| 1. |
- Alligier, M, et al.
(författare)
-
OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions
- 2020
-
Ingår i: Obesity facts. - : S. Karger AG. - 1662-4033 .- 1662-4025. ; 13:1, s. 1-28
-
Tidskriftsartikel (refereegranskat)abstract
- Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing – focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals’ responses to an intervention for obesity – ultimately leading to better patient care and improved obesity outcomes.
|
|
| 2. |
|
|
| 3. |
- Sevastianova, K., et al.
(författare)
-
Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans
- 2012
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 96:4, s. 727-734
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD). Objective: We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss. Design: Sixteen subjects [BMI (kg/m(2)): 30.6 +/- 1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL. Results: Carbohydrate overfeeding increased weight (+/- SEM) by 2% (1.8 +/- 0.3 kg; P < 0.0001) and liver fat by 27% from 9.2 +/- 1.9% to 11.7 +/- 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148II but not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 +/- 0.6 kg; P < 0.0001) and 25% of their liver fat content (from 11.7 +/- 1.9% to 8.8 +/- 1.8%; P < 0.05). Conclusions: Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial was registered at www.hus.fi as 235780. Am J Clin Nutr 2012;96:727-34.
|
|
| 4. |
- Sutinen, J, et al.
(författare)
-
Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy
- 2004
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 286:6, s. E941-E949
-
Tidskriftsartikel (refereegranskat)abstract
- Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPARγ), and PPARγ coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPARδ, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.
|
|
| 5. |
- Adiels, Martin, 1976, et al.
(författare)
-
Acute suppression of VLDL(1) secretion rate by insulin is associated with hepatic fat content and insulin resistance
- 2007
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:11, s. 2356-2365
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver fat content. METHODS: A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group. RESULTS: The results showed a rapid drop in VLDL(1)-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin infusion whereas VLDL(2) secretion increased. CONCLUSIONS/INTERPRETATION: Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat is associated with lack of VLDL(1) suppression in response to insulin.
|
|
| 6. |
- Adiels, Martin, 1976, et al.
(författare)
-
Overproduction of large VLDL particles is driven by increased liver fat content in man
- 2006
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:4, s. 755-65
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production. METHODS: A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI. RESULTS: Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB. CONCLUSIONS/INTERPRETATION: We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
|
|
| 7. |
- Andrew, R, et al.
(författare)
-
The contribution of visceral adipose tissue to splanchnic cortisol production in healthy humans
- 2005
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 54:5, s. 1364-1370
-
Tidskriftsartikel (refereegranskat)abstract
- Cortisol is regenerated from cortisone by 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), amplifying glucocorticoid action in adipose tissue and liver. 11HSD1 inhibitors are being developed for type 2 diabetes and may be most effective in obesity, where adipose 11HSD1 is increased. However, the magnitude of regeneration of cortisol in different tissues in humans is unknown, hindering understanding of the pathophysiological and therapeutic importance of 11HSD1. In eight healthy men, we infused 9,11,12,12-2H4-cortisol and measured tracer enrichment in the hepatic vein as an indicator of total splanchnic cortisol generation. Oral cortisone (25 mg) was then given to measure first-pass hepatic cortisol generation. In steady state, splanchnic cortisol production was 45 ± 11 nmol/min when arterialized plasma cortisone concentration was 92 ± 7 nmol/l. Extrapolation from hepatic cortisol generation after oral corti-sone suggested that, at steady state, the liver contributes 15.2 nmol/min and extrahepatic splanchnic tissue contributes 29.8 nmol/min to the total splanchnic cortisol production. We conclude that tissues draining into the portal vein, including visceral adipose tissue, contribute substantially to the regeneration of cortisol. Thus, in addition to free fatty acids and adipokines, the portal vein delivers cortisol to the liver, and inhibition of 11HSD1 in visceral adipose tissue may indeed be valuable in ameliorating insulin resistance in obesity.
|
|
| 8. |
- Bunck, M. C., et al.
