Differences in Sympathetic Nervous Stimulation of Brown Adipose Tissue Between the Young and Old, and the Lean and Obese.

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.

(18)F-fluorodeoxyglucose uptake in brown adipose tissue during insulin-induced hypoglycemia and mild cold exposure in non-diabetic adults.

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.

[Lifestyle-recommendations on weight loss in type 2 diabetes--useful, or not?]. / Leefstijladvies over afvallen bij diabetes type 2--zinvol of niet?

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.

Intensive lifestyle intervention in general practice to prevent type 2 diabetes among 18 to 60-year-old South Asians: 1-year effects on the weight status and metabolic profile of participants in a randomized controlled trial.

AIM: To study 1-year effectiveness of an intensive, culturally targeted lifestyle intervention in general practice for weight status and metabolic profile of South-Asians at risk of type 2 diabetes. METHODS: 536 South-Asians at risk of type 2 diabetes were randomized to an intervention (n = 283) or control (n = 253) group. The intervention, which was targeted culturally to the South-Asian population, consisted of individual lifestyle counselling, a family session, cooking classes, and supervised physical activity programme. All components of the intervention were carried out by professionals as part of their daily clinical practice. The control group received generic lifestyle advice. Change in weight status and metabolic profile were assessed after 1 year. RESULTS: After 1 year, 201 participants were lost to follow-up. Remaining participants in intervention (n = 177) and control (n = 158) group had similar baseline characteristics. Weight loss in the intervention group was 0.2±3.3 kg, weight gain in the control group was 0.4±3.1 kg (p = 0.08). Changes in other weight-related measurements did not differ significantly between groups. Furthermore, there were no differences between groups in changes of metabolic profile. All results remained similar after repeating analyses in a multiple imputed dataset. DISCUSSION: An intensive, culturally targeted, lifestyle intervention of 1 year did not improve weight status and metabolic profile of South-Asians at risk of type 2 diabetes. The laborious recruitment, high drop-out, and lack of effectiveness emphasise the difficulty of realising health benefits in practice and suggest that this strategy might not be the optimal approach for this population. TRIAL REGISTRATION: Nederlands Trial Register NTR1499.

Screening South Asians for type 2 diabetes and prediabetes: (1) comparing oral glucose tolerance and haemoglobin A1c test results and (2) comparing the two sets of metabolic profiles of individuals diagnosed with these two tests.

BACKGROUND: The glycated haemoglobin A1c (HbA1c) level may be used for screening for type 2 diabetes and prediabetes instead of a more burdensome oral glucose tolerance test (OGTT). However, among the high-risk South Asian population, little is known about the overlap of the methods or about the metabolic profiles of those disconcordantly diagnosed. METHODS: We included 944 South Asians (18-60 years old), whom we screened with the HbA1c level and the OGTT in The Hague, the Netherlands. We calculated the area under the receiver-operator characteristic curve (AUROC) with a 95% confidence interval of HbA1c using the American Diabetes Association classifications, and determined the sensitivity and specificity with 95% confidence intervals at different thresholds. Moreover, we studied differences in metabolic characteristics between those identified by HbA1c and by the OGTT alone. RESULTS: The overlap between HbA1c and OGTT classifications was partial, both for diabetes and prediabetes. The AUROC of HbA1c for OGTT defined diabetes was 0.86 (0.79-0.93). The sensitivity was 0.46 (0.29-0.63); the specificity 0.98 (0.98-0.99). For prediabetes, the AUROC was 0.73 (0.69-0.77). Each of the 31 individuals with diabetes and 353 with prediabetes identified with the HbA1c level had a high body mass index, large waist circumference, high blood pressure, and low insulin sensitivity, all of which were similar to the values shown by those among the 19 with diabetes or 62 with prediabetes who only met the OGTT criteria, but not the HbA1c criteria. CONCLUSIONS: The HbA1c level identified a partially different group than the OGTT did. However, both those identified with the HbA1c level and those identified with the OGTT alone were at increased metabolic risk. TRIAL REGISTRATION: Dutch Trial Register: NTR1499.

Combining 123I-metaiodobenzylguanidine SPECT/CT and 18F-FDG PET/CT for the assessment of brown adipose tissue activity in humans during cold exposure.

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.

The Diabetes Pearl: Diabetes biobanking in The Netherlands.

BACKGROUND: Type 2 diabetes is associated with considerable comorbidity and severe complications, which reduce quality of life of the patients and require high levels of healthcare. The Diabetes Pearl is a large cohort of patients diagnosed with type 2 diabetes, covering different geographical areas in the Netherlands. The aim of the study is to create a research infrastructure that will allow the study of risk factors, including biomarkers and genetic determinants for severe diabetes complications. METHODS/DESIGN: Baseline examinations began November 2009 and will continue through 2012. By the end of 2012, it is expected that 7000 patients with type 2 diabetes will be included in the Diabetes Pearl cohort. To ensure quality of the data collected, standard operation procedures were developed and used in all 8 recruitment centers. From all patients who provide informed consent, the following information is collected: personal information, medication use, physical examination (antropometry, blood pressure, electrocardiography (ECG), retina photographs, ankle-brachial index, peripheral vibration perception), self-report questionnaire (socio-economic status, lifestyle, (family) history of disease, and psychosocial well-being), laboratory measurements (glucose, A1c, lipid profile, kidney function), biobank material (storage of urine and blood samples and isolated DNA). All gathered clinical data and biobank information is uploaded to a database for storage on a national level. Biobanks are maintained locally at all recruitment centers. DISCUSSION: The Diabetes Pearl is large-scale cohort of type 2 diabetes patients in the Netherlands aiming to study risk factors, including biomarkers and genetic markers, for disease deterioration and the development of severe diabetes complications. As a result of the well-designed research design and the national coverage, the Diabetes Pearl data can be of great value to national and international researchers with an interest in diabetes related research.

Fasting and postprandial activity of brown adipose tissue in healthy men.

UNLABELLED: The role of brown adipose tissue (BAT) in adult metabolism is poorly understood. This study aimed to examine the differential effects of an overnight fast and the postprandial state on BAT activity. METHODS: We included 10 healthy, lean male volunteers. BAT uptake of glucose was visualized using (18)F-FDG PET/CT during mild cold exposure. Each subject underwent PET/CT twice. The first scan was obtained after an overnight fast; the second after a standardized meal. RESULTS: (18)F-FDG uptake in BAT was observed in 6 of 10 volunteers. These subjects were found to have a higher maximal standardized uptake value when fasting (median, 13.1 g/mL; range, 6.1-27.6 g/mL) than when in the postprandial state (median, 6.8 g/mL; range, 2.1-13.4 g/mL) (P = 0.03). CONCLUSION: Cold-stimulated (18)F-FDG uptake by BAT in humans is more pronounced during fasting. The lower maximal standardized uptake value in the postprandial state may be explained by increased insulin-stimulated glucose uptake in muscle.

Ethnic differences in weight loss and diabetes remission after bariatric surgery: a meta-analysis.

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.