A qualitative study of the perceptions and experiences of participants and healthcare professionals in the DiRECT-Australia type 2 diabetes remission service.

BACKGROUND: The UK Diabetes Remission Clinical Trial (DiRECT) study was replicated in an Australian primary care setting. This qualitative study aimed to explore and understand the perceptions and experiences of both participants and healthcare professionals (HCPs) involved in the DiRECT-Australia Type 2 Diabetes Remission Service. METHODS: All participants and HCPs delivering the service were invited to participate in semi-structured interviews via online videoconferencing. The interview guides explored perceptions and experiences in DiRECT-Australia, covering aspects such as barriers and facilitators to recruitment and participation, motivations and challenges across service phases, adequacy of support provided and the overall acceptability of the service. All interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Eight DiRECT-Australia participants and six HCPs (three general practitioners, two practice nurses and one dietitian) participated. Four overarching themes were identified: (1) Enablers and barriers to recruitment and continuous participation in DiRECT-Australia; (2) Motivators and overcoming barriers across the total diet replacement, food reintroduction and weight maintenance phases; (3) Importance of participant-HCP interactions and continuous support; (4) Acceptance and long-term need for DiRECT-Australia. Adherence to total diet replacement was less challenging than anticipated by participants. Transitioning to the food reintroduction phase was difficult but overcome through HCP support. DiRECT-Australia was well accepted by both participants and HCPs, and participants expressed willingness to continue with the service, if provided on a long-term basis. CONCLUSIONS: Both participants and HCPs were highly interested in the new diabetes remission service set up in an Australian primary care setting. The acceptability of DiRECT-Australia was underscored by participants emphasising the effectiveness of the service in achieving significant weight loss and diabetes remission. There is a need for long-term and wider implementation of the service to ensure that anyone with recent onset type 2 diabetes is offered the best possible chance to achieve remission.

Prevalence and factors associated with mental health problems of psychological distress and depression among rural Victorians - analysis of cross-sectional data (Crossroads II).

BACKGROUND: Research suggests that rates of mental illness are similar in rural and urban Australia, although there are significant workforce shortages in rural regions along with higher rates of chronic disease and obesity and lower levels of socioeconomic status. However, there are variations across rural Australia and limited local data on mental health prevalence, risk, service use and protective factors. This study describes the prevalence of self-reported mental health problems of psychological distress and depression, in a rural region in Australia and aims to identify the factors associated with these problems. METHODS: The Crossroads II study was a large-scale cross-sectional study undertaken in the Goulburn Valley region of Victoria, Australia in 2016-18. Data were collected from randomly selected households across four rural and regional towns and then screening clinics from individuals from these households. The main outcome measures were self-reported mental health problems of psychological distress assessed by the Kessler 10 and depression assessed by Patient Health Questionnaire-9. Unadjusted odd ratios and 95% confidence intervals of factors associated with the two mental health problems were calculated using simple logistic regression with multiple logistic regression using hierarchical modelling to adjust for the potential confounders. RESULTS: Of the 741 adult participants (55.6% females), 67.4% were aged ≥ 55 years. Based on the questionnaires, 16.2% and 13.6% had threshold-level psychological distress and depression, respectively. Of those with threshold-level K-10 scores, 19.0% and 10.5% had seen a psychologist or a psychiatrist respectively while 24.2% and 9.5% of those experiencing depression had seen a psychologist or a psychiatrist, respectively in the past year. Factors such as being unmarried, current smoker, obesity, were significantly associated with a higher prevalence of mental health problems whereas physical activity, and community participation reduced the risk of mental health problems. Compared to rural towns, the regional town had higher risk of depression which was non-significant after adjusting for community participation and health conditions. CONCLUSIONS: The high prevalence of psychological distress and depression in this rural population was consistent with other rural studies. Personal and lifestyle factors were more relevant to mental health problems than degree of rurality in Victoria. Targeted lifestyle interventions could assist in reducing mental illness risk and preventing further distress.

Factors associated with long intensive care unit (ICU) admission among inpatients with and without diabetes in South Western Sydney public hospitals using the New South Wales admission patient data collection (2014-2017).

