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Objective: It has been postulated that the effectiveness of bariatric surgery varies between ethnic groups. However, data regarding this topic are inconclusive, as most studies included few patients from minority groups. We conducted a meta-analysis to determine the difference in percentage of excess weight loss (%EWL) 1-2 years after bariatric surgery in people of African and Caucasian descent. We also studied differences in diabetes mellitus (DM) remission.Research Design and Methods: We performed a MEDLINE and EMBASE search for studies reporting %EWL and/or DM remission after bariatric surgery and including both African Americans and Caucasians. The 613 publications obtained were reviewed. We included 14 studies (1,087 African Americans and 2,714 Caucasians); all provided data on %EWL and 3 on DM remission. We extracted surgery type, %EWL, and DM remission 1-2 years after surgery. After analyzing %EWL for any surgery type, we performed subanalyses for malabsorptive and restrictive surgery.Results: The overall absolute mean %EWL difference between African Americans and Caucasians was -8.36% (95% CI -10.79 to -5.93) significantly in favor of Caucasians. Results were similar for malabsorptive (-8.39% [-11.38 to -5.40]) and restrictive (-8.46% [-12.95 to -3.97]) surgery. The remission of DM was somewhat more frequent in African American patients than in Caucasian patients (1.41 [0.56-3.52]). However, this was not statistically significant.Conclusions: In %EWL terms, bariatric surgery is more effective in Caucasians than in African Americans, regardless of procedure type. Further studies are needed to investigate the exact mechanisms behind these disparities and to determine whether ethnic differences exist in the remission of comorbidities after bariatric surgery. [ABSTRACT FROM AUTHOR]

Introduction: Critically ill patients with diabetes are at increased risk for the development of complications, but the impact of diabetes on mortality is unclear. We conducted a systematic review and meta-analysis to determine the effect of diabetes on mortality in critically ill patients, making a distinction between different ICU types.Methods: We performed an electronic search of MEDLINE and Embase for studies published from May 2005 to May 2010 that reported the mortality of adult ICU patients. Two reviewers independently screened the resultant 3,220 publications for information regarding ICU, in-hospital or 30-day mortality of patients with or without diabetes. The number of deaths among patients with or without diabetes and/or mortality risk associated with diabetes was extracted. When only crude survival data were provided, odds ratios (ORs) and standard errors were calculated. Data were synthesized using inverse variance with ORs as the effect measure. A random effects model was used because of anticipated heterogeneity.Results: We included 141 studies comprising 12,489,574 patients, including 2,705,624 deaths (21.7%). Of these patients, at least 2,327,178 (18.6%) had diabetes. Overall, no association between the presence of diabetes and mortality risk was found. Analysis by ICU type revealed a significant disadvantage for patients with diabetes for all mortality definitions when admitted to the surgical ICU (ICU mortality: OR [95% confidence interval] 1.48 [1.04 to 2.11]; in-hospital mortality: 1.59 [1.28 to 1.97]; 30-day mortality: 1.62 [1.13 to 2.34]). In medical and mixed ICUs, no effect of diabetes on all outcomes was found. Sensitivity analysis showed that the disadvantage in the diabetic surgical population was attributable to cardiac surgery patients (1.77 [1.45 to 2.16], P < 0.00001) and not to general surgery patients (1.21 [0.96 to 1.53], P = 0.11).Conclusions: Our meta-analysis shows that diabetes is not associated with increased mortality risk in any ICU population except cardiac surgery patients. [ABSTRACT FROM AUTHOR]

Continuous subcutaneous insulin infusion (CSII) is an alternative to multiple daily insulin injections (MDII) as intensive insulin therapy for optimising glycaemic control in type 1 diabetes. The Diabetes Control and Complications Trial (DCCT) showed the benefits of intensive insulin therapy in reducing the risk of microvascular complications. CSII was an option in the intensive control arm of the study. However, the value and place of CSII in the management of type 1 diabetes remains controversial. In this article we will present what we until recently do know about the benefits of CSII therapy and shall especially give some information about the recently published 5-Nations Study. In our view CSII usage offers significant benefits over NPH-based MDI for individuals with type 1 diabetes with improvement in all significant metabolic parameters as well as in patients' quality of life. [ABSTRACT FROM AUTHOR]

The development of a truly non-invasive continuous glucose sensor is an elusive goal. We describe the rise and fall of the Pendra(R) device. In 2000 the company Pendragon Medical introduced a truly non-invasive continuous glucose monitoring device. This system was based on impedance spectroscopy. Pendra was CE approved in May 2003. For a short time, the Pendra was available on the Dutch direct to consumer market. A post-marketing reliability study was performed in 6 type 1 diabetes patients. Mean Absolute Difference between Pendra glucose values and values obtained through self monitoring of blood glucose was 52%, the Pearson's correlation coefficient was 35.1% and a Clark Error grid showed 4.3% of the Pendra readings in the potentially dangerous zone E. We argue that the CE certification process for continuous glucose sensors should be made more transparent, and that a consensus on specific requirements for continuous glucose sensors is needed, to prevent patients from exposure to potentially dangerous situations. This manuscript is a shortened and adapted version of Wentholt IM, Zwart A, Hoekstra JB, DeVries JH. Pendra goes Dutch; lessons for the CE mark in Europe. Diabetologia 2005; 48: 1055-8 and is published with consent of the editor of Diabetologia. [ABSTRACT FROM AUTHOR]

Objective: Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking., Research Design and Methods: We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured., Results: Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA., Conclusions: We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.

Objective: Letters from the hospital to the general practitioner are important for maintaining continuity of care. Although doctors feel letters are important, they are often not written on time. To improve the number and timeliness of letters sent from the hospital outpatient department to the general practitioner using an email-based intervention evaluated in a randomized controlled trial., Materials and Methods: Users were interviewed to determine the requirements for the intervention. Due to high between-doctor variation at baseline, doctors were matched for baseline performance and pair-randomized. The effectiveness of the intervention was assessed using meta-analytic methods. The primary outcome was the number of patient visits which should have generated a letter that had a letter by 90 days after the visit. Satisfaction was assessed with an anonymous survey., Results: The intervention consisted of a monthly email reminder for each doctor containing a list of his or her patients who were (over)due for a letter. Doctors in the intervention group had 21% fewer patient visits which did not have a letter by 90 days (OR = 5.7, p = 0.0020). Satisfaction with the system was very high., Discussion: This study examines the effect of a simple reminder in absence of other interventions, and provides an example of an effective non-interruptive decision support intervention., Conclusion: A simple email reminder improved the number and timeliness of letters from the outpatient department to the general practitioner, and was viewed as a useful service by its users.

