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- Fagerberg, Björn, 1943, et al.
(författare)
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Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population
- 2005
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 48:9, s. 1716-25
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Insulin resistance is associated with abnormalities in lipid and glucose metabolism, which are major components of metabolic syndrome and risk factors for vascular disease. This study examined the effect of tesaglitazar (Galida), a novel, dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, on lipid and glucose metabolism in patients with evidence of insulin resistance. METHODS: A 12-week, multicentre, randomised, double-blind, placebo-controlled, dose-finding study compared the efficacy and safety of oral tesaglitazar (0.1, 0.25, 0.5 and 1.0 mg/day) and placebo in 390 non-diabetic patients with hypertriglyceridaemia (plasma triglyceride concentration >1.7 mmol/l) and abdominal obesity (waist-to-hip ratio >0.90 for men and >0.85 for women). RESULTS: A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the primary endpoint) by 37% (95% CI: -43% to -30%; p<0.0001), non-HDL-cholesterol by 15% (95% CI: -20% to -10%; p<0.0001) and NEFA by 40% (95% CI: -51% to -27%; p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to -24%; p<0.0001). At the end of treatment there was a dose-dependent increase in patients with pattern A LDL particle diameter (40% at baseline vs 87% at 12 weeks for tesaglitazar 1.0 mg). Tesaglitazar produced significant reductions in fasting insulin concentration (-35%; p<0.0001) and plasma glucose concentration (-0.47 mmol/l; p<0.0001). Respiratory infection and gastrointestinal symptoms were the most common adverse events and were similarly frequent in all groups. CONCLUSIONS/INTERPRETATION: Tesaglitazar was well tolerated and produced significant, dose-dependent improvements in lipid and glucose metabolism and insulin sensitivity. Tesaglitazar may have the potential to prevent vascular complications and delay progression to diabetes in these patients.
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- Graff-Iversen, S., et al.
(författare)
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Hormone therapy and mortality during a 14-year follow-up of 14 324 Norwegian women
- 2004
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Ingår i: J Intern Med. - 0954-6820. ; 256:5, s. 437-45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We evaluated mortality from cardiovascular disease (CVD), coronary heart disease (CHD) and all causes in relation to use of any hormone therapy (HT) and HT with oestradiol and norethisterone or levonorgestrel. DESIGN: Population-based cohort study. SETTING AND SUBJECTS: Women in three Norwegian counties were invited to a health survey in 1985-88 and 82.8% participated. In all 14 324 post- or perimenopausal women aged 35-62 years, including 702 HT users with a mean age of 48.8 years, were followed for 14 years. RESULTS: Women using HT had mortality from all causes and CVD comparable with that of nonusers. The relative risk (RRs) for CVD mortality amongst all women were 0.69 (95% CI: 0.35-1.33) for users of HT, and 0.96 (95% CI: 0.43-2.17) for users of HT with norethisterone or levonorgestrel. Amongst women free of self-reported cardiovascular health problems at baseline all-cause, CVD and CHD mortality tended to be lower amongst users of HT whilst HT use was linked with increased mortality amongst women with cardiovascular health problems. CONCLUSIONS: In this cohort of women around the usual age of menopause all-cause or CVD mortality amongst users of HT, most often oestradiol combined with norethisterone or levonorgestrel, was not markedly different from that of nonusers. Early CHD events amongst HT users prior to the baseline survey, together with selective inclusion of healthy subjects, may in part explain protective effects of HT on CHD reported from previous observational studies.
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