A pilot study to assess the feasibility and uptake of MindDEC, a mindfulness-based self-management course for type 2 diabetes.

OBJECTIVE: The study aimed to investigate the feasibility of a remote mindfulness based self-management intervention for individuals with type 2 diabetes. It is important to further our understanding of how to improve self-management to improve health outcomes and low levels of uptake to self-management courses. METHOD: 29 participants with type 2 diabetes were recruited from the University Hospital Coventry and Warwickshire NHS trust. Three groups of participants engaged with a remote mindfulness based self-management intervention, which were delivered sequentially. After each intervention was complete, patient feedback was retrieved and implemented into the following intervention. The quantitative analysis comprised of descriptive statistics, independent sample t-test, paired sample t-test and multiple regression analysis. A qualitative analysis was also conducted through reflexive thematic analysis (RTA) to understand participant's perspective on the intervention. RESULTS: There was a total of 17 who attended the course (59 %) and a total drop out of 12 participants over the three courses (41 %). The qualitative findings reported three main themes: (1) Eating to manage my emotions rather than my diabetes (2) Implementing mindfulness has helped me manage my emotions (3) Medication rather than self-management behaviours control my diabetes. The focus group feedback included participants' appreciation of the community aspect of the intervention and their perception that the current course was more interactive compared to previous interventions. In addition, participants highlighted the importance of offering the course at an earlier stage of diagnosis to provide further support at the beginning of their diabetes journey. No significant findings were reported for the independent sample t-test, paired sample t-test and multiple regression analysis. CONCLUSION: The qualitative findings suggested that the course was beneficial, especially in demonstrating how mindfulness could aid self-management for individuals living with type 2 diabetes. Further funding and trials are warranted to improve the quality of technology used and to assess impact on diabetes control and mental health.

Why are women with polycystic ovary syndrome obese?

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common condition characterized by reproductive, hyperandrogenic and dysmetabolic features, and often becomes clinically manifest during adolescence, particularly with weight-gain. SOURCES OF DATA: Pubmed search. AREAS OF AGREEMENT: PCOS is heritable and closely associates with obesity (based on data from both epidemiological and genetic studies). Furthermore, insulin resistance forms a central cornerstone of the pathogenesis of PCOS and mediates a close association between obesity and the severity of the phenotypic features of PCOS. AREAS OF CONTROVERSY: Our understanding of the pathogenesis of PCOS remains incomplete, especially regarding its missing heritability (with only a small fraction having been identified from the genome-wide association studies reported to date), and its developmental origins. GROWING POINTS: A challenge for the future is to explore a role for epigenetic modifications in the development of PCOS, and implications for the in utero environment and novel therapeutic opportunities.

Erythroderma (exfoliative dermatitis). Part 2: energy homeostasis and dietetic management strategies.

Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition.

Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

Painful fat necrosis resulting from insulin injections.

UNLABELLED: The case is a 34-year-old woman with long-standing type 1 diabetes mellitus with existing follow-up in the outpatient clinic at the Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, UHCW. She had maintained good glycaemic control and glycaemic stability with basal bolus regimen for many years. She had not developed any diabetes-related complications and had no other co-morbidities. Six months ago, she presented to A&E with sudden-onset, well-localised and severe pain in the right iliac fossa, just lateral to the para-umbilical area. Her biochemistry was normal. Ultrasound scan, however, revealed a right-sided ovarian cyst, which was thought to have caused pain to her. She was discharged from A&E with simple analgesia. On subsequent gynaecological follow-up 4 weeks later, her pain remained severe and examination revealed an exquisitely tender subcutaneous nodule at the same location measuring 2 cm in diameter. Magnetic resonance imaging (MRI) scan at the time revealed a 1 cm mass in the subcutaneous adipose tissue, which co-localised to her pain. The mass demonstrated a central fat signal surrounded by a peripheral ring: observations consistent with fat necrosis. There were other smaller subcutaneous nodules also observed in the left para-umbilical area. Subsequent surgical resection of the main area of fat necrosis was performed. The patient made an excellent recovery and her pain resolved post-operatively. Histology confirmed the presence of fat necrosis. Fat necrosis is a rare complication of s.c. insulin injection. This case illustrates the importance of considering this diagnosis in patients who inject insulin and develop localised injection-site pain. LEARNING POINTS: Fat necrosis is a rare complication of insulin injections that can manifest with severe, persistent and well-localised pain.Fat necrosis can masquerade as other pathologies causing diagnostic confusion.The imaging modality of choice for accurate diagnosis of fat necrosis is MRI.Histological confirmation of fat necrosis is important.Appropriate management of localised fat necrosis is surgical excision, with avoidance of further insulin injections into the affected area.

