| 1. |
- Eriksson, Jan W., et al.
(författare)
-
Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation : the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study
- 2008
-
Ingår i: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 52:6, s. 1030-1037
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P
|
|
| 2. |
|
|
| 3. |
- Eriksson, Olof, et al.
(författare)
-
The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
- 2014
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
-
Tidskriftsartikel (refereegranskat)abstract
- In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
|
|
| 4. |
- Oscarsson, Jan, et al.
(författare)
-
Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease : A double-blind, randomized, placebo-controlled study
- 2018
-
Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 12:6, s. 1390-1403
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. OBJECTIVE: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. METHODS: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. RESULTS: Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, -2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P = .02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs 3%, P = .04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (-26%, P = .02) and fenofibrate (-38%, P < .001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. CONCLUSIONS: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.
|
|
| 5. |
- Palming, Jenny, 1975, et al.
(författare)
-
Hydrochlorothiazide Compared to Candesartan Treatment Increases Adipose Tissue Gene Expression and Circulating Levels of Serum Amyloid A in Hypertensive Patients
- 2011
-
Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 43:5, s. 319-324
-
Tidskriftsartikel (refereegranskat)abstract
- Treatment of hypertension with angiotensin receptor blockers has been shown to reduce the risk of developing type 2 diabetes in comparison to thiazide diuretics and beta adrenergic blockers. Therefore, we wanted to study the effect of antihypertensive drugs on adipose tissue with respect to insulin resistance. In the MEDICA (MEchanisms for the DIabetes preventing effects of CAndesartan) study, 22 hypertensive, nondiabetic patients with abdominal obesity (10 men, 12 women) were randomized into 12-week treatment periods with candesartan, hydrochlorothiazide, and placebo according to a 3-way cross-over design. Subcutaneous adipose tissue biopsies were taken after 8 weeks treatment to analyze gene expression, glucose uptake capacity, insulin-signaling, and adipocyte size. Adipose tissue gene expression of serum amyloid A (SAA) was higher after hydrochlorothiazide treatment compared to candesartan (p = 0.036), and this was in accordance with our previous finding on circulating SAA levels. Serum levels of E selectin were increased after hydrochlorothiazide compared to candesartan treatment (p = 0.002) and lower after candesartan compared to placebo (p = 0.002). In adipocytes, there were no significant differences between the treatments with respect to cell size, glucose uptake capacity, or insulin-signaling. In comparison to candesartan, hydrochlorothiazide raised the adipose tissue gene expression of SAA and the serum level of SAA as well as E selectin in hypertensive patients. Less adipose and systemic inflammation may be one explanation why candesartan is favorable in comparison to thiazide diuretics with respect to development of insulin resistance and type 2 diabetes.
|
|
