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The authors regret that Alexandra Bargiota's name was spelt incorrectly in the author list. The details given in this correction are correct.

ObjectiveShort-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting and the effects of exogenous ghrelin on lipid mobilisation.DesignRandomised placebo-controlled study.MethodsIn this study, ten controls (body mass index (BMI) 23.3±3.2), ten morbidly obese subjects (BMI 50.1±10.6) and six post-gastrectomy subjects (BMI 25.2±1.0) were fasted for 36 h undergoing regular blood sampling. On a separate occasion, subjects were infused with either i.v. ghrelin (5 pmol/kg per min) or saline over 270 min.ResultsObese and post-gastrectomy subjects had lower ghrelin compared with controls (ANOVA, P=0.02) during the fast. Controls and gastrectomy subjects showed a similar increase in GH pulsatility, circulating non-esterified fatty acids (NEFA) and 3β-hydroxybutyrate (3 HB). Obese subjects had an impaired GH response (PP=0.01) but no change in NEFA excursions (P=0.09) compared with controls. Ghrelin infusion increased GH, NEFA and ketone bodies (ANOVA, PP=0.001). Ghrelin also induced a significant (ANOVA, P=0.004) biphasic NEFA response to meals in all the subjects.ConclusionsDespite low circulating ghrelin, gastrectomy subjects maintain a normal metabolic response to fasting, implying that ghrelin plays a minimal role. In contrast, infused ghrelin has significant effects on lipid mobilisation and induces a marked biphasic NEFA response to meals. Hence, ghrelin may play a significant role in meal-related substrate utilisation and metabolic flexibility.

Diabet. Med. 27, 1289–1294 (2010) Abstract Aims At any given time, people with diabetes occupy approximately 10–20% of acute hospital beds. In addition, diabetes is associated with a greater length of stay. Patients undergoing elective procedures occupy approximately 50% of hospital beds. The aim of this 12-month project was to improve the quality of diabetes care for elective inpatients. The primary outcome measure was length of stay. Methods A team was established to improve the quality of care and reduce the length of stay of all patients admitted electively with diabetes. Specific areas of focus were surgical pre-assessment, planning the admission, post-operative care and planning a safe discharge. A retrospective audit of all elective patients with a coded diagnosis of diabetes admitted between June 2008 and June 2009 was performed. Results Comparing the year of the project with the preceding year day-case rates for patients with diabetes increased by 34.8% for diabetes vs. 13.7% for the total hospital population (P for difference = 0.048). There was a significant fall in diabetes length of stay of 0.34 days comparing 2008 and 2009 (P = 0.040). Over the same period, we have shown a smaller reduction in length of stay for all other admissions of 0.08 days (p = 0.039). Conclusion A team specifically employed to focus on elective inpatient diabetes care have a significant impact on length of stay of this patient group with potential cost savings.

The aim of this study was to test the hypothesis that specific referral guidelines are unhelpful because of wide variations in individual clinical practice. A series of representative diabetes case studies were given to a group of primary care, general practice (GP) clinicians for comment. The same cases were given to a group of secondary care clinicians. The suggested management strategies were compared. Overall the results show very little agreement among either primary care or secondary care clinicians for a series of commonly presenting clinical cases. Approximately a third of GP responses for each group of cases suggested primary care management with a third each split between secondary or shared care. Long term follow up of the cases was also disputed but a greater proportion felt that continuing specialist input would not be required. Patient choice was not considered an important factor in deciding the most appropriate place for care. Although specific management strategies would be helpful for service planners, in reality clinicians differ greatly in what they feel should be managed in primary or secondary care. This variability needs to be considered in future planning for long term conditions such as diabetes. Copyright © 2009 John Wiley & Sons, Ltd.