Nelson syndrome: definition and management.

Nelson syndrome is an important complication of treatment with total bilateral adrenalectomy (TBA) for patients with refractory Cushing's disease. Although early cases of Nelson syndrome often presented with the clinical features of large sellar masses, the modern face of Nelson syndrome has changed primarily due to earlier detection (with highly resolved magnetic resonance imaging (MRI) and sensitive ACTH assays) and greater awareness of the condition, resulting in reduced morbidity and mortality. Although lack of administration of neoadjuvant pituitary radiotherapy post-TBA surgery may predict future development of Nelson syndrome, other predictive factors remain controversial. Therefore, Nelson syndrome should be screened for closely and long-term in all patients with a history of Cushing's disease and TBA. The diagnosis of Nelson syndrome remains controversial, and the pathogenesis of this condition is incompletely understood. Current hypotheses include the "released negative feedback" mechansism (residual pituitary corticotropinoma cells are "released" from the negative feedback effects of cortisol following TBA), and the "aggressive corticotropinoma" mechanism (Nelson syndrome is most likely to develop in those patients with refractory treatments - including TBA - for an underlying aggressive corticotropinoma). Effective management of Nelson syndrome with pituitary surgery and radiotherapy is often a challenge. Other therapies (such as Gamma Knife surgery and temozolomide) play an important role and merit further research into their efficacy and placement in the management pathway of Nelson syndrome.

Serum sex hormone-binding globulin and testosterone in relation to cardiovascular disease risk factors in young men: a population-based study.

OBJECTIVE: Reduced sex hormone-binding globulin (SHBG) concentration predicts insulin resistance and type 2 diabetes, but its association with cardiovascular disease (CVD) risk is unclear. We examined the association between SHBG and cardiovascular risk factors, independently of total testosterone (TT), in young men. DESIGN: Observational, cross-sectional study. SETTING: General community. PARTICIPANTS: The study included 2716 men aged 31 years in the Northern Finland Birth Cohort in 1996 with clinical examination data and fasting blood samples. OUTCOME VARIABLES: Blood pressure (BP), lipids and C-reactive protein (CRP) as biological CVD risk markers. RESULTS: SHBG concentration was significantly and inversely related to systolic and diastolic BP, triglycerides and CRP, but positively to HDL cholesterol after adjusting for insulin, BMI, waist circumference, smoking, education and physical activity (all P<0.05). These linearly graded associations persisted with additional adjustment for TT. SHBG was significantly associated with total cholesterol only with adjustment for covariates and TT (P<0.05). The direction and magnitude of associations between TT and risk factors were variable, but further adjustment for insulin, adiposity and SHBG showed positive associations between TT and BP, total and LDL-cholesterol and triglycerides and an inverse association with CRP (all P<0.05), but its relation with HDL-cholesterol was no longer significant. CONCLUSIONS: In this cohort of young adult men, higher SHBG concentration was associated with a more favourable CVD risk profile, independently of TT. SHBG concentration modified the associations of TT with CVD risk factors.

Predictors of weight loss at 1 year after laparoscopic adjustable gastric banding and the role of presurgical quality of life.