Purpose: Physiological colonic 18F-fluorodeoxyglucose (18F-FDG) uptake is a frequent finding on 18F-FDG positron emission tomography computed tomography (PET-CT). Interestingly, metformin, a glucose lowering drug associated with moderate weight loss, is also associated with an increased colonic 18F-FDG uptake. Consequently, increased colonic glucose use might partly explain the weight losing effect of metformin when this results in an increased energy expenditure and/or core body temperature. Therefore, we aimed to determine whether metformin modifies the metabolic activity of the colon by increasing glucose uptake., Methods: In this open label, non-randomized, prospective mechanistic study, we included eight lean and eight overweight males. We measured colonic 18F-FDG uptake on PET-CT, energy expenditure and core body temperature before and after the use of metformin. The maximal colonic 18F-FDG uptake was measured in 5 separate segments (caecum, colon ascendens,-transversum,-descendens and sigmoid)., Results: The maximal colonic 18F-FDG uptake increased significantly in all separate segments after the use of metformin. There was no significant difference in energy expenditure or core body temperature after the use of metformin. There was no correlation between maximal colonic 18F-FDG uptake and energy expenditure or core body temperature., Conclusion: Metformin significantly increases colonic 18F-FDG uptake, but this increased uptake is not associated with an increase in energy expenditure or core body temperature. Although the colon might be an important site of the glucose plasma lowering actions of metformin, this mechanism of action does not explain directly any associated weight loss.

The haemoglobin glycation index (HGI) quantifies the interindividual variation in the propensity for glycation and is a predictor of diabetes complications and adverse effects of intensive glucose lowering. We investigated the relevance of HGI as independent predictor of complications by using data of the AleCardio trial. The AleCardio trial randomized 7226 type 2 diabetes patients with an acute coronary syndrome to aleglitazar or placebo. From 6458 patients with baseline glycated haemoglobin (HbA 1c ) and fasting plasma glucose (FPG), a linear regression equation, HbA 1c (%) = 5.45 + 0.0158 * FPG (mg/dl), was used to calculate predicted HbA 1c and derive HGI (= observed - predicted HbA 1c ). With multivariate Cox regression we examined the association with major adverse cardiac events, cardiovascular mortality, total mortality and hypoglycaemia, irrespective of treatment allocation, using HGI subgroups (low, intermediate and high) and HGI as continuous variable. Patients with high HGI were younger, more often non-Caucasian, had a longer duration of diabetes, showed more retinopathy and used insulin more often. Hypoglycaemia occurred less often in the low HGI subgroup, but this difference disappeared after adjustment for duration of diabetes, insulin and sulphonylurea use. Low HGI patients were at lower risk for cardiovascular mortality (hazard ratio 0.64; 95% confidence interval 0.44-0.93, p = 0.020) and total mortality (hazard ratio 0.69; 95% confidence interval 0.50-0.95, p = 0.025), as compared with high HGI patients. Every percentage increase in HGI was associated with a 16% increase in the risk for cardiovascular mortality ( p = 0.005). The association between HGI and mortality disappeared with additional adjustment for HbA 1c . HGI predicts mortality in diabetes patients with acute coronary syndromes, but no better than HbA 1c .

Brown adipose tissue is able to increase energy expenditure by converting glucose and fatty acids into heat. Therefore, BAT is able to increase energy expenditure and could thereby facilitate weight loss or at least weight maintenance. Since cold is a strong activator of BAT, most prospective research is performed during cold to activate BAT. In current research, there are roughly two methods of cooling. Cooling by lowering ambient air temperature, which uses a fixed temperature for all subjects and personalized cooling, which uses cooling blankets or vests with temperatures that can be adjusted to the individual set point of shivering. These methods might trigger mechanistically different cold responses and hence result in a different BAT activation. This hypothesis is underlined by two studies with the same research question (difference in BAT activity between Caucasians and South Asians) one study found no differences in BAT activity whereas the other did found differences in BAT activity. Since most characteristics (e.g. age, BMI) were similar in the two studies, the best explanation for the differences in outcomes is the use of different cooling protocols. One of the reasons for differences in outcomes might be the sensory input from the facial skin, which might be important for the activation of BAT. In this review we will elaborate on the differences between the two cooling protocols used to activate BAT., (Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: Although the course of disease of type 1 and type 2 diabetes differs, the distinction is rarely made when patients are admitted to the intensive care unit (ICU). Here, we report patient- and admission-related characteristics in relation to glycemic measures of patients with type 1 and type 2 diabetes admitted to the ICU., Materials and Methods: A retrospective chart review was performed of 1574 patients with diabetes admitted between 2004 and 2011 to our ICU. Glycemic measures included mean glucose, the incidence of hypoglycemia and hyperglycemia, percentage of glucose values in/below/above target, and glucose variability. The ICU and hospital mortality were secondary outcomes., Results: We classified 2% (n=27) of patients as having type 1 diabetes and 98% (n=1547) as having type 2 diabetes. Patients with type 1 diabetes were significantly younger, had a lower body mass index, and were more frequently admitted to the ICU for medical diagnoses. No differences in glycemic measures were found, apart from a 20% higher glucose variability in the type 1 diabetes group., Conclusions: Patients with type 1 diabetes showed a higher glucose variability, but overall glycemic control was not different between patients with type 1 and type 2 diabetes. Very few diabetes patients admitted to the ICU have type 1 diabetes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening) results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC) 742 mmol/L * 120 min (695-818) vs 641 (504-750), P = 0.036, AUC for insulin did not change, P = 0.575). In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236-96,831) vs 36,448 (25,213-57,711), P = 0.012) and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614-988) vs 644 (568-829), P = 0.017) and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration., (© 2016 The authors.)

