Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1RA decreases risk scores for cardiovascular events.

INTRODUCTION: Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycaemia and metabolic health in patients with type 2 diabetes mellitus (T2DM). DMR has an insulin sensitizing effect in patients with T2DM. Reducing hyperinsulinemia can improve cardiovascular health. In the INSPIRE trial, we combined a single DMR with a glucagon-like-peptide-1 receptor agonist (GLP-1RA) and demonstrated elimination of insulin treatment in 69% of patients at 6 months and 53% of patients at 18 months while improving glycaemic control and metabolic health. We hypothesized that this treatment approach is associated with improved cardiovascular health, by reducing hyperinsulinemia. METHODS: Before and 6 months after starting the combination treatment to replace insulin, the following assessments were performed to evaluate cardiovascular health: magnetic resonance imaging (MRI) to measure abdominal visceral adipose tissue volume, ambulatory 24 h blood pressure (ABPM) analysis, postprandial insulin and triglycerides, fasting lipid panel and urine microalbumin. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated to estimate 10-year risk of cardiovascular disease or stroke and the diabetes lifetime-perspective prediction (DIAL) score was calculated to estimate years free of cardiovascular disease. RESULTS: Six months after replacing exogenous insulin by DMR and GLP-1RA, visceral adipose tissue decreased significantly by 24%. Postprandial triglyceride and insulin concentrations decreased significantly (p < 0.001), as did total cholesterol (from median 3.64 (IQR 3.34-4.89) to 3.48 (3.18-3.97) mmol/l, p = 0.008), LDL (from median 1.92 (IQR 1.49-2.30) to 1.79 (1.49-2.08 mmol/l, p = 0.044), and urine microalbumin (from median 7 (IQR 3-27) to 4 (3-8) mg/l, p = 0.018). All daytime blood pressure values decreased significantly. The ASCVD 10-year risk score decreased (from median 13.6 (IQR 5.7-26.0) to 11.5 (4.2-22.5) %, p = 0.030)) and the DIAL score increased (from median 82 (IQR 81-83) to 83 (81-84) years, (p = 0.039)). DISCUSSION: The combination of DMR and GLP-1RA to replace insulin therapy in patients with T2DM is associated with a positive effect on multiple parameters of cardiovascular health. Taken together, they show a pattern of overall improvement in cardiovascular health, as evidenced by decreased risk scores for cardiovascular complications. However, it is not yet clear whether these improvements will translate into a true reduction in cardiovascular events.

Cocoon vaccination for influenza in patients with a solid tumor: a retrospective study.

PURPOSE: Oncological patients are susceptible to various severe viral infections, including influenza. Vaccinating oncological patients and their household contacts ("cocoon vaccination") may protect these patients from contracting influenza. To understand the potential of cocoon vaccination in oncological patients, this study assesses the influenza vaccination status of oncological patients and their household contacts and their considerations regarding the vaccination. METHODS: In this retrospective study, oncological patients with a solid tumor were asked to fill in a questionnaire about their own and their household contacts' influenza vaccination status in the influenza season of 2018-2019. RESULTS: Ninety-eight patients were included (response rate 88%). The influenza vaccination rates of oncological patients and their first household contacts were 43.9% and 44.9%, respectively. The majority of vaccinated patients and vaccinated first household contacts had been advised by their general practitioner to get the vaccination. A minority of the first household contacts reported getting vaccinated specifically because of the patient's vulnerability. Unvaccinated patients and unvaccinated household contacts mainly believed the vaccination was unnecessary or were afraid of side effects. None of the included patients had been hospitalized with influenza. CONCLUSION: The oncological patients' and first household contacts' vaccination rates in this study were lower than the vaccination rates of the general Dutch population of over 60 years old, possibly due to a lack of knowledge and misconceptions about the vaccination. Further research is required to establish whether cocoon vaccination can contribute to protecting oncological patients from contracting an influenza infection.

A healthcare failure mode and effect analysis to optimise the process of blood culture performance.