(författare)
-
Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetes
- 2011
-
Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 13:4, s. 374-377
-
Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies suggest that incretin-based therapies may be beneficial for the bone; however, clinical data are largely lacking. We assessed whether the differential effects of these therapies on body weight differed with respect to their effect on bone mineral density (BMD) and markers of calcium homeostasis in patients with type 2 diabetes (T2D). Sixty-nine metformin-treated patients with T2D were randomized to exenatide twice daily (n = 36) or insulin glargine once daily (n = 33). Total body BMD, measured by dual-energy X-ray absorptiometry, and serum markers of calcium homeostasis were assessed before and after 44-week treatment. Exenatide or insulin glargine treatment decreased body weight by 6%. Endpoint BMD was similar in both groups after 44-week therapy (LSmean +/- s.e.m. between-group difference -0.002 +/- 0.007 g/cm(2) ; p = 0.782). Fasting serum alkaline phosphatase, calcium and phosphate remained unaffected. Forty-four-week treatment with exenatide or insulin glargine had no adverse effects on bone density in patients with T2D, despite differential effects on body weight.
|
|
| 9. |
- Bunck, M. C., et al.
(författare)
-
One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial
- 2009
-
Ingår i: Diabetes Care. - 1935-5548. ; 32:5, s. 762-8
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Traditional blood glucose-lowering agents do not sustain adequate glycemic control in most type 2 diabetic patients. Preclinical studies with exenatide have suggested sustained improvements in beta-cell function. We investigated the effects of 52 weeks of treatment with exenatide or insulin glargine followed by an off-drug period on hyperglycemic clamp-derived measures of beta-cell function, glycemic control, and body weight. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomly assigned to exenatide (n = 36) or insulin glargine (n = 33). beta-Cell function was measured during an arginine-stimulated hyperglycemic clamp at week 0, at week 52, and after a 4-week off-drug period. Additional end points included effects on glycemic control, body weight, and safety. RESULTS: Treatment-induced change in combined glucose- and arginine-stimulated C-peptide secretion was 2.46-fold (95% CI 2.09-2.90, P < 0.0001) greater after a 52-week exenatide treatment compared with insulin glargine treatment. Both exenatide and insulin glargine reduced A1C similarly: -0.8 +/- 0.1 and -0.7 +/- 0.2%, respectively (P = 0.55). Exenatide reduced body weight compared with insulin glargine (difference -4.6 kg, P < 0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell function during 1 year of treatment compared with titrated insulin glargine. After cessation of both exenatide and insulin glargine therapy, beta-cell function and glycemic control returned to pretreatment values, suggesting that ongoing treatment is necessary to maintain the beneficial effects of either therapy.
|
|
| 10. |
- Frayn, KN, et al.
(författare)
-
Fatty acid metabolism in adipose tissue, muscle and liver in health and disease
- 2006
-
Ingår i: Essays in biochemistry. - : Portland Press Ltd.. - 0071-1365 .- 1744-1358. ; 42, s. 89-103
-
Tidskriftsartikel (refereegranskat)abstract
- Fat is the largest energy reserve in mammals. Most tissues are involved in fatty acid metabolism, but three are quantitatively more important than others: adipose tissue, skeletal muscle and liver. Each of these tissues has a store of triacylglycerol that can be hydrolysed (mobilized) in a regulated way to release fatty acids. In the case of adipose tissue, these fatty acids may be released into the circulation for delivery to other tissues, whereas in muscle they are a substrate for oxidation and in liver they are a substrate for re-esterification within the endoplasmic reticulum to make triacylglycerol that will be secreted as very-low-density lipoprotein. These pathways are regulated, most clearly in the case of adipose tissue. Adipose tissue fat storage is stimulated, and fat mobilization suppressed, by insulin, leading to a drive to store energy in the fed state. Muscle fatty acid metabolism is more sensitive to physical activity, during which fatty acid utilization from extracellular and intracellular sources may increase enormously. The uptake of fat by the liver seems to depend mainly upon delivery in the plasma, but the secretion of very-low-density lipoprotein triacylglycerol is suppressed by insulin. There is clearly cooperation amongst the tissues, so that, for instance, adipose tissue fat mobilization increases to meet the demands of skeletal muscle during exercise. When triacylglycerol accumulates excessively in skeletal muscle and liver, sometimes called ectopic fat deposition, then the condition of insulin resistance arises. This may reflect a lack of exercise and an excess of fat intake.
|
|
