes in a primary care population. METHODS: We conducted a randomised parallel-group two-arm single-blinded superiority trial in the primary care setting in two regions of New Zealand. Eligible participants were identified through Primary Health Organisations and participating practices. Eligibility criteria were as follows: age 18-75 years, HbA1c 41-70 mmol/mol (5.9-8.6%), not taking insulin, and daily access to the internet. BetaMe/Melon is a 12 month mobile-device and web-based programme with four components: health coaching; evidence-based resources; peer support; and goal tracking. Participants were randomised into the intervention or control arm (1:1 allocation) based upon baseline HbA1c (prediabetes or diabetes range), stratified by practice and ethnicity. Research nurses and the study biostatistician were blind to study arm. Primary outcomes of the study were changes in HbA1c and weight at 12 months, using an intention-to-treat analysis. RESULTS: Four hundred and twenty-nine individuals were recruited between 20 June 2017 and 11 May 2018 (n = 215 intervention arm, n = 214 control arm), most of whom were included in analyses of co-primary outcomes (n = 210/215, 97.7% and n = 213/214, 99.5%). HbA1c levels at 12 months did not differ between study arms: mean difference was -0.9 mmol/mol (95% CI -2.9, 1.1) (-0.1% [95% CI -0.3, 0.1]) for the diabetes group and was 0.0 mmol/mol (95% CI -0.9, 0.9) (0.0% [95% CI -0.1, 0.1]) for the prediabetes group. Weight reduced slightly at 12 months for participants in both study arms, with no difference between arms (mean difference -0.4 kg [95% CI -1.3, 0.5]). CONCLUSIONS/INTERPRETATION: This study did not demonstrate clinical effectiveness for this particular programme. Given their high costs, technology-assisted self-management programmes need to be individually assessed for their effectiveness in improving clinical outcomes for people with diabetes. TRIAL REGISTRATION: www.anzctr.org.au ACTRN12617000549325 (universal trial number U1111-1189-9094) FUNDING: This study was funded by the Health Research Council of New Zealand, the Ministry of Health New Zealand and the Healthier Lives National Science Challenge. Graphical abstract.

A Mobile- and Web-Based Health Intervention Program for Diabetes and Prediabetes Self-Management (BetaMe/Melon): Process Evaluation Following a Randomized Controlled Trial.

BACKGROUND: Technology-assisted self-management programs are increasingly recommended to patients with long-term conditions such as diabetes. However, there are a number of personal and external factors that affect patients' abilities to engage with and effectively utilize such programs. A randomized controlled trial of a multi-modal online program for diabetes self-management (BetaMe/Melon) was conducted in a primary care setting, and a process evaluation was completed at the end of the study period. OBJECTIVE: This process evaluation aimed to examine the utilization patterns of BetaMe/Melon, identify which components participants found most (and least) useful, and identify areas of future improvement. METHODS: Process evaluation data were collected for intervention arm participants from 3 sources: (1) the mobile/web platform (to identify key usage patterns over the 16-week core program), (2) an online questionnaire completed during the final study assessment, and (3) interviews conducted with a subset of participants following the study period. Participants were classified as "actively engaged" if any usage data was recorded for the participant (in any week), and patterns were reported by age, gender, ethnicity, and diabetes/prediabetes status. The online questionnaire asked participants about the usefulness of the program and whether they would recommend BetaMe/Melon to others according to a 5-point Likert Scale. Of 23 invited participants, 18 participated in a digitally recorded, semistructured telephone interview. Interview data were thematically analyzed. RESULTS: Out of the 215 participants, 198 (92%) received an initial health coaching session, and 160 (74%) were actively engaged with the program at some point during the 16-week core program. Engagement varied by demographic, with women, younger participants, and ethnic majority populations having higher rates of engagement. Usage steadily declined from 50% at Week 0 to 23% at Week 15. Participants ranked component usefulness as education resources (63.7%), health coaches (59.2%), goal tracking (48.8%), and online peer support (42.1%). Although 53% agreed that the program was easy to use, 64% would recommend the program to others. Interview participants found BetaMe/Melon useful overall, with most identifying beneficial outcomes such as increased knowledge, behavioral changes, and weight loss. Barriers to engagement were program functionality, internet connectivity, incomplete delivery of all program components, and participant motivation. Participants suggested a range of improvements to the BetaMe/Melon program. CONCLUSIONS: The program was generally well received by participants; active engagement was initially high, although it declined steadily. Maintaining participant engagement over time, individualizing programs, and addressing technical barriers are important to maximize potential health benefits from online diabetes self-management programs. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12617000549325; https://tinyurl.com/y622b27q.