BACKGROUND: Blood cultures are essential diagnostic tools to identify pathogens in systemic infections. However, logistics of blood culture performance is often suboptimal. This study analyses the pre-analytic phase of blood culture processing through different types of risk assessments. METHODS: We performed direct observations to gain in-depth knowledge of the root causes of suboptimal blood culture performance. These findings were summarised in a Bow-Tie chart. We then utilised a healthcare failure mode and effect analysis to prioritise failures per step in the process and to organise improvement activities. Finally, improvement actions were planned. RESULTS: Not obtaining a second set of blood cultures in the logistics of blood culture performance had the highest priority for action. Several failure modes, including human and system factors, were identified. Improvement actions included training and clinical lessons for nurses in the emergency department, updating hospital search engines to ease identification of relevant protocols, and an evaluation of the workload at the emergency department. Failure modes caused by human factors appear easy to address, however changing human behaviour is challenging. CONCLUSIONS: The analysis provided useful insight into the different steps in the logistics of blood culture performance and facilitated the organisation of actions focused on addressing the most urgent root causes.

Classifying sepsis patients in the emergency department using SIRS, qSOFA or MEWS.

OBJECTIVE: To determine the effect of qSOFA and SOFA compared with the MEWS and SIRS criteria on the classification of emergency department (ED) patients with an infection as having sepsis. METHODS: A retrospective single-centre study was performed in a random sample of 600 medical patients who visited the ED of the Academic Medical Centre Amsterdam between 1 November 2015 and 1 November 2016. Data for the different sepsis scores, as well as general data and demographics were retrieved. Descriptive analytics and sensitivity/specificity analysis were used to evaluate the performance of the different sepsis tools. RESULTS: Of 577 evaluable medical patients, 198 patients (34.3%) had a probable infection. The SIRS sepsis criteria, severe sepsis criteria, MEWS ≥ 5 and qSOFA criteria classified 141/198 (71.2%), 55/198 (27.8%), 58/198 (29.3%) and 17/198 patients (8.6%) respectively, as septic. The in-hospital mortality of patients classified as septic by the SIRS and qSOFA score was 6.4% and 29.4%. The qSOFA and SIRS score of ≥ 2 had a specificity of 93.7% (95% CI: 91.3-95.6) and 56.9% (52.7-61.1) in predicting in-hospital mortality. CONCLUSION: No major differences in gender, age, comorbidity and site of infection between patients with sepsis or severe sepsis classified by the SIRS, qSOFA criteria or MEWS of ≥ 5 were found. The qSOFA criteria classifies a smaller group of patients as septic compared with the SIRS or MEWS. Due to this strict selection, the qSOFA score seems unsuitable as a bedside tool in the work-up and treatment of sepsis at the ED.

Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects.

BACKGROUND: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. METHODS: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6-2H2]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. RESULTS: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 µmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). CONCLUSIONS: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus.

[Bariatric surgery: who, when and where?; an overview for the referring physician]. / Bariatrische chirurgie: hoe, wanneer, wat en bij wie?

- Bariatric surgery is performed in patients with a body mass index (BMI) > 40kg/m2, or BMI > 35 kg/m2 with obesity-related comorbidities. The Roux-en-Y gastric bypass and sleeve gastrectomy are the most frequently used procedures.- On average, patients have lost 25-27% of their original weight 10 years after surgery.- Obesity-related comorbidities improve dramatically in many patients following surgery. The effect is most noticeable in patients with diabetes mellitus type 2 and obstructive sleep apnoea syndrome. - The prevalence of 30-day complications is < 5%. Mortality is < 0.2% in centres with a lot of experience. - Commonly occurring long-term complications of bariatric surgery include deficiencies, particularly of iron and vitamin B12, along with gallstone disease and sagging skin. - Specific complications can arise following Roux-en-Y gastric bypass, such as internal herniation and hypoglycaemia, and these are often not recognised.

Individual and partner's level of occupation and the association with HbA1c levels in people with Type 2 diabetes mellitus: the Dutch Diabetes Pearl cohort.

