Search

Objective To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. Design, setting Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. Participants Patients aged 18 years or more admitted to hospital from EDs. Intervention Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. Main outcome measure New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. Results Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. Conclusion Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

Identification of mental health risk is important for optimising diabetes care in type 2 diabetes mellitus (T2DM). Personality is linked to diabetes health and may assist detection of individuals with T2DM most at risk of chronic mental health difficulties. This study examined the moderator effect of personality factors on changes in psychological distress and functioning in adults with T2DM and mild-to-moderate depressive symptoms across a 12-month period. Data were obtained from participants in a randomised controlled trial of adults with T2DM. Participants completed measures of depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), general functioning (Work and Social Adjustment Scale), diabetes distress (Diabetes Distress Scale), and diabetes self-management (Self-Management Profile for Type 2 Diabetes) at baseline, 3-, 6- and 12-months. Glycaemic control (HbA1c) was measured at baseline, 6- and 12-months. Two hundred trial completers agreed to complete a personality inventory (Big Five Inventory). Low neuroticism was linked with reduced depression, anxiety, functional impairment and diabetes distress over the year. High extraversion was associated with decreased anxiety and functional impairment. High conscientiousness was linked to increased healthy eating. No personality trait moderated HbA1c levels. Personality screening may help identify mental health risk and guide medical carer approach in T2DM patients.

We conducted three single-day point type 2 diabetes prevalence surveys of all inpatient clinical records in November 2013, 2014 and 2016. The prevalence of diabetes was 19.7-25.3%. The majority (63.4-76%) had type 2 diabetes. Twenty-one percent (n = 21) in 2013, 12% (n = 9) in 2014 and 22.6% (n = 21) in 2016 were diagnosed with diabetes during hospital admission; 41.8% (n = 41) in 2013, 46.7% (n = 35) in 2014 and 51.6% (n = 48) in 2016 required insulin. The high prevalence of diabetes among inpatients mandates active detection and specialist management of diabetes during the admission.

Background Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post-transplantation partly due to lack of detection protocols. Aim To determine the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post-transplantation. Methods We analysed patients on the St Vincent's Heart Lung database from 1 April 2014 to 30 September 2015 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non-diabetic patients to have an oral glucose tolerance test (modified for patients with cystic fibrosis (CF) to screen for CF-related hyperglycaemia (CFRH) (plasma glucose ≥8.2 mmol/L at 60 or 90 min). Results Study 1 included 114 patients (32 with CF and 82 without CF). Of 30 CF patients with glycaemic data, 27 (90%) had abnormal glucose metabolism: 18 had diabetes and nine had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism: eight had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF and 53 without CF). Fourteen CF patients had pre-existing diabetes and seven had pre-existing CFRH. All but one patient were diagnosed with diabetes post-transplantation. Hence, diabetes prevalence in CF patients post-transplantation was 96%. Among 53 transplanted patients without CF, seven (13%) had abnormal glucose metabolism but 30 (57%) were diagnosed with post-transplant diabetes. Conclusion There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes-related morbidity and mortality further.

Background Young people with type 1 diabetes are at increased risk of mental disorders. Whereas treatment need is high, difficulty recruiting young people with type 1 diabetes into psychosocial studies complicates development, testing and dissemination of these interventions. Objective Interviews with young adults with type 1 diabetes were conducted to examine attitudes towards mental health and mental health research, including barriers and motivators to participation in mental health studies and preferred sources of mental health support. The interviews were audio‐taped, transcribed and evaluated via thematic analysis. Setting and participants Young adults with type 1 diabetes were recruited via social media channels of 3 advocacy organizations. A total of 31 young adults (26 females and 5 males) with an average age of 22 years were interviewed between October 2015 and January 2016. Results Participants were largely unaware of their increased vulnerability to common mental health problems and knew little about mental health research. Major barriers to participation included perceived stigma and lifestyle issues and low levels of trust in researchers. Opportunities to connect with peers and help others were described as key motivators. Psychological distress was considered normal within the context of diabetes. A need for some level of human contact in receiving psychosocial support was expressed. Discussion and conclusion Findings provide valuable insights into the complex dynamics of engaging young adults with type 1 diabetes in mental health studies. Interviewees provided practical suggestions to assist investigation and delivery of psychosocial interventions for this vulnerable group.

Background: The imprinted small nucleolar RNA (snoRNA) Snord116 is implicated in the aetiology of Prader-Willi syndrome (PWS), a disease associated with hyperphagia and obesity. Germline deletion of Snord116 in mice has been found to lead to increased food intake but not to the development of obesity. To determine the role of Snord116 independent of potential compensatory developmental factors, we investigated the effects of conditional adult-onset deletion of Snord116 in mice. Methods: Deletion of Snord116 was induced at 8 weeks of age by oral administration of tamoxifen to male Snord lox/lox ; ROSA cre/+ mice, with vehicle-treated mice used as controls. Body weight (BW) was monitored weekly and body composition was measured by dual-energy X-ray absorptiometry and tissue dissection. Non-fasted and fasting-induced food intake was determined, and glucose and insulin tolerance tests were performed. Twenty-four-hour energy expenditure and physical activity were assessed by indirect calorimetry. Results: Adult-onset deletion of Snord116 led to reduced food intake and increased adiposity, albeit with no concomitant change in BW or lean mass compared to controls. Adult onset Snord116 deletion was also associated with worsened glucose tolerance and insulin sensitivity. Conclusions: This study identified a key role for Snord116 in feeding behaviour and growth. Further, it is likely that the effects of this gene are modulated by developmental stage, as mice with adult-onset deletion showed an opposite phenotype, with respect to food intake and body composition, to previously published data on mice with germline deletion.

