Associations between weight loss history and factors related to type 2 diabetes risk in the Stop Diabetes study.

BACKGROUND: Frequent weight loss attempts are related to maladaptive eating behaviours and higher body mass index (BMI). We studied associations of several type 2 diabetes (T2D) risk factors with weight loss history, defined as the frequency of prior weight loss attempts, among Finnish adults at increased risk for T2D. METHODS: This study (n = 2684, 80% women) is a secondary analysis of the 1-year StopDia lifestyle intervention with digital intervention group, digital intervention + face-to-face counselling group, or control group. The frequency of prior weight loss attempts was categorized into five groups: no attempts/no attempts to lose weight, but trying to keep weight stable/1-2 attempts/3 or more attempts/ continuous attempts. Data on emotional eating and social/emotional nutrition self-efficacy were collected with a digital questionnaire. We assessed baseline differences between categories of weight loss history as well as the intervention effects. RESULTS: Altogether 84% of participants had attempted weight loss. Those with one or more weight loss attempts had higher BMI, larger waist circumference, and more emotional eating compared to 'no attempts' and 'no attempts to lose weight, but trying to keep weight stable' categories. The 'no attempts' category had the highest baseline fasting insulin, whereas it showed the largest decrease in this measure with the intervention. This change in fasting insulin in the 'no attempts' category was significantly different from all the other categories. Emotional nutrition self-efficacy slightly improved in the 'no attempts' category, which was significantly different from its concomitant decrease in the categories '1-2 attempts' and '3 or more attempts'. The intervention group assignment did not affect the results. CONCLUSIONS: Multiple attempts to lose weight may unfavourably affect T2D risk factors as well as lifestyle intervention outcomes. More research is needed on how weight loss frequency could affect T2D risk factors and how to design lifestyle interventions for individuals with frequent previous weight loss attempts.

Faecal microbiota signatures of IBD and their relation to diagnosis, disease phenotype, inflammation, treatment escalation and anti-TNF response in a European Multicentre Study (IBD-Character).

METHOD: We examined faecal samples, using the GA-map™ Dysbiosis Test, to associate gut microbiota composition with Crohn's disease (CD) and ulcerative colitis (UC) and to identify markers for future biomarker identification. We conducted a prospective case-control study (EU-ref. no. 305676) in an inception cohort of 324 individuals (64 CD, 84 UC, 116 symptomatic non-IBD controls and 44 healthy controls) across five European centres and examined 54 predetermined bacterial markers. We categorized patients according to the Montreal Classification and calculated the dysbiosis index (DI). Non-parametric tests were used to compare groups and the Bonferroni correction to adjust for multiple comparisons. RESULTS: The fluorescent signals (FSSs) for Firmicutes and Eubacterium hallii were lower in inflammatory bowel disease (IBD) vs. symptomatic controls (p<.05). FSS for Firmicutes, Lachnospiraceae, Eubacterium hallii and Ruminococcus albus/bromii were lower, whereas the signal for Bacteroides Fragilis was higher in UC vs. symptomatic controls (p<.05). FSS was higher for Bifidobacterium spp., Eubacterium hallii, Actinobacteria and Firmicutes among patients with ulcerative proctitis, compared to extensive colitis (p<.05). In CD, we observed no association with disease location. The DI correlated with faecal-calprotectin in both CD and in UC (p<.001). In terms of treatment escalation and anti-TNF response, differences were observed for some bacterial markers, but none of these associations were statistically significant. CONCLUSION: Our data reveal that the GA-map™ Dysbiosis Test holds the potential to characterize the faecal microbiota composition and to assess the degree of dysbiosis in new-onset IBD. On the other hand, our results cannot demonstrate any proven diagnostic or predictive value of this method to support clinical decision making.

The effect of pre-pregnancy lifestyle counselling on food intakes and association between food intakes and gestational diabetes in high-risk women: results from a randomised controlled trial.