AIMS: Individual indicators of socio-economic status have been associated with glycaemic control in people with Type 2 diabetes, but little is known about the association between partner's socio-economic status and HbA1c levels. We therefore examined the cross-sectional association between individual and partner's level of occupation on HbA1c levels in people with Type 2 diabetes in the Netherlands. METHODS: We included people with Type 2 diabetes with a partner who were treated in primary, secondary and tertiary care in the Diabetes Pearl cohort. Occupational level was classified according to International Standard Classification of Occupations (ISCO)-08 skill levels. Linear regression analyses were performed stratified for sex, and corrected for age, recruitment centre and diabetes medication. RESULTS: In total, 3257 participants (59.8% men, mean 62.2±9.4 years) were included. For men, having a partner with an intermediate level of occupation was associated with lower HbA1c levels [e.g. ISCO level 3: -2 mmol/mol (95% CI -4;-1) or -0.2% (95% CI -0.4;-0.1)], compared with having a partner of the highest occupational level (ISCO level 4). In women, having an unemployed partner was associated with higher HbA1c levels [14 mmol/mol (95% CI 6; 22) or 1.3% (95% CI 0.6; 2.0)], compared with having a partner of the highest occupational level. CONCLUSIONS: Partner's occupational status provided additional information on the association between socio-economic status and HbA1c levels in people with Type 2 diabetes. Women seemed to benefit from a partner with a higher occupational status, while men seemed to benefit from a partner with a lower status. Because of the cross-sectional nature of the present study, more research is necessary to explore this association.

Bromocriptine and insulin sensitivity in lean and obese subjects.

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.

Role of the autonomic nervous system in activation of human brown adipose tissue: A review of the literature.

Brown adipose tissue (BAT) is able to convert calories into heat rather than storing them. Therefore, activated BAT could be a potential target in the battle against obesity and type 2 diabetes. This review focuses on the role of the autonomic nervous system in the activation of human BAT. Although the number of studies focusing on BAT in humans is limited, involvement of the sympathetic nervous system (SNS) in BAT activation is evident. Metabolic BAT activity can be visualized with (18)F-fluorodeoxyglucose, whereas sympathetic activation of BAT can be visualized with nuclear-medicine techniques using different radiopharmaceuticals. Also, interruption of the sympathetic nerves leading to BAT activation diminishes sympathetic stimulation, resulting in reduced metabolic BAT activity. Furthermore, both ß- and α-adrenoceptors might be important in the stimulation process of BAT, as pretreatment with propranolol or α-adrenoceptor blockade also diminishes BAT activity. In contrast, high catecholamine levels are known to activate and recruit BAT. There are several interventional studies in which BAT was successfully inhibited, whereas only one interventional study aiming to activate BAT resulted in the intended outcome. Most studies have focused on the SNS for activating BAT, although the parasympathetic nervous system might also be a target of interest. To better define the possible role of BAT in strategies to combat the obesity epidemic, it seems likely that future studies focusing on both histology and imaging are essential for identifying the factors and receptors critical for activation of human BAT.

¹8F-FDG PET/CT in inflammation of unknown origin: a cost-effectiveness pilot-study.

PURPOSE: Patients with increased inflammatory parameters, nonspecific signs and symptoms without fever and without a diagnosis after a variety of diagnostic procedures are a diagnostic dilemma and are referred to as having inflammation of unknown origin (IUO). The objective of this pilot study was to compare the cost-effectiveness of a diagnostic work-up/strategy with and without (18)F-FDG PET/CT in patients with IUO using a published dataset as a reference. METHODS: IUO patients without (18)F-FDG PET/CT (group A, 46 patients) and IUO patients referred for (18)F-FDG PET/CT (group B, 46 patients) were selected. IUO was defined as the combination of nonspecific signs and symptoms and a prolonged erythrocyte sedimentation rate (ESR), defined as ≥age/2 in men and ≥(age + 10)/2 in women (ESR in millimetres per hour and age in years), and/or C-reactive protein (CRP) ≥15 mg/l. The costs of all tests and procedures and the number of hospitalization days in each patient to reach a diagnosis were calculated using current Dutch tariffs. RESULTS: In group A a diagnosis was reached in 14 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 2,051, and including the cost of hospitalization was 12,614. In group B a diagnosis was reached in 32 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 1,821, significantly lower than in group A (p < 0.0002), and including the cost of hospitalization was 5,298. CONCLUSION: In IUO (18)F-FDG PET/CT has the potential to become a cost-effective routine imaging technique indicating the direction for further diagnostic decisions thereby allowing unnecessary, invasive and expensive diagnostic investigations to be avoided and possibly the duration of hospitalization to be reduced. However, a prospective multicentre "bottom-up microcosting" cost-effectiveness study is warranted before these preliminary data can be extrapolated to clinical practice.