The continuing increase in many countries in adult body mass index (BMI kg/m2) and its dispersion is contributed to by interaction between genetic susceptibilities and an increasingly obesogenic environment (OE). The determinants of OE-susceptibility are unresolved, due to uncertainty around relevant genetic and environmental architecture. We aimed to test the multi-modal distributional predictions of a Mendelian genetic architecture based on collectively common, but individually rare, large-effect variants and their ability to account for current trends in a large population-based sample. We studied publicly available adult BMI data (n = 9102) from 3 cycles of NHANES (1999, 2005, 2013). A first degree family history of diabetes served as a binary marker (FH0/FH1) of genetic obesity susceptibility. We tested for multi-modal BMI distributions non-parametrically using kernel-smoothing and conditional quantile regression (CQR), obtained parametric fits to a Mendelian model in FH1, and estimated FH x OE interactions in CQR models and ANCOVA models incorporating secular time. Non-parametric distributional analyses were consistent with multi-modality and fits to a Mendelian model in FH1 reliably identified 3 modes. Mode separation accounted for ~40% of BMI variance in FH1 providing a lower bound for the contribution of large effects. CQR identified strong FH x OE interactions and FH1 accounted for ~60% of the secular trends in BMI and its SD in ANCOVA models. Multimodality in the FH effect is inconsistent with a predominantly polygenic, small effect architecture and we conclude that large genetic effects interacting with OE provide a better quantitative explanation for current trends in BMI.

Background: Depressive symptoms are common in people with type 2 diabetes mellitus (T2DM). Effective depression treatments exist; however, access to psychological support is characteristically low. Web-based cognitive behavioral therapy (CBT) is accessible, nonstigmatizing, and may help address substantial personal and public health impact of comorbid T2DM and depression. Objective: The aim of this study was to evaluate the Web-based CBT program, myCompass, for improving social and occupational functioning in adults with T2DM and mild-to-moderate depressive symptoms. myCompass is a fully automated, self-guided public health treatment program for common mental health problems. The impact of treatment on depressive symptoms, diabetes-related distress, anxiety symptoms, and self-care behavior was also examined. Methods: Participants with T2DM and mild-to-moderate depressive symptoms (N=780) were recruited online via Google and Facebook advertisements targeting adults with T2DM and via community and general practice settings. Screening, consent, and self-report scales were all self-administered online. Participants were randomized using double-blind computerized block randomization to either myCompass (n=391) for 8 weeks plus a 4-week tailing-off period or an active placebo intervention (n=379). At baseline and postintervention (3 months), participants completed the Work and Social Adjustment Scale, the primary outcome measure. Secondary outcome measures included the Patient Health Questionnaire-9 item, Diabetes Distress Scale, Generalized Anxiety Disorder Questionnaire-7 item, and items from the Self-Management Profile for Type 2 Diabetes. Results: myCompass users logged in an average of 6 times and completed an average of .29 modules. Healthy Lifestyles users logged in an average of 4 times and completed an average of 1.37 modules. At baseline, mean scores on several outcome measures, including the primary outcome of work and social functioning, were near to the normal range, despite an extensive recruitment process. Approximately 61.6% (473/780) of participants completed the postintervention assessment. Intention-to-treat analyses revealed improvement in functioning, depression, anxiety, diabetes distress, and healthy eating over time in both groups. Except for blood glucose monitoring and medication adherence, there were no specific between-group effects. Follow-up analyses suggested the outcomes did not depend on age, morbidity, or treatment engagement. Conclusions: Improvement in social and occupational functioning and the secondary outcomes was generally no greater for myCompass users than for users of the control program at 3 months postintervention. These findings should be interpreted in light of near-normal mean baseline scores on several variables, the self-selected study sample, and sample attrition. Further attention to factors influencing uptake and engagement with mental health treatments by people with T2DM, and the impact of illness comorbidity on patient conceptualization and experience of mental health symptoms, is essential to reduce the burden of T2DM. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12615000931572; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368109&isReview=true (Archived by WebCite at http://www.webcitation.org/7850eg8pi)

Purpose: Analyze a survey of feelings and perspective on past diabetes education and care and compare with literature, highlighting continuing gaps in current care, especially noting gender differences. Results could provide insights to help improve diabetes care and reduce mental health burden.

Background: E-mental health (eMH) interventions are now widely available and they have the potential to revolutionize the way that health care is delivered. As most health care is currently delivered by primary care, there is enormous potential for eMH interventions to support, or in some cases substitute, services currently delivered face to face in the community setting. However, randomized trials of eMH interventions have tended to recruit participants using online recruitment methods. Consequently, it is difficult to know whether participants who are recruited online differ from those who attend primary care. Objective: This paper aimed to document the experience of recruiting to an eMH trial through primary care and compare the characteristics of participants recruited through this and other recruitment methods. Methods: Recruitment to the SpringboarD randomized controlled trial was initially focused on general practices in 2 states of Australia. Over 15 months, we employed a comprehensive approach to engaging practice staff and supporting them to recruit patients, including face-to-face site visits, regular contact via telephone and trial newsletters, and development of a Web-based patient registration portal. Nevertheless, it became apparent that these efforts would not yield the required sample size, and we therefore supplemented recruitment through national online advertising and promoted the study through existing networks. Baseline characteristics of participants recruited to the trial through general practice, online, or other sources were compared using the analysis of variance and chi square tests. Results: Between November 2015 and October 2017, 780 people enrolled in SpringboarD, of whom 740 provided information on the recruitment source. Of these, only 24 were recruited through general practice, whereas 520 were recruited online and 196 through existing networks. Key barriers to general practice recruitment included perceived mismatch between trial design and diabetes population, prioritization of acute health issues, and disruptions posed by events at the practice and community level. Participants recruited through the 3 different approaches differed in age, gender, employment status, depressive symptoms, and diabetes distress, with online participants being distinguished from those recruited through general practice or other sources. However, most differences reached only a small effect size and are unlikely to be of clinical importance. Conclusions: Time, labor, and cost-intensive efforts did not translate into successful recruitment through general practice in this instance, with barriers identified at several different levels. Online recruitment yielded more participants, who were broadly similar to those recruited via general practice.

