Management of type 2 diabetes: now and the future.

There are about 4.7 million people living with diabetes mellitus in the UK and 90% have type 2 diabetes mellitus (T2DM). This burden will only get worse as there are currently about 12.3 million more at risk of T2DM. Moreover, up to 30% of diagnosed patients already have eye, foot, kidney or nerve complications. This impacts the NHS considerably as it spends about £10 billion annually on diabetes (80% on complications alone). Atherosclerotic cardiovascular disease (ASCVD), the leading cause of death in diabetes, contributes significantly to this. Therefore, there is significant emphasis on the prevention of T2DM especially in at-risk groups with the setting up of initiatives like the Diabetes Prevention Programme. When prevention fails, it is essential to commence glucose-lowering agents to reduce the burden of disease, prevent associated complications and improve quality of life. A patient-centred approach is required to ensure efficacy of treatment strategies and the presence of co-morbidities such as cardiovascular and renal disease should be considered.

Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes.

BACKGROUND: There is evidence that reducing blood glucose concentrations, inducing weight loss, and improving the lipid profile reduces cardiovascular risk in people with type 2 diabetes. OBJECTIVE: We assessed the effect of various diets on glycemic control, lipids, and weight loss. DESIGN: We conducted searches of PubMed, Embase, and Google Scholar to August 2011. We included randomized controlled trials (RCTs) with interventions that lasted ≥6 mo that compared low-carbohydrate, vegetarian, vegan, low-glycemic index (GI), high-fiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets. RESULTS: A total of 20 RCTs were included (n = 3073 included in final analyses across 3460 randomly assigned individuals). The low-carbohydrate, low-GI, Mediterranean, and high-protein diets all led to a greater improvement in glycemic control [glycated hemoglobin reductions of -0.12% (P = 0.04), -0.14% (P = 0.008), -0.47% (P < 0.00001), and -0.28% (P < 0.00001), respectively] compared with their respective control diets, with the largest effect size seen in the Mediterranean diet. Low-carbohydrate and Mediterranean diets led to greater weight loss [-0.69 kg (P = 0.21) and -1.84 kg (P < 0.00001), respectively], with an increase in HDL seen in all diets except the high-protein diet. CONCLUSION: Low-carbohydrate, low-GI, Mediterranean, and high-protein diets are effective in improving various markers of cardiovascular risk in people with diabetes and should be considered in the overall strategy of diabetes management.

Should diabetes be commissioned through multidisciplinary networks, rather than Practice Based Commissioning?

AIMS: Diabetes is recognized as a complex, long term, largely asymptomatic condition requiring self management skills, a range of health care professionals and articulated health services. Diabetes Networks have been introduced to provide guidance from people with diabetes and local health professionals with different skills to ensure that diabetes care is well organized, sustainable and delivers quality care. We have considered the role of Diabetes Networks in the English setting. METHODS: Drawing on studies of health service organization and health policy, we describe the context in which diabetes commissioning is currently occurring in England, the role of Diabetes Networks and key components for an effective Diabetes Network. RESULTS: We have identified that Diabetes Networks are not currently mandatory and discovered policy approaches that are likely to work against safe, timely, integrated approaches to diabetes services with potentially harmful impacts on people with diabetes in the future. Practice Based Commissioning, where it sidelines Diabetes Networks, is a particular concern. We have identified key components of Diabetes Networks including explicit frameworks for leadership, membership, funding, decision making, communication and action. CONCLUSIONS: Diabetes is a condition requiring collaboration between all involved. Diabetes Networks include patients and all relevant health professionals and should dictate what and how diabetes care should be commissioned within the local health economy.

Improving glycaemic control in African diabetic patients on insulin: a resource-free approach.

In the resource-poor areas of the tropics, diabetic patients requiring insulin are often treated with once-daily injections of intermediate-acting insulin. Glycaemic control on this regime is usually poor. We trialled a simple change to twice-daily insulin (same total daily dose, two-thirds given in morning, and one-third in evening) in a group of 20 Ethiopian diabetic patients treated in this way. Nurse support and contact, and self-glucose monitoring were not available. After three months, the haemoglobin Alc (HbAlc) had improved from 10.5 +/- 1.8 to 8.0 +/- 1.5% (P < 0.001). No improvement occurred in the 20 control patients who remained on once-daily insulin. Among the twice-daily insulin group there was a small increase in weight and mild hypoglycaemic episodes. However, all patients were very satisfied and wished to continue the new system. We conclude that a simple change from once- to twice-daily insulin, without monitoring or support, can lead to a significant improvement in the overall glycaemic control, and is suitable for resource-limited tropical countries.