Effects of sitagliptin on counter-regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double-blind placebo-controlled crossover study.

AIMS: To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes. METHODS: We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction. RESULTS: Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008]. CONCLUSIONS: Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia.

Factors that drive insulin-dosing decisions of diabetes care providers: a vignette-based study in the Netherlands.

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.

Physical characteristics that predict final basal insulin dose in type 2 diabetes mellitus, with a special focus on BMI.

BACKGROUND AND AIMS: The possibility to predict final insulin dose based on patient's characteristics would allow for efficient titration for patients with higher dose needs. The primary aim of this post-hoc analysis of the L2T3 study was to determine predictors for final dose. Specifically, we focused on the relationship between BMI and dose. The secondary aims were to investigate (i) the predictive value of BMI and age on final dose and (ii) the possibility to tailor the starting dose of insulin based on BMI and age. METHODS AND RESULTS: We performed two stepwise regression analyses, one using all baseline characteristics, and one using physical characteristics and FPG which can be assessed "at the bedside" only. Furthermore, median [min, max] final doses of groups stratified according to BMI and age were calculated. BMI clearly correlated with final dose in IU (Pearson correlation 0.42 [0.37; 0.48], p < 0.001). Characteristics which can be assessed "at the bedside" that predict high final dose were allocation to detemir, absence or discontinuation of insulin secretagogues, high BMI, low age, male gender and high FPG. Final dose varied among strata (BMI ≥30 kg/m(2): 64 IU; BMI <30 kg/m(2): 38 IU, p < 0.001 and age <59 years: 52 IU; age ≥59 years: 44 IU, p < 0.001). All groups stratified for both BMI and age showed similarly low minimal final dose (5-17 IU). CONCLUSION: Our data showed a high predictive value of BMI on final dose. However, it does not seem possible to tailor starting dose based on BMI and age.

The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis.

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.

Ethnic disparities in the association of impaired fasting glucose with the 10-year cumulative incidence of type 2 diabetes.

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.

Ethnicity influences weight loss 1 year after bariatric surgery: a study in Turkish, Moroccan, South Asian, African and ethnic Dutch patients.

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.

Cold-induced activity of brown adipose tissue in young lean men of South-Asian and European origin.

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.

Insulin-dependent diabetic patients with macrovascular complications suffer from many geriatric conditions.

BACKGROUND: Current diabetic care guidelines focus mainly on managing metabolic control and macro- and microvascular comorbidities. This focus may be too narrow given the number of geriatric conditions present in these often aged patients. METHODS: We studied the prevalence of multimorbidity, (undiagnosed) geriatric conditions and disabilities in diabetic patients with macrovascular complications. RESULTS: One hundred forty-three community dwelling, insulin-dependent diabetic patients with macrovascular complications, aged 55 years and above, who were concurrently enrolled in the diabetes care clinic in a university hospital in the Netherlands, participated. Data on healthcare utilization, activities of daily living, geriatric conditions and quality of life were self-reported using a systematic diagnostic questionnaire. Mean age was 66.9 years (8.5 years), 62% were male and 22% were of Surinamese-South Asian descent. Loneliness was reported by 47%. The majority rated their quality of life (QoL) from 'reasonable' (45%) to 'good' (31%). In patients without ADL impairments, 60% were in need of assistance, compared to 95% among those with more than one impairment (p<0.01). In total, 19% had cognitive impairment, and 63% perceived pain. 84% of patients with impairments experienced social problems compared to 32% of patients in the other group. CONCLUSIONS: This study demonstrates that the current focus of diabetes care may be too restricted given the high number of geriatric conditions that these patients present.