BACKGROUND: Long stay in intensive care unit (ICU) is associated with poor outcomes, particularly in people with diabetes. It increases the financial burden of care and this is a challenge to the South Western Sydney region, which is already a hotspot for diabetes in Australia. This study compared ICU admission characteristics of people with and without diabetes and the factors associated with long ICU stay among patients admitted to public hospitals in this metropolitan health district from 2014 to 2017. METHODS: Cross-sectional datasets on 187,660, including all ICU admissions in the New South Wales Admitted Patient Data Collection (APDC) from June 2014 - July 2017 in public hospital were extracted. Data on demographic and health insurance status, primary admission diagnosis using ICD-10, comorbidities including death among hospital inpatients aged ≥18 years residing in SWS were analysed. The ICU length of stay was the outcome variable and were classified into short stay (≤48 h) and long stay (> 48 h), and were examined against potential confounding factors using bivariate and multiple logistic regression analyses. RESULTS: Our results showed higher ICU admissions in patients with diabetes than in those without diabetes (5% vs. 3.3%, P < 0.001) over three years. The median and interquartile range (IQR) of length of the ICU stay were similar in both groups [diabetes: 40 h, IQR = 16-88 h vs. non-diabetes: 43 h, IQR = 19-79 h]. The prevalence of long ICU stays among people with and without diabetes were 44.9% [95% CI 42.1, 47.7%] and 43.6% [95% CI 42.2, 44.9%], respectively. For both groups, increased odds of long ICU stay were associated with death and circulatory system disease admissions, while musculoskeletal disease admissions were associated with lower risk of long ICU stay. In the non-diabetes group, male sex, nervous system disease admissions and living in peri-urban areas were associated with higher odds of long ICU stay. CONCLUSIONS: The rate of ICU admissions among inpatients remain higher in people with diabetes. One in every two admissions to ICU had a long stay. Additional care for those admitted with circulatory system diseases are needed to reduce long ICU stay related deaths in SWS.

The impact of nursing staff education on diabetes inpatient glucose management: a pilot cluster randomised controlled trial.

BACKGROUND: An increasing number of patients in hospital have diabetes, with most of them cared for by non-specialist staff. The effect of diabetes education for staff on patient outcomes, as well as the most effective method of staff education is unclear. Therefore, the aim of this study was to compare diabetes outcomes in medical wards where nursing staff were offered one face-to-face (F2F) session followed by access to online education (online), F2F education only, or standard care (control). METHODS: We conducted a pilot cluster randomised controlled trial involving 16-weeks baseline/rollout followed by a 28-week post-intervention period across three medical wards (clusters) in a Sydney Teaching Hospital. The online ward provided an online competency-based diabetes education program and 1-h F2F teaching from a diabetes nurse educator (DNE), the F2F ward provided four separate 1-h teaching sessions by a DNE, with no additional sessions in the control ward. The primary outcome was length of stay (LOS); secondary outcomes included good diabetes days (GDD), hypoglycaemia and medication errors. Poisson and binary logistic regression were used to compare clusters. RESULTS: Staff attendance/completion of ≥ 2 topics was greater with online than F2F education [39/48 (81%) vs 10/33 (30%); p < 0.001]. Among the 827/881 patients, there was no difference in LOS change between online [Median(IQR) 5(2-8) to 4(2-7) days], F2F [7(4-14) to 5(3-13) days] or control wards [5(3-9) to 5(3-7) days]. GDD improved only in the online ward 4.7(2.7-7.0) to 6.0(2.3-7.0) days; p = 0.038. Total patients with hypoglycaemia and appropriately treated hypoglycaemia increased in the online ward. CONCLUSIONS: The inclusion of online education increased diabetes training uptake among nursing staff. GDD and appropriate hypoglycaemia management increased in the online education wards. TRIAL REGISTRATION: Prospectively registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) on 24/05/2017: ACTRN12617000762358 .

Effectiveness of a locality-based integrated diabetes care service on clinical outcomes.