Adiponectin in childhood.

Adiponectin, a hormone produced and secreted by adipocytes, is present in circulation in high circulating concentrations, suggesting an important physiological role. An indirect regulator of glucose metabolism, adiponectin increases insulin sensitivity, improves glucose tolerance and inhibits inflammation. Plasma adiponectin relates inversely to adiposity and, importantly, reflects the sequelae of accumulation of excess adiposity. The role of adiponectin in adults has been explored in detail. Studies in children are now available and, given the increasing rates of childhood obesity, it is important to establish the role of adiponectin in mediating insulin resistance and cardiovascular disease in this age group. This paper reviews the regulation of adiponectin, its effect on body mass, glucose metabolism and cardiovascular risk in infants, children and adolescents. It demonstrates clear links between adiponectin and features of the metabolic syndrome in obese children and adolescents. However, adiponectin's role as a predictor of metabolic dysfunction in healthy, normal-weight youngsters is less clear.

Critical illness with hyponatraemia and impaired cell membrane integrity--the "sick cell syndrome" revisited.

OBJECTIVE: To determine whether impaired cell membrane permeability exists in critically ill patients with "sick cell" type hyponatraemia. DESIGN AND METHODS: A 36 year old male patient was identified in an intensive care unit (ICU) with liver disease and multi-organ failure. His initial serum sodium (Na) was 101 mmol/L and osmolar gap + 35 mmol/L. A flow cytometric system was used to assess lymphocyte membrane integrity using fluorescein diacetate (FDA) and propidium iodide (PI). Following this, similar studies were carried out in 17 hyponatraemic (Na < 130 mmol/L) and 19 normonatraemic (Na > 136 mmol/L) ICU patients. RESULTS: Flow cytometry in the index patient showed two clear populations of cells-one was normal (with identical characteristics to a healthy control) and the other had dysfunctional cell membrane integrity. The extended patient series, however, revealed only 2 other patients with similar flow cytometric patterns-one hyponatraemic and one normonatraemic. CONCLUSIONS: Cell membrane studies in the index patient demonstrated supportive evidence for the "sick cell syndrome" in critically ill patients. The extended series revealed that 3/37 (8%) had this abnormality, which was however not consistently associated with hyponatraemia.

Is there a role for ghrelin and peptide-YY in the pathogenesis of obesity in adults with acquired structural hypothalamic damage?

CONTEXT: Obesity is a common sequel to hypothalamic tumors and their treatment, but the underlying mechanisms are not fully established. OBJECTIVE: Our objective was to evaluate the role of ghrelin and peptide-YY (PYY) in human hypothalamic obesity. SETTING: The study took place at a University Medical Center. PARTICIPANTS: Subjects included 14 adult patients (six male, eight female) with tumors of the hypothalamic region and 15 healthy controls (six male and nine female) matched for age, body mass index, and percentage of body fat. INTERVENTIONS: Plasma ghrelin and total PYY were measured using RIAs after an overnight fast and 15, 30, 60, 120, and 180 min after a mixed meal. MAIN OUTCOME MEASURES: We assessed ghrelin, PYY, and appetite ratings. RESULTS: The fall in ghrelin levels after the test meal was similar in the two groups. There was no statistically significant change postprandially in circulating PYY in the patients with hypothalamic damage. Fasting leptin levels and postprandial insulin responses were also similar in the two groups. Patients with hypothalamic damage reported higher hunger ratings at 3 h after the meal (P = 0.01) and a stronger desire to eat at 2 h (P = 0.01) and 3 h (P = 0.02) compared with the control group. CONCLUSIONS: Adult patients with structural hypothalamic damage show impaired satiety, but the changes observed in circulating ghrelin and PYY concentrations in response to a test meal do not indicate a central role for these gut hormones in the control of appetite and the pathogenesis of obesity in these patients.

The relationship of ghrelin to biochemical and anthropometric markers of adult growth hormone deficiency.