The aim of this study was to compare the effectiveness and safety of intermediate-acting insulin (IMI) titrated on body weight and glucocorticoid dose with that of short-acting sliding-scale insulin (SSI) in patients on recurrent high-dose glucocorticoid-containing chemotherapy. We enrolled 26 patients with type 2 diabetes mellitus or random blood glucose level >12 mmol/l in a previous cycle of chemotherapy in a randomized crossover study. In two consecutive cycles of glucocorticoid-containing chemotherapy, participants were treated with either IMI or SSI, as add-on to routine diabetes medication. We compared time spent in target range (3.9-10 mmol/l), measured by continuous glucose monitoring (CGM), and the occurrence of hypoglycaemia. IMI resulted in a higher proportion of glucose values within target range than SSI (34.4 vs 20.9%; p < 0.001). There were no severe or symptomatic hypoglycaemic events. Two participants in each group had a subclinical hypoglycaemia detected only by CGM. Once-daily IMI resulted in better glycaemic control than SSI in patients with glucocorticoid-induced hyperglycaemia during chemotherapy. Safety was not compromised as the incidence of hypoglycaemia was low and not different between both regimens., (© 2016 John Wiley & Sons Ltd.)

Retrospective studies have shown that outdoor temperature influences the prevalence of detectable brown adipose tissue (BAT). Prospective studies use acute cold exposure to activate BAT. In prospective studies, BAT might be preconditioned in winter months leading to an increased BAT response to various stimuli. Therefore the aim of this study was to assess whether outdoor temperatures and other weather characteristics modulate the response of BAT to acute cold. To assess metabolic BAT activity and sympathetic outflow to BAT, 64 (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography-computed tomography (PET-CT) and 56 additional (123)I-meta-iodobenzylguanidine ((123)I-mIBG) single-photon emission computed tomography-CT (SPECT-CT) scans, respectively, of subjects participating in previously executed trials were retrospectively included. BAT activity was measured in subjects after an overnight fast, following 2 h of cold exposure (∼17°C). The average daytime outdoor temperatures and other weather characteristics were obtained from the Dutch Royal Weather Institute. Forty-nine subjects were BAT positive. One week prior to the scan, outdoor temperature was significantly lower in the BAT-positive group compared with the BAT-negative group. Higher outdoor temperatures on preceding days resulted in lower stimulated metabolic BAT activity and volume (all P < 0.01). Outdoor temperatures did not correlate with sympathetic outflow to BAT. In conclusion, outdoor temperatures influence metabolic BAT activity and volume, but not sympathetic outflow to BAT, in subjects exposed to acute cold. To improve the consistency of the findings of future BAT studies in humans and to exclude bias introduced by outdoor temperatures, these studies should be planned in periods of similar outdoor temperatures., (Copyright © 2016 the American Physiological Society.)

Aim: The use of metformin has been associated with diffusely increased colonic (18)F-fluorodeoxyglucose ((18)F-FDG) uptake. Interestingly, metformin use is associated with moderate weight loss. It could be hypothesized that increased colonic glucose disposal is related to this weight loss. It is unknown whether other factors influence (18)F-FDG uptake in the colon. The aim of this study was to retrospectively assess independent determinants of colonic (18)F-FDG uptake., Methods: We retrospectively analysed 270 (18)F-FDG PET-CTs which were made for diagnostic purposes. Colonic (18)F-FDG uptake was assessed using a 4-point scale using the liver as a reference (1; lower, 2; similar, 3; moderately higher than hepatic activity, 4; intense diffuse increased uptake). Determinants of (18)F-FDG uptake in the colon were assessed using forward logistic regression (i.e., grade 1&2 vs 3&4)., Results: The patients had a mean age of 60.2±14.8 years, a BMI of 25.8±5.2kg/m(2) and 52% were female. Most patients had a grade 2 (44%) or grade 3 (39%) (18)F-FDG uptake in the colon. Diabetes mellitus type 2 was observed in 14% of the patients. In total, 5% of the patients used insulin, 12% used metformin and 5% used sulfonylurea derivatives (SU). While there seemed to be an effect of SU on (18)F-FDG uptake in the ileum [OR 3.6 (95% CI: 1.3-33.1), p=0.03], metformin was the only drug associated with (18)F-FDG uptake for both the whole colon [OR 10.0 (95% CI: 2.9-34.7), p<0.001] and all individual segments., Conclusion: Metformin use is an independent determinant of increased colonic (18)F-FDG uptake, suggesting a potential role for increasing colonic glucose disposal., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Measurement of brown adipose tissue (BAT) activity is the focus of intensive research, among others as a potential target for weight-lowering strategies. In this, BAT activity is visualized and quantified using F-fluorodeoxyglucose (F-FDG) PET-CT. The aim of this study was to determine the interobserver and intraobserver variability for detecting and quantifying BAT on F-FDG PET-CTs., Methods: Three observers retrospectively independently assessed 55 F-FDG PET-CTs (performed between April 2013 and January 2014) for BAT activity parameters: BAT volume, the maximal and mean standardized uptake value (SUVmax and SUVmean) obtained in healthy male controls. One observer reassessed the scans after 2 months for the intraobserver variability. Interobserver and intraobserver variability were expressed using Lin's concordance coefficient (LCC) and Bland-Altman plots. Correlations between the three parameters were assessed using Spearman's correlation., Results: The LCCs for the interobserver and intraobserver concordance for SUVmax were the highest (LCC SUVmax varied between 0.998 and 0.999, for SUVmean between 0.989 and 0.991 and for volume between 0.947 and 0.972). The Bland-Altman analysis showed a small absolute mean difference between all observers for both SUVmax and SUVmean, but the differences for volume were markedly higher. All parameters correlated statistically strongly and positively., Conclusion: The SUVmax showed the lowest interobserver and intraobserver variation. Although SUVmean and BAT volume had a higher interobserver and intraobserver variation, the variation is still within acceptable limits. Therefore, all parameters can be used to describe BAT activity. However, for an adequate comparison between studies, we recommend the use of SUVmax.