Background People with type 2 diabetes mellitus (T2DM) often experience mental health symptoms that exacerbate illness and increase mortality risk. Access to psychological support is low in people with T2DM. Detection of depression is variable in primary care and can be further hampered by mental health stigma. Electronic mental health (eMH) programs may provide an accessible, private, nonstigmatizing mental health solution for this group. Objective This study aims to evaluate the efficacy over 12 months of follow-up of an eMH program (myCompass) for improving social and occupational functioning in a community sample of people with T2DM and self-reported mild-to-moderate depressive symptoms. myCompass is a fully automated and self-guided web-based public health program for people with depression or anxiety. The effects of myCompass on depressive symptoms, diabetes-related distress, anxiety symptoms, and self-care behavior were also examined. Methods Adults with T2DM and mild-to-moderate depressive symptoms (N=780) were recruited via online advertisements, community organizations, and general practices. Screening, consent, and self-report questionnaires were administered online. Eligible participants were randomized to receive either myCompass (n=391) or an attention control generic health literacy program (Healthy Lifestyles; n=379) for 8 weeks. At baseline and at 3, 6, and 12 months postintervention, participants completed the Work and Social Adjustment Scale, the Patient Health Questionnaire-9 item, the Diabetes Distress Scale, the Generalized Anxiety Disorder Questionnaire-7 item, and items from the Self-Management Profile for Type 2 Diabetes. Glycosylated hemoglobin measurements were obtained at baseline and 6 and 12 months postintervention. Results A total of 38.9% (304/780) of the trial participants completed all postintervention assessments. myCompass users logged in on an average of 6 times and completed an average of 0.29 modules. Healthy Lifestyles users logged in on an average of 4 times and completed an average of 1.37 modules. At baseline, the mean scores on several outcome measures, including the primary outcome of work and social functioning, were close to the normal range, despite a varied and extensive recruitment process. Intention-to-treat analyses revealed slightly greater improvement at 12 months in work and social functioning for the Healthy Lifestyles group relative to the myCompass group. All participants reported equivalent improvements in depression anxiety, diabetes distress, diabetes self-management, and glycemic control across the trial. Conclusions The Healthy Lifestyles group reported higher ratings of social and occupational functioning than the myCompass group, but no differences were observed for any secondary outcome. Although these findings should be interpreted in light of the near-floor symptom scores at baseline, the trial yields important insights into how people with T2DM might be engaged in eMH programs and the challenges of focusing specifically on mental health. Several avenues emerge for continued investigation into how best to deal with the growing mental health burden in adults with T2DM. Trial Registration Australian New Zealand Clinical Trials Registry Number (ACTRN) 12615000931572; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368109&isReview=true

Aims Analyze cosegregation of aniridia and diabetes to identify genetic criteria for detection and early treatment of diabetes-susceptible aniridia patients. Methods We assessed a two-generation family: three individuals with aniridia, two previously diagnosed as type 2 diabetes. One individual with aniridia, with unknown diabetes status, was evaluated by oral glucose tolerance test. Genetic analysis of aniridia-associated genes was performed on all available family members. Candidate genes were functionally tested by gene silencing in MIN6 pancreatic β-cells. Results A 25 year old male with aniridia had a diabetic oral glucose tolerance test despite a normal fasting blood glucose. A 484–630 kb deletion ∼120 kb distal to PAIRED BOX 6 (PAX6) showed dominant cosegregation with aniridia and diabetes in all affected family members. The deleted region contains regulatory elements for PAX6 expression and four additional coding regions. Knockdown of two of the deleted genes (Dnajc24 or Immp1l) with Pax6 impaired glucose-stimulated insulin secretion. Conclusions We demonstrate dominant cosegregation of diabetes and aniridia with a deletion distal to PAX6, which is clinically distinct from the mild glucose intolerance previously reported with PAX6 coding mutations. Asymptomatic aniridia individuals appear at risk of diabetes (and its complications) and could benefit from earlier diagnosis and treatment.

While obesity has been linked with lower quality of life in the general adult population, the prospective effects of present obesity on future quality of life amongst the elderly is unclear. This article investigates the cross-sectional and longitudinal relationships between obesity and aspects of quality of life in community-dwelling older Australians. A 2-year longitudinal sample of community dwellers aged 70–90 years at baseline, derived from the Sydney Memory and Ageing Study (MAS), was chosen for the study. Of the 1037 participants in the original MAS sample, a baseline (Wave 1) sample of 926 and a 2-year follow-up (Wave 2) sample of 751 subjects were retained for these analyses. Adiposity was measured using body mass index (BMI) and waist circumference (WC). Quality of life was measured using the Assessment of Quality of Life (6 dimensions) questionnaire (AQoL-6D) as well as the Satisfaction with Life Scale (SWLS). Linear regression and analysis of covariance (ANCOVA) were used to examine linear and non-linear relationships between BMI and WC and measures of health-related quality of life (HRQoL) and satisfaction with life, adjusting for age, sex, education, asthma, osteoporosis, depression, hearing and visual impairment, mild cognitive impairment, physical activity, and general health. Where a non-linear relationship was found, established BMI or WC categories were used in ANCOVA. Greater adiposity was associated with lower HRQoL but not life satisfaction. Regression modelling in cross-sectional analyses showed that higher BMI and greater WC were associated with lower scores for independent living, relationships, and pain (i.e. worse pain) on the AQoL-6D. In planned contrasts within a series of univariate analyses, obese participants scored lower in independent living and relationships, compared to normal weight and overweight participants. Longitudinal analyses found that higher baseline BMI and WC were associated with lower independent living scores at Wave 2. Obesity is associated with and predicts lower quality of life in elderly adults aged 70–90 years, and the areas most affected are independent living, social relationships, and the experience of pain.

BACKGROUND Diabetic patients are commonly hyperglycaemic on presentation. Admission hyperglycaemia is associated with adverse outcomes, particularly prolonged hospitalisation. Improving inpatient glycaemia may reduce length of hospital stay (LOS) in diabetic patients. AIMS To determine whether in-hospital recognition and treatment of admission hyperglycaemia in diabetic patients is associated with reduced LOS. METHODS Medical records were reviewed from 1 November 2011 to 31 May 2012 for 162 diabetic patients admitted with a blood glucose level (BGL) ≥11.1mmol/L. In-hospital outcomes were compared. Stepwise multiple regression was used to evaluate factors contributing to LOS. RESULTS Compared to the untreated individuals (n=67), hyperglycaemia treatment (n=95) was associated with a longer LOS (median eight vs. four days, p

Objective Individuals with Prader–Willi syndrome (PWS) are commonly restricted to 60-75% of height-appropriate calorie intake because they rapidly become obese on a normal diet. This study measured changes in energy expenditure, glucose and lipid homeostasis, and metabolic flexibility in response to a meal in PWS adults. Methods 11 adults with PWS were compared with 12 adiposity-matched and 10 lean subjects. Indirect calorimetry was conducted at baseline and 210 min after a standardized 600 kCal breakfast to assess energy expenditure and substrate utilization. Circulating glucose, insulin, C-peptide, glucagon, nonesterified fatty acids, and triglycerides were measured up to 240 min. Insulin sensitivity and insulin secretion rate were assessed by HOMA-IR and C-peptide deconvolution, respectively. Body composition was determined by dual-energy X-ray absorptiometry. Results The PWS group had lower lean mass than the obesity control group. Corrected for lean mass, there were no differences between the PWS and obesity groups in resting metabolic rate or metabolic flexibility. Total and abdominal fat mass, insulin sensitivity, and insulin secretion rate were also similar between these groups. Conclusions This study did not detect an intrinsic metabolic defect in individuals with PWS. Rather, lower lean mass, combined with lower physical activity, may contribute to weight gain on an apparent weight-maintenance diet.

