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- Daka, Bledar, 1976, et al.
(författare)
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Low agreement between radio binding assays in analyzing glutamic acid decarboxylase (GAD65Ab) autoantibodies in patients classified with type 2 diabetes.
- 2009
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Ingår i: Autoimmunity. - : Informa UK Limited. - 1607-842X .- 0891-6934. ; 42:6, s. 507-14
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies against glutamic acid decarboxylase (GAD65Ab) are used in the classification of diabetes in adults. We assessed the concordance in GAD65 autoantibody levels within subjects between three different GAD65Ab radio binding assays (RBA). Plasma samples from 112 diabetes patients (median age 50 years) initially classified with type 2 diabetes was randomly selected from a local diabetes registry. Coded samples were analyzed with two RBA employing (35)S-labeled GAD65. The first used the pEx9 plasmid (pEx9 RBA), the second employed the pThGAD65 plasmid (pThGAD65 RBA) to label GAD65 by in vitro transcription translation. We also used a commercial kit employing plasmid pGAD17 labelled with (125)I (pGAD17 RBA). Subsequent analyses followed standard procedures. Two different cut-offs for GAD65Ab positivity were used in all three assays. We calculated the correlation, concordance, and agreement between the assays. The proportion of GAD65Ab positivity differed between assays when low cut-offs were used (pEx9 RBA 25%, pThGAD65 RBA 17.9%, and pGAD17 RBA 12.5%, respectively). When high cut-offs were applied, the concordance between the pEx9 RBA and the pThGAD65 RBA was 97.3 while their concordance to the pGAD17 RBA was lower (88.4 and 87.4, respectively). There was a low agreement between both pEx9 RBA and pGAD17 RBA (0.45, 95% CI 0.20-0.70) and between pThGAD65 RBA and pGAD17 RBA (0.43, 95% CI 0.18-0.68). We found discrepancies in determining the GAD65Ab positivity, which constitutes a problem when GAD65Ab are used clinically. Further methodological GAD65Ab assays studies are warranted.
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- Fellström, Bengt, et al.
(författare)
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Cardiovascular disease in patients with renal disease: the role of statins.
- 2009
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Ingår i: Current medical research and opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 25:1, s. 271-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Atherosclerosis is common in patients with chronic kidney disease (CKD), and cardiovascular disease (CVD) represents a major cause of death. The National Kidney Foundation guidelines favour the use of statin therapy for treatment of dyslipidaemia in patients with CKD. Much evidence supports statin therapy for reducing CVD and improving outcomes in the general population, but there is less evidence in patients with CKD. Consequently, prevention of CVD in CKD is based primarily on extrapolation from non-CKD trials. Significantly, in trials specifically designed to investigate patients with CKD, evidence is emerging for improved cardiovascular outcomes with statin therapy. This review describes available data relating to cardiovascular outcomes and the role of statins in patients with CKD, including pre-dialysis, dialysis, and renal transplant patients. RESEARCH DESIGN AND METHODS: The PubMed database was searched (1998-present) to ensure comprehensive identification of publications (including randomised clinical trials) relevant to CKD patients, patterns of cardiovascular outcome in such patients and their relationship to lipid profile, and the role of statins for the prevention and treatment of cardiovascular complications. RESULTS: There are conflicting data on the relationship between dyslipidaemia and cardiovascular outcomes, with one major study of statin therapy (4D--Deutsche Diabetes Dialyse Studie) providing equivocal results. Further studies, including AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events; NCT00240331) in patients receiving haemodialysis, and SHARP (Study of Heart And Renal Protection; NCT00125593) in patients with CKD including those on dialysis, should help to clarify the role of statin therapy in these populations. CONCLUSIONS: More studies are needed to elucidate the role of statins in improving cardiovascular outcomes for CKD patients. It is anticipated that ongoing clinical trials geared towards the optimal prevention and treatment of CVD in patients with CKD will help guide clinicians in the management of CKD.
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- Renström, Frida, et al.