BACKGROUND: Diabetes management often requires close cooperation between primary and specialist services, but a range of challenges in Australia and elsewhere make seamless care difficult. AIMS: To evaluate the effectiveness of a new locality-based integrated diabetes care service for people with Type 2 diabetes in an inner regional area. METHODS: A quasi-experimental evaluation comparing baseline and follow-up clinical data collected from general practices and specialist services participating in an integrated diabetes care programme in an inner-regional area. Patients had at least one specialist service consultation. The primary outcome was glycated haemoglobin (HbA1c). RESULTS: Clinical data were collected for 178 (74.5%) of 239 patients (age ± standard deviation, 65 ± 11 years; 46% female; median (interquartile range) diabetes duration, 19 (11.0-24.0) years) from seven general practices over 33 months (median 18.5 months). There were reductions in HbA1c (0.7 ± 1.6% (8 ± 18 mmol/mol); P < 0.001), systolic blood pressure (5.8 ± 19.5 mmHg; P < 0.001), diastolic blood pressure (2.4 ± 14.3 mmHg; P = 0.04), total cholesterol (0.5 ± 1.3 mmoL/L; P < 0.001), low-density lipoprotein (0.4 ± 0.9 mmoL/L; P < 0.001), body mass index (0.5 ± 1.6 kg/m2 ; P < 0.001) and weight (1.8 ± 4.7 kg; P < 0.001). The proportion without microalbuminuria increased from 48.4% to 59.3% (P = 0.03). CONCLUSIONS: Glycaemia and cardiovascular risk factors can be reduced in patients with long-standing Type 2 diabetes by moving to a locality-based integrated primary-secondary care diabetes care service.

Obstructive sleep apnoea and 12-month weight loss in adults with class 3 obesity attending a multidisciplinary weight management program.

BACKGROUND: Although there is a strong association between obesity and obstructive sleep apnoea (OSA), the effects of OSA and CPAP therapy on weight loss are less well known. The aim of this study in adults with class 3 obesity attending a multidisciplinary weight management program was to assess the relationship between OSA and CPAP usage, and 12-month weight change. METHODS: A retrospective cohort study of all patients commencing an intensive multidisciplinary publicly funded weight management program in Sydney, Australia, between March 2018 and March 2019. OSA was diagnosed using laboratory overnight sleep studies. Demographic and clinical data, and use of CPAP therapy was collected at baseline and 12 months. CPAP use was confirmed if used ≥4 h on average per night on download. RESULTS: Of the 178 patients who joined the program, 111 (62.4 %) completed 12 months in the program. At baseline, 63.1 % (n=70) of patients had OSA, of whom 54.3 % (n=38) were using CPAP. The non-OSA group had more females compared to the OSA with CPAP group and OSA without CPAP group (90.2 % vs. 57.9 % and 62.5 %, respectively; p=0.003), but there were no significant baseline differences in BMI (50.4±9.3 vs. 52.1±8.7 and 50.3±9.5 kg/m2, respectively; p=0.636). There was significant weight loss across all three groups at 12 months. However, there were no statistically significant differences across groups in the percentage of body weight loss (OSA with CPAP: 6.3±5.6 %, OSA without CPAP: 6.8±6.9 %, non-OSA: 7.2±6.5 %; p=0.844), or the proportion of patients who achieved ≥5 % body weight loss (OSA with CPAP: 57.9 %, OSA without CPAP: 59.4 %, non-OSA: 65.9 %; p=0.743). In patients with T2DM, there was a significant reduction in HbA1c from baseline to 12 months (7.8±1.7 % to 7.3±1.4 %, p=0.03), with no difference between groups (p=0.997). CONCLUSIONS: This multidisciplinary weight management program resulted in significant weight loss at 12 months, regardless of OSA diagnosis or CPAP use in adults with class 3 obesity. Larger studies are needed to further investigate the effects of severity of OSA status and CPAP use in weight management programs. Until completed, this study suggests that the focus should remain on implementing lifestyle changes and weight management regardless of OSA status.

Analysis of in-hospital mortality among people with and without diabetes in South Western Sydney public hospitals (2014-2017).