Objectives: To determine whether obesity, estimated according to body mass index (BMI), waist circumference, and body fat and abdominal fat assessed using dual-energy X-ray absorptiometry (DEXA), was associated with cognitive performance. Design: Cross-sectional. Setting: Community based. Participants: Individuals aged 74–94 (N = 406). Measurements: BMI, waist circumference, body fat, and abdominal fat were assessed using DEXA. Cognitive performance was assessed using a comprehensive neuropsychological battery. Results: When categorized using BMI, overweight individuals had higher global cognitive function and executive function scores than normal-weight individuals. This relationship did not differ according to sex. When categorized according to DEXA, there were no relationships between body fat and cognitive function in the whole group, but women in the middle and highest tertiles of DEXA body fat had better executive function than those in the lowest tertile. Men in the middle tertile of DEXA body fat had significantly better executive function and memory than those in the lowest tertile. BMI had greater power to predict executive function than DEXA body fat. No significant associations were found between cognition and estimates of abdominal adiposity. Conclusion: This study found an association between being overweight and better executive function in elderly adults; this association was stronger for the simpler BMI than the more-elaborate DEXA measures.

Diabetes increases morbidity and mortality of lung transplantation. However, the reported prevalence of diabetes varies post-transplantation partly due to lack of detection protocols.To determine the prevalence of diabetes in patients (i) waitlisted for lung transplant and (ii) early post-transplantation.We analysed patients on the St Vincent's Heart Lung database from 1 April 2014 to 30 September 2015 on the waitlist (Study 1) and those transplanted (Study 2). Standard of care required all non-diabetic patients to have an oral glucose tolerance test (modified for patients with cystic fibrosis (CF) to screen for CF-related hyperglycaemia (CFRH) (plasma glucose ≥8.2 mmol/L at 60 or 90 min).Study 1 included 114 patients (32 with CF and 82 without CF). Of 30 CF patients with glycaemic data, 27 (90%) had abnormal glucose metabolism: 18 had diabetes and nine had CFRH. In 50 patients without CF, 20 (40%) had abnormal glucose metabolism: eight had diabetes and 12 had impaired fasting glucose and/or impaired glucose tolerance. Study 2 included 78 transplanted patients (25 with CF and 53 without CF). Fourteen CF patients had pre-existing diabetes and seven had pre-existing CFRH. All but one patient were diagnosed with diabetes post-transplantation. Hence, diabetes prevalence in CF patients post-transplantation was 96%. Among 53 transplanted patients without CF, seven (13%) had abnormal glucose metabolism but 30 (57%) were diagnosed with post-transplant diabetes.There is a high prevalence of diabetes in lung transplant patients. Earlier endocrine participation in lung transplant services is likely to lower diabetes-related morbidity and mortality further.

The prevalence and cost of overweight and obesity are projected to continue to rise in our current sedentary, energy-rich environment. The heritability of obesity is reported to be 40-80%.The objectives of this article are to review recent genetic discoveries about the basis of human obesity; describe familial or syndromic obesity, which is rare but presents early and should, if suspected, be referred for full specialist diagnosis of the underlying genetic disorder; and summarise immediate implications for general practice.Increasingly, specialised genetic studies are helping to unravel the complex physiology underlying the regulation and control of body fatness. Rare but serious syndromic obesity can now be identified early in life. Possible targets for future drug treatment are currently being found and tested, offering hope for the future. Understanding the heritable nature of obesity should also help to relieve the blame and guilt from the professional's approach to current weight management.

enhance recovery after surgery or trauma. It has also been reported to have beneficial effects on glycaemic control in diabetic patients, while rodent studies suggest that it may reduce body weight and lessen hyperglycaemia. Objective: The present study aimed to investigate the effects of daily supplementation of glutamine to high fat diet and to assess this in a mouse model with abnormal feeding behaviour: the Snord116 knockout mouse. Research methods: Adult male C57BL/6 mice and mice with deletion of the Snord116 gene cluster (implicated in Prader-Willi syndrome) were given ad libitum access to HFD for 12 weeks. Mice of both genotypes were randomly assigned to either the treatment or non-treatment group. Animals were supplemented with glutamine in food (40 mg/g HFD). Body weight was monitored weekly. Spontaneous and fasting-induced food intake, glucose tolerance and insulin sensitivity, energy expenditure and body composition were assessed between 14 and 18 weeks of age. Results: Glutamine treatment did not attenuate the development of HFD-induced obesity in either WT or Snord116 knockout mice, with treatment and non-treatment groups within genotypes gaining weight at a similar rate during the monitoring period. There was also no difference between treatment groups within genotypes in food intake, glucose tolerance, insulin tolerance, energy expenditure or adiposity. Conclusion: Our results did not find evidence that would support beneficial metabolic effects of glutamine when administered daily; either in WT or Snord116 knockout mice fed a HFD.