Unlabelled: Brown adipose tissue (BAT) could facilitate weight loss by increasing energy expenditure. Cold is a potent stimulator of BAT, activating BAT primarily through the sympathetic nervous system (SNS). Older or overweight individuals have less metabolic BAT activity than the lean and young, but the role of the SNS in this decline is unknown. We aimed to determine whether this lower metabolic BAT activity in older or overweight individuals can be explained by a lower SNS response to cold., Methods: This was a prospective observational study. We included 10 young obese, 11 old lean, and 14 young lean healthy men. All subjects underwent (18)F-FDG PET/CT and (123)I-meta-iodobenzylguanidine ((123)I-mIBG) SPECT/CT after an overnight fast and 2 h of cold exposure. Metabolic BAT activity was expressed as volume and as SUVmax of (18)F-FDG. BAT SNS activity was expressed as volume and as the ratio between (123)I-mIBG uptake in BAT and a reference region (SQUVmax of (123)I-mIBG)., Results: SUVmax, BAT volume, and SQUVmax were significantly different between young and old (SUVmax, 7.9 [range, 4.2-17.3] vs. 2.9 [range, 0.0-4.0]; volume, 124.8 [range, 10.9-338.8] vs. 3.4 [range, 0.0-10.9]; and SQUVmax, 2.7 [range, 1.9-4.7] vs. 0.0 [range, 0.0-2.2], respectively) (all P < 0.01) but not between lean and obese (SUVmax, 7.9 [range, 4.2-17.3] vs. 4.0 [range, 0.0-13.5] [P = 0.69]; volume, 124.8 [range, 10.9-338.8] vs. 11.8 [range, 0.0-190.2] [P = 0.64]; and SQUVmax, 2.7 [range, 1.9-4.7] vs. 1.7 [range, 0-3.5] [P = 0.69], respectively). We found a strong positive correlation between BAT activity measured with (18)F-FDG and (123)I-mIBG in the whole group of BAT-positive subjects (ρ = 0.82, P < 0.01)., Conclusion: Both sympathetic drive and BAT activity are lower in older but not in obese men., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Diabetes care includes annual evaluation of micro- and macrovascular complications, however, oral pathologies are not included. We studied retrieving oral health information, in particular periodontal disease, from the dentist and studied the association between the reported periodontal condition and variables of both diabetes and dental care., Methods: During their annual comprehensive diabetes evaluation, patients were asked to deliver an oral health questionnaire (OHQ) to their dentist. Based on the returned OHQs, the process of retrieving oral health information from the dentist was analyzed. In addition, reported oral health measures with special emphasis to periodontitis, using a Periodontal Screening Index (PSI), were related to diabetes-related variables., Results: We included 889 patients of whom 102 patients (11%) did not visit a dentist at all and 252 (28%) were edentulous. The response rate was <50% for oral information on patients with diabetes. For the second aim, OHQs of 207 patients could be further analyzed. A moderate to high PSI-score was found in 106 patients, of whom 65% were untreated for periodontitis. Furthermore high PSI-scores were associated with poor oral hygiene, soft tissue pathologies and periodontal treatment, but not significantly with glycemic control and presence of diabetes complications., Conclusion: The transfer of information from the dentist to the diabetologist is far from optimal. An OHQ can be a valuable tool for the identification of patients with diabetes with poor oral health especially untreated periodontal disease, which is helpful for proper diabetes management., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aims: Treatment with glucocorticoids for neoplasms and inflammatory disorders is frequently complicated by glucocorticoid induced hyperglycaemia (GCIH). GCIH is associated with adverse outcomes and its treatment has short term and long term benefits. Currently, treatment targets and modalities depend on local protocols and habits of individual clinicians. We explored current practice of screening and treatment of GCIH in patients receiving glucocorticoid pulse therapy., Methods: A factorial survey with written case vignettes. All vignette patients received glucocorticoid pulse therapy. Other characteristics (e.g., indication for glucocorticoid therapy, pre-existent diabetes) varied. The survey was held between November 2013 and May 2014 on 2 nationwide conferences and in hospitals across The Netherlands. Pulmonologists and internists expressed their level of agreement with statements on ordering capillary glucose testing and treatment initiation., Results: Respondents ordered screening for GCIH in 85% of vignette patients and initiated treatment in 56%. When initiating treatment, respondents opt for sliding scale insulin in 62% of patients. Sliding scale insulin was more frequently prescribed in patients with pre-existent insulin dependent diabetes (OR 2.4, CI 1.3-4.2) and by residents (vs. specialists, OR 2.1, CI 1.2-3.5). Sixty-nine percent of clinicians experienced a lack of guidelines for GCIH., Conclusions: Clinicians have a strong tendency to screen for GCIH but subsequent initiation of treatment was low. Sliding scale insulin is still widely used in episodic GCIH despite evidence against its effectiveness. This may be due to lacking evidence on feasible treatment options for GCIH., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Hyperglycaemia during and after hip surgery is associated with coagulation activation and an increased risk of venous thromboembolism. Whether lowering of glucose levels during hip surgery diminishes coagulation activation is unknown. We investigated the efficacy of the human GLP-1 analogue liraglutide to lower glucose during and after hip surgery and studied its influence on coagulation activation., Methods: A total of 37 obese subjects who underwent hip surgery were randomized to subcutaneous liraglutide or placebo for 4 consecutive days, starting one day prior to surgery. Glucose levels and coagulation indices at three fixed time-points (pre-operative, 2 h post-operative and 3 days post-operative) were measured., Results: Liraglutide reduced glucose at day three post-surgery (median glucose (IQR) liraglutide 5.5 (5.2-5.7) vs. placebo 5.8 (5.5-6.2); difference 0.3 mmol/L, P = 0.04). Changes in 6 out of 8 coagulation indices studied did not differ between the two groups. Only D-dimer levels were significantly lower in the liraglutide group at day three post-surgery and FVIII levels were significantly higher in the liraglutide group 2 h post-surgery., Conclusion: Although the human GLP-1 analogue liraglutide moderately reduced post-operative blood glucose levels in non-diabetic and prediabetic obese patients undergoing elective hip surgery, no changes were observed with respect to coagulation activation.

