Intestinal microbiota and their metabolic contribution to type 2 diabetes and obesity.

Obesity and type 2 diabetes mellitus (T2DM) are common, chronic metabolic disorders with associated significant long-term health problems at global epidemic levels. It is recognised that gut microbiota play a central role in maintaining host homeostasis and through technological advances in both animal and human models it is becoming clear that gut microbiota are heavily involved in key pathophysiological roles in the aetiology and progression of both conditions. This review will focus on current knowledge regarding microbiota interactions with short chain fatty acids, the host inflammatory response, signaling pathways, integrity of the intestinal barrier, the interaction of the gut-brain axis and the subsequent impact on the metabolic health of the host.

Gut microbiota influence in type 2 diabetes mellitus (T2DM).

A strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.

A review on gut microbiota: a central factor in the pathophysiology of obesity.

Obesity and its complications constitute a substantial burden. Considerable published research describes the novel relationships between obesity and gut microbiota communities. It is becoming evident that microbiota behave in a pivotal role in their ability to influence homeostatic mechanisms either to the benefit or detriment of host health, the extent of which is not fully understood. A greater understanding of the contribution of gut microbiota towards host pathophysiology is revealing new therapeutic avenues to tackle the global obesity epidemic. This review focuses on causal relationships and associations with obesity, proposed central mechanisms encouraging the development of obesity and promising prospective methods for microbiota manipulation.

Temporal Effects of Sleeve Gastrectomy on Glucose-Insulin Homeostasis and Incretin Hormone Response at 1 and 6 Months.

BACKGROUND: Bariatric surgery is an effective treatment for morbid obesity and glycaemic dysfunction. OBJECTIVES: The aim of the work was to examine both the static and dynamic changes of glucose-insulin homeostasis and incretin hormone response following sleeve gastrectomy (SG) in a sample of 55 participants preoperatively and 1 month and 6 months postoperatively. The focus was on a sample of patients with impaired glucose tolerance and type 2 diabetes (T2D). SETTING: Morriston Hospital, UK. METHODS: Prospective study comprising of 55 participants with impaired glucose homeostasis and T2D undergoing SG (mean body mass index [BMI] 50.4 kg/m2, mean glycated haemoglobin [A1C] 7.4%). Serial measurements of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic hormone (GIP) were performed during oral glucose tolerance testing preoperatively and 1 and 6 months postoperatively. Areas under the curve (AUC) were examined at 30, 60, and 120 min. RESULTS: We observed significant improvements in measures of obesity, as well as static and dynamic measures of glucose, insulin, C-peptide and HOMA. Furthermore, significant increases in GLP-1 response as early as 6 months postoperatively were also seen. CONCLUSIONS: To our knowledge, no study has examined the detailed dynamic changes in glucose and insulin homeostasis in this number of participants undergoing SG in relation to incretin hormones GIP and GLP-1. This current study supports the role of SG for the treatment of obesity-related glucose dysregulation.

Cardiovascular risk assessments at occupational health services: employee experiences.

BACKGROUND: Across England in the UK, population screening for cardiovascular disease (CVD) primarily takes place within general practice in the form of the National Health Service Health Check. Additional screening sites such as occupational health are advocated to improve the population impact. AIMS: To investigate participant experiences with cardiovascular and type 2 diabetes risk assessment (RA) at occupational health and subsequent support-seeking at general practice. METHODS: Face-to-face interviews were conducted for this qualitative study. Participants were recruited at three workplaces; a steel works and two hospital sites. Using interpretive phenomenological analyses, themes were drawn from salient narratives and categorically organized. RESULTS: There were 29 participants. Themes (n = 16) were organized into two domains; factors that facilitated (n = 9) or thwarted (n = 7) participant engagement with the RA and general practice. All participants described the RA as worthwhile and strongly valued RA at occupational health. Those with obesity and high CVD risk highlighted their difficulties in making lifestyle changes. Participants reported confusion and anxiety when GP advice about medication appeared to contradict what participants had interpreted during RA at occupational health. CONCLUSIONS: This study highlights factors that facilitate or thwart engagement in cardiovascular RA at occupational health services and general practice follow-up. Stakeholders can integrate these factors into standard operating procedures to enhance participant engagement and enable safeguards that minimize potential harm to participants.

Physical exercise and non-insulin glucose-lowering therapies in the management of Type 2 diabetes mellitus: a clinical review.

In the UK the National Institute of Health and Care Excellence (NICE) advocates intensive lifestyle programmes that attain the levels of daily physical activity set out by the Chief Medical Officer as a first-line strategy for improving the health of people at risk of developing diabetes or reducing the risk of development of Type 2 diabetes. For people with Type 2 diabetes, lifestyle measures complement pharmacological treatments that include both oral and injectable therapies. In line with this, NICE guidelines also support intensification of efforts to improve patient lifestyle along with these glucose-lowering therapies. There is a paucity of evidence, however, in the available published literature examining the association between glucose-lowering therapies and exercise metabolism. In the present review we explore the current knowledge with regard to the potential interactions of oral and non-insulin injectable therapies with physical activity in people at risk of, or who have, Type 2 diabetes, and present evidence that may inform healthcare professionals of the need to monitor patients more closely in their adaptation to both pharmacological therapy and physical activity.