(författare)
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Factors in serum from type 2 diabetes patients can cause cellular insulin resistance
- 2009
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Ingår i: Horm Metab Res. - : Georg Thieme Verlag KG. - 1439-4286 .- 1439-4286 .- 0018-5043. ; 41:10, s. 767-72
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Tidskriftsartikel (refereegranskat)abstract
- This pilot study was aimed to investigate whether there are humoral factors in serum from type 2 diabetic subjects that, in addition to glucose, insulin and free fatty acids are able to induce or contribute to peripheral insulin resistance with respect to glucose transport. Isolated subcutaneous adipocytes from 11 type 2 diabetic subjects and 10 nondiabetic controls were incubated for 24-h in medium supplemented with 25 % serum from a control or a type 2 diabetic donor, in the presence of a low (5 mM) or a high (15 mM) glucose concentration, respectively. After the incubation period glucose uptake capacity was assessed. Serum from type 2 diabetic donors, compared to serum from controls, significantly reduced the maximal insulin eff ect to stimulate glucose uptake (approximately 40 %, p < 0.05) in adipocytes from control subjects, independent of surrounding glucose concentrations. Glucose uptake capacity in adipocytes isolated from type 2 diabetic subjects was similar regardless of culture condition. No significant alterations were found in cellular content of key proteins in the insulin signaling cascade (insulin receptor substrate-1 and -2, and glucose transporter 4) that could explain the impaired insulin-stimulated glucose transport in control adipocytes incubated with serum from type 2 diabetic donors. The present findings indicate the presence of biomolecules in the circulation of type 2 diabetic subjects, apart from glucose, insulin, and free fatty acids with the ability to induce peripheral insulin resistance. This further implies that even though normoglycemia is achieved other circulating factors can still negatively aff ect insulin sensitivity in type 2 diabetic patients.
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- Ruge, T., et al.
(författare)
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Acute hyperinsulinemia raises plasma interleukin-6 in both nondiabetic and type 2 diabetes mellitus subjects, and this effect is inversely associated with body mass index
- 2009
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Ingår i: Metabolism. - 1532-8600 .- 1532-8600. ; 58:6, s. 860-6
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Tidskriftsartikel (refereegranskat)abstract
- Hyperinsulinemia is a characteristic of type 2 diabetes mellitus (T2DM) and is believed to play a role in the low-grade inflammation seen in T2DM. The main aim was to study the effect of hyperinsulinemia on adipokines in individuals with different levels of insulin resistance, glycemia, and obesity. Three groups of sex-matched subjects were studied: young healthy subjects (YS; n = 10; mean age, 26 years; body mass index [BMI], 22 kg/m(2)), patients with T2DM (DS; n = 10; 61 years; BMI, 27 kg/m(2)), and age- and BMI-matched controls to DS (CS; n = 10; 60 years; BMI, 27 kg/m(2)). Plasma concentrations of adipokines were measured during a hyperinsulinemic euglycemic clamp lasting 4 hours. Moreover, insulin-stimulated glucose uptake in isolated adipocytes was analyzed to address adipose tissue insulin sensitivity. Plasma interleukin (IL)-6 increased significantly (P < or = .01) in all 3 groups during hyperinsulinemia. However, the increase was smaller in both DS (P = .06) and CS (P < .05) compared with YS (approximately 2.5-fold vs approximately 4-fold). A significant increase of plasma tumor necrosis factor (TNF) alpha was observed only in YS. There were only minor or inconsistent effects on adiponectin, leptin, and high-sensitivity C-reactive protein levels during hyperinsulinemia. Insulin-induced rise in IL-6 correlated negatively to BMI (P = .001), waist to hip ratio (P = .05), and baseline (fasting) insulin (P = .03) and IL-6 (P = .02) levels and positively to insulin-stimulated glucose uptake in isolated adipocytes (P = .07). There was no association with age or insulin sensitivity. In a multivariate analysis, also including T2DM/no T2DM, an independent correlation (inverse) was found only between BMI and fold change of IL-6 (r(2) = 0.41 for model, P < .005). Hyperinsulinemia per se can produce an increase in plasma IL-6 and TNFalpha, and this can potentially contribute to the low-grade inflammation seen in obesity and T2DM. However, obesity seems to attenuate the ability of an acute increase in insulin to further raise circulating levels of IL-6 and possibly TNFalpha.
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