BACKGROUND: There is uncertainty regarding preoperative predictors of a successful outcome for bariatric surgery (BarSurg), on which to determine appropriateness for such a procedure. Our aims were to identify preoperative clinical and psychosocial predictors of success following BarSurg and to explore the influence of body mass index (BMI) on these parameters. METHODS: Preoperative data, including Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scores transformed to Health-Related Quality of Life (HRQOL) scores, were accrued from 76 morbidly obese adults awaiting BarSurg. Pre- and postoperative data were also accrued for 26 patients who had completed 1-year follow-up post-bariatric surgery (laparoscopic adjustable gastric banding-LAGB). Statistical analysis was performed to assess the relationships between preoperative HRQOL scores, preoperative BMI and excess weight loss 1 year following BarSurg (EWL-1 year). RESULTS: Preoperative BMI showed a significant independent, negative linear correlation with the public distress domain of preoperative quality of life (QOL) (r = -0.368, p = 0.001; ß = -0.245, p = 0.009). Preoperative BMI had a significant, positive and independent association with EWL-1 year (r = 0.499, p = 0.009; ß = 0.679, p = 0.015). Preoperative QOL scores had no association with EWL-1 year. CONCLUSIONS: Preoperative BMI appears to predict EWL-1 year following restrictive bariatric surgery (LAGB). Preoperatively, patients with higher BMI appear to manifest greater public distress. Preoperative QOL scores, however, do not appear to have any predictive value for EWL-1 year post-LAGB. Preoperative BMI should therefore be employed as a predictor of EWL-1 year post-LAGB. Other measures of successful outcomes of bariatric surgeries (such as effects on QOL scores at 1 year) should be explored in future, larger and longer term studies.

The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism.

Obesity, secondary (hypogonadotrophic) hypogonadism (SH), sleep disorders [such as obstructive sleep apnoea (OSA)] and type 2 diabetes mellitus (T2DM) in men have complex interlinks both with respect to mutual aetiopathogenesis as well as therapeutics. Correction of the attendant hypogonadism in obese men may serve to break this link and have beneficial effects beyond restoration of normal sexual function. Male obesity-associated secondary hypogonadism (MOSH) should be regarded as a distinct clinical entity and subtype of SH. A high index of suspicion for the presence of MOSH must be maintained by clinicians when assessing obese men. The pathogenesis of MOSH remains incompletely understood. Furthermore, the optimal management of MOSH and its associated sequelae will require long-term prospective studies that in turn will inform the development of future clinical guidelines for this important and prevalent condition.

Adipocyte biology in polycystic ovary syndrome.

Polycystic Ovary Syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including insulin resistance. There is a clear association between obesity, the development of PCOS and the severity of its phenotypic, biochemical and metabolic features. Evidence to support this link includes data from epidemiological, pathophysiological and genetic studies. Given the importance of obesity in the development and manifestation of PCOS, ongoing research into the many facets of adipocyte biology in women with the condition is important and should continue to be a priority. In this review article, we discuss the existing literature on fat distribution, adipokines, adipocyte hypertrophy and adipocyte steroid metabolism in women with PCOS.

Identification of a novel heterozygous mutation in exon 50 of the COL1A1 gene causing osteogenesis imperfecta.