BACKGROUND: Diabetes is a major public health problem affecting about 1.4 million Australians, especially in South Western Sydney, a hotspot of diabetes with higher than average rates for hospitalisations. The current understanding of the international burden of diabetes and related complications is poor and data on hospital outcomes and/or what common factors influence mortality rate in people with and without diabetes in Australia using a representative sample is lacking. This study determined in-hospital mortality rate and the factors associated among people with and without diabetes. METHODS: Retrospective data for 554,421 adult inpatients was extracted from the population-based New South Wales (NSW) Admitted Patient Data over 3 financial years (from 1 July 2014-30 June 2015 to 1 July 2016-30 June 2017). The in-hospital mortality per 1000 admitted persons, standardised mortality ratios (SMR) were calculated. Binary logistic regression was performed, adjusting for potential covariates and co-morbidities for people with and without diabetes over three years. RESULTS: Over three years, 8.7% (48,038 people) of admissions involved people with diabetes. This increased from 8.4% in 2014-15 to 8.9% in 2016-17 (p = 0.007). Across all age groups, in-hospital mortality rate was significantly greater in people with diabetes (20.6, 95% Confidence intervals CI 19.3-21.9 per 1000 persons) than those without diabetes (11.8, 95%CI 11.5-12.1) and more in men than women (23.1, 95%CI 21.2-25.0 vs 17.9, 95%CI 16.2-19.8) with diabetes. The SMR for those with and without diabetes were 3.13 (95%CI 1.78-4.48) and 1.79 (95%CI 0.77-2.82), respectively. There were similarities in the factors associated with in hospital mortality in both groups including: older age (> 54 years), male sex, marital status (divorced/widowed), length of stay in hospital (staying longer than 4 days), receiving intensive care in admission and being admitted due to primary respiratory and cardiovascular diagnoses. The odds of death in admission was increased in polymorbid patients without diabetes (28.68, 95%CI 23.49-35.02) but not in those with diabetes. CONCLUSIONS: In-patients with diabetes continue to have higher mortality rates than those without diabetes and the Australian population. Overall, similar factors influenced mortality rate in people with and without diabetes, but significantly more people with diabetes had two or more co-morbidities, suggesting that hospital mortality may be driven by those with pre-existing health/comorbidities. Urgent measures in primary care to prevent admissions among people with multiple co-morbidities are needed.

Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery.

BACKGROUND: The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT). METHODS: Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed. RESULTS: All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P < 0.01). CONCLUSIONS: Elevated serum FGF-19 levels post-surgery were associated with improved mitochondrial health in AT and overall diabetic remission. Changes in circulating FGF-19 levels were surgery-specific, with BPD producing the best metabolic outcomes among the study procedures (BPD > LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission.

Foot insensitivity is associated with renal function decline in patients with type 2 diabetes: a cohort study.

BACKGROUND: Identifying patients with diabetes at increased risk of chronic kidney disease (CKD) is essential to prevent/slow the progression to end-stage renal disease (ESRD). CKD and diabetic peripheral neuropathy (DPN) share common mechanisms. Hence, we aimed to examine the relationship between foot insensitivity and CKD in patients with Type 2 diabetes. METHODS: A prospective observational cohort study in adults with Type 2 diabetes. Patients with ESRD were excluded. Foot insensitivity was assessed using the 10-g monofilament test. Renal function was assessed using estimated glomerular filtration rate (eGFR) based on the MDRD equation. Albuminuria was defined as the presence of urinary albumin/creatinine ratio (ACR) >3.4 mg/mmol. RESULTS: Two hundred and twenty eight patients were recruited and followed-up for 2.5 years. One hundred and ninety patients (83.4%) had eGFR ≥ 60 ml/min/1.73 m2. Seventy six (33.3%) patients had foot insensitivity (i.e. abnormal monofilament test). Patients with foot insensitivity had lower eGFR and higher prevalence of albuminuria compared to patients with normal monofilament test. After adjustment for age, gender, ethnicity, diabetes duration, HbA1c, body mass index, insulin treatment, number of anti-hypertensives, history of peripheral vascular disease, and baseline eGFR (R2 0.87), baseline foot insensitivity was associated with study-end eGFR (B = -3.551, p = 0.036). CONCLUSIONS: Patients with Type 2 diabetes and foot insensitivity are at increased risk of eGFR decline. Identifying these patients offers an opportunity to intensify metabolic and blood pressure control to prevent/retard the development of CKD. Future studies of larger sample size and longer follow up from multiple centres are needed to assess the diagnostic performance of our findings in predicting CKD development, and to compare the performance of the monofilament test with albuminuria.

Enhanced thermic effect of food, postprandial NEFA suppression and raised adiponectin in obese women who eat slowly.