Aim: While the impact of major depression on diabetes has gained increasing attention, the role of minor depression is less well investigated. This observational study compared three groups of adults with Type 1 (T1DM) or Type 2 (T2DM) diabetes mellitus: with me) no depressive symptoms (NODEP), ii) mild depressive symptoms (MILD) and iii) moderate-to-severe symptoms (MOD/SEVERE)-on diabetes distress, psychological distress, anxiety and somatic symptoms, quality of life and HbA1c levels. Methods: 245 outpatients attending two hospital diabetes services (27% with T1DM; 73% with T2DM) completed self-report measures including patient health questionnaire (PHQ), problem areas in diabetes (PAID) scale and short form health survey (SF12). Participants were interviewed by a psychiatrist and HbA1c levels recorded. Results: Half the sample reported depressive symptoms on the PHQ-9 (29% in the MILD group, 21% in MOD/ SEVERE and the remaining 50% in the NODEP group). Compared to the NODEP group, MILD group participants had significantly higher levels of diabetes distress, psychological distress, anxiety and somatic symptoms and significantly lower mental-health related quality of life. Participants in the MOD/SEVERE group had significantly higher levels of diabetes distress, psychological distress, anxiety, and somatic symptoms than either of the other two groups, and significantly lower quality of life. The groups did not differ significantly on HbA1c. Conclusions: Mild symptoms of depression in patients with diabetes are common and are associated with higher levels of diabetes distress, psychological distress, anxiety and somatic symptoms and lower quality of life. Addressing mild depression provides a potential avenue for preventing clinical depression in patients with diabetes.

Objectives While chronic obesity is associated with alterations in circulating glycerolipids, sphingolipids and plasmalogens, the effects of short-term overfeeding in humans are unclear. Design and Methods Healthy individuals (n = 40) were overfed by 1,250 kcal day−1 for 28 days. Insulin sensitivity (hyperinsulinemic-euglycemic clamp), abdominal fat distribution and serum lipidomics (mass spectrometry) were assessed. Results Overfeeding increased liver fat, insulin resistance, serum C-reactive protein and urinary F2-isoprostanes. HDL increased (11% ± 2%, P < 0.001) while LDL, triglycerides and nonesterified fatty acids were unchanged. Three hundred and thirty three serum lipids were detected, of which 13% increased and 20% decreased with overfeeding. Total diacylglycerol and lysoalkylphosphatidylcholine (LPC(O)) concentrations decreased (P < 0.01), while total ceramide, Cer22:0 and Cer24:0 increased (P ≤ 0.01). The most notable increases were observed in the HDL-associated phosphatidylethanolamine-based plasmalogens and their precursors alkylhosphatidylethanolamine (18 ± 5% and 38 ± 8% respectively, P ≤ 0.01). Conclusions Overfeeding led to weight gain and changes in the serum lipid profile. Increases in ceramides were noted, which left unchecked may promote systemic insulin resistance. Uniform increases were observed in plasmalogens and their precursors. Because plasmalogens are powerful antioxidants, this may be an appropriate response against increased oxidative stress generated by over-nutrition. The metabolic consequences of changes in concentrations of many circulating lipid species with overfeeding require further study. Copyright © 2013 The Obesity Society

Summary Higher levels of macrophage inhibitory cytokine-1, also known as growth differentiation factor 15 (MIC-1/GDF15), are associated with adverse health outcomes and all-cause mortality. The aim of this study was to examine the relationships between MIC-1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70–90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C-reactive protein, tumor necrosis factor-a, interleukins 6 and 12, and apolipoprotein e4 genotype. Higher MIC-1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross-sectional associations were found between MIC-1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC-1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC-1/ GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC-1/GDF15 cutoff values associated with cognitive decline and showed that a MIC-1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC-1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship.

SummaryContext Individuals with Prader–Willi syndrome (PWS) have a high cardiovascular risk, the mechanism of which is unclear. There may be dysfunction in the autonomic nervous system (ANS) in PWS. Objective To measure, as indicators of cardiac autonomic function, postprandial heart rate variability (HRV) and arterial stiffness in adults with PWS. Methods Ten adults with PWS were compared with 11 matched healthy obese subjects and 9 healthy lean subjects. Electrocardiographic traces and arterial stiffness were recorded over a period of 10 minutes at −60, 0, 30, 60, 120 and 240 minutes after consumption of a standardized 600-kCal breakfast. Frequency domain analysis was performed using fast Fourier transform to estimate power spectral density in the full spectrum and in low-frequency (LF 0·04–0·15 Hz) and high-frequency (HF 0·15–0·40 Hz) bands. Results ANCOVA revealed a reduced LF HRV meal response in adults with PWS compared with obese controls, with no differences in HF HRV, LF/HF ratio, heart rate, total power or arterial stiffness meal responses. Conclusions This study assessed cardiac autonomic function in adults with PWS compared with matched obese and lean subjects in response to a meal. Results suggest impaired postprandial ANS responsiveness in PWS, which could contribute to both the known increased cardiovascular risk and obesity.

Investigations into serotonin transporter and anxiety and depression have shown an association between stress, depression onset and genotype. We investigated the relationship between 5-HTTLPR genotype and depression and anxiety in a population with diabetes mellitus, a condition associated with high rates of stress and depression. Participants were classified according to 'S' and 'L' alleles as well as the modification of the single nucleotide polymorphism (SNP) rs25531. The 5-HTTLPR low-expression genotype group (S or L(G) allele carriers) had significantly higher psychological distress (K10) scores (N=234, P=0.047). Subsequent analysis revealed that the effect of genotype was related to anxiety symptoms rather than depression symptoms. Furthermore, the main effect of genotype was not observed when the modification of the SNP polymorphism was not taken into account. Findings suggest that 5-HTTLPR/rs25531 genotype is associated with psychological distress in a sample of subjects with diabetes.

The Snord116 gene cluster has been recognised as a critical contributor to the Prader-Willi syndrome (PWS), with mice lacking Snord116 displaying many classical PWS phenotypes, including low postnatal body weight, reduced bone mass and increased food intake. However, these mice do not develop obesity as a result of increased energy expenditure. To understand the physiological function of SNORD116 better and potentially rescue the altered metabolism of Snord116-/- mice, we used an adeno-associated viral (AAV) approach to reintroduce the product of the Snord116 gene into the hypothalamus in Snord116-/- mice at different ages. The results obtained show that mid-hypothalamic re-introduction of SNORD116 in 6-week-old Snord116-/- mice leads to significantly reduced body weight and weight gain, which is associated with elevated energy expenditure. Importantly, when the intervention targets other areas such as the anterior region of the hypothalamus or the reintroduction occurs in older mice, the positive effects on energy expenditure are diminished. These data indicate that the metabolic symptoms of PWS develop gradually and the Snord116 gene plays a critical role during this process. Furthermore, when we investigated the consequences of SNORD116 re-introduction under conditions of thermoneutrality where the mild cold stress influences are avoided, we also observed a significant increase in energy expenditure. In conclusion, the rescue of mid-hypothalamic Snord116 deficiency in young Snord116 germline deletion mice increases energy expenditure, providing fundamental information contributing to potential virus-mediated genetic therapy in PWS.