UNLABELLED: A 19-year-old woman was diagnosed with osteogenesis imperfecta (OI). She had sustained numerous low-trauma fractures throughout her childhood, including a recent pelvic fracture (superior and inferior ramus) following a low-impact fall. She had the classical blue sclerae, and dual energy X-ray absorptiometry (DEXA) bone scanning confirmed low bone mass for her age in the lumbar spine (Z-score was -2.6). However, despite these classical clinical features, the diagnosis of OI had not been entertained throughout the whole of her childhood. Sequencing of her genomic DNA revealed that she was heterozygous for the c.3880_3883dup mutation in exon 50 of the COL1A1 gene. This mutation is predicted to result in a frameshift at p.Thr1295, and truncating stop codon 3 amino acids downstream. To our knowledge, this mutation has not previously been reported in OI. LEARNING POINTS: OI is a rare but important genetic metabolic bone and connective tissue disorder that manifests a diverse clinical phenotype that includes recurrent low-impact fractures.Most mutations that underlie OI occur within exon 50 of the COL1A1 gene (coding for protein constituents of type 1 pro-collagen).The diagnosis of OI is easily missed in its mild form. Early diagnosis is important, and there is a need for improved awareness of OI among health care professionals.OI is a diagnosis of exclusion, although the key diagnostic criterion is through genetic testing for mutations within the COL1A1 gene.Effective management of OI should be instituted through a multidisciplinary team approach that includes a bone specialist (usually an endocrinologist or rheumatologist), a geneticist, an audiometrist and a genetic counsellor. Physiotherapy and orthopaedic surgery may also be required.

Impact of FTO genotypes on BMI and weight in polycystic ovary syndrome: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: FTO gene single nucleotide polymorphisms (SNPs) have been shown to be associated with obesity-related traits and type 2 diabetes. Several small studies have suggested a greater than expected effect of the FTO rs9939609 SNP on weight in polycystic ovary syndrome (PCOS). We therefore aimed to examine the impact of FTO genotype on BMI and weight in PCOS. METHODS: A systematic search of medical databases (PubMed, EMBASE and Cochrane CENTRAL) was conducted up to the end of April 2011. Seven studies describing eight distinct PCOS cohorts were retrieved; seven were genotyped for SNP rs9939609 and one for SNP rs1421085. The per allele effect on BMI and body weight increase was calculated and subjected to meta-analysis. RESULTS: A total of 2,548 women with PCOS were included in the study; 762 were TT homozygotes, 1,253 had an AT/CT genotype, and 533 were AA/CC homozygotes. Each additional copy of the effect allele (A/C) increased the BMI by a mean of 0.19 z score units (95% CI 0.13, 0.24; p = 2.26 × 10(-11)) and body weight by a mean of 0.20 z score units (95% CI 0.14, 0.26; p = 1.02 × 10(-10)). This translated into an approximately 3.3 kg/m(2) increase in BMI and an approximately 9.6 kg gain in body weight between TT and AA/CC homozygotes. The association between FTO genotypes and BMI was stronger in the cohorts with PCOS than in the general female populations from large genome-wide association studies. Deviation from an additive genetic model was observed in heavier populations. CONCLUSIONS/INTERPRETATION: The effect of FTO SNPs on obesity-related traits in PCOS seems to be more than two times greater than the effect found in large population-based studies. This suggests an interaction between FTO and the metabolic context or polygenic background of PCOS.

Nelson's syndrome.

Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre. Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (>500 ng/l) in addition to progressive elevations of ACTH (a rise of >30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.

Genetic basis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with obesity and manifests with reproductive, hyperandrogenic and metabolic features. Although the etiology of PCOS is complex and incompletely understood, genetics plays an important role (heritability: ∼70%). Potential problems with studying the genetics of PCOS include the heterogeneity of the condition and associated sub-fertility. A candidate gene approach has been used in over 70 published studies on PCOS, most of which have been inadequately powered to detect a statistically meaningful association. Furthermore, these studies often fail to replicate prior published studies on the same candidate gene in different populations. The first genome-sequence variant (identified from a genome-wide association study in subjects with Type 2 diabetes mellitus) to be studied in PCOS (FTO gene) has been shown by our group to associate with susceptibility for the development of PCOS. This is the first genetic corroboration of a link between PCOS and obesity. Future directions include a genome-wide association study in PCOS.

Association of variants in the fat mass and obesity associated (FTO) gene with polycystic ovary syndrome.