OBJECTIVE: Meal duration may influence cardiometabolic health. The aim of this study was to explore postprandial effects of meal duration on human metabolism and appetite. DESIGN: Postprandial comparisons following a standard meal eaten slowly over 40 min ('D40') and the same meal eaten quickly over 10 min ('D10') on a different day. Each participant therefore acted as their own control, thereby limiting confounding factors. PATIENTS: Obese premenopausal Caucasian women (n = 10) with confirmed normoglycaemia were recruited from an obesity clinic at UHCW, Coventry UK. Subjects underwent whole-body calorimetry (8-h) on two separate days. MEASUREMENTS: Following standard lunch (D40 vs D10), 4-h postprandial analysis included thermic effect of food (TEF) and bloods taken at predefined times (including baseline fasting). Analytes included lipid profile, adiponectin, insulin, glucose, ghrelin, leptin, endotoxin, gut and pancreatic hormones. Appetite was measured using visual-analogue scales and ad libitum food intake at subsequent meal. Paired sample t-tests [including area under the curve (AUC)] were used to compare D40 and D10 trials. RESULTS: Postprandial TEF (over 240-min) was significantly greater for D40 than D10 [mean (SEM): 80·9 kcal (3·8) vs 29·9 kcal (3·4); 10·6% vs 3·9%, respectively, P = 0·006; AUC 71·7 kcal.h vs 22·4 kcal.h, respectively, P = 0·02]. Postprandial plasma NEFA was significantly lower, and adiponectin levels were significantly higher for D40 than D10 [AUC (SEM): NEFA 627 µmol.h/l (56) vs 769 µmol.h/l (60), respectively, P = 0·02; adiponectin 33·4 µg.h/ml (3·9) vs 27·3 µg.h/ml (3·8), respectively, P = 0·04]. Other postprandial analytes and appetite measures were equivalent. CONCLUSIONS: In obese women, eating slowly associates with enhanced TEF, elevated serum adiponectin and suppressed NEFA.

Habitual physical activity is associated with circulating irisin in healthy controls but not in subjects with diabetes mellitus type 2.

BACKGROUND: Irisin, a novel myokine, has been shown to increase following vigorous exercise, with studies suggesting that it mediates some of the beneficial effects of exercise. Irisin might play a role in 'browning' of white adipocytes, thus increasing energy expenditure. The role of irisin in exercise and energy expenditure in subjects with diabetes mellitus type 2 (DMT2) remains largely unknown. We aimed to investigate the association between circulating irisin and habitual physical activity in subjects with and without DMT2. MATERIAL AND METHODS: In this cross-sectional study, 164 Saudi adults: 81 non-DMT2 controls [age: (mean ± SD) 51.6 ± 10.9; BMI: 29.6 ± 4.3 kg/m(2) ] and 83 DMT2 subjects [age: 54.3 ± 10.3 year; BMI: 29.4 ± 4.7 kg/m(2) ] were studied. Anthropometric and fasting serum biochemical data were collected. Circulating irisin was measured using an enzyme-linked immunosorbent assay (ELISA). Frequency intensity time (FIT) index was used to assess the level of habitual physical activity. RESULTS: We observed significantly higher levels of irisin in DMT2 subjects than in controls (P < 0.001). FIT index was positively associated (r = 0.20, P = 0.03) with circulating irisin in controls only. Additionally, irisin levels were significantly higher in tertile 3 (0.75 ± 0.07 µg/mL) than tertile 1 (0.49 ± 0.06 µg/mL) of the FIT index in healthy controls, whilst no such relation with physical activity was observed in DMT2 subjects. CONCLUSION: This cross-sectional study has shown a weak association of irisin with physical activity levels in healthy controls but not in DMT2 subjects, suggesting the possibility of discordant regulation in the condition of DMT2.

Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study.

AIMS/HYPOTHESIS: The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. METHODS: We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR > 3.4 mg/mmol) or an estimated (eGFR) < 60 ml min(-1) 1.73 m(-2). CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability. RESULTS: Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (-9.0 ± 17.8% vs -3.3 ± 10.3%, p = 0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (ß = -3.5, p = 0.03). Spectral analysis variables were also independent predictors of eGFR decline. CONCLUSIONS/INTERPRETATION: CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.

The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes.