BACKGROUND: Healthy diets before and during pregnancy have been suggested to reduce the risk of gestational diabetes (GDM). Several lifestyle intervention studies for pregnant women have reported dietary improvements after counselling. However, evidence concerning the effect of counselling initiated before pregnancy on diets is limited. METHODS: This randomised controlled study explored whether pre-pregnancy lifestyle counselling influenced food intakes, as well as whether changes in food intakes were associated with GDM. The participants comprised 75 women with prior GDM and/or a body mass index ≥ 30 kg m-2 . Women were randomised into a control or an intervention group, and their food intakes were followed from pre-pregnancy to early pregnancy using a food frequency questionnaire. The control and intervention groups were combined to assess the association between changes in food intakes and GDM. The diagnosis of GDM was based on a 75-g oral glucose tolerance test conducted in the first and second trimester of pregnancy. RESULTS: Pre-pregnancy lifestyle counselling showed no major overall effect on food intakes. The intake of low-fat cheese increased significantly in women who did not develop GDM compared to women who did after adjusting for potential confounders (P = 0.028). This association was not observed for regular-fat cheese. CONCLUSIONS: The findings obtained in the present study suggest that an increased intake of low-fat but not regular-fat cheese between pre-pregnancy and early pregnancy is associated with a lower risk of GDM in high-risk women.

Bowel function and quality of life after superior mesenteric nerve plexus transection in right colectomy with D3 extended mesenterectomy.

BACKGROUND: The aim of this study was to ascertain the impact of injury to the superior mesenteric nerve plexus caused by right colectomy with D3 extended mesenterectomy as performed in the prospective multicenter trial: "Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic Multi-detector Computed Tomography" in which all soft tissue surrounding the superior mesenteric vessels from the level of the middle colic artery to that of the ileocolic artery was removed. METHODS: Bowel function and gastrointestinal quality of life in two consecutive cohorts that underwent right colectomy with and without D3 extended mesenterectomy were compared. Main outcome measures were the Diarrhea Assessment Scale (DAS) and Gastrointestinal Quality of Life Index (GIQLI). The data were collected prospectively through telephone interviews. RESULTS: Forty-nine patients per group, comparable for age, sex, length of bowel resected but with significantly shorter follow-up time in the experimental group, were included. There was no difference in total DAS scores, subscores or additional questions except for higher bowel frequency scores in the D3 group (p = 0.02). Comparison of total GIQLI scores and subscales showed no difference between groups. Regression analysis with correction for confounding factors showed 0.48 lower bowel frequency scores in the D2 group (p = 0.022). Within the D3 group presence of jejunal arteries cranial to the D3 dissection area showed 1.78 lower DAS scores and 0.7 lower bowel frequency scores. CONCLUSIONS: Small bowel denervation after right colectomy with D3 extended mesenterectomy leads to increased bowel frequency but does not impact gastrointestinal quality of life. Individual anatomical variants can affect postoperative bowel function differently despite standardized surgery.

Markers of cholesterol metabolism as biomarkers in predicting diabetes in the Finnish Diabetes Prevention Study.

BACKGROUND AND AIMS: We examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention Study (DPS). We also explored a possible interaction of ABCG8 rs4299376 on sterol levels and lifestyle intervention. METHODS AND RESULTS: We conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994-2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had ß-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in ß-sitosterol and campesterol: 0.76 [0.63-0.92], and 0.81 [0.67-0.99], respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 [1.13-1.62]). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on ß-sitosterol (p = 0.001) and campesterol (p = 0.004) levels during the follow-up. CONCLUSIONS: Markers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.

National diabetes prevention program (DEHKO): awareness and self-reported lifestyle changes in Finnish middle-aged population.

OBJECTIVES: The national development programme for the prevention and care of diabetes was carried out in Finland during 2000-2010. One of the programme goals was to raise awareness of diabetes and its risk factors in the whole population through various activities, e.g. media campaigns and health fares. In addition, a targeted implementation project on the prevention of type 2 diabetes, FIN-D2D, was carried out in selected districts during 2003-2008. The aim of this analysis was to examine the changes in overall awareness of the programme and its association with self-reported lifestyle changes within the adult population during the FIN-D2D project period in the FIN-D2D area compared with the area not participating in the FIN-D2D (the control area). STUDY DESIGN: Health behaviour and health among the Finnish Adult Population -postal survey. METHODS: The structured questionnaire mailed to a random population sample included questions on participants' sociodemographic background, medical history, health habits, and recent lifestyle changes. Awareness of the national diabetes programme was also enquired. Data (n = 10 831) from the 2004-2008 postal surveys were used for this investigation. RESULTS: In the FIN-D2D area, 25% (347/1384) of men and 48% (797/1674) of women reported being aware of the programme. In the control area, the proportions were 20% (702/3551) and 36% (1514/4222), respectively. The overall awareness increased among both genders and in all areas during the project period, but the level of awareness was consistently higher in the FIN-D2D area. Female gender and higher age were associated with increasing awareness of the programme in both areas. Self-reported lifestyle changes were more common among women, but associated with the level of awareness of the programme more often among men than women. CONCLUSIONS: The awareness of diabetes and its risk factors increased among men and women in both implementation and control areas during the FIN-D2D project period. The activities of the implementation project may at least partly explain the differences in lifestyle changes between areas, especially among men. The results suggest that health promotion campaigns increase the population awareness about the prevention of chronic diseases and as a result, especially men may be prompted to make beneficial lifestyle changes.