Acyl-ghrelin mediated lipid retention and inflammation in obesity-related Type 2 diabetes.

Acyl-ghrelin has various peripheral effects including the potential role in mediating cellular lipid removal and macrophage polarization. Previous reports are contradictory as to how glycaemia and acyl-ghrelin mediates lipid retention and inflammation within individuals with Type 2 diabetes (T2D). Our aim was to explore acyl-ghrelin levels and ghrelin expression in relation to lipid and inflammatory markers within an ex vivo human model, biopsied visceral adipose tissue. Results indicated that acyl-ghrelin was associated with a decline in key lipid homeostasis genes ABCG1 and LXRß expression. Within T2D there was also a down regulation of these genes which was independent of acyl-ghrelin levels. Circulatory pro-inflammatory markers (IL-6 and TNFα) had no association with ghrelin expression nor circulating acyl-ghrelin levels. Anti-inflammatory marker (IL-10) and total antioxidant status (TAOS%) were positively associated with ghrelin expression across samples from all groups combined (total sample cohort) and specifically within the obesity sample cohorts. Data supported the hypothesis that hyperglycaemia and acyl-ghrelin have a regulatory role in lipid retention. Furthermore, that both acyl- and desacyl-ghrelin is responsible for a protective inflammatory response; however this response is diminished in T2D.

A pilot service-evaluation examining change in HbA1c related to the prescription of internet-based education films for type 2 diabetes.

We undertook a pilot service-evaluation of prescribed internet-based patient education films for patients with type 2 diabetes. The uptake was 28% and film watching was associated with a relative mean difference in HbA1c of -9.0mmol/mol in the film watchers compared to non-watchers over a three-month period (P=0.0008).

Ghrelin function in human obesity and type 2 diabetes: a concise review.

The 28 amino acid hormone, ghrelin, has been found to have various effects on metabolism. This review will focus on the pathways integrated into ghrelin's effect within the hypothalamus, pancreas and adipocytes. The identification of molecules and pathways that regulate ghrelin-mediated lipid retention could establish new mechanisms underlying cellular energy homeostasis. The impact of acyl-ghrelin on glucose metabolism and lipid homeostasis may allow for novel preventative or early intervention therapeutic strategies to treat obesity related type 2 diabetes and associated metabolic dysfunction.

Cardiorespiratory fitness testing and cardiovascular disease risk in male steelworkers.

BACKGROUND: The workplace has been advocated as a setting to perform cardiovascular disease (CVD) risk assessments. These risk assessments usually focus on traditional risk factors rather than cardiorespiratory fitness (CRF) despite established associations between CRF and CVD. The lack of guidance on interpreting health-related CRF values has been suggested as a barrier to utilizing CRF in practice. AIMS: To assess the merits of CRF testing in the workplace and explore whether a CRF value identified male individuals above the recommended threshold for further clinical investigation. METHODS: Cross-sectional analysis of male steelworkers from Carmarthenshire, South Wales, UK who completed a workplace-based CVD risk assessment with an added CRF protocol based on heart rate responses (Chester Step Test). Receiver operating characteristic (ROC) analysis was undertaken to explore the possibility of a CRF value to identify individuals at an increased 10-year risk of CVD (QRISK2 ≥ 10%). RESULTS: There were 81 participants. ROC analysis revealed that a CRF level of 34.5ml/kg/min identified those individuals above the ≥10% QRISK2 threshold with the best sensitivity (0.800) and specificity (0.687) to discriminate against true- and false-positive rates. Further analysis revealed that individuals with either 'Average' or 'Below Average' CRF would be five times more likely to have a 10-year CVD risk above the ≥10% QRISK2 threshold than individuals with an 'Excellent' or 'Good' level of fitness [OR 5.10 (95% CI 1.60-16.3)]. CONCLUSIONS: This study suggests CRF assessments are a useful addition to a workplace CVD assessment and could identify male individuals at increased predicted risk of the condition.

Simulated games activity vs continuous running exercise: a novel comparison of the glycemic and metabolic responses in T1DM patients.