Background Weight loss is difficult to achieve in type 2 diabetes and many therapies are associated with weight gain, an effect attenuated by metformin. We studied the effects of metformin on energy expenditure, appetite and the regulation of PYY and ghrelin in type 2 diabetes. Methods Plasma peptide YY (PYY), ghrelin, resting metabolic rate (RMR), postprandial thermogenesis (PPTG), and appetite ratings were measured at baseline and following a mixed meal in 11 type 2 diabetic subjects treated with diet alone (T2D) and 10 treated with metformin monotherapy (T2MF). The groups were similar in age, gender and adiposity. Results There were no differences in baseline anthropometric, or metabolic variables between the groups. Postprandially, plasma ghrelin fell equally in both groups (23% versus 24.5%, p < 0.05 versus baseline, p = NS between groups) but were reduced for longer in T2MF (below baseline 60–240 min T2MF versus 60–180 min T2D) coincidentally with a prolonged sensation of fullness and suppression of hunger in the metformin-treated group. There were no differences in PYY concentrations, RMR or PPTG. Conclusions Metformin prolongs the postprandial fall in ghrelin concentrations. These effects may prolong the inter-meal interval, thereby decreasing snack intake and daily energy intake, promoting weight loss. Copyright © 2006 John Wiley & Sons, Ltd.

Obesity is a common sequel to hypothalamic tumors and their treatment, but the underlying mechanisms are not fully established.Our objective was to evaluate the role of ghrelin and peptide-YY (PYY) in human hypothalamic obesity.The study took place at a University Medical Center.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.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.We assessed ghrelin, PYY, and appetite ratings.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.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.

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) μg/mL vs. 8.6 (6.5 to 11.3) μg/mL], but rose 4-fold postprandially in the obese group, reaching a peak at 60 minutes [baseline: 2.9 (2.1 to 4.1) μg/mL vs. 60 minutes: 12.1 (8.5 to 17.4) μg/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.

To the Editor: Weight loss appears to be particularly difficult to achieve in patients with type 2 diabetes compared to their non-diabetic counterparts [1]. The hormones peptide YY3–36 (PYY) and ghrelin are implicated in the regulation of appetite, energy balance and the pathophysiology of obesity. PYY is released from L-cells in the gut in response to food [2]. Fasting concentrations are lower and postprandial responses attenuated in obese subjects [3], and infusions of PYY to mimic the postprandial concentrations found in lean subjects reduce appetite and food intake in obese subjects [3, 4], suggesting a potential role in the pathogenesis of obesity. Peripheral administration of ghrelin increases food ingestion [5, 6], and prolonged administration leads to obesity [5, 7]. Circulating ghrelin shows preprandial peaks and postprandial troughs suggesting a role in meal initiation. Against this background, we sought to determine whether type 2 diabetes, independent of obesity status, affected the prandial regulation of PYY and ghrelin in a manner that would explain both the predisposition to increased energy intake and weight gain, and the difficulties in achieving weight loss seen in type 2 diabetes. The study was approved by the local ethics committee and subjects, who were volunteers, gave written informed consent. We studied 11 subjects with diet-controlled type 2 diabetes and 16 control subjects of similar age, sex and BMI. All subjects with diabetes were free from complications and had an HbA1c

A case is presented of a 39-year-old male with Down's Syndrome, who also had type 1 diabetes of 22 years duration. He presented with diabetic ketoacidosis (DKA)-arterial blood pH 7.17, plasma bicarbonate 13.6mmol/l, plasma glucose 26.4mmol/l and urine heavily positive for ketones. He recovered with standard intravenous fluid and insulin treatment, but on the third day of admission developed a swollen left arm (which had not been used for intravenous cannulation). Doppler ultrasound confirmed a left axillary vein thrombosis. This slowly resolved with anticoagulation. Review of the available literature revealed that though arterial thrombosis is a common complication of DKA, venous thromboembolism is surprisingly rare, and there appear to be no previous specific reports of axillary vein thrombosis complicating DKA.