Aim: To test how certain patient factors would influence the decision of Dutch care providers regarding insulin dose adjustments. We hypothesize that some of these decisions would diverge from recent evidence and consensus statements., Methods: We developed narrative vignettes describing clinical scenarios of patients receiving basal insulin therapy. For each vignette, the respondents were asked to indicate whether they would advise a change in insulin dose. A total of 520 paper questionnaires were distributed among physicians and nurses in primary and secondary care in the Netherlands. Multivariate linear and logistic regression analyses were performed to identify factors associated with dosing decisions., Results: A total of 190 (37%) questionnaires were returned. In cases of a severe rather than mild hypoglycaemic event, care providers were nearly five times more likely to decrease the dose (odds ratio 4.77, 95% CI 1.65-13.75). Care providers were six times more likely to increase the dose when the patient's current dose was low (30 units) rather than high (90 units) (odds ratio 6.38, 95% CI 3.04-13.37). The plasma glucose concentration during a hypoglycaemic event and a known history of cardiovascular disease did not influence the care providers' dosing decisions., Conclusion: Evidence regarding the optimum insulin titration is not always translated into clinical practice. When formulating guidelines, misconceptions should be identified and addressed., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function assessed by examining the antibody response to polysaccharide antigens (pneumococcal 23-valent polysaccharide vaccine), B-cell subsets, and the presence of Howell-Jolly bodies (HJB). The data were compared to those obtained from splenectomized patients and healthy controls (HC) who had been included in a previously conducted study. A total of 30 patients were studied: 5 who had proximal SAE, 7 who had distal SAE, 8 who had a splenectomy, and 10 HC. The median vaccine-specific antibody response of the SAE patients (fold increase, 3.97) did not differ significantly from that of the HC (5.29; P = 0.90); however, the median response of the splenectomized patients (2.30) did differ (P = 0.003). In 2 of the proximally embolized patients and none of the distally embolized patients, the ratio of the IgG antibody level postvaccination compared to that prevaccination was <2. There were no significant differences in the absolute numbers of lymphocytes or B-cell subsets between the SAE patients and the HC. HJB were not observed in the SAE patients. The splenic immune function of embolized patients was preserved, and therefore routine vaccination appears not to be indicated. Although the median antibody responses did not differ between the patients who underwent proximal SAE and those who underwent distal SAE, 2 of the 5 proximally embolized patients had insufficient responses to vaccination, whereas none of the distally embolized patients exhibited an insufficient response. Further research should be done to confirm this finding., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Background: Computer-assisted decision support is an emerging modality to assist patients with type 2 diabetes mellitus (T2DM) in insulin self-titration (ie, self-adjusting insulin dose according to daily blood glucose levels). Computer-assisted insulin self-titration systems mainly focus on helping patients overcome barriers related to the cognitive components of insulin titration. Yet other (eg, psychological or physical) barriers could still impede effective use of such systems., Objective: Our primary aim was to identify experiences with and barriers to self-monitoring of blood glucose, insulin injection, and insulin titration among patients with T2DM. Our research team developed a computer-assisted insulin self-titration system, called PANDIT. The secondary aim of this study was to evaluate patients' perceptions of computer-assisted insulin self-titration. We included patients who used PANDIT in a 4-week pilot study as well as patients who had never used such a system., Methods: In-depth, semi-structured interviews were conducted individually with patients on insulin therapy who were randomly recruited from a university hospital and surrounding general practices in the Netherlands. The interviews were transcribed verbatim and analyzed qualitatively. To classify the textual remarks, we created a codebook during the analysis, in a bottom-up and iterative fashion. To support examination of the final coded data, we used three theories from the field of health psychology and the integrated model of user satisfaction and technology acceptance by Wixom and Todd., Results: When starting insulin therapy, some patients feared a lifelong commitment to insulin therapy and disease progression. Also, many barriers arose when implementing insulin therapy (eg, some patients were embarrassed to inject insulin in public). Furthermore, patients had difficulties increasing the insulin dose because they fear hypoglycemia, they associate higher insulin doses with disease progression, and some were ignorant of treatment targets. Patients who never used a computer-assisted insulin self-titration system felt they had enough knowledge to know when their insulin should be adjusted, but still believed that the system advice would be useful to confirm their reasoning. Furthermore, the time and effort saved with automated insulin advice was considered an advantage. Patients who had used PANDIT found the system useful if their glycemic regulation improved. Nevertheless, for some patients, the absence of personal contact with their caregiver was a drawback. While guidelines state that adjustment of basal insulin dose based on fasting plasma glucose values is sufficient, both patients who had and those who had not used PANDIT felt that such a system should take more patient data into consideration, such as lifestyle and diet factors., Conclusions: Patients encounter multiple obstacles when implementing insulin therapy. Computer-assisted insulin self-titration can increase patient awareness of treatment targets and increase their confidence in self-adjusting the insulin dose. Nevertheless, some barriers may still exist when using computer-assisted titration systems and these systems could also introduce new barriers.

