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Aims/hypothesis: Low-grade inflammation and endothelial dysfunction may play a role in the pathogenesis of type 2 diabetes and cardiovascular disease. We evaluated whether a diet high in fatty fish, bilberries and wholegrain products (Healthy Diet) improves biomarkers reflecting inflammation and endothelial dysfunction in individuals with impaired glucose metabolism. Methods: We recruited individuals with impaired glucose metabolism and features of the metabolic syndrome into a 12 week, parallel design, dietary intervention trial conducted at the Department of Clinical Nutrition, University of Eastern Finland (Kuopio, Finland). Randomisation was performed by matching according to sex and medians of age, BMI and fasting plasma glucose of the study population at screening. The primary endpoint in the present study was the change in plasma inflammatory markers and the measurements were performed blinded to group assignment. High-sensitivity (hs) C-reactive protein (CRP) and E-selectin responses were also analysed separately in participants not using statins ( n = 76). Results: Altogether, 131 individuals were assigned to either the Healthy Diet ( n = 44), a whole-grain-enriched diet (WGED) ( n = 42) or a control ( n = 45) diet, and 104 participants (mean ± SD: age 59 ± 7 years; BMI 31.1 ± 3.5 kg/m) who had completed the study, were analysed (Healthy Diet n = 36, WGED n = 34 and control diet n = 34). Plasma E-selectin decreased only in the Healthy Diet group. This occurred in all group participants ( p < 0.05) and also after excluding participants using statins ( p < 0.05). Plasma hsCRP levels decreased in the Healthy Diet (median −17%, p < 0.05) and WGED (median −27%, p < 0.01) groups in participants not using statins. Controlling for confounding factors, including BMI or insulin sensitivity, did not alter the results. A greater increase in plasma concentration of very-long-chain n-3 fatty acids and in the intake of fibre during the study was associated with a greater decrease in plasma E-selectin ( p < 0.05). The intake of test breads consumed during the Healthy Diet and WGED interventions was inversely associated with the change in hsCRP levels ( p < 0.001). Conclusions/interpretation: Our results suggest that the combined effect of fatty fish, bilberries and wholegrain products may improve endothelial dysfunction and inflammation in overweight and obese individuals at high risk of developing diabetes. Trial registration:: ClinicalTrials.gov NCT00573781 Funding:: The study was funded by the Academy of Finland (117844 and 118590 [to M. Uusitupa]; 131460 [to K. Poutanen]; 130469 [to H. Mykkänen] and 131593 [to V. D. F. de Mello]); the Kuopio University Hospital (5106, 5168, 5254 [to M. Uusitupa]); the Finnish Diabetes Research Foundation; the Sigrid Juselius Foundation; the Nordic Centre of Excellence on 'Systems biology in controlled dietary interventions and cohort studies' (SYSDIET; 070014); and the European Commission in the Communities 6th Framework Programme, Project HEALTHGRAIN (FOOD-CT-2005-514008). [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up)., Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at ~18 months (both cohorts) and at ~48 months (cohort 1) or ~36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe., Results: Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean ± SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m 2 ; fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m 2 ; fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l., Conclusions/interpretation: The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.

Aim: Neurofilament light (NfL) chain, a putative cerebrospinal fluid biomarker, can support neurodegenerative disease diagnosis and indicate disease severity and prognosis. Universal validation protocols when used to measure biomarkers can reduce pre and analytical laboratory variation, thus increasing end-user confidence in the consistency of validation data across sites., Methodology: Here, a commercially available NfL ELISA (UmanDiagnostics, Umeå, Sweden) was validated in a multicentered setting using comprehensive newly developed standard operating procedures., Results: The data showed good assay sensitivity and intra and interassay precision. Interlaboratory precision was, however, suboptimal., Conclusion: The UmanDiagnostics assay is suitable for the quantification of NfL in human cerebrospinal fluid. However, sources of interlaboratory variation in the data require further investigation.

Background: TDP-43 is the main protein component of ubiquitinated inclusions in a subgroup of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) patients. The C9ORF72 hexanucleotide expansion is one of the main mutations associated with TDP-43 pathology in FTLD and ALS. Our aim was to analyze cerebrospinal fluid (CSF) TDP-43 levels and Alzheimer's disease biomarkers in FTLD and ALS patients and to test whether the C9ORF72 expansion carrier status affects these variables., Methods: The patient cohort consisted of 90 clinically well-characterized FTLD (n = 69) and ALS (n = 21) patients. There were 30 patients with the C9ORF72 expansion and 60 patients without the expansion. CSF TDP-43, AΒ1-42, t-tau, and phospho-tau levels were measured using commercial ELISA kits., Results: There was no difference in CSF TDP-43 levels between the C9ORF72 expansion carriers and the noncarriers. CSF TDP-43 levels were higher in ALS patients than in FTLD patients, and this finding was independent of the C9ORF72 expansion carrier status. Males had significantly higher TDP-43 levels than females (p = 0.008 in the total cohort)., Conclusion: CSF TDP-43 does not seem to distinguish the C9ORF72 expansion carriers from noncarriers. However, higher CSF TDP-43 levels were detected in ALS than in FTLD, which might be an indicator of a more rapid progression of TDP-43 pathology in ALS.