To compare the glycemic and metabolic responses to simulated intermittent games activity and continuous running exercise in type 1 diabetes. Nine patients (seven male, two female; 35 ± 4 years; HbA1c 8.1 ± 0.2%/65 ± 2 mmol/mol) treated on a basal-bolus regimen completed two main trials, a continuous treadmill run (CON) or an intermittent running protocol (INT). Patients arrived to the laboratory fasted at ∼ 08:00 h, replicating their usual pre-exercise meal and administering a 50% reduced dose of rapid-acting insulin before exercising. Blood glucose (BG), K(+) , Na(++) , pH, triglycerides, serum cortisol and NEFA were measured at baseline and for 60 min post-exercise. Interstitial glucose was measured for a further 23 h under free-living conditions. Following exercise, BG declined under both conditions but was less under INT (INT -1.1 ± 1.4 vs CON -5.3 ± 0.4 mmol/L, P = 0.037), meaning more patients experienced hypoglycemia (BG ≤ 3.5 mmol/L; CON n = 3 vs INT n = 2) but less hyperglycemia (BG ≥ 10.9 mmol/L; CON n = 0 vs INT n = 6) under CON. Blood lactate was significantly greater, and pH lower, with a temporal delay in K(+) under INT (P < 0.05). No conditional differences were observed in other measures during this time, or in interstitial glucose concentrations during the remaining 23 h after exercise. Simulated games activity carries a lower risk of early, but not late-onset hypoglycemia than continuous running exercise in type 1 diabetes.

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

AIMS: In the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes. METHODS: Visceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage. RESULTS: No significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (P<0.05). Lower MDA concentration and longer telomere length were seen in subjects with diabetes compared to those without (P<0.05). DNA damage, analysed via Comet assay, was significantly lower in subjects with diabetes compared to those without (P<0.05). CONCLUSION: A paradoxical decrease in oxidative stress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue.

'Prosiect Sir Gâr': workplace-based cardiovascular disease and diabetes risk assessments.

BACKGROUND: Cardiovascular disease (CVD) and diabetes remain two of the greatest health challenges in the UK. Government guidelines recommend screening for both of these conditions to identify individuals at high risk. Assessing individuals in the work environment for these two conditions as part of routine annual medicals could have benefits for both the employee and employer. AIMS: To introduce the Prosiect Sir Gâr workplace-based initiative for CVD and diabetes prevention and report some of the baseline measurements in regards to CVD and diabetes risk. METHODS: Individuals from two workplaces (local health board and steelworks) attended a medical health check with an added CVD and diabetes risk assessment component. Demographic and anthropometric data, systolic and diastolic blood pressure, smoking status and family and medical histories were recorded. Blood samples were analysed for total and high-density lipoprotein cholesterol and HbA1c. Ten year risk of CVD and diabetes were predicted using the QRISK2 and QDiabetes algorithms. Individuals at high risk of either condition were referred to a lifestyle intervention programme. RESULTS: Among over 800 individuals screened a high prevalence of central obesity (75%), systolic hypertension (20%) and diastolic hypertension (23%) were observed in both workforces. In addition, a substantial proportion of the workers were either 'overweight' (42%) or 'obese' (28%). CONCLUSIONS: Introducing CVD and diabetes risk assessments to routine annual medicals in the workplace uncovered significant isolated risk factors for both CVD and diabetes that may otherwise have remained undiagnosed. This approach also gave employers a more detailed awareness of the current health of their employees.

Cutaneous allergy to insulin: could statins and ACE inhibitors play a role? A case report.

Insulin allergy is rare. Both statins and angiotensin converting enzyme (ACE) inhibitors may cause local urticarial skin reactions and have been implicated to precipitate local reactions to insulin. We describe a case of a localised urticarial allergic reaction related to insulin use in a patient co-prescribed an ACE inhibitor and statin.

The causes of hypopituitarism in the absence of abnormal pituitary imaging.

BACKGROUND: Hypopituitarism in the absence of a history of pituitary pathology or abnormal pituitary imaging is rare. AIM: To identify the cause of hypopituitarism in individuals in whom pituitary imaging was normal. DESIGN: Retrospective analysis of electronic patient record. METHOD: A review of the pituitary function in the 506 patients on the Morriston Hospital pituitary database revealed 230 had some degree of hypopituitarism and of these, 21 (9%) had normal pituitary imaging. RESULTS: Of this group, six patients had a past medical history of subarachnoid haemorrhage, head injury or meningitis, and mainly suffered from a deficiency of antidiuretic hormone. One patient had a stroke resulting in multiple anterior hormone deficiencies and six individuals had idiopathic cranial diabetes insipidus (DI). Subsequent investigations of the remaining eight patients with normal pituitary imaging revealed that two had neurosarcoidosis both of whom had panhypopituitarism. Four patients had haemochromatosis which resulted in gonadotropin deficiency in two, DI in one and panhypopituitarism in the other. There were two individuals with confirmed hypopituitarism and multiple hormone deficiencies in which no cause could be identified. CONCLUSION: These results show that hypopituitarism in the absence of pituitary pathology or an identifiable cause is rare. In patients with multiple anterior pituitary hormone deficiencies haemochromatosis and sarcoidosis should be considered.