| 1. |
|
|
| 2. |
|
|
| 3. |
- Bohm, M., et al.
(författare)
-
Time to benefit of heart rate reduction with ivabradine in patients with heart failure and reduced ejection fraction
- 2023
-
Ingår i: European Journal of Heart Failure. - 1388-9842. ; 25:8, s. 1429-1435
-
Tidskriftsartikel (refereegranskat)abstract
- Aims In the SHIFT (Systolic Heart failure treatment with the I-f inhibitor ivabradine Trial, ISRCTN70429960) study, ivabradine reduced cardiovascular death or heart failure (HF) hospitalizations in patients with HF and reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate (HR) >= 70 bpm. In this study, we sought to determine the clinical significance of the time durations of HR reduction and the significant treatment effect on outcomes among patients with HFrEF. Methods and results The time to statistically significant reduction of the primary outcome (HF hospitalization and cardiovascular death) and its components, all-cause death, and HF death, were assessed in a post-hoc analysis of the SHIFT trial in the overall population (HR >= 70 bpm) and at HR >= 75 bpm, representing the approved label in many countries. Compared to placebo, the primary outcome and HF hospitalizations were significantly reduced at 102 days, while there was no effect on cardiovascular death, all-cause death, and HF death at HR >= 70 bpm. In the population with a baseline HR >= 75 bpm, a reduction of the primary outcome occurred after 67 days, HF hospitalization after 78 days, cardiovascular death after 169 days, death from HF after 157 days and all-cause death after 169 days. Conclusion Treatment with ivabradine should not be deferred in patients in sinus rhythm with a HR of >= 70 bpm to reduce the primary outcome and HF hospitalizations, in particular in patients with HR >= 75 bpm. At HR >= 75 bpm, the time to risk reduction was shorter for reduction of hospitalization and mortality outcomes in patients with HFrEF after initiation of guideline-directed medication, including beta-blockers at maximally tolerated doses.
|
|
| 4. |
- Betz, Mattias J., et al.
(författare)
-
Presence of Brown Adipocytes in Retroperitoneal Fat From Patients With Benign Adrenal Tumors: Relationship With Outdoor Temperature
- 2013
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:10, s. 4097-4104
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Brown adipose tissue (BAT) is a metabolically highly active organ with increased thermogenic activity in rodents exposed to cold temperature. Recently its presence in the cervical adipose tissue of human adults and its association with a favorable metabolic phenotype have been reported. Objective: The objective of the study was to determine the prevalence of retroperitoneal BAT in human adults. Patients: Fifty-seven patients who underwent surgery for benign adrenal tumors were included in this study. Main Outcome Measures: Prevalence of retroperitoneal BAT adjacent to the removed adrenal tumor as determined by uncoupling protein 1 (UCP1) protein and mRNA expression was measured. Results: Using protein and mRNA expression analysis, we detected UCP1 protein in 26 of 57 patients (45.6%) as well as high mRNA expression of genes characteristic for brown adipocytes, independent of the adrenal tumor type. The presence of brown adipocytes within the retroperitoneal fat was associated with a significantly lower outdoor temperature during the month prior to surgery. Importantly, UCP1 expression on both mRNA and protein level was inversely correlated to outdoor temperature, whereas body mass index, sex, age, and diabetes status were not. Conclusions: These findings suggest that human retroperitoneal adipose tissue can acquire a BAT phenotype, thereby adapting to environmental challenges. These adaptive processes might provide a valuable therapeutic target in the treatment of obesity and insulin resistance.
|
|
| 5. |
- Carobbio, Stefania, et al.
(författare)
-
Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity
- 2013
-
Ingår i: Diabetes. - : Cell Press. - 0012-1797 .- 1939-327X. ; 62:11, s. 3697-3708
-
Tidskriftsartikel (refereegranskat)abstract
- The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.
|
|
| 6. |
- Lidell, Martin, 1970, et al.
(författare)
-
Evidence for two types of brown adipose tissue in humans
- 2013
-
Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:5, s. 631-634
-
Tidskriftsartikel (refereegranskat)abstract
- The previously observed supraclavicular depot of brown adipose tissue (BAT) in adult humans was
|
|