Helicobacter pylori infection as a risk factor for serum bilirubin change and less favourable lipid profiles: a hospital-based health examination survey.

BACKGROUND: Helicobacter pylori infection is associated with several extragastric conditions including dyslipidemia and metabolic syndrome. This study aimed to investigate additional metabolic parameters associated with H. pylori infection in a Chinese population. METHODS: Using a case-control approach we studied 617 subjects with 13C-urea breath test (13C-UBT) values ≥10‰ who were defined as being positive for H. pylori (cases), while 617 sex and age- matched subjects with 13C-UBT values ≤1‰ were defined as H. pylori negative (controls) in Beijing Tongren Hospital from March 2016 to May 2017. Biochemical parameters including serum bilirubin and lipids were tested. RESULTS: A total of 1982 subjects participated in this study. The H. pylori infected subjects had significantly lower serum direct bilirubin concentrations (2.34 ± 0.38 vs. 2.47 ± 0.90 µmol/L, P = 0.008). H. pylori infection was independently associated with lower direct bilirubin levels (OR = 1.497, 95% CI =1.121-1.999, P = 0.006) or total bilirubin levels (OR = 1.322, 95% CI =1.005-1.738, P = 0.046) after adjustment for age, sex, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) and triglycerides(TG). In addition, the H. pylori infected subjects had higher LDL-C levels (2.98 ± 0.76 vs. 2.89 ± 0.75 mmol/L, P = 0.033) and lower HDL-C levels (1.39 ± 0.37 vs. 1.44 ± 0.41 mmol/L, P = 0.044). LDL-C was negatively correlated with direct bilirubin concentration (R = - 0.260, P < 0.0001). CONCLUSIONS: Bilirubin has been found to be a potent endogenous antioxidant and negatively associated with metabolic syndrome. Our results suggest that H. pylori infection is an independent risk factor for serum bilirubin reduction and less favorable lipid profiles.

Optimizing the management of hypoglycaemia in individuals with type 2 diabetes: A randomized crossover comparison of a weight-based protocol compared with two fixed-dose glucose regimens.

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.

The effect of additional mealtime insulin bolus using an insulin-to-protein ratio compared to usual carbohydrate counting on postprandial glucose in those with type 1 diabetes who usually follow a carbohydrate-restricted diet: A randomized cross-over trial.

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.

Cardiovascular disease and prediabetes as complex illness: People's perspectives.

Cardiovascular disease (CVD) and sustained high blood glucose as prediabetes are an established comorbidity. People's experience in reconciling these long-term conditions requires deeper appreciation if nurses are to more effectively support person-centred care for people who have them. Our analysis explores the initial experience of people admitted to hospital with CVD who then find they also have sustained high blood glucose. Our methodology is informed by the philosophy of Gadamer and applies interpretive description to develop an interpretation of participant experiences. The major theme emerging from participant interviews was the 'invisible disequilibrium' characterised by three subthemes: 'losing equilibrium', 'becoming embattled' and 'evolving illness'. This study examines CVD and prediabetes in conjunction with the Gadamerian notion of the 'whole', as being in a social and emotional world in which illness is also a component part. We explore how participants lived within an 'invisible disequilibrium', with prediabetes frequently remaining unnoticed, while CVD was manifest. To identify multiple conditions and support effective intervention to manage them as part of person-centric care, nursing practice should explore the 'whole' of the person's experience, value people's knowledge as potential indicators of complex illness, thereby reducing the risk of accelerating complex illness.

The effect of a cinnamon-, chromium- and magnesium-formulated honey on glycaemic control, weight loss and lipid parameters in type 2 diabetes: an open-label cross-over randomised controlled trial.