Rare human nicotinic acetylcholine receptor α4 subunit (CHRNA4) variants affect expression and function of high-affinity nicotinic acetylcholine receptors.

Nicotine, the primary psychoactive component in tobacco smoke, produces its behavioral effects through interactions with neuronal nicotinic acetylcholine receptors (nAChRs). α4ß2 nAChRs are the most abundant in mammalian brain, and converging evidence shows that this subtype mediates the rewarding and reinforcing effects of nicotine. A number of rare variants in the CHRNA4 gene that encode the α4 nAChR subunit have been identified in human subjects and appear to be underrepresented in a cohort of smokers. We compared three of these variants (α4R336C, α4P451L, and α4R487Q) to the common variant to determine their effects on α4ß2 nAChR pharmacology. We examined [(3)H]epibatidine binding, interacting proteins, and phosphorylation of the α4 nAChR subunit with liquid chromatography and tandem mass spectrometry (LC-MS/MS) in HEK 293 cells and voltage-clamp electrophysiology in Xenopus laevis oocytes. We observed significant effects of the α4 variants on nAChR expression, subcellular distribution, and sensitivity to nicotine-induced receptor upregulation. Proteomic analysis of immunopurified α4ß2 nAChRs incorporating the rare variants identified considerable differences in the intracellular interactomes due to these single amino acid substitutions. Electrophysiological characterization in X. laevis oocytes revealed alterations in the functional parameters of activation by nAChR agonists conferred by these α4 rare variants, as well as shifts in receptor function after incubation with nicotine. Taken together, these experiments suggest that genetic variation at CHRNA4 alters the assembly and expression of human α4ß2 nAChRs, resulting in receptors that are more sensitive to nicotine exposure than those assembled with the common α4 variant. The changes in nAChR pharmacology could contribute to differences in responses to smoked nicotine in individuals harboring these rare variants.

Megaesophagus in a line of transgenic rats: a model of achalasia.

Megaesophagus is defined as the abnormal enlargement or dilatation of the esophagus, characterized by a lack of normal contraction of the esophageal walls. This is called achalasia when associated with reduced or no relaxation of the lower esophageal sphincter (LES). To date, there are few naturally occurring models for this disease. A colony of transgenic (Pvrl3-Cre) rats presented with megaesophagus at 3 to 4 months of age; further breeding studies revealed a prevalence of 90% of transgene-positive animals having megaesophagus. Affected rats could be maintained on a total liquid diet long term and were shown to display the classic features of dilated esophagus, closed lower esophageal sphincter, and abnormal contractions on contrast radiography and fluoroscopy. Histologically, the findings of muscle degeneration, inflammation, and a reduced number of myenteric ganglia in the esophagus combined with ultrastructural lesions of muscle fiber disarray and mitochondrial changes in the striated muscle of these animals closely mimic that seen in the human condition. Muscle contractile studies looking at the response of the lower esophageal sphincter and fundus to electrical field stimulation, sodium nitroprusside, and L-nitro-L-arginine methyl ester also demonstrate the similarity between megaesophagus in the transgenic rats and patients with achalasia. No primary cause for megaesophagus was found, but the close parallel to the human form of the disease, as well as ease of care and manipulation of these rats, makes this a suitable model to better understand the etiology of achalasia as well as study new management and treatment options for this incurable condition.

Development of intestinal ion-transporting mechanisms during smoltification and seawater acclimation in Atlantic salmon Salmo salar.