Peripheral action of irisin improves glucose homeostasis and increases energy expenditure, with no data on a central role of irisin in metabolism. These studies sought to examine 1) presence of irisin in human cerebrospinal fluid (CSF) and banked human hypothalamic tissue, 2) serum irisin in maternal subjects across varying adiposities with or without gestational diabetes (GDM), and 3) their respective neonate offspring. CSF, serum, and neonatal cord serum were collected from 91 pregnant women with and without GDM attending for an elective cesarean section [body mass index (BMI): 37.7 ± 7.6 kg/m(2); age: 32 ± 8.3 yr]. Irisin was assessed by ELISA and correlated with biochemical and anthropometric data. Irisin expression was examined in human hypothalamus by immunohistochemical staining. Serum irisin in pregnant women was significantly lower in nonobese compared with obese and GDM subjects, after adjusting for BMI, lipids, and glucose. Irisin was present in neonatal cord serum (237 ± 8 ng/ml) and maternal CSF (32 ± 1.5 ng/ml). CSF irisin correlated positively with serum irisin levels from nonobese and obese pregnant women (P < 0.01), with CSF irisin significantly raised in GDM subjects (P < 0.05). Irisin was present in human hypothalamic sections in the paraventricular neurons, colocalized with neuropeptide Y. Irisin was detectable in CSF and in paraventricular neurons. Maternal serum irisin was lower in nonobese pregnant women after adjusting for BMI and a number of metabolic parameters. These studies indicate that irisin may have a central role in metabolism in addition to the known peripheral role. Further studies investigating the central action of irisin in human metabolic disease are required.

Irisin as a predictor of glucose metabolism in children: sexually dimorphic effects.

BACKGROUND: Irisin, a novel myokine, increases energy expenditure and glucose tolerance and, thus, improves carbohydrate homeostasis in humans. This hormone has potential therapeutic applications for weight loss and improvement in insulin resistance in subjects with obesity and diabetes mellitus type 2 (T2DM). In this cross-sectional study, we aimed to associate circulating levels of irisin and several anthropometric and metabolic parameters among Arab children. METHODS: A cohort of 153 Saudi children, 81 boys [age: 12·4 ± 3·2 years; BMI: 19·5 ± 5·9 kg/m(2) ] and 72 girls: [age: 12·9 ± 3·2 years; BMI: 20·6 ± 5·2], were examined. Anthropometry was obtained, and fasted bloods were collected for biochemical analyses. Irisin was assessed by a specific enzyme-linked immunosorbent assay (ELISA). RESULTS: Girls had higher circulating irisin levels than boys (P = 0·04). There were several significant correlations between circulating irisin and fasting blood glucose (FBG) (r = -0·35, P < 0·001), sagittal abdominal diameter (SAD) (r = -0·34, P < 0·001) and HDL cholesterol (r = 0·17, P = 0·04) across the entire cohort studied. Notably in girls, but not in boys, HOMA-IR correlated negatively with irisin levels (r = -0·32, P = 0·02), as previously noted in adults. FBG was a significant predictor of circulating irisin (R(2)  = 0·16) followed by SAD. In multivariate linear regression analysis, after controlling for potential confounders such as gender, age and BMI, irisin levels were independently associated with FBG (ß = -0·34, P = 0·01), particularly in girls. CONCLUSION: Serum irisin levels were higher in girls than in boys and correlated negatively with HOMA-IR. They were also independently associated with FBG predominantly in girls, suggesting that this hormone may play a crucial role in glucose metabolism from an early age.

A dose-response strategy reveals differences between normal-weight and obese men in their metabolic and inflammatory responses to a high-fat meal.

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.

Maternal inheritance of circulating irisin in humans.

The recently discovered myokine irisin has been implicated in several observational studies as a potential therapeutic target for obesity-related diseases. However, no information is available as to the heritability of this hormone. The present study aims to fill this gap. A total of 120 families (n=254; 121 adults and 133 children) were included in the study taken from the Riyadh Biomarkers Research Program cohort. Information gathered include anthropometrics, and glycaemic, lipid and adipocytokine profiles. Irisin was measured using ELISA. Examining heritability between mother and offspring, the most significant heritable traits in sons included irisin (P=1.6×10(-5)), systolic blood pressure (P=3.6×10(-4)), total cholesterol (P=3.5×10(-7)) and LDL (low-density lipoprotein)-cholesterol (P=1.2×10(-6)). Heritable traits between mother and daughter again included irisin (P<0.002), as well as anthropometric associations such as waist (P<0.01) and hip (P<0.005) circumference and blood pressure (P<0.002); biochemically, principal associations were observed with HDL (high-density lipoprotein)-cholesterol (P<0.04) and TNF-α (tumour necrosis factor-α) (P<0.002). HDL-cholesterol was the single most significant predictor for irisin levels in adults, explaining 17% of the variance, whereas in children AngII (angiotensin II) was the most significant predictor of irisin levels, explaining 19% of the variance (P=0.003). Circulating irisin appears to be maternally inherited and is predicted by HDL-cholesterol in adults and AngII in children, both factors influenced by energy expenditure and regulation. Taken together, these findings suggest a significant role of irisin in energy-generating processes.