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.

The necessity of identifying the basal glucose set-point in the IVGTT for patients with Type 2 Diabetes.

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.

Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.

Epigenomic regulation of the transcriptome by DNA methylation and posttranscriptional gene silencing by miRNAs are potential environmental modulators of skeletal muscle plasticity to chronic exercise in healthy and diseased populations. We utilized transcriptome networks to connect exercise-induced differential methylation and miRNA with functional skeletal muscle plasticity. Biopsies of the vastus lateralis were collected from middle-aged Polynesian men and women with morbid obesity (44 kg/m(2) ± 10) and Type 2 diabetes before and following 16 wk of resistance (n = 9) or endurance training (n = 8). Longitudinal transcriptome, methylome, and microRNA (miRNA) responses were obtained via microarray, filtered by novel effect-size based false discovery rate probe selection preceding bioinformatic interrogation. Metabolic and microvascular transcriptome topology dominated the network landscape following endurance exercise. Lipid and glucose metabolism modules were connected to: microRNA (miR)-29a; promoter region hypomethylation of nuclear receptor factor (NRF1) and fatty acid transporter (SLC27A4), and hypermethylation of fatty acid synthase, and to exon hypomethylation of 6-phosphofructo-2-kinase and Ser/Thr protein kinase. Directional change in the endurance networks was validated by lower intramyocellular lipid, increased capillarity, GLUT4, hexokinase, and mitochondrial enzyme activity and proteome. Resistance training also lowered lipid and increased enzyme activity and caused GLUT4 promoter hypomethylation; however, training was inconsequential to GLUT4, capillarity, and metabolic transcriptome. miR-195 connected to negative regulation of vascular development. To conclude, integrated molecular network modelling revealed differential DNA methylation and miRNA expression changes occur in skeletal muscle in response to chronic exercise training that are most pronounced with endurance training and topographically associated with functional metabolic and microvascular plasticity relevant to diabetes rehabilitation.

Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment are associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes.

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.

Tailored Prompting to Improve Adherence to Image-Based Dietary Assessment: Mixed Methods Study.

Background: Accurately assessing an individual's diet is vital in the management of personal nutrition and in the study of the effect of diet on health. Despite its importance, the tools available for dietary assessment remain either too imprecise, expensive, or burdensome for clinical or research use. Image-based methods offer a potential new tool to improve the reliability and accessibility of dietary assessment. Though promising, image-based methods are sensitive to adherence, as images cannot be captured from meals that have already been consumed. Adherence to image-based methods may be improved with appropriately timed prompting via text message. Objective: This study aimed to quantitatively examine the effect of prompt timing on adherence to an image-based dietary record and qualitatively explore the participant experience of dietary assessment in order to inform the design of a novel image-based dietary assessment tool. Methods: This study used a randomized crossover design to examine the intraindividual effect of 3 prompt settings on the number of images captured in an image-based dietary record. The prompt settings were control, where no prompts were sent; standard, where prompts were sent at 7:15 AM, 11:15 AM, and 5:15 PM for every participant; and tailored, where prompt timing was tailored to habitual meal times for each participant. Participants completed a text-based dietary record at baseline to determine the timing of tailored prompts. Participants were randomized to 1 of 6 study sequences, each with a unique order of the 3 prompt settings, with each 3-day image-based dietary record separated by a washout period of at least 7 days. The qualitative component comprised semistructured interviews and questionnaires exploring the experience of dietary assessment. Results: A total of 37 people were recruited, and 30 participants (11 male, 19 female; mean age 30, SD 10.8 years), completed all image-based dietary records. The image rate increased by 0.83 images per day in the standard setting compared to control (P=.23) and increased by 1.78 images per day in the tailored setting compared to control (P≤.001). We found that 13/21 (62%) of participants preferred to use the image-based dietary record versus the text-based dietary record but reported method-specific challenges with each method, particularly the inability to record via an image after a meal had been consumed. Conclusions: Tailored prompting improves adherence to image-based dietary assessment. Future image-based dietary assessment tools should use tailored prompting and offer both image-based and written input options to improve record completeness.