Germline deletion of the Prader-Willi syndrome (PWS) candidate gene Snord116 in mice leads to some classical symptoms of human PWS, notably reductions in body weight, linear growth and bone mass. However, Snord116 deficient mice (Snord116−/−) do not develop an obese phenotype despite their increased food intake and the underlying mechanism for that is unknown. We tested the phenotypes of germline Snord116−/− as well as neuropeptide Y (NPY) neuron specific Snord116lox/lox/NPYcre/+ mice at 30 °C, the thermoneutral temperature of mice, and compared these to previous reports studies conducted at normal room temperature. Snord116−/− mice at 30 °C still weighed less than wild type but had increased body weight gain. Importantly, food intake and energy expenditure were no longer different at 30 °C, and the reduced bone mass and nasal-anal length observed in Snord116−/− mice at room temperature were also normalized. Mechanistically, the thermoneutral condition led to the correction of the mRNA expression of NPY and pro-opiomelanocortin (POMC), which were both previously observed to be significantly up-regulated at room temperature. Importantly, almost identical phenotypes and NPY/POMC mRNA expression alterations were also observed in Snord116lox/lox/NPYcre/+ mice, which lack the Snord116 gene only in NPY neurons. These data illustrate that mild cold stress is a critical factor preventing the development of obesity in Snord116−/− mice via the NPY system. Our study highlights that the function of Snord116 in the hypothalamus may be to enhance energy expenditure, likely via the NPY system, and also indicates that Snord116 function in mice is strongly dependent on environmental conditions such as cold exposure.

The Asia Pacific region, with its rapid economic development and changes in lifestyles, has been identified as an epicenter of diabetes. However, the prevalence of diabetes in this region has not been well documented. Glycated hemoglobin (HbA1c) has been introduced as a new diagnostic test for diabetes, but its impact on disease prevalence is unknown. In this study, we sought to estimate the prevalence of undiagnosed diabetes in an urban population in Vietnam by using new HbA1c diagnostic criteria. The study was designed as a population-based investigation that involved 1,339 individuals (973 women) randomly sampled from Ho Chi Minh City, Vietnam. All individuals were aged 30 years and above (average age ∼53 years, no significant difference between women and men). Blood samples were collected after overnight fasting and analyzed within 24 h after collection. HbA1c was measured with high-performance liquid chromatography (ARKRAY, …

Objectives: To determine whether the metabolic syndrome (MetS) or its components were more closely associated with disease states and inflammation in elderly adults. Design: Sydney Memory and Ageing Study. Cross-sectional, observational cohort. Setting: Population-derived, community-dwelling elderly adults. Participants: Nine hundred thirty individuals aged 70 to 90. Measurements: Age- and sex-adjusted odds ratios (ORs) for disease states; fasting circulating inflammatory markers and oxidative metabolism byproducts. Results: MetS was associated with diabetes mellitus (OR = 4.1, P < .001) and bowel cancer (OR = 9.1, P = .03) but not in analyses that controlled for component conditions. Models containing component conditions had the strongest association with heart disease. Disease associations were improved after addition of component conditions to the MetS model. The reverse did not hold: disease associations were not improved when MetS was added to the components model. Low high-density lipoprotein cholesterol (HDL-C) was independently associated with myocardial infarction (OR = 2.32) and angina pectoris (OR = 2.59) (both P < .008). Waist circumference was independently associated with cancer (OR = 1.82, P = .008). Although MetS was associated with higher C-reactive protein, vascular cell adhesion molecule, interleukin-6, amyloid A, homocysteine, and malondialdehyde, it explained less than half of the variance of models containing its components. Conclusion: The observation that MetS is associated with disease states and markers of circulating inflammation in the elderly is explained mainly by abdominal obesity and low HDL-C. Longitudinal data will further clarify these cross-sectional findings that MetS appears to be less than the sum of its parts in elderly adults.

Background Obesity and type 2 diabetes mellitus are characterized by insulin resistance and ‘low-grade inflammation’; however, the pathophysiological link is poorly understood. To determine the relative contribution of obesity and insulin resistance to systemic ‘inflammation’, this study comprehensively characterized circulating immune cells in different grades of obesity. Methods Immune cell phenotypes and activation status were analysed by flow cytometry cross-sectionally in morbidly obese (n = 16, body mass index (BMI) 42.2 ± 5.4 kg/m2), overweight (n = 13, BMI 27.4 ± 1.6 kg/m2) and normal weight (n = 12, BMI 22.5 ± 1.9 kg/m2) subjects. Results Obese, but not overweight subjects, had increased activation marker expression on neutrophils, monocytes, T-lymphocytes and polarization of T helper cells towards a pro-inflammatory type 1-phenotype (Th1). Th1 numbers correlated positively with the degree of insulin resistance (homeostasis model assessment, p

Recreational drug use during 'rave' parties is increasingly popular, but the impact of recreational drug use in type 1 diabetes (T1D) is not known. We determined the self-reported pattern and effects of recreational/illicit drug use in Australians with T1D people by inviting people with T1D to participate in an anonymous online/paper survey of drug use, through national radio broadcast and online/hospital advertising. Of the people with T1D who responded to our survey, more than three quarters reported having used recreational/illicit drug, but few people had informed health professionals about drug use. Drug use was associated with worse glycaemic control and higher risk of diabetic ketoacidosis. Medical awareness of common, currently underreported, drug use in young people with T1D is essential. It offers the possibility of helping such patients improve related suboptimal metabolic control.