This study investigated the expression of ion transporters involved in intestinal fluid absorption and presents evidence for developmental changes in abundance and tissue distribution of these transporters during smoltification and seawater (SW) acclimation of Atlantic salmon Salmo salar. Emphasis was placed on Na(+) , K(+) -ATPase (NKA) and Na(+) , K(+) , Cl(-) co-transporter (NKCC) isoforms, at both transcriptional and protein levels, together with transcription of chloride channel genes. The nka α1c was the dominant isoform at the transcript level in both proximal and distal intestines; also, it was the most abundant isoform expressed in the basolateral membrane of enterocytes in the proximal intestine. This isoform was also abundantly expressed in the distal intestine in the lower part of the mucosal folds. The protein expression of intestinal Nkaα1c increased during smoltification. Immunostaining was localized to the basal membrane of the enterocytes in freshwater (FW) fish, and re-distributed to a lateral position after SW entry. Two other Nka isoforms, α1a and α1b, were expressed in the intestine but were not regulated to the same extent during smoltification and subsequent SW transfer. Their localization in the intestinal wall indicates a house-keeping function in excitatory tissues. The absorptive form of the NKCC-like isoform (sub-apically located NKCC2 and/or Na(+) , Cl(-) co-transporter) increased during smoltification and further after SW transfer. The cellular distribution changed from a diffuse expression in the sub-apical regions during smoltification to clustering of the transporters closer to the apical membrane after entry to SW. Furthermore, transcript abundance indicates that the mechanisms necessary for exit of chloride ions across the basolateral membrane and into the lateral intercellular space are present in the form of one or more of three different chloride channels: cystic fibrosis transmembrane conductance regulator I and II and chloride channel 3.

Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS).

AIMS/HYPOTHESIS: This study aimed to determine whether lifestyle intervention lasting for 4 years affected diabetes incidence, body weight, glycaemia or lifestyle over 13 years among individuals at high risk of type 2 diabetes. METHODS: Overweight, middle-aged men (n = 172) and women (n = 350) with impaired glucose tolerance were randomised in 1993-1998 to an intensive lifestyle intervention group (n = 265), aiming at weight reduction, dietary modification and increased physical activity, or to a control group (n = 257) that received general lifestyle information. The primary outcome was a diagnosis of diabetes based on annual OGTTs. Secondary outcomes included changes in body weight, glycaemia, physical activity and diet. After active intervention (median 4 years, range 1-6 years), participants still free of diabetes and willing to continue their participation (200 in the intervention group and 166 in the control group) were further followed until diabetes diagnosis, dropout or the end of 2009, with a median total follow-up of 9 years and a time span of 13 years from baseline. RESULTS: During the total follow-up the adjusted HR for diabetes (intervention group vs control group) was 0.614 (95% CI 0.478, 0.789; p < 0.001). The corresponding HR during the post-intervention follow-up was 0.672 (95% CI 0.477, 0.947; p = 0.023). The former intervention group participants sustained lower absolute levels of body weight, fasting and 2 h plasma glucose and a healthier diet. Adherence to lifestyle changes during the intervention period predicted greater risk reduction during the total follow-up. CONCLUSIONS/INTERPRETATION: Lifestyle intervention in people at high risk of type 2 diabetes induces sustaining lifestyle change and results in long-term prevention of progression to type 2 diabetes.

Delaying progression to type 2 diabetes among high-risk Spanish individuals is feasible in real-life primary healthcare settings using intensive lifestyle intervention.

AIMS/HYPOTHESIS: To assess the feasibility and effectiveness of an active real-life primary care lifestyle intervention in preventing type 2 diabetes within a high-risk Mediterranean population. METHODS: A prospective cohort study was performed in the setting of Spanish primary care. White-European individuals without diabetes aged 45-75 years (n = 2,054) were screened using the Finnish Diabetes Risk Score (FINDRISC) and a subsequent 2 h OGTT. Where feasible, high-risk individuals who were identified were allocated sequentially to standard care, a group-based or an individual level intervention (intensive reinforced DE-PLAN [Diabetes in Europe-Prevention using Lifestyle, Physical Activity and Nutritional] intervention). The primary outcome was the development of diabetes according to WHO criteria. Analyses after 4-year follow-up were performed based on the intention-to-treat principle with comparison of standard care and the combined intervention groups. RESULTS: The standard care (n = 219) and intensive intervention (n = 333) groups were comparable in age (62.0/62.2 years), sex (64.4/68.2% women), BMI (31.3/31.2 kg/m(2)), FINDRISC score (16.2/15.8 points), fasting (5.3/5.2 mmol/l), 2 h plasma glucose (7.1/6.9 mmol/l) and self-reported interest to make lifestyle changes at baseline. Diabetes was diagnosed in 124 individuals: 63 (28.8%) in the standard care group and 61 (18.3%) in the intensive intervention group. During a 4.2-year median follow-up, the incidences of diabetes were 7.2 and 4.6 cases per 100 person-years, respectively (36.5% relative risk reduction, p < 0.005). The number of participants needed to be treated by intensive intervention for 4 years to reduce one case of diabetes was 9.5. CONCLUSIONS/INTERPRETATION: Intensive lifestyle intervention is feasible in a primary care setting and substantially reduces diabetes incidence among high-risk individuals. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov NCT01519505. FUNDING: Commission of the European Communities, Institute of Health Carlos III, Spanish Ministry of Health and Department of Health, Generalitat de Catalunya.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 ± 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood.

Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance.

AIMS: The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort. METHODS: Two hundred and sixty-eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow-up, were studied for cardiovascular autonomic neuropathy. At the second annual follow-up visit after the end of lifestyle intervention, we performed deep-breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA(1c,) serum lipids and blood pressure were carried out. RESULTS: Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight, waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P<0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA(1c) . Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women. CONCLUSIONS: Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy.

HbA(1c) in diagnosing and predicting Type 2 diabetes in impaired glucose tolerance: the Finnish Diabetes Prevention Study.

AIMS: We analysed the Finnish Diabetes Prevention Study data in order to evaluate how the new HbA(1c) -based criterion compares with the oral glucose tolerance test in diagnosing Type 2 diabetes among high-risk individuals during a prospective average follow-up of 4 years. METHODS: In the Diabetes Prevention Study, 172 men and 350 women who were overweight and had impaired glucose tolerance at baseline were randomized into an intensive lifestyle intervention or a control group. The oral glucose tolerance test and HbA(1c) measurements were performed annually until the diagnosis of diabetes using the World Health Organization 1985 criteria. RESULTS: The sensitivity of the HbA(1c) ≥ 6.5% (≥ 48 mmol/mol) as a diagnostic criterion for Type 2 diabetes was 35% (95% CI 24%, 47%) in women and 47% (95% CI 31%, 64%) in men compared with diagnosis based on two consecutive oral glucose tolerance tests. The corresponding sensitivities for HbA(1c) ≥ 6.0% (≥ 42 mmol/mol) were 67% (95% CI 55%, 77%) and 68% (95% CI 51%, 82%). The participants with HbA(1c) ≥ 6.5% (≥ 48 mmol/mol) and diabetes based on the oral glucose tolerance test were more obese and had higher fasting glucose and 2-h glucose concentrations than those who had a diabetic oral glucose tolerance test but HbA(1c) < 6.5% (< 48 mmol/mol). There were no differences in the predictive performance of baseline fasting glucose, oral glucose tolerance test and HbA(1c) . CONCLUSIONS: Of those with diabetes diagnosis based on two oral glucose tolerance tests during the Diabetes Prevention Study follow-up, 60% would have remained undiagnosed if diagnosis had been based on HbA(1c) ≥ 6.5% (≥ 48 mmol/mol) criterion.

Shifting from glucose diagnostic criteria to the new HbA(1c) criteria would have a profound impact on prevalence of diabetes among a high-risk Spanish population.

AIM: To investigate changes in the prevalence of diabetes and pre-diabetes by shifting from 2-h plasma glucose and/or fasting plasma glucose diagnostic criteria to the proposed new HbA(1c) -based criteria when applied to a Mediterranean population detected to have a high risk of Type 2 diabetes. METHODS: Individuals without diabetes aged 45-75 years (n = 2287) were screened using the Finnish Diabetes Risk Score questionnaire, a 2-h oral glucose tolerance test plus HbA(1c) test. Prevalence and degree of diagnostic overlap between three sets of criteria (2-h plasma glucose, fasting plasma glucose and HbA(1c) ) and three diagnostic categories (normal, pre-diabetes and diabetes) were calculated. RESULTS: Defining diabetes by a single HbA(1c) measurement resulted in a dramatic decrease in prevalence (1.3%), particularly in comparison with diabetes defined by 2-h plasma glucose (8.6%), but was also significant with regard to fasting plasma glucose (2.8%). A total of 201 screened subjects (8.8%) were classified as having diabetes and 1023 (44.7%) as having pre-diabetes based on at least one of these criteria; among these, the presence of all three criteria simultaneously classified only 21 and 110 individuals respectively, about ten percent of each group. The single overlap index between subjects diagnosed as having diabetes by 2-h plasma glucose/fasting plasma glucose vs. HbA(1c) was 13.9/28%. Similarly, the single overlap index regarding pre-diabetes was 19.2/27.1%. CONCLUSIONS: A shift from the glucose-based diagnosis to the HbA(1c) -based diagnosis for diabetes will reduce diabetes prevalence with a low overall or single degree of overlap between diagnostic categories in this high-risk Spanish population.

Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism--the Finnish Diabetes Prevention Study.

BACKGROUND AND AIM: The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C - reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM). METHODS AND RESULTS: In the DPS, altogether 490 (BMI≥25kg/m(2)) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men. In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17-3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes. CONCLUSION: We suggest that the variation in the FTO gene may contribute to the development of CVD in men with an abnormal glucose metabolism.

Gustatory and olfactory dysfunction in older adults: a national probability study.

BACKGROUND: Olfactory and gustatory functions have not been well characterized in older adults in the US. Consequently, their relationships to sociodemographic characteristics, as well as physical and mental health, were studied in a large national probability sample using brief validated tests of chemosensory function. METHODS: A five-odour identification test and taste-impregnated strips of filter paper (sweet, sour, bitter, and salty) assessed the ability to identify chemosensory stimuli. RESULTS: Severe gustatory dysfunction was more prevalent than severe olfactory dysfunction. Age, education and sex were independently associated with performance on both the olfactory and gustatory identification tasks. Higher scores were associated with female sex, higher level of education, and lower age. Odour identification scores exhibited a positive, albeit weak, correlation with BMI, and food-related odours were better identified than non-food odours. In addition, odour identification performance was also negatively associated with depressive symptoms. CONCLUSIONS: These data demonstrate a high prevalence of severe gustatory and, to a somewhat lesser extent, olfactory dysfunction in a population-based sample and demonstrate that even brief tests are capable of detecting correlations between both chemical senses and relevant health measures outside a clinical setting.

Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease.

BACKGROUND: Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]. METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins. RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10-23] and oncostatin-M [OSM; p = 3.7 × 10-16]. Nine of these proteins are associated with cis-germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224-756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43-6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn's disease respectively. CONCLUSION: We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.

Experimental autoimmune myasthenia: A model of myasthenia gravis in rats and guinea pigs.

Immunization of animals with acetylcholine receptor (AChR) protein from the electric organs of Electrophorus electricus and Torpedo californica induces an autoimmune response to the AChR of mammalian skeletal muscle. Rats and guinea pigs develop experimental autoimmune myasthenia gravis (EAMG) after a single inoculation with small quantities of AChR and adjuvant. The indicence and severity of disease appears to depend on the dose of AChR and stability of the emulsion. EAMG is strikingly similar to myasthenia gravis (MG) of man in its clinical picture and its electrophysiological abnormalities. The presence of antibodies to syngeneic rat muscle AChR in the serum of rats with EAMG documents the existence of autoimmunity in the experimental disease. A common immunopathogenesis is suggested for both EAMG and mg.

Role of complement in the pathogenesis of experimental autoimmune myasthenia gravis.

An acute phase of experimental autoimmune myasthenia gravis (EAMG) occurs transiently early in the immune response of Lewis rats to nicotinic acetylcholine receptors (AChR) when Bordetella pertussis is used as adjuvant. It is characterized by a destructive cellular attack directed at the postsynaptic membranes of muscle. Acute EAMG can be passively transferred to normal rats by IgG from serum of rats with chronic EAMG. In the present study, acute EAMG, induced either by passive transfer of syngeneic antibodies or by active immmunization, was inhibited in rats depleted of complement by treatment with cobra venom factor (CoF). Furthermore, passive transfer of antibodies in excess of the muscle's content of AChR was without any measurable effect in rats treated with CoF. Although 60% of the muscle's AChR was complexed with antibody, there was no reduction in the muscle's content of AChR, and neuromuscular transmission was not compromised as judged electromyographically by curare sensitivity. These data imply that redistribution, accelerated degradation, and impairment of the ionophore function of AChR, effects of antibodies described in vitro on extrajunctional AChR, do not play a significant role in vivo in impairing neuromuscular transmission in an intact neuromuscular junction. Complement appears to be a critical mediator of anti-AChR antibodies' pathogenicity in vivo.