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- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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- Muskiet, M H A, et al.
(författare)
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Exenatide twice-daily does not affect renal function or albuminuria compared to titrated insulin glargine in patients with type 2 diabetes mellitus: A post-hoc analysis of a 52-week randomised trial.
- 2019
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Ingår i: Diabetes research and clinical practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 153, s. 14-22
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Tidskriftsartikel (refereegranskat)abstract
- To compare the effects of long-term treatment with the GLP-1RA exenatide twice-daily versus titrated insulin glargine (iGlar) on renal function and albuminuria in type 2 diabetes (T2DM) patients.We post-hoc evaluated renal outcome-data of 54 overweight T2DM patients (mean ±SD age 60±8years, HbA1c 7.5±0.9%, eGFR 86±16mL/min/1.73m2, median [IQR] urinary albumin-to-creatinine-ratio (UACR) 0.75 [0.44-1.29]mg/mmol) randomised to exenatide 10µg twice-daily or titrated iGlar on-top-of metformin for 52-weeks. Renal efficacy endpoints were change in creatinine clearance (CrCl) and albuminuria (urinary albumin-excretion [UAE] and UACR) based on 24-h urines, collected at baseline and Week-52. eGFR and exploratory endpoints were collected throughout the intervention-period, and after a 4-week wash-out.HbA1c-reductions were similar with exenatide (mean±SEM -0.80±0.10%) and iGlar (-0.79±0.14%; treatment-difference 0.02%; 95% CI -0.31 to 0.42%). Change from baseline to Week-52 in CrCl, UAE or UACR did not statistically differ; only iGlar reduced albuminuria (P<0.05; within-group). eGFR decreased from baseline to Week-4 with exenatide (-3.9±2.1mL/min/1.73m2; P=0.069) and iGlar (-2.7±1.2mL/min/1.73m2; P=0.034), without treatment-differences in ensuing trajectory. Exenatide versus iGlar reduced bodyweight (-5.4kg; 2.9-7.9; P<0.001), but did not affect blood pressure, lipids or plasma uric acid.Among T2DM patients without overt nephropathy, one-year treatment with exenatide twice-daily does not affect renal function-decline or onset/progression of albuminuria compared to titrated iGlar.ClinicalTrials.gov ID: NCT00097500.
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| 8. |
- Westerbacka, J, et al.
(författare)
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Insulin regulation of MCP-1 in human adipose tissue of obese and lean women
- 2008
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 294:5, s. E841-E845
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Tidskriftsartikel (refereegranskat)abstract
- CCL2 (MCP-1, monocyte chemoattractant protein 1) and CCL3 (MIP-1α, macrophage inflammatory protein 1α) are required for macrophage infiltration in adipose tissue. Insulin increases CCL2 expression in adipose tissue and in serum more in insulin-resistant obese than in insulin-sensitive lean mice, but whether this is true in humans is unknown. We compared basal expression and insulin regulation of CCL2 and CCL3 in adipose tissue and MCP-1 and MIP-1α in serum between insulin-resistant and insulin-sensitive human subjects. Subcutaneous adipose tissue biopsies and blood samples were obtained before and at the end of 6 h of in vivo euglycemic hyperinsulinemia (maintained by the insulin clamp technique) in 11 lean insulin-sensitive and 10 obese insulin-resistant women, and before and after a 6-h saline infusion in 8 women. Adipose tissue mRNA concentrations of monocyte/macrophage markers CD68, EMR1, ITGAM, ADAM8, chemokines CCL2 and CCL3, and housekeeping gene ribosomal protein large P0 (RPLP0) were measured by means of real-time PCR at baseline. In addition, mRNA concentrations of CCL2, CCL3, and RPLP0 were measured after insulin infusion. Levels of MCP-1 and MIP-1α were determined in serum, and protein concentration of MCP-1 was determined in adipose tissue at baseline and after insulin infusion. Basally, expression of the macrophage markers CD68 and EMR1 were increased in adipose tissue of insulin-resistant subjects. Insulin increased MCP-1 gene and protein expression significantly more in the insulin-resistant than in the insulin-sensitive subjects. Basally expression of CCL2 and CCL3 and expression of macrophage markers CD68 and ITGAM were significantly correlated. In serum, MCP-1 decreased significantly in insulin-sensitive but not insulin-resistant subjects. MIP-1α was undetectable in serum. Insulin regulation of CCL2 differs between insulin-sensitive and -resistant subjects in a direction that could exacerbate adipose tissue inflammation.
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| 9. |
- Bunck, M. C., et al.
(författare)
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Exenatide affected circulating cardiovascular risk biomarkers independently of changes in body composition
- 2010
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Ingår i: Diabetes Care. - 0149-5992. ; 33:8, s. 1734-1737
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To study the effect of exenatide on body composition and circulating cardiovascular risk biomarkers. RESEARCH DESIGN AND METHODS Metformin-treated patients with type 2 diabetes (N = 69) were randomized to exenatide or insulin glargine and treated for 1 year. Body composition was evaluated by dual-energy X-ray absorptiometry. Additionally, body weight, waist circumference, and cardiovascular biomarkers were measured. RESULTS Treatment with exenatide for 1 year significantly reduced body weight, waist circumference, and total body and trunkal fat mass by 6, 5, 11, and 13%, respectively. In addition, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. Insulin glargine significantly reduced endothelin-1 by 7%. These changes were statistically independent of the change in total body fat mass and body weight. CONCLUSIONS Exenatide treatment for 1 year reduced body fat mass and improved the profile of circulating biomarkers of cardiovascular risk. No significant changes were seen with insulin glargine except a trend for reduced endothelin-1 levels.
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| 10. |
- Bunck, M. C., et al.
(författare)
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Exenatide treatment did not affect bone mineral density despite body weight reduction in patients with type 2 diabetes
- 2011
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Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1463-1326 .- 1462-8902. ; 13:4, s. 374-377
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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.
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