Articles in the December 2016 issue of Diabetes Care addressing psychosocial issues are important for diabetes care (1). Our recent comment in The Lancet also addresses the “forgotten burden” of mental illness in diabetes (2). We highlight our concerns below. Although the recommendations of the American Diabetes Association (ADA) (3) are based on “patient-centered care” (now becoming cliche), we have yet to see this model in action, despite extensive publication about it over past decades. Many well-intentioned care providers, believing they already practice “patient-centered care,” continue to increase the patient’s anxiety and guilt by implying blame for above-target glycemic control and emphasizing the patient’s risk of complications because of “noncompliance.” We are concerned that these traditional attitudes, ingrained …

Summary Recent research suggests that increased adiposity is associated with poor cognitive performance, independently of associated medical conditions. The evidence regarding this relationship is examined in this review article. A relatively consistent finding across the lifespan is that obesity is associated with cognitive deficits, especially in executive function, in children, adolescents and adults. However, as illustrated by contradictory studies, the relationship between obesity and cognition is uncertain in the elderly, partly because of inaccuracy of body mass index as a measure of adiposity as body composition changes with aging. This review further discusses whether obesity is a cause or a consequence of these cognitive deficits, acknowledging the possible bidirectional relationship. The possible effects of increased adiposity on the brain are summarized. Our investigations suggest that weight gain results, at least in part, from a neurological predisposition characterized by reduced executive function, and in turn obesity itself has a compounding negative impact on the brain via mechanisms currently attributed to low-grade systemic inflammation, elevated lipids and/or insulin resistance. The possible role of cognitive remediation treatment strategies to prevent and/or treat obesity is discussed.

Background: Diabetes diagnosis is delayed 4–7 years and 50% are undiagnosed. Forty percent of hospitalized patients with any blood glucose level (BGL) ≥10 mmol/L have diabetes 3 months post-discharge, yet less than 5% are detected in hospital. We review identification of, and responses to, hyperglycaemia in inpatients at a teaching hospital. Methods: The world's largest retrospective review of medical records for inpatients with venous BGL ≥11.1 mmol/L without known diabetes over 12 months (2005–2006). The primary outcome was recognition of hyperglycaemia; secondary outcomes were treatment and documentation of follow up. Logistic regression was performed with variables including BGL, admitting team, length of stay and endocrine team review. Results: Of 10 973 people screened, 162 were eligible. The median age was 58 years and BGL 13.3 mmol/L, with increased mortality and length of stay. Hyperglycaemia was noted as definitely in 26%, maybe in 24% and definitely not in 50%. Forty percent of patients were treated in hospital and 19% on discharge. Follow up was documented for 24%. A higher BGL and review by the endocrine team were strongly associated with clinical recognition on uni- and multivariate analyses. However, where an endocrine review was sought for non-hyperglycaemia reasons, similar rates of non-recognition occurred. Conclusion: Despite evidence for improved inpatient outcomes when treated, and high short-term progression to frank diabetes, inpatient hyperglycaemia remains frequently missed. In-hospital recognition is cheap, and vital for the implementation of activities to improve outcomes and prevent progression and complications. Changes to systems for checking pathology results, medical officer education and inpatient screening guidelines are indicated.

The purpose of the study was to test prospectively whether healthy individuals with a family history of type 2 diabetes are more susceptible to adverse metabolic effects during experimental overfeeding. We studied the effects of 3 and 28 days of overfeeding by 5,200 kJ/day in 41 sedentary individuals with and without a family history of type 2 diabetes (FH+ and FH− respectively). Measures included body weight, fat distribution (computed tomography) and insulin sensitivity (hyperinsulinaemic–euglycaemic clamp). Body weight was increased compared with baseline at 3 and 28 days in both groups (p

Background/Aims: Raised low-grade systemic inflammation has been associated with dementia, and preliminary studies suggest an association with mild cognitive impairment (MCI). This study examines the relationship between systemic inflammation and MCI subtypes. Methods: We measured the inflammatory markers C-reactive protein, interleukins (IL)-1β, -6, -8, -10 and -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A (SAA), tumor necrosis factor-α (TNF-α) and vascular adhesion molecule-1 (VCAM-1) in the Sydney Memory and Ageing Study (MAS) cohort, a longitudinal study of 1,037 Australians aged 70–90 years. Results: After adjusting for possible confounding variables, levels of TNF-α and SAA were higher in participants with MCI compared to cognitively normal individuals, and some sex differences were apparent. Nonamnestic multiple domain MCI was associated with higher levels of IL-1β and IL-12, TNF-α and SAA compared to cognitively normal, amnestic MCI (single and multiple domain) and nonamnestic single domain MCI. PAI-1 levels were higher in cognitively normal and nonamnestic multiple domain MCI than in amnestic multiple domain MCI. Conclusion: Our findings suggest an association between specific inflammatory markers and MCI subtypes, highlight sex differences in the association with MCI, and point to a discrete impact of systemic inflammation on cognition.

OBJECTIVE Chronic low-grade inflammation is a feature of obesity and is postulated to be causal in the development of insulin resistance and type 2 diabetes. The aim of this study was to assess whether overfeeding induces peripheral insulin resistance in lean and overweight humans, and, if so, whether it is associated with increased systemic and adipose tissue inflammation. RESEARCH DESIGN AND METHODS Thirty-six healthy individuals undertook 28 days of overfeeding by +1,250 kcal/day (45% fat). Weight, body composition, insulin sensitivity (hyperinsulinemic-euglycemic clamp), serum and gene expression of inflammation markers, immune cell activation, fat cell size, macrophage and T-cell numbers in abdominal subcutaneous adipose tissue (flow cytometry and immunohistochemistry) were assessed at baseline and after 28 days. RESULTS Subjects gained 2.7 ± 1.6 kg (P < 0.001) and increased fat mass by 1.1 ± 1.6% (P < 0.001). Insulin sensitivity decreased by 11% from 54.6 ± 18.7 to 48.9 ± 15.7 μmol/(kg of FFM)/min (P = 0.01). There was a significant increase in circulating C-reactive protein (P = 0.002) and monocyte chemoattractant protein-1 (P = 0.01), but no change in interleukin-6 and intercellular adhesion molecule-1. There were no changes in fat cell size, the number of adipose tissue macrophages or T-cells, or inflammatory gene expression and no change in circulating immune cell number or expression of their surface activation markers after overfeeding. CONCLUSIONS Weight gain-induced insulin resistance was observed in the absence of a significant inflammatory state, suggesting that inflammation in subcutaneous adipose tissue occurs subsequent to peripheral insulin resistance in humans.

