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211.
Anthony A. Menditto Charles J. Wallace Robert P. Liberman Jillon Vander Wal Nicole Tuomi Jones Paul Stuve 《American journal of psychiatric rehabilitation》2013,16(2):200-219
Abstract Functional assessment of persons with psychiatric disabilities requires reliable and valid instruments that can be used by clinicians for planning psychosocial rehabilitation services. Two such instruments, the Independent Living Skills Inventory and the Independent Living Skills Survey are operationalized and behaviorally specific tools that can be administered as questionnaires or interviews. Both instruments have well-documented reliability and validity and are ‘user-friendly.” 相似文献
212.
213.
Mette K. Andersen Maria Sterner Tom Forsén Annemari Käräjämäki Olov Rolandsson Carol Forsblom Per-Henrik Groop Kaj Lahti Peter M. Nilsson Leif Groop Tiinamaija Tuomi 《Diabetologia》2014,57(9):1859-1868
Aims/hypothesis
Latent autoimmune diabetes in adults (LADA) is phenotypically a hybrid of type 1 and type 2 diabetes. Genetically LADA is poorly characterised but does share genetic predisposition with type 1 diabetes. We aimed to improve the genetic characterisation of LADA and hypothesised that type 2 diabetes-associated gene variants also predispose to LADA, and that the associations would be strongest in LADA patients with low levels of GAD autoantibodies (GADA).Methods
We assessed 41 type 2 diabetes-associated gene variants in Finnish (phase I) and Swedish (phase II) patients with LADA (n?=?911) or type 1 diabetes (n?=?406), all diagnosed after the age of 35 years, as well as in non-diabetic control individuals 40 years or older (n?=?4,002).Results
Variants in the ZMIZ1 (rs12571751, p?=?4.1?×?10?5) and TCF7L2 (rs7903146, p?=?5.8?×?10?4) loci were strongly associated with LADA. Variants in the KCNQ1 (rs2237895, p?=?0.0012), HHEX (rs1111875, p?=?0.0024 in Finns) and MTNR1B (rs10830963, p?=?0.0039) loci showed the strongest association in patients with low GADA, supporting the hypothesis that the disease in these patients is more like type 2 diabetes. In contrast, variants in the KLHDC5 (rs10842994, p?=?9.5?×?10?4 in Finns), TP53INP1 (rs896854, p?=?0.005), CDKAL1 (rs7756992, p?=?7.0?×?10?4; rs7754840, p?=?8.8?×?10?4) and PROX1 (rs340874, p?=?0.003) loci showed the strongest association in patients with high GADA. For type 1 diabetes, a strong association was seen for MTNR1B (rs10830963, p?=?3.2?×?10?6) and HNF1A (rs2650000, p?=?0.0012).Conclusions/interpretation
LADA and adult-onset type 1 diabetes share genetic risk variants with type 2 diabetes, supporting the idea of a hybrid form of diabetes and distinguishing them from patients with classical young-onset type 1 diabetes. 相似文献214.
215.
B. Isomaa B. Forsén K. Lahti N. Holmström J. Wadén O. Matintupa P. Almgren J. G. Eriksson V. Lyssenko M.-R. Taskinen T. Tuomi L. C. Groop 《Diabetologia》2010,53(8):1709-1713
Aims/hypothesis
We studied the impact of a family history of type 2 diabetes on physical fitness, lifestyle factors and diabetes-related metabolic factors.Methods
The Prevalence, Prediction and Prevention of Diabetes (PPP)–Botnia study is a population-based study in Western Finland, which includes a random sample of 5,208 individuals aged 18 to 75 years identified through the national Finnish Population Registry. Physical activity, dietary habits and family history of type 2 diabetes were assessed by questionnaires and physical fitness by a validated 2 km walking test. Insulin secretion and action were assessed based upon OGTT measurements of insulin and glucose.Results
A family history of type 2 diabetes was associated with a 2.4-fold risk of diabetes and lower physical fitness (maximal aerobic capacity 29.2?±?7.2 vs 32.1?±?7.0, p?=?0.01) despite having similar reported physical activity to that of individuals with no family history. The same individuals also had reduced insulin secretion adjusted for insulin resistance, i.e. disposition index (p?<?0.001) despite having higher BMI (27.4?±?4.6 vs 26.0?±?4.3 kg/m2, p?<?0.001).Conclusions/interpretation
Individuals with a family history of type 2 diabetes are characterised by lower physical fitness, which cannot solely be explained by lower physical activity. They also have an impaired capacity of beta cells to compensate for an increase in insulin resistance imposed by an increase in BMI. These defects should be important targets for interventions aiming at preventing type 2 diabetes in individuals with inherited susceptibility to the disease. 相似文献216.