Metabolic endotoxaemia: is it more than just a gut feeling?

PURPOSE OF REVIEW: This article reviews the evidence linking gut bacteria, endotoxin, and its circulating levels with inflammatory induced obesity and metabolic disease (metabolic endotoxaemia). RECENT FINDINGS: Gut flora analyses have allowed gut microbiota signatures (GMS) to be observed in animal studies of obesity/metabolic disease. In these studies, specific GMS result in a change in obesity and metabolic disease state whereas in humans, analysis remains unclear. Serum studies, examining metabolic endotoxaemia as a biomarker, appear to link long-term cardiovascular disease and type 2 diabetes mellitus (T2DM) through activation of inflammatory pathways. More recent studies note the importance of diet, which shows the dramatic rise in endotoxin following acute or long-term high-fat diet, with the effects exacerbated in T2DM. SUMMARY: Gut flora appears to act as an important determinant in the pathogenesis of inflammatory induced obesity/T2DM. Endotoxin may act as the systemic insult, impacted by a high-fat diet, which may regulate this effect, combined with an altered GMS. As such, clinical and dietary intervention to affect this process - on the gut flora, the 'leaky' mucosal membrane and endotoxin coupled lipid absorption or removal of circulating endotoxin - could reduce the progression of inflammatory induced metabolic disease.

Community-based care needs for adults with class III obesity before and after tertiary weight management: An exploratory study.

Objective: Class 3 obesity (severe obesity) is defined by a body mass index ≥40 kg/m2. Tertiary weight-management programs (WMPs) are hospital-based multidisciplinary services that aim to support individuals with severe obesity. Severe shortage of WMPs has led to waitlists and pressure on clinicians to discharge patients. Community obesity management often fails to support patients in maintaining weight loss/health gains. This study aimed to explore the needs of patients for community-based obesity care. Methods: A qualitative study was undertaken via a tertiary WMP in Sydney, Australia. Semi-structured interviews/focus groups explored perceptions of purposively sampled patients and their clinicians on the community-based support needs of people with severe obesity. Data were audio-recorded, transcribed verbatim, and then thematically analyzed. Results: Eleven patients and seven clinicians were interviewed. Four themes were identified: the importance of accountability and motivation to maintain weight-loss/health gains; limitations within community-based obesity management for those with severe obesity; perspectives on structured community programs for patients transitioning into/out of tertiary WMPs; and impact of mental health, stigma, and social isolation on engagement with community-based services. Conclusions: Community-based programs are needed to support those awaiting access to tertiary WMPs and to help maintain health gains once discharged. Such programs should address issues of social isolation and integrate with current models of tertiary metabolic and primary health care.

Predictors of Mental Health Outcomes in a Multidisciplinary Weight Management Program for Class 3 Obesity.

This study aimed to examine the potential predictors of improvement in mental health outcomes following participation in an intensive non-surgical outpatient weight management program (WMP) in an Australian public hospital. This was a retrospective cohort study of all adults with Class 3 obesity (BMI ≥ 40 kg/m2) who enrolled in the WMP from March 2018 to June 2021. The participants completed the Eating Disorder Examination Questionnaire Short Version (EDE-QS), Kessler-10 Psychological Distress Scale, and 36-Item Short-Form Survey (SF-36) at baseline and 12-month follow-up. A total of 115 patients completed 12 months in the WMP and were included in the study, with 76.5% being female, a mean ± SD age at baseline of 51.3 ± 13.8 years, a weight of 146 ± 26 kg, and a BMI of 51.1 ± 8.6 kg/m2. The participants lost an average of 8.6 ± 0.2 kg over 12 months, and greater weight loss at follow-up was significantly associated with improved global EDE-QS scores, psychological distress, and improved mental health quality of life. However, improvements in most mental health outcomes were not predicted by weight loss alone. Notably, a lower eating disorder risk at baseline was associated with less psychological distress at follow-up and greater weight loss at follow-up. Our results also found an association between reduced psychological distress and reduced binge eating frequency. These findings support the inclusion components of obesity interventions that target the psychological correlates of obesity to support improved outcomes in people with Class 3 obesity. Future studies should aim to identify which aspects of the WMP helped improve people's psychological outcomes.