| 1. |
- Basu, Samar, et al.
(författare)
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Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men
- 2011
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Ingår i: International Journal of Clinical and Experimental Medicine. - : E-Century Publishing. - 1940-5901. ; 4:2, s. 164-168
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Tidskriftsartikel (refereegranskat)abstract
- Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).
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| 2. |
- Basu, Samar, et al.
(författare)
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Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation
- 2005
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 28:6, s. 1371-1375
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood. RESEARCH DESIGN AND METHODS: Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects. RESULTS: The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements. CONCLUSIONS: These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.
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| 3. |
- Steer, Peter, et al.
(författare)
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Acute elevations of medium- and long-chain fatty acids have different impacts on endothelium-dependent vasodilation in humans
- 2003
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Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 38:1, s. 15-19
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Tidskriftsartikel (refereegranskat)abstract
- It has previously been shown that acute elevation of long-chain fatty acids (LCFA) impairs endothelium-dependent vasodilation (EDV) in humans. In this study, we tested the hypothesis that an elevation of both medium-chain fatty acids (MCFA) and LCFA affects the endothelium differently from LCFA elevation alone. Ten healthy volunteers received an intravenous infusion of Structolipid (structured TG, MCFA/LCFA ratio 1:1) and heparin for 2 h, while another 10 subjects received an infusion of Intralipid (LCFA only) and heparin. EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm after local administration of methacholine chloride (2 and 4 microg/min) and sodium nitroprusside (5 and 10 microg/min). Forearm blood flow was determined by venous occlusion plethysmography. Intralipid and heparin increased circulating FA levels from 0.2 +/- 0.1 to 1.4 +/- 0.5 mmol/L (P < 0.001) and reduced EDV by 20% (P < 0.01). Although Structolipid and heparin increased circulating FA levels to a similar extent (from 0.4 +/- 0.1 to 1.8 +/- 0.4 mmol/L after 2 h), EDV was not significantly changed. EIDV increased slightly during both interventions (P < 0.05). In conclusion, an acute elevation of LCFA attenuated EDV, whereas an elevation of both MCFA and LCFA did not influence EDV. Thus, FA composition seems to be of importance for EDV in healthy humans.
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| 4. |
- Steer, Peter, et al.
(författare)
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The effect of a mixed meal on endothelium-dependent vasodilation is dependent on fat content in healthy humans
- 2003
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Ingår i: Clinical Science. - 0143-5221 .- 1470-8736. ; 105:1, s. 81-87
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Tidskriftsartikel (refereegranskat)abstract
- Impaired endothelium-dependent vasodilation (EDV) is an early marker of atherosclerosis. The aim of the present study was to investigate how meals with different fat contents influence endothelial vasodilatory function. A total of 26 young, healthy men and women aged 20-30 years ingested an ordinary Western meal [34 energy% (E%) fat, n =10], or isocaloric meals with low-fat (20 E%, n =8), or minimal-fat (3 E%, n =8) content. EDV was assessed as forearm blood flow (FBF) during local administration of 4 microg/min methacholine chloride (Mch-FBF) and endothelium-independent vasodilation as FBF during administration of 10 microg/min sodium nitroprusside (SNP-FBF) at baseline and 1 and 2 h after each meal. FBF was determined by venous occlusion plethysmography. An endothelial function index (EFI) was calculated as the Mch-FBF/SNP-FBF ratio. Both Mch-FBF and the EFI were decreased at 1 h after the 34 E% fat meal ( P <0.01 and P <0.05 respectively), but approached fasting levels after 2 h. Mch-FBF and EFI did not change significantly in the group consuming the 20 E% fat meal, but increased in the 3 E% fat group ( P <0.01 and P <0.05 compared with baseline for Mch-FBF and EFI respectively). SNP-FBF was not significantly affected by any of the meals. In conclusion, low-fat meals did not attenuate EDV, in contrast with an ordinary Western meal, which transiently impaired EDV. Our findings indicate that a dietary fat content of 20 E% or less might be beneficial to endothelial vasodilatory function.
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| 5. |
- Steer, Peter, et al.
(författare)
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Vitamin C, diclophenac and L-arginine protect endothelium-dependent vasodilation against elevated circulating fatty acid levels in humans
- 2003
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 168:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- An acute elevation of circulating non-esterified fatty acids (NEFAs) has previously been shown to impair endothelium-dependent vasodilation (EDV). In this study, we investigated if local administration of vitamin C (n=8, 18 mg/min), L-arginine (n=8, 12.5 mg/min), or the cyclooxygenase (COX) inhibitor diclophenac (n=8, 0.5 mg/min) can counteract the endothelial dysfunction seen during infusion of Intralipid plus heparin (n=10). EDV and endothelium-independent vasodilation (EIDV) were studied in the forearm after local administration of methacholine chloride (Mch; 2 and 4 microg/min) and sodium nitroprusside (SNP; 5 and 10 microg/min). Forearm blood flow (FBF) was determined with venous occlusion plethysmography. Intralipid and heparin increased circulating NEFA levels sevenfold and impaired EDV (P<0.001 vs baseline). Concomitant administration of L-arginine or diclophenac abolished the NEFA-induced impairment in EDV. Concomitant vitamin C administration actually improved EDV (P<0.05 vs baseline). NEFA elevation increased EIDV (P<0.01), but this effect was not significant after L-arginine or diclophenac infusions. In conclusion, an acute elevation of circulating NEFAs led to impaired EDV. Administration of L-arginine, vitamin C or COX inhibition abolished this effect, suggesting that NEFAs might interact with endothelial vasodilatory function through multiple mechanisms.
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| 6. |
- Vessby, Johan, et al.
(författare)
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Oxidative stress and antioxidant status in type 1 diabetes mellitus
- 2002
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 251:1, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To test the hypothesis that type 1 diabetes is associated with increased oxidative stress and/or antioxidant status by investigating concentrations of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) in urine and plasma and malondialdehyde (MDA) in plasma as indicators of lipid peroxidation in vivo, and antioxidant status in diabetic subjects compared with healthy control subjects. DESIGN AND SUBJECTS: Thirty-eight subjects with type 1 diabetes mellitus and 41 healthy age- and sex-matched control subjects were included in the study. Blood and urine samples were obtained and analysed for 8-iso-PGF2alpha with a newly developed radioimmunoassay, as well as for MDA, total antioxidant capacity (TAOC) and serum tocopherol levels. RESULTS: None of the variables of lipid peroxidation showed any significant difference between the two groups. Similarly, there were no significant correlations between the levels of 8-iso-PGF2alpha or MDA, and degree of glycemic control (HbA1c). Total antioxidant capacity in plasma was 16% lower amongst the subjects with type 1 diabetes than in the control group (P < 0.0005). Lipid corrected levels of alpha-tocopherol in serum were significantly increased in type 1 diabetic subjects (P < 0.05), as were gamma-tocopherol levels (P < 0.005). CONCLUSIONS: In spite of lower total antioxidant defence, our results do not support the oxidative stress hypothesis for type 1 diabetes mellitus. The higher tocopherol levels suggest that no vitamin E supplementation is necessary for subjects with type 1 diabetes mellitus.
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