INTRODUCTION: Ghrelin is the natural ligand of the growth hormone secretagogue receptor (GHS-R) and potently stimulates GH release in humans. Ghrelin is found in the hypothalamus, but most circulating ghrelin is derived from the stomach. Ghrelin stimulates food intake but circulating levels are low in obesity. We hypothesized that GH deficiency (GHD) might be associated with increased circulating ghrelin concentrations as a result of low GH levels. We therefore measured circulating ghrelin concentrations, leptin and body composition in subjects with GHD and healthy controls. METHODS: Subjects with GHD (n = 18) were compared to healthy control subjects (n = 18), matched for body mass index (BMI). They underwent assessment of body composition [waist circumference, BMI and percentage body fat (using bioimpedance)]. Plasma ghrelin, leptin, insulin, GH and IGF-1 were measured in the fasting state. Plasma ghrelin was measured using a specific radioimmunassay, and the other hormones using commercially available assays. RESULTS: The groups were well-matched for BMI (GHD vs. control; 32.9 +/- 10.8 vs. 31.3 +/- 11.7, P = ns) and waist circumference (GHD vs. control; 102.9 +/- 20.0 vs. 99.8 +/- 25.2, P = ns), but percentage body fat (GHD vs. control; 37.0 +/- 9.1 vs. 29.4 +/- 13.0, P = 0.06) tended to be higher in the GHD group. As expected, IGF-1 was lower in GHD (GHD vs. control; 12.5 +/- 6.8 vs. 19.2 +/- 5.8 nmol/l, P = 0.003). Ghrelin [GHD vs. controls; geometric mean (95% CI); 828.8 (95% CI 639.9-1074.2) vs. 487.9 (95% CI 297.2-800.2) pmol/l] and leptin [GHD vs. controls; 13.2 (95% CI 6.6-26.5) vs. 7.9 (95% CI 3.7-16.9) ng/ml] were similar in the two groups. Plasma ghrelin correlated inversely with waist circumference and waist hip ratio in GHD subjects (r = -0.6, P = 0.02) but not with IGF-1 or GH concentrations. There was no significant correlation in the control subjects. CONCLUSION: Circulating ghrelin concentrations are influenced by body fat distribution, but not by levels of either GH or IGF-1. However, given that obesity is associated with reduced ghrelin concentrations and that GHD is commonly associated with increased body fat, it is possible that these two opposing influences on circulating ghrelin levels result in normal concentrations in subjects with GHD.

Plasma adiponectin increases postprandially in obese, but not in lean, subjects.

OBJECTIVE: We investigated the acute responses of plasma adiponectin levels to a test meal in lean and obese subjects. RESEARCH METHODS AND PROCEDURES: We studied 13 lean and 11 obese subjects after a 10-hour overnight fast. Glucose, insulin, and adiponectin concentrations were measured at baseline and 15, 30, 60, 120, and 180 minutes after a fixed breakfast. RESULTS: At baseline, fasting adiponectin concentrations were lower in the obese group vs. the lean group [mean (95% confidence interval): 2.9 (2.1 to 4.1) microg/mL vs. 8.6 (6.5 to 11.3) microg/mL], but rose 4-fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) microg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) microg/mL; p< 0.0001] and remaining elevated for the remainder of the study. There were no postprandial changes in plasma adiponectin concentrations in lean subjects. DISCUSSION: This increase of adiponectin concentrations in obese individuals might have important beneficial effects on postprandial glucose and lipid metabolism and might be viewed as a mechanism for maintaining normal glucose tolerance in those who are obese and insulin resistant.

Aortic dissection and rupture presenting as suprasternal bruising and neck swelling.

BACKGROUND: a 76-year-old man presented with transient loss of consciousness associated with swelling of the neck, bruising in the suprasternal notch and an absent left carotid pulse. Blood pressure was equal in both arms and chest x-ray was normal, but computed tomography of the neck and thorax showed dissection and rupture of the thoracic aorta with extensive intra-mediastinal bleeding. OUTCOME: surgical intervention was inappropriate in this situation and the patient died within 4 hours of presentation. CONCLUSION: syncope is a common presentation to hospital in older people and its cause may be difficult to elucidate, particularly if the patient is unable to provide a reliable history. Syncope without pain is a rare presentation of aortic dissection and the occurrence of anterior chest wall bruising has not been described previously. Pulse deficits and abnormal chest x-ray findings are often cited as indicative of aortic dissection but are rare manifestations and their absence should not be used to exclude this diagnosis.