Aims/hypothesis To assess thiamine status by analysis of plasma, erythrocytes and urine in type 1 and type 2 diabetic patients and links to markers of vascular dysfunction. Methods Diabetic patients (26 type 1 and 48 type 2) with and without microalbuminuria and 20 normal healthy control volunteers were recruited. Erythrocyte activity of transketolase, the concentrations of thiamine and related phosphorylated metabolites in plasma, erythrocytes and urine, and markers of metabolic control and vascular dysfunction were determined. Results Plasma thiamine concentration was decreased 76% in type 1 diabetic patients and 75% in type 2 diabetic patients: normal volunteers 64.1 (95% CI 58.5-69.7) nmol/l, type 1 diabetes 15.3 (95% CI 11.5-19.1) nmol/l, p< 0.001, and type 2 diabetes 16.3 (95% CI 13.0-9.6) nmol/l, p<0.001. Renal clearance of thiamine was increased 24-fold in type 1 diabetic patients and 16-fold in type 2 diabetic patients. Plasma thiamine concentration correlated negatively with renal clearance of thiamine (r=−0.531, p< 0.001) and fractional excretion of thiamine (r=−0.616, p< 0.001). Erythrocyte transketolase activity correlated negatively with urinary albumin excretion (r=−0.232, p<0.05). Thiamine transporter protein contents of erythrocyte membranes of type 1 and type 2 diabetic patients were increased. Plasma thiamine concentration and urinary excretion of thiamine correlated negatively with soluble vascular adhesion molecule-1 (r=−0.246, p<0.05, and −0.311, p<0.01, respectively). Conclusions/interpretation Low plasma thiamine concentration is prevalent in patients with type 1 and type 2 diabetes, associated with increased thiamine clearance. The conventional assessment of thiamine status was masked by increased thiamine transporter content of erythrocytes.
OBJECTIVEThe aim of this study was to investigate whether apolipoprotein B100 of LDL suffers increased damage by glycation, oxidation, and nitration in patients with type 2 diabetes, including patients receiving metformin therapy.RESEARCH DESIGN AND METHODSFor this study, 32 type 2 diabetic patients and 21 healthy control subjects were recruited; 13 diabetic patients were receiving metformin therapy (median dose: 1.50 g/day). LDL was isolated from venous plasma by ultracentrifugation, delipidated, digested, and analyzed for protein glycation, oxidation, and nitration adducts by stable isotopic dilution analysis tandem mass spectrometry.RESULTSAdvanced glycation end product (AGE) content of apolipoprotein B100 of LDL from type 2 diabetic patients was higher than from healthy subjects: arginine-derived AGE, 15.8 vs. 5.3 mol% (P < 0.001); and lysine-derived AGE, 2.5 vs. 1.5 mol% (P < 0.05). Oxidative damage, mainly methionine sulfoxide residues, was also increased: 2.5 vs. 1.1 molar equivalents (P < 0.001). 3-Nitrotyrosine content was decreased: 0.04 vs. 0.12 mol% (P < 0.05). In diabetic patients receiving metformin therapy, arginine-derived AGE and methionine sulfoxide were lower than in patients not receiving metformin: 19.3 vs. 8.9 mol% (P < 0.01) and 2.9 vs. 1.9 mol% (P < 0.05), respectively; 3-nitrotyrosine content was higher: 0.10 vs. 0.03 mol% (P < 0.05). Fructosyl-lysine residue content correlated positively with fasting plasma glucose. Arginine-derived AGE residue contents were intercorrelated and also correlated positively with methionine sulfoxide.CONCLUSIONSPatients with type 2 diabetes had increased arginine-derived AGEs and oxidative damage in apolipoprotein B100 of LDL. This was lower in patients receiving metformin therapy, which may contribute to decreased oxidative damage, atherogenicity, and cardiovascular disease.
Education and psychosocial factors are widely believed to contribute to diabetes control. However, there is no systematic way of measuring or recording these factors, or for transfer of information to future care‐givers. We developed a 41‐question questionnaire to measure the skills and contributory factors to self‐management in diabetes, and examined the relationship between these factors and glycaemic control. The questionnaire was assessed for construct validity, and for content validity by independent diabetes health professionals, and easily completed by 128 insulin‐treated diabetic patients (mean age 42 ± 13(SD) yr, diabetes duration 17 ±9 yr, HbA1 10.5 ± 1.8 %). Principle Components Factor analysis revealed nine factors explaining 63 % of variance (Eigen values 1.2–5.8). Five of these were significantly related to HbA1. These were: practical self‐management skills, p <0.001; emotional adjustment, p <0.002; perceived goals, p < 0.01; perceived self‐efficacy, p <0.005; and costs–benefit analysis, p <0.01. Multiple regression revealed that these five predictor variables (factors) explain 21 % of variance in HbA1, combined r = 0.46. The questionnaire also distinguished between patients with good and poor control (HbA1 8.2 vs 13.4 %, p <0.001), p for differences in question responses, 0.014–0.001. Four factors (lifestyle, influence of other people, diet concerns, and weight concerns) were unrelated to HbA1. In conclusion, we have developed a single, patient‐completed questionnaire of high content and construct validity, which identifies alterable factors (in contrast to fixed demographic variables) which may be specifically targeted in individual patients on the one hand to improve glycaemic control and, on the other, to enable more satisfactory adjustment to life with diabetes. It may be used in day‐to‐day practice to identify patient needs, and their barriers to effective self‐management, and to transfer this information to future care‐givers.
J (2020) Do probiotics prevent antibiotic associated diarrhoea? Results of a multicentre randomised placebo controlled trial. Journal of Hospital Infection.
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