The Molecular Basis for Oat Intolerance in Patients with Celiac Disease

BACKGROUND: Celiac disease is a small intestinal inflammatory disorder characterized by malabsorption, nutrient deficiency, and a range of clinical manifestations. It is caused by an inappropriate immune response to dietary gluten and is treated with a gluten-free diet. Recent feeding studies have indicated oats to be safe for celiac disease patients, and oats are now often included in the celiac disease diet. This study aimed to investigate whether oat intolerance exists in celiac disease and to characterize the cells and processes underlying this intolerance. METHODS AND FINDINGS: We selected for study nine adults with celiac disease who had a history of oats exposure. Four of the patients had clinical symptoms on an oats-containing diet, and three of these four patients had intestinal inflammation typical of celiac disease at the time of oats exposure. We established oats-avenin-specific and -reactive intestinal T-cell lines from these three patients, as well as from two other patients who appeared to tolerate oats. The avenin-reactive T-cell lines recognized avenin peptides in the context of HLA-DQ2. These peptides have sequences rich in proline and glutamine residues closely resembling wheat gluten epitopes. Deamidation (glutamine→glutamic acid conversion) by tissue transglutaminase was involved in the avenin epitope formation. CONCLUSIONS: We conclude that some celiac disease patients have avenin-reactive mucosal T-cells that can cause mucosal inflammation. Oat intolerance may be a reason for villous atrophy and inflammation in patients with celiac disease who are eating oats but otherwise are adhering to a strict gluten-free diet. Clinical follow-up of celiac disease patients eating oats is advisable

Measurement of complement receptor 1 on neutrophils in bacterial and viral pneumonia

BACKGROUND: A reliable prediction of the causative agent of community-acquired pneumonia (CAP) is not possible based on clinical features. Our aim was to test, whether the measurement of the expression of complement receptors or Fcγ receptors on neutrophils and monocytes would be a useful preliminary test to differentiate between bacterial and viral pneumonia. METHODS: Sixty-eight patients with CAP were studied prospectively. Thirteen patients had pneumococcal pneumonia; 13 patients, influenza A pneumonia; 5 patients, atypical pneumonia, and 37 patients, aetiologically undefined pneumonia. Leukocyte receptor expression was measured within 2 days of hospital admission. RESULTS: The mean expression of complement receptor 1 (CR1) on neutrophils was significantly higher in the patients with pneumococcal pneumonia than in those with influenza A pneumonia. The mean expression of CR1 was also significantly higher in aetiologically undefined pneumonia than in influenza A pneumonia, but there was no difference between pneumococcal and undefined pneumonia. CONCLUSION: Our results suggest that the expression of CR1 is higher in classical bacterial pneumonia than in viral pneumonia. Determination of the expression of CR1 may be of value as an additional rapid tool in the aetiological diagnosis, bacterial or viral infection, of CAP. These results are preliminary and more research is needed to assess the utility of this new method in the diagnostics of pneumonia

Sense of coherence and intentions to retire early among Finnish women and men

Peer reviewe

Increased fat mass compensates for insulin resistance in abdominal obesity and type 2 diabetes - A positron-emitting tomography study

To evaluate the relative impact of abdominal obesity and newly diagnosed type 2 diabetes on insulin action in skeletal muscle and fat tissue, we studied 61 men with (n = 31) or without (n = 30) diabetes; subgrouped into abdominally obese or nonobese according to the waist circumference. Adipose tissue depots were quantified by magnetic resonance imaging, and regional glucose uptake was measured using 2-[F-18]fluoro-2-deoxyglucose/positron emission tomography during euglycemic hyperinsulinemia. Across groups, glucose uptake per unit tissue weight was higher in visceral (20.5 +/- 1.4 mu mol . min(-1) . kg(-1)) than in abdominal (9.8 +/- 0.9 mu mol min(-1) . kg(-1), P < 0.001) or femoral (12.3 +/- 0.6 mu mol . min(-1). kg(-1), P < 0.001) subcutaneous tissue and similar to 40% lower than in skeletal muscle (33.1. +/- 2.5 mu mol . min(-1) . kg(-1), P < 0.0001). Abdominal obesity was associated with a marked reduction in glucose uptake per unit tissue weight in all fat depots and in skeletal muscle (P < 0.001 for all regions). Recent type 2 diabetes per se had little additional effect. In both intra-abdominal adipose (r = -0.73, P < 0.0001) and skeletal muscle (r = -0.53, P < 0.0001) tissue, glucose uptake was reciprocally related to intra-abdominal fat mass in a curvilinear fashion. When regional glucose uptake was multiplied by tissue mass, total glucose uptake per fat depot was similar irrespective of abdominal obesity or type 2 diabetes, and its contribution to whole-body glucose uptake increased by similar to 40% in obese nondiabetic and nonobese diabetic men and was doubled in obese diabetic subjects. We conclude that 1) in abdominal obesity, insulin-stimulated glucose uptake rate is markedly reduced in skeletal muscle and in all fat depots; 2) in target tissues, this reduction is reciprocally (and nonlinearly) related to the amount of intra-abdominal fat; 3) mild, recent diabetes adds little insulin resistance to that caused by abdominal obesity; and 4) despite fat insulin resistance, an expanded fat mass (especially subcutaneous) provides a sink for glucose, resulting in a compensatory attenuation of insulin resistance at the whole-body level in men

Symptom clustering in subjects with and without diabetes mellitus: A population-based study of 15,000 Australian adults

OBJECTIVES: GI symptoms form distinct symptom clusters in community samples when factor and cluster analysis is applied. However, this has not been studied in diabetic populations, despite clear evidence that GI complaints are common in patients with diabetes mellitus (DM). This study aimed to describe clustering of GI symptoms among individuals with and without diabetes mellitus, and to describe associations of symptom clustering in diabetes mellitus, with self-reported glucose control and treatment. METHODS: A large population survey (n = 15,000) was used to identify a cohort with diabetes mellitus. Items assessing therapy and quality of glycemic control were included, as were those assessing 16 common GI symptoms. Latent GI symptom factors were extracted by factor analysis and used in a k-means cluster analysis. The latter serves to group individuals according to commonalities in symptom profiles. The association of cluster group membership to glycemic control and diabetic treatment was described by logistic regression. RESULTS: Factor analysis identified four latent symptom factors, which accounted for 69.3% of the total variance. These were labeled Upper GI/Dysmotility, Diarrhea, Constipation, and Vomiting/Nausea. The k-means analysis produced a five-cluster solution, which included a "health" group and four "diseased" groups, each identified by a predominant symptom: Upper GI/Dysmotility symptoms, Nausea/Vomiting, Diarrhea, and Constipation. After adjustment for age and gender, poor glycemic control predicted membership in all disease clusters, when compared separately with the health group. Oral hypoglycemic drugs predicted membership in the Nausea/Vomiting cluster (OR = 5.13) when used alone, and membership in the Nausea/Vomiting (OR = 10.12) and Upper GI/Dysmotility cluster (OR = 10.12) when used in combination with insulin. CONCLUSIONS: Diabetes can be grouped according to common GI symptoms. Glycemic control and treatment for DM predict membership of symptom clusters.Johann Hammer, Stuart Howell, Peter Bytzer, Michael Horowitz, and Nicholas J. Talle