The aetiology of obesity is multi-factorial. Recent research has identified a novel association between endotoxaemia (circulating lipopolysaccharide in the systemic circulation) and low-grade inflammation in the adipose organ, which may contribute to obesity. The mechanisms for the low-grade elevation of circulating lipopolysaccharide in obesity are poorly understood. Vitamin D has been increasingly recognised for its pleiotropic actions beyond maintenance of musculoskeletal health. The parathyroid-vitamin D axis is altered in obesity. Circulating vitamin D levels are lower in obese individuals. The regulatory role of vitamin D in the immune system and colonic mucosa may explain the under-appreciated contribution of vitamin D deficiency in the obese to the pathogenesis of endotoxaemia and adipose inflammation. We propose a hypothetical model linking metabolic endotoxaemia with vitamin D deficiency in obesity. A therapeutic approach involving the use of probiotics and vitamin D metabolites in the obese is described.

Background: Secondary prevention of ischaemic stroke (IS) and transient ischaemic attack (TIA) mandates identification and treatment of multiple metabolic risk factors. The aim was to determine the prevalence of abnormal glycaemia, hypertension and dyslipidaemia in patients presenting to an Acute Stroke Unit of a tertiary referral teaching hospital with IS or TIA. Methods: We reviewed the clinical characteristics of consecutive patients presenting with symptoms of acute stroke or TIA between 1 February 2006 and 30 June 2007 to determine the prevalence of diabetes, impaired fasting glucose (IFG), post-stroke dysglycaemia (PSD), hypertension and dyslipidaemia. Results: Mean age ± SD of the 224 patients (84 female) was 71 ± 15 years. Seventy per cent (n= 157) of patients presented with IS and 30% (n= 67) with TIA. Of the cohort, 15% (n= 33) had previously diagnosed diabetes, 10% (n= 22) were diagnosed with diabetes during admission and 19% (n= 42) had IFG diagnosed during admission. A further 4% (n= 9) were classified as having PSD. Sixty-two per cent (n= 139) of patients had previously diagnosed hypertension; another 7% (n= 15) were diagnosed during admission. Eighty-eight per cent (n= 197) of patients had dyslipidaemia. Thirty per cent had all three risk factors concurrently. Conclusion: Abnormal glycaemia was present in almost half the patients presenting with IS/TIA, with the majority of cases undiagnosed. One-third of patients had abnormal glycaemia, hypertension and dyslipidaemia concurrently. Patients presenting with stroke should be routinely screened for abnormal glycaemia in concert with other vascular risk factors.

Calciphylaxis is a rare disorder with high mortality, which commonly occurs, but not limited to, patients with end-stage renal disease. We present a successful case in which a patient survived this serious disorder of vasculopathy, highlighting the physical and emotional morbidities associated with this condition and alerting physicians of the key elements in its management. Further understanding of calciphylaxis may advance our knowledge in endotheliopathy and vascular ossification.

Background: The aim of this study was to determine whether pre-existing diabetes mellitus increases the risk of rejection, infection and/or death in cystic fibrosis patients undergoing bilateral sequential single-lung transplantation. Methods: A retrospective audit of 25 consecutive patients with cystic fibrosis who underwent bilateral sequential single-lung transplantation between 1 January 2003 and 31 December 2005 at a tertiary referral hospital was carried out. Results: Although 32% patients had diabetes diagnosed before lung transplantation, 92% had random blood glucose levels ≥11.1 mmol/L requiring insulin during admission. Patients with pre-existing diabetes had increased infection-related (3.9 vs 1.2, P= 0.01) and putative rejection-related (1.4 vs 0.5, P= 0.04) hospital admissions post-transplantation compared with those without diabetes pre-transplant. During the period of observation, four of eight patients with a prior diagnosis of diabetes died compared with none of 17 patients without prior diabetes (P= 0.0055). Conclusion: Almost all cystic fibrosis patients develop hyperglycaemia after lung transplantation, but patients with prior diabetes have more complication-related admissions to hospital and a higher mortality rate.

Obesity was first described as a low-grade inflammatory condition more than a decade ago. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well as an increase in the number of "M1" or "classically activated" macrophages. Furthermore, macrophages have been identified as the primary source of many of the circulating inflammatory molecules that are detected in the obese state and are postulated to be causal both in the development of insulin resistance and in the progression to type 2 diabetes. There is also novel evidence to suggest that macrophages inhibit adipocyte differentiation, potentially leading to adipocyte hypertrophy, altered secretion of adipokines and ectopic storage of lipid within liver, muscle and other non-adipose tissues. Currently, it is not clear what causes increased macrophage infiltration of adipose tissue in obese individuals. Theories include altered signalling by adipocytes, nutritional induction of metabolic endotoxemia or reduced angiogenesis and local adipose cell hypoxia. Importantly, PPAR-gamma agonists have been shown to alter macrophage phenotype to "M2" or an "alternatively activated" anti-inflammatory phenotype and may induce macrophage specific cell death. Consequently, excitement surrounds the potential for specific inhibition of macrophage infiltration of adipose tissue via pharmacotherapy for obese patients and more particularly as adjunct therapy to improve insulin sensitivity in obese individuals with insulin resistance and overt type 2 diabetes.

Individuals with insulin resistance and type 2 diabetes have an impaired ability to switch appropriately between carbohydrate and fatty acid oxidation. However, whether this is a cause or consequence of insulin resistance is unclear, and the mechanism(s) involved in this response is not completely elucidated. Whole-body fat oxidation and transcriptional regulation of genes involved in lipid metabolism in skeletal muscle were measured after a prolonged fast and after consumption of either high-fat (76%) or high-carbohydrate (76%) meals in individuals with no family history of type 2 diabetes (control, n = 8) and in age- and fatness-matched individuals with a strong family history of type 2 diabetes (n = 9). Vastus lateralis muscle biopsies were performed before and 3 h after each meal. Insulin sensitivity and fasting measures of fat oxidation were not different between groups. However, subjects with a family history of type 2 diabetes had an impaired ability to increase fatty acid oxidation in response to the high-fat meal (P < 0.05). This was related to impaired activation of genes involved in lipid metabolism, including those for peroxisome proliferator–activated receptor coactivator-1α (PGC1α) and fatty acid translocase (FAT)/CD36 (P < 0.05). Of interest, adiponectin receptor-1 expression decreased 23% after the high-fat meal in both groups, but it was not changed after the high-carbohydrate meal. In conclusion, an impaired ability to increase fatty acid oxidation precedes the development of insulin resistance in genetically susceptible individuals. PGC1α and FAT/CD36 are likely candidates in mediating this response.