Objective: Hypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glucose analogue (18)F-fluorodeoxyglucose in brown adipose tissue using positron emission tomography and computer tomography., Methods: In nine healthy adults (18)F-fluorodeoxyglucose uptake as measure of brown adipose tissue activity was assessed in a cold environment (17 °C) during euglycemia (blood glucose 4.5 mmol/L) and hypoglycemia (2.5 mmol/L) using a hyperinsulinemic glucose clamp., Results: Brown adipose tissue activity was observed in all participants. No difference was observed in the median (range) maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue between euglycemia and hypoglycemia: 4.2 (1.0-7.7) versus 3.1 (2.2-12.5) g/mL (p=0.7). Similarly there were no differences in mean standardized (18)F-fluorodeoxyglucose uptake values or total brown adipose tissue volume between euglycemia and hypoglycemia. Body temperature dropped by 0.6 °C from baseline during the hypoglycemic condition and remained unchanged during the euglycemic condition. There was no correlation between the maximal standardized uptake values of (18)F-fluorodeoxyglucose in brown adipose tissue and levels of counterregulatory hormones., Conclusions: This study shows that there is a similar amount of (18)F-fluorodeoxyglucose uptake in brown adipose tissue during hypoglycemia when compared to euglycemia, which makes a role for systemic catecholamines in brown adipose tissue activation and a role for brown adipose tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future studies in humans should determine whether hypoglycemia indeed increases energy expenditure, and if so which alternative source can explain this increase., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background & Aims: Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile acid and glucose metabolism., Methods: In this single blinded randomized controlled trial, 20 male obese subjects with metabolic syndrome were randomized to 7 days of amoxicillin 500 mg t.i.d. or 7 days of vancomycin 500 mg t.i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured., Results: Vancomycin reduced fecal microbial diversity with a decrease of gram-positive bacteria (mainly Firmicutes) and a compensatory increase in gram-negative bacteria (mainly Proteobacteria). Concomitantly, vancomycin decreased fecal secondary bile acids with a simultaneous postprandial increase in primary bile acids in plasma (p<0.05). Moreover, changes in fecal bile acid concentrations were predominantly associated with altered Firmicutes. Finally, administration of vancomycin decreased peripheral insulin sensitivity (p<0.05). Amoxicillin did not affect any of these parameters., Conclusions: Oral administration of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid and glucose metabolism in humans. This trial is registered at the Dutch Trial Register (NTR2566)., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: This study assessed the feasibility of a portable bihormonal closed-loop system at home., Subjects and Methods: Sixteen pump-treated patients with type 1 diabetes received 48 h of closed-loop therapy with a telemonitored insulin- and glucagon-delivering closed-loop system and 48 h of patient-managed open-loop therapy., Results: Owing to technical problems in five cases, only 11 patients could be analyzed. Whereas median (interquartile range) glucose levels were not significantly different during Day 1 of open-loop control (OL1) from closed-loop control (CL1) (8.27 [0.83] mmol/L vs. 8.84 [1.47] mmol/L; P=0.206), they were significantly lower during Day 2 of closed-loop control (CL2) versus open-loop control (OL2) (7.70 [2.29] mmol/L vs. 8.84 [0.87] mmol/L; P=0.027). Time spent in euglycemia (3.9-10 mmol/L) was comparable with 67.2% (38.5%) in OL1 versus 79.2% (16.9%) in CL1 (P=0.189) and 66.0% (29.8%) in OL2 versus 76.5% (23.9%) in CL2 (P=0.162). Time spent in hypoglycemia (<3.9 mmol/L) was comparable on Day 1 of control (OL1, 0.68% [8.68%]; CL1, 2.08% [7.61%]; P=0.593) but significantly higher during Day 2 of control (OL2, 0.00% [11.07%]; CL2, 2.8% [9.8%]; P=0.0172) (P=0.017)., Conclusions: Bihormonal closed-loop control is feasible at home, with comparable time in euglycemia to open-loop control and significantly lower median glucose levels on Day 2 of control at the expense of more time in hypoglycemia, albeit still at a very low percentage of time.

It is important that junior doctors in training conduct research for a number of years, culminating in a PhD. This is crucial to their development as critical and versatile doctors, which is exactly what is required now, in 2014. Hospitals are keen to have doctors with a broad education, and conducting scientific research is an enrichment for the investigators themselves. It is not necessarily undesirable that they do this principally to increase their chances of trainee posts; even those who have almost completed a PhD can be rejected for trainee positions if they do not seem to be competent.

Aims: Evidence of ethnic disparities in the conversion of prediabetes to type 2 diabetes is scarce. We studied the association of impaired fasting glucose (IFG) and fasting plasma glucose (FPG) with the 10-year cumulative incidence of type 2 diabetes in three ethnic groups., Methods: We analyzed data for 90 South-Asian Surinamese, 190 African-Surinamese, and 176 ethnic Dutch that were collected in the periods 2001-2003 and 2011-2012. We excluded those with type 2 diabetes or missing FPG data. We defined baseline IFG as FPG of 5.7-6.9 mmol/L. We defined type 2 diabetes at follow-up as FPG ≥ 7.0 mmol/L, HbA1c ≥ 48 mmol/mol (6.5%), or self-reported type 2 diabetes., Results: 10-Year cumulative incidences of type 2 diabetes were: South-Asian Surinamese, 18.9%; African-Surinamese, 13.7%; ethnic Dutch, 4.5% (p<0.05). The adjusted association of baseline IFG and FPG with the 10-year cumulative incidence of type 2 diabetes was stronger for South-Asian Surinamese than for African-Surinamese and ethnic Dutch. The IFG (compared to normoglycaemia) ORs were 11.1 [3.0-40.8] for South-Asian Surinamese, 5.1 [2.0-13.3] for African-Surinamese, and 2.2 [0.5-10.1] for ethnic Dutch., Conclusions: The 10-year cumulative incidence of type 2 diabetes was higher and associations with baseline IFG and FPG were stronger among South-Asian Surinamese and African-Surinamese than among ethnic Dutch. Our findings confirm the high risk of type 2 diabetes in South-Asians and suggest more rapid conversion in populations of South-Asian origin and (to a lesser extent) African origin than European origin., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We describe the course of two complaints that were filed by patients to the Dutch Medical Disciplinary Board against two internal medicine residents. In the procedure following the complaints the supervisor and the teacher were actively involved, which resulted in one complaint being dropped. We describe the importance of adequate moral support in such cases, as the complaint may lead to loss of work satisfaction or self-esteem, especially for those in training. We make some recommendations on how the resident and the supervisor/head of the department should engage in complaints filed to the Medical Disciplinary Board. In addition, we suggest that routine 'error-meetings' may help to provide an open atmosphere where disclosure of errors and the various procedures at the hospital or disciplinary boards are promoted.

Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin may experience hypoglycaemia. However, recent data regarding the incidence of hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to determine the proportion of patients with type 2 diabetes mellitus that experience hypoglycaemia when treated with sulfonylurea or insulin. We searched MEDLINE and EMBASE for randomized controlled trials that compared incretin-based drugs to sulfonylureas or insulin and assessed hypoglycaemia incidence in the latter therapies. Subgroup and meta-regression analyses were performed to study possible associations with potential risk factors for hypoglycaemia. Data of 25 studies were extracted, 22 for sulfonylurea and 3 for insulin. Hypoglycaemia with glucose ≤3.1 mmol/L or ≤2.8 mmol/L was experienced by 10.1% [95% confidence interval (CI) 7.3-13.8%] and 5.9% (95% CI 2.5-13.4%) of patients with any sulfonylurea treatment. Severe hypoglycaemia was experienced by 0.8% (95% CI 0.5-1.3%) of patients. Hypoglycaemia with glucose ≤3.1 mmol/L and severe hypoglycaemia occurred least frequently with gliclazide: in 1.4% (95% CI 0.8-2.4%) and 0.1% (95% CI 0-0.7%) of patients, respectively. None of the risk factors were significant in a stepwise multivariate meta-regression analysis. Too few studies had insulin as comparator, so these data could not be meta-analysed. The majority of patients with type 2 diabetes mellitus on sulfonylurea therapy in clinical trials remain free of any relevant hypoglycaemia. Gliclazide was associated with the lowest risk of hypoglycaemia. Because participants in randomized controlled trials differ from the general population, care should be taken when translating these data into clinical practice., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: Continuous glucose monitoring could be helpful for glucose regulation in critically ill patients; however, its accuracy is uncertain and might be influenced by microcirculation. We investigated the microcirculation and its relation to the accuracy of 2 continuous glucose monitoring devices in patients after cardiac surgery., Methods: The present prospective, observational study included 60 patients admitted for cardiac surgery. Two continuous glucose monitoring devices (Guardian Real-Time and FreeStyle Navigator) were placed before surgery. The relative absolute deviation between continuous glucose monitoring and the arterial reference glucose was calculated to assess the accuracy. Microcirculation was measured using the microvascular flow index, perfused vessel density, and proportion of perfused vessels using sublingual sidestream dark-field imaging, and tissue oxygenation using near-infrared spectroscopy. The associations were assessed using a linear mixed-effects model for repeated measures., Results: The median relative absolute deviation of the Navigator was 11% (interquartile range, 8%-16%) and of the Guardian was 14% (interquartile range, 11%-18%; P = .05). Tissue oxygenation significantly increased during the intensive care unit admission (maximum 91.2% [3.9] after 6 hours) and decreased thereafter, stabilizing after 20 hours. A decrease in perfused vessel density accompanied the increase in tissue oxygenation. Microcirculatory variables were not associated with sensor accuracy. A lower peripheral temperature (Navigator, b = -0.008, P = .003; Guardian, b = -0.006, P = .048), and for the Navigator, also a higher Acute Physiology and Chronic Health Evaluation IV predicted mortality (b = 0.017, P < .001) and age (b = 0.002, P = .037) were associated with decreased sensor accuracy., Conclusions: The results of the present study have shown acceptable accuracy for both sensors in patients after cardiac surgery. The microcirculation was impaired to a limited extent compared with that in patients with sepsis and healthy controls. This impairment was not related to sensor accuracy but the peripheral temperature for both sensors and patient age and Acute Physiology and Chronic Health Evaluation IV predicted mortality for the Navigator were., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Aims/hypothesis: South Asians have a disproportionately high risk of developing abdominal obesity, insulin resistance and type 2 diabetes. Brown adipose tissue (BAT) has been identified as a possible target to fight obesity and protect against metabolic disturbance. We explored whether lower BAT activity in South Asians compared with Europids may contribute to the high risk of metabolic disturbance., Methods: We studied 20 healthy men (ten Europids/ten South Asians, BMI 19-25 kg/m(2), age 18-32 years). Following 2 h of cold exposure (16-18°C) after an overnight fast, (18)F-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography-computed tomography (CT) and (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission computed tomography-CT were performed to visualise metabolic BAT activity and sympathetic stimulation of BAT. Metabolic BAT activity was defined as maximal standardised uptake value (SUV(max)) of (18)F-FDG, and sympathetic stimulation of BAT as semiquantitative uptake value (SQUV) of (123)I-MIBG. We performed hyperinsulinaemic-euglycaemic clamps to assess insulin sensitivity. Spearman's correlations for SUV(max) of (18)F-FDG and both SQUV of (123)I-MIBG and insulin sensitivity were determined., Results: The median (interquartile range) SUV(max) of (18)F-FDG in South Asians (7.5 [2.2-10.6] g/ml) was not different from the median SUV(max) obtained in Europids (4.5 [2.2-8.4] g/ml; p = 0.59). There was no correlation between BAT activity and insulin sensitivity. Correlations between SQUV of (123)I-MIBG and SUV(max) of (18)F-FDG were positive, both in the total population (ρ = 0.80, p < 0.001) and after stratification by ethnicity (Europids, ρ = 0.65, p = 0.04; South Asians, ρ = 0.83, p = 0.01)., Conclusions/interpretation: This is the first study to prospectively investigate ethnic differences in metabolic BAT activity during cold exposure. We did not find differences in BAT activity between South Asians and Europids. Therefore, it seems unlikely that BAT plays an important role in the development of unfavourable metabolic profiles in South Asians.

Objective: The rising incidence of type 2 diabetes mellitus (T2DM) induces severe challenges for the health care system. Our research group developed a web-based system named PANDIT that provides T2DM patients with insulin dosing advice using state of the art clinical decision support technology. The PANDIT interface resembles a glucose diary and provides advice through pop-up messages. Diabetes nurses (DNs) also have access to the system, allowing them to intervene when needed. The objective of this study was to establish whether T2DM patients can safely use PANDIT at home. To this end, we assessed whether patients experience usability problems with a high risk of compromising patient safety when interacting with the system, and whether PANDIT's insulin dosing advice are clinically safe., Research Design and Methods: The study population consisted of patients with T2DM (aged 18-80) who used a once daily basal insulin as well as DNs from a university hospital. The usability evaluation consisted of think-aloud sessions with four patients and three DNs. Video data, audio data and verbal utterances were analyzed for usability problems encountered during PANDIT interactions. Usability problems were rated by a physician and a usability expert according to their potential impact on patient safety. The usability evaluation was followed by an implementation with a duration of four weeks. This implementation took place at the patients' homes with ten patients to evaluate clinical safety of PANDIT advice. PANDIT advice were systematically compared with DN advice. Deviating advice were evaluated with respect to patient safety by a panel of experienced physicians, which specialized in diabetes care., Results: We detected seventeen unique usability problems, none of which was judged to have a high risk of compromising patient safety. Most usability problems concerned the lay-out of the diary, which did not clearly indicate which data entry fields had to be entered in order to obtain an advice. 27 out of 74 (36.5%) PANDIT advice differed from those provided by DNs. However, only one of these (1.4%) was considered unsafe by the panel., Conclusion: T2DM patients with no prior experience with the web-based self-management system were capable of consulting the system without encountering significant usability problems. Furthermore, the large majority of PANDIT advice were considered clinically safe according to the expert panel. One advice was considered unsafe. This could however easily be corrected by implementing a small modification to the system's knowledge base., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Several studies conducted in the USA have demonstrated that the effectiveness of bariatric surgery differs between patients from African and European origin. However, little is known on differences in outcomes after bariatric surgery between individuals from other ethnic backgrounds. In this retrospective study, we found that, in terms of weight loss, gastric bypass surgery is less effective in African, South Asian, Turkish and Moroccan patients than in their ethnic Dutch counterparts. Our results underscore that ethnic differences in the effectiveness of bariatric surgery are not limited to those between patients of African and European origin, but extend to other minority groups as well. Therefore, it is important that prospective studies both determine ethnic differences in weight loss-related improvement of co-morbidities and elucidate the exact reasons for these ethnic disparities.