Virve M. Lundgren Bo Isomaa Valeriya Lyssenko Esa Laurila Pasi Korhonen Leif C. Groop Tiinamaija Tuomi for the Botnia Study Group 《Diabetes》2010,59(2):416-422
OBJECTIVE
To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FHT1) or type 2 diabetes (FHT2) in nondiabetic subjects.RESEARCH DESIGN AND METHODS
GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA+—a total of 253 GADA+ and 2,511 GADA− subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis.RESULTS
Subjects within the highest quartile of GADA+ (GADA+high) had more often first-degree FHT1 (29.2 vs. 7.9%, P < 0.00001) and GADA+ type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA− subjects. During the follow-up, the GADA+ subjects developed diabetes significantly more often than the GADA− subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA+high conferred a 4.9-fold increased risk of diabetes (95% CI 2.8–8.5) compared with GADA−—seroconversion to positive during the follow-up was associated with 6.5-fold (2.8–15.2) and first-degree FHT1 with 2.2-fold (1.2–4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non–insulin-dependent phenotype 1 year after diagnosis. GADA+ and GADA− subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes.CONCLUSIONS
GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.Latent autoimmune diabetes in adults (LADA) was introduced nearly 2 decades ago to separate a GAD antibody (GADA)-positive subgroup of adult patients initially diagnosed with type 2 diabetes (1,2). Using this definition with the add-on criteria of no exogenous insulin during the first 6–12 months, the prevalence of LADA among unselected “type 2 diabetic patients” is ∼25% in subjects younger than 35 years and between 4 and 13% in subjects older than 35 years at diagnosis in populations of European origin (3–9). In follow-up studies, a progressive defect in insulin secretion was observed in ∼50–60% of LADA patients within 6–10 years (3,10), which led to the inclusion of these patients as a slowly progressing form of type 1 diabetes in the last World Health Organization (WHO) classification of diabetes (11). However, both the existence of LADA as a distinct subgroup of diabetes and the criteria that should be used to diagnose it have been challenged (e.g., (12,13). The LADA group is heterogeneous, and most studies have been cross-sectional, whereas prospective studies including patients at or before diagnosis and population-based studies are few (3,4,14–16). Genetic background, especially for type 1 diabetes, may be a confounding factor, and we have shown that LADA was more frequent in families with both type 1 and type 2 diabetes than in families with type 2 diabetes only (17). Moreover, some data support that type 1 and type 2 diabetes cluster in same families (17–20), although this has been contradicted in a large U.K. study on parents of type 1 diabetic patients (21).In children, progression to diabetes has been associated with high antibody levels and early development of multiple autoantibodies, whereas subjects with a later appearance of antibodies had a slower progression (22–25). We have previously hypothesized that GADAs would be a marker of a subclinical autoimmune process and showed that GADA positivity was associated with a decrease in maximal insulin secretory capacity in nondiabetic subjects (26). If that is the case, GADAs should also be a predictor of future diabetes in adults. This was not supported by two studies on the general population (16,27), but a Swedish study reported a sixfold increased risk for diabetes in GADA+ subjects (15).In a prospective follow-up study of a large cohort of relatives of type 2 diabetic patients and population control subjects from Finland, we have now evaluated the predictive value of GADAs and family history for type 1 or type 2 diabetes in conjunction with the traditional risk factors for diabetes. 相似文献217.
Florez JC Sjögren M Agapakis CM Burtt NP Almgren P Lindblad U Berglund G Tuomi T Gaudet D Daly MJ Ardlie KG Hirschhorn JN Altshuler D Groop L 《Diabetologia》2007,50(6):1209-1217
Aims/hypothesis Activation of the insulin receptor substrate-1 (IRS1) is a key initial step in the insulin signalling pathway. Despite several
reports of association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we and others have not observed this association in well-powered samples. However, other nearby variants
might account for the putative association signal.
Subjects and methods We characterised the haplotype map of IRS1 and selected 20 markers designed to capture common variations in the region. We genotyped this comprehensive set of markers
in several family-based and case-control samples of European descent totalling 12,129 subjects.
Results In an initial sample of 2,235 North American and Polish case-control pairs, the minor allele of the rs934167 polymorphism
showed nominal evidence of association with type 2 diabetes (odds ratio [OR] 1.25, 95% CI 1.03–1.51, p = 0.03). This association showed a trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96–1.39,
p = 0.059). The combined OR was 1.20 (p = 0.008), but statistical correction for the number of variants examined yielded a p value of 0.086. We detected no differences across rs934167 genotypes in insulin-related quantitative traits.
Conclusions/interpretation Our data do not support an association of common variants in IRS1 with type 2 diabetes in populations of European descent.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.
D. Altshuler and L. Groop jointly supervised this project. 相似文献
218.
Snoring is a prevalent condition with a variety of negative social effects and associated health problems. Treatments, both surgical and therapeutic, have been developed, but the objective non-invasive monitoring of their success remains problematic. We present a method which allows the automatic monitoring of snoring characteristics, such as intensity and frequency, from audio data captured via a freestanding microphone. This represents a simple and portable diagnostic alternative to polysomnography. Our system is based on methods that have proved effective in the field of speech recognition. Hidden Markov models (HMMs) were employed as basic elements with which to model different types of sound by means of spectrally based features. This allows periods of snoring to be identified, while rejecting silence, breathing and other sounds. Training and test data were gathered from six subjects, and annotated appropriately. The system was tested by requiring it to automatically classify snoring sounds in new audio recordings and then comparing the result with manually obtained annotations. We found that our system was able to correctly identify snores with 82-89% accuracy, despite the small size of the training set. We could further demonstrate how this segmentation can be used to measure the snoring intensity, snoring frequency and snoring index. We conclude that a system based on hidden Markov models and spectrally based features is effective in the automatic detection and monitoring of snoring from audio data. 相似文献