6. Yang WS, Lee WJ, Funahashi T, et al. Weight reductionincreases plasma levels of an adipose-derived anti-inflamma-tory protein, adiponectin. J Clin Endocrinol Metab. 2001;86:3815–9.7. Holdstock C, Ede´n Engstro¨m B, O¨ hrvall M, Lind L, Sund-bom M, Karlsson FA. Ghrelin and adipose tissue regulatorypeptides: effect of gastric bypass surgery in obese humans.J Clin Endocrinol Metab. 2003;88:3177– 83.8. English PJ, Coughlin SR, Hayden K, Malik IA, Wild-ing JP. Plasma adiponectin increases postprandially inobese, but not in lean, subjects. Obes Res. 2003;11:839–44.9. Peake PW, Kriketos AD, Denyer GS, Campbell LV, Char-lesworth JA. The postprandial response of adiponectin to ahigh-fat meal in normal and insulin-resistant subjects.Int JObes Relat Metab Disord. 2003;27:657– 62.10. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrationsof a novel, adipose-specific protein, adiponectin, in type 2diabetic patients. Ateriosclero Thromb Vasc Biol. 2000;20:1595–9.

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Surveys in northern Ethiopia have demonstrated that apparent type 1 diabetes occurs more frequently than elsewhere in Africa and, indeed, in other parts of the world. We therefore investigated in detail a cohort of diabetic patients from this region to clarify the nature of this type of diabetes. All patients attending the diabetic clinic at Mekelle Hospital in the Tigray region of northern Ethiopia were investigated over a 6 week period. Clinical, demographic and anthropometric data were collected, as well as measurements of HbA1c, fasting lipid profile, fasting serum C-peptide and serum markers of beta cell autoimmunity, i.e. islet antigen-2 and GAD antibodies (GADA). Of 105 patients seen, 69 (66%) were on insulin treatment and had been from or close to diagnosis. Their median age and diabetes duration were 30 and 5 years, respectively, with a male excess of 2:1. Median BMI was 20.6 kg/m2. Despite these clinical characteristics suggestive of type 1 diabetes, only 42 of 69 (61%) patients were C-peptide-negative and 35% GADA-positive. Overall, 38 (36%) of the total group (n = 105) had immunological or C-peptide characteristics inconsistent with typical type 1 or type 2 diabetes. The clinical characteristics, local prevalence of undernutrition, and GADA and C-peptide heterogeneity suggest a malnutrition-related form of diabetes. Not all patients in northern Ethiopia with apparent type 1 diabetes appear to have the form of disease seen in Europids; their disease may, in fact, be related to malnutrition.

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.

To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects.A randomized, double-blind, placebo-controlled study.Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m(2)).Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion.Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry.Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P0.001).Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome.Plasma levels of adiponectin, leptin, resistin, IL-1beta, IL-6 and TNF-alpha in 30 subjects (ten patients, 20 controls) were correlated with indices of metabolic syndrome.Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7+/-1.0 in FDLP cases vs 7.1+/-0.72 mug/ml in controls, p=0.02), leptin (1.23+/-0.4 vs 9.0+/-1.3 ng/ml, p=0.002) and IL-6 (0.59+/-0.12 vs 1.04+/-0.17 pg/ml, p=0.047) and elevated TNF-alpha (34.8+/-8.1 vs 13.7+/-2.7 pg/ml, p=0.028), whereas IL-1beta and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body fat mass (controls, r=-0.44, p=0.036; FDLP, r=-0.67, p=0.025), insulin resistance (controls, r=-0.62, p=0.003; FDLP, r=-0.70, p=0.025) and other features of the metabolic syndrome. TNF-alpha concentrations were positively related to fat mass (controls, r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1beta and resistin did not demonstrate any correlations with the metabolic syndrome in either group.Low adiponectin and leptin and high TNF-alpha were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-alpha production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.

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.

We describe a 71-year-old female diabetic patient with sensory distal lower limb neuropathy, who presented with painless swelling and erythema of the left ankle and lower shin. Diagnoses of cellulitis, deep venous thrombosis and Charcot neuroarthropathy were considered, but eventually a magnetic resonance scan showed complete rupture of the Achilles tendon. There was no history of trauma, and the absence of pain was presumed to be due to her dense sensory neuropathy. Copyright © 2007 John Wiley & Sons.