The differential diagnosis of chest pain in a patient with sickle cell disease is difficult and may encompass several serious conditions, including chest syndrome, pulmonary embolism and infectious complications. In this manuscript we provide an overview on the various underlying diseases that may cause chest pain in patients with sickle cell disease and provide clues for a proper diagnostic workup.

Introduction: In critical illness, four measures of glycaemic control are associated with ICU mortality: mean glucose concentration, glucose variability, the incidence of hypoglycaemia (≤2.2 mmol/l) or low glucose (2.3 to 4.7 mmol/l). Underlying diabetes mellitus (DM) might affect these associations. Our objective was to study whether the association between these measures of glycaemic control and ICU mortality differs between patients without and with DM and to explore the cutoff value for detrimental low glucose in both cohorts., Methods: This retrospective database cohort study included patients admitted between January 2004 and June 2011 to a 24-bed medical/surgical ICU in a teaching hospital. We analysed glucose and outcome data from 10,320 patients: 8,682 without DM and 1,638 with DM. The cohorts were subdivided into quintiles of mean glucose and quartiles of glucose variability. Multivariable regression models were used to examine the independent association between the four measures of glycaemic control and ICU mortality, and for defining the cutoff value for detrimental low glucose., Results: Regarding mean glucose, a U-shaped relation was observed in the non-DM cohort with an increased ICU mortality in the lowest and highest glucose quintiles (odds ratio=1.4 and 1.8, P<0.001). No clear pattern was found in the DM cohort. Glucose variability was related to ICU mortality only in the non-DM cohort, with highest ICU mortality in the upper variability quartile (odds ratio=1.7, P<0.001). Hypoglycaemia was associated with ICU mortality in both cohorts (odds ratio non-DM=2.5, P<0.001; odds ratio DM=4.2, P=0.001), while low-glucose concentrations up to 4.9 mmol/l were associated with an increased risk of ICU mortality in the non-DM cohort and up to 3.5 mmol/l in the DM cohort., Conclusion: Mean glucose and high glucose variability are related to ICU mortality in the non-DM cohort but not in the DM cohort. Hypoglycaemia (≤2.2 mmol/l) was associated with ICU mortality in both. The cutoff value for detrimental low glucose is higher in the non-DM cohort (4.9 mmol/l) than in the DM cohort (3.5 mmol/l). While hypoglycaemia (≤2.2 mmol/l) should be avoided in both groups, DM patients seem to tolerate a wider glucose range than non-DM patients.

Unlabelled: Brown adipose tissue (BAT) has become a focus of research in the hope of finding a new target to fight obesity. Metabolic BAT activity can be visualized with (18)F-FDG PET/CT. Furthermore, the sympathetic innervation of BAT can be visualized with the radiolabeled norepinephrine analog (123)I-metaiodobenzylguanidine ((123)I-MIBG). We aimed to determine whether (123)I-MIBG SPECT/CT and (18)F-FDG PET/CT identify the same anatomic regions as active BAT in adult humans. Furthermore, we investigated whether the magnitude of BAT activity measured by these techniques correlated. Finally, we tried to establish the optimal time interval between (123)I-MIBG administration and subsequent SPECT/CT acquisition to visualize sympathetic stimulation of BAT., Methods: Ten lean (body mass index, 19-25 kg/m(2)), healthy Caucasian men (age, 18-32 y) underwent one (18)F-FDG PET/CT and two (123)I-MIBG-SPECT/CT scans within a 2-wk interval. On 2 separate occasions, the subjects were exposed to mild cold (17°C) for 2 h after an overnight fast. After 1 h of cold exposure, (18)F-FDG (one occasion) or (123)I-MIBG (other occasion) was administered. (18)F-FDG PET/CT was performed at 1 h after (18)F-FDG administration, and (123)I-MIBG-SPECT/CT was performed at 4 and 24 h after (123)I-MIBG injection., Results: (18)F-FDG uptake in BAT was observed in 8 of 10 subjects, whereas (123)I-MIBG uptake was observed in 7 of 10 subjects in both the SPECT/CT scans acquired at 4 h after (123)I-MIBG administration and the SPECT/CT scans acquired at 24 h after (123)I-MIBG administration. All subjects who showed (123)I-MIBG uptake in BAT also showed (18)F-FDG uptake in BAT. There was no statistically significant correlation between maximal standardized uptake value of (18)F-FDG and semiquantitative uptake of (123)I-MIBG at 4 h after administration. However, a positive correlation was found between the maximal standardized uptake value of (18)F-FDG and semiquantitative uptake of (123)I-MIBG at 24 h after administration (r = 0.64, P = 0.04)., Conclusion: (123)I-MIBG SPECT/CT, as a marker of sympathetic activity, and (18)F-FDG PET/CT, as a marker of metabolic activity, identified the same anatomic regions as active BAT. Moreover, when (123)I-MIBG SPECT/CT was performed at 24 h after (123)I-MIBG administration, the magnitude of BAT activity measured with these techniques correlated strongly. This finding not only supports that BAT activity in humans is sympathetically influenced but also identifies (123)I-MIBG SPECT/CT, when performed 24 h after (123)I-MIBG injection, as a method to visualize and quantify sympathetic stimulation of BAT.

Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but the long-term effects of weight loss on cardiovascular disease are unknown. The recently published Look AHEAD (Action for health in diabetes) study investigated the 10-year effect of an intensive lifestyle intervention designed to achieve weight loss on cardiovascular morbidity and mortality among overweight or obese adults with type 2 diabetes. In this commentary, we discuss the results and clinical implications of this study.