AIMS/HYPOTHESIS: Variants in the fat-mass and obesity-associated gene (FTO) influence susceptibility to type 2 diabetes via an effect on adiposity/obesity. Given the important role of obesity in the aetiology of both polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus, our aim was to establish whether FTO variants are also implicated in PCOS susceptibility. METHODS: We performed a genetic association study of FTO variant rs9939609 using case-control analyses, conducted in 463 PCOS patients (geometric mean BMI 27.5 kg/m(2)) and 1,336 female controls (geometric mean BMI 25.3 kg/m(2)) of UK British/Irish origin. We also sought evidence for associations between FTO variation and circulating testosterone levels in 324 UK PCOS patients and 1,000 women from the Northern Finland Birth Cohort of 1966. Outcome measures included FTO rs9939609 genotype frequencies by participant group and androgen measures (testosterone, free androgen index) by genotype. RESULTS: There was a significant association between FTO genotype and PCOS status in the UK case-control analysis, which was attenuated by adjustment for BMI (Cochran-Armitage test, odds ratio [per minor allele copy] 1.30 [95% CI 1.12, 1.51], p = 7.2 x 10(-4) [unadjusted], p = 2.9 x 10(-3) [adjusted]). This association was most evident in obese PCOS patients (PCOS patients below median BMI vs UK controls, p = 0.11; above median BMI vs controls, p = 2.9 x 10(-4)). No relationship between FTO genotype and androgen levels was seen. CONCLUSIONS/INTERPRETATION: We provide the first evidence that variants that predispose to common obesity also result in altered susceptibility to PCOS, confirming the mechanistic link between these conditions. The predominant effect of FTO variants on PCOS susceptibility is probably mediated through adiposity.

Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS.

AIMS/HYPOTHESIS: Common variants of the gene encoding transcription factor 7-like 2 (TCF7L2) have a powerful effect on individual risk of type 2 diabetes (per allele odds ratio approximately 1.35). Polycystic ovary syndrome (PCOS) and type 2 diabetes are familial conditions sharing common features. Based on this, the aim of the present study was to establish whether variation in TCF7L2 also influences the development of PCOS. METHODS: We conducted a genetic association study of variants of TCF7L2 (rs7903146 and rs12255372) using both case-control and quantitative trait approaches. Case-control analyses were conducted in (1) 369 PCOS cases and 2574 controls of UK British/Irish origin, and (2) 540 women with PCOS symptoms and 1083 controls from the Northern Finland Birth Cohort of 1966. Quantitative trait analyses (androgen levels) were also performed (1249 individuals). RESULTS: There was no association between rs7903146 and PCOS in the UK case-control study (Cochran-Armitage test, p = 0.51); nor with symptomatic status in the Finnish cohort (p = 0.36). In addition, there were no relationships between the TCF7L2 single nucleotide polymorphism rs7903146 and androgen levels (UK cases, p = 0.99; Finnish controls, p = 0.57; Finnish symptomatic cases, p = 0.80). Results at rs12255372 were similar, reflecting strong linkage disequilibrium with rs7903146. CONCLUSIONS/INTERPRETATION: Our study was powered to detect an effect on PCOS susceptibility similar to that previously reported for these variants on type 2 diabetes. Failure to detect any evident association with PCOS provides the strongest evidence yet that the genetic architecture of these related conditions is qualitatively distinct.

Obesity and polycystic ovary syndrome.

The aetiology of Polycystic Ovary Syndrome (PCOS) is complex and multifactorial. There is much evidence, however, to suggest that adipose tissue plays an important role in the development and maintenance of PCOS pathology. There is a close correlation between adiposity and symptom severity in women with PCOS, and even modest reductions in weight generally translate into significant improvements in menstrual regularity, fertility and hyperandrogenic features. This review article considers the various mechanisms that might underlie this link between excess adiposity and PCOS - including the effects of differential insulin sensitivity, abnormal steroid hormone metabolism and adipocytokine secretion. Greater attention to the therapeutic options available to reduce the impact of excess adiposity on ovarian and metabolic function is essential to the management of PCOS.