Dietary fiber (DF) and protein are essential constituents of a healthy diet and are well known for their high satiety impact. However, little is known about their influence on postprandial gastrointestinal (GI) peptide release. Our aim in this single-blind, randomized, cross-over study was to investigate the effects of DF and/or protein enrichments on satiety-related metabolic and hormonal responses. Sixteen healthy, nonobese volunteers participated in the study and ingested 1 of 5 isoenergetic test meals in a randomized order on separate days. The test meals were as follows: 1) low in protein (2.8 g) and fiber (7.6 g); 2) low in protein (2.6 g) and high in soluble fiber (psyllium, 23.0 g); 3) high in protein (soy, 19.7 g) and low in fiber (6.2 g); 4) high in protein (18.4 g) and fiber (23.0 g); and 5) white wheat bread. Serum insulin and plasma glucose, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) concentrations were determined for 2 h following the meals. In addition, hunger and satiety ratings were collected. Postprandial glucose, insulin, ghrelin, GLP-1, and PYY responses all differed among the meals (P

Ghrelin is an orexigenic peptide produced in the stomach and its plasma levels are decreased acutely in response to ingested nutrients. To further clarify the role of insulin on ghrelin secretion, the present study was designed to investigate whether circulating ghrelin is affected differently by two mixtures of whole-grain breads known to produce low or high insulin responses in obese non-diabetic subjects with metabolic syndrome. After an overnight fast eight obese subjects with the metabolic syndrome (3 men and 5 women; BMI 33.7+/-0.7 kg/m(2); age 55.6+/-1.8 y) received two different meals consisting of whole-grain rye or wheat breads. The comparison group (3 men and 5 women; BMI 22.5+/-0.5 kg/m(2); age 26.0+/-0.9 y) received a wheat bread meal. Blood samples were collected postprandially at time intervals for 2 h. Feelings of hunger and satiety were analyzed using the visual analogue scales. Ghrelin concentrations decreased after bread meals in lean individuals, but not in obese individuals with the metabolic syndrome. Despite the difference in plasma insulin response, there was no difference in plasma ghrelin or feelings of hunger and satiety in patients with metabolic syndrome. After both rye and wheat bread meals, the decrease in ghrelin concentrations seen in normal-weight individuals after wheat bread meal was absent in subjects with metabolic syndrome. Despite the different plasma insulin response in obese patients, ghrelin levels did not change in response to either type of bread meals. In addition, ghrelin levels did not correlate with insulin, glucose, HOMA1-IR and satiety and hunger ratings in either study groups. This indicates that regulation of ghrelin might be altered in obese patients with metabolic syndrome independently of insulin.

The aim of the study was to discover how an implemented quality system succeeded in fulfilling the personnel and management expectations and to identify the factors that facilitate or hinder quality management implementation in clinical laboratories. The concepts assessed include leadership (commitment and change management), clear and common goals, human recourses focus, client focus, management by fact and process improvement. The quality process in the laboratories had not, even after 3-4 years, reached a level of acceptance allowing its use as a daily development tool. The factors that predict a success of the quality system include willingness to improve the laboratory services and to keep the process going and good atmosphere at work. However, the study showed that the senior managers of the laboratory should take a more visible role in leading the change, and emphasize more explicitly the long-term goals. The middle managers (physicians, biochemists and head technologists) should arrange opportunities for the staff to participate in the system and disseminate the information on, and practical applications of, the quality principles and tools. The staff should be more active in finding new information and in participating in the system.

Objective: To determine whether the measurement error of saline PCO2, using blood gas analyzers, is relevant for the interpretation and clinical use of the gastric intramucosal pH measurement., Design: A comparison of four different blood gas analyzers (ABL-520, Ciba Corning, IL-1302, and Nova), using tonometered saline as the reference., Setting: Clinical laboratory of a university hospital intensive care unit., Interventions: None., Measurements and Main Results: The bias and the precision of each blood gas analyzer was determined for measurements of PCO2 in saline samples. These samples had been balanced to PCO2 levels of 30, 45, and 68 torr (4, 6, and 9 kPa, respectively). In addition, the effect of buffering the saline was evaluated. The bias of the PCO2 measurement increased (p < .001) at the higher PCO2 levels. The bias ranged from -5.2 to -25.9 torr (-0.69 to -3.45 kPa) at a PCO2 of 45 torr (6 kPa) and from -5.2 to -33.1 torr (-0.69 to -4.41 kPa) at a PCO2 of 68 torr (9 kPa), and there was a significant (p < .001) analyzer-PCO2 level interaction. The type of the analyzer also influenced the bias (p < .001). The Nova analyzer underestimated the PCO2 by 50% to 60%. The other analyzers underestimated the PCO2 by 5% to 19%. The use of the buffer reduced the bias of all analyzers (p < .001). Based on the precision of the saline PCO2 measurement, a difference in gastric intramucosal pH of 0.06 pH units can be reliably detected at a PCO2 of 45 torr (6 kPa) by all analyzers, with the exception of the Nova analyzer., Conclusions: Measurement of saline PCO2 is an important source of error in the assessment of gastric intramucosal pH, and the error depends on both the analyzer used and the actual PCO2 level. Direct comparison of pH values obtained by different analyzers is not valid. Changes in gastric intramucosal pH of 0.06 pH units can be detected by most analyzers in the clinically relevant PCO2 level.