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Diabetes Risk (diabetes + risk)
Terms modified by Diabetes Risk Selected AbstractsUnivariate and Bivariate Linkage Analysis Identifies Pleiotropic Loci Underlying Lipid Levels and Type 2 Diabetes RiskANNALS OF HUMAN GENETICS, Issue 4 2010Sandra J. Hasstedt Summary Dyslipidemia frequently co-occurs with type 2 diabetes (T2D) and with obesity. To investigate whether the co-occurrence is due to pleiotropic genes, we performed univariate linkage analysis of lipid levels and bivariate linkage analysis of pairs of lipid levels and of lipid levels paired with T2D, body mass index (BMI), and waist-hip ratio (WHR) in the African American subset of the Genetics of NIDDM (GENNID) sample. We obtained significant evidence for a pleiotropic low density lipoprotein cholesterol (LDL-C),T2D locus on chromosome 1 at 16,19 megabases (MB) (bivariate lod = 4.41), as well as a non-pleiotropic triglyceride (TG) locus on chromosome 20 at 28,34 MB (univariate lod = 3.57). In addition, near-significant evidence supported TG,T2D loci on chromosome 2 at 81,101 MB (bivariate lod = 4.23) and 232,239 MB (bivariate lod = 4.27) and on chromosome 7 at 147,151 MB (univariate lod = 3.08 for TG with P = 0.041 supporting pleiotropy with T2D), as well as an LDL-C,BMI locus on chromosome 3 at 137,147 MB (bivariate lod score = 4.25). These findings provide evidence that at least some of the co-occurrence of dyslipidemia with T2D and obesity is due to common underlying genes. [source] Genetic and perinatal factors as risk for childhood type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2004Karin Larsson Abstract The mechanisms by which gestational infections, blood incompatibility, birth weight, mother's age and other prenatal or neonatal events increase the risk for type 1 diabetes are not understood. Studies so far have been retrospective, and there is a lack of population-based prospective studies. The possibility of identifying children at type 1 diabetes risk among first-degree relatives has resulted in prospective studies aimed at identifying postnatal events associated with the appearance of autoantibody markers for type 1 diabetes and a possible later onset of diabetes. However, the majority (85%) of new onset type 1 diabetes children do not have a first-degree relative with the disease. Population-based studies are therefore designed to prospectively analyse pregnant mothers and their offspring. One such study is DiPiS (Diabetes Prediction in Skåne), which is examining a total of about 10 000 pregnancies expected every year in the Skåne (Scania) region of Sweden that has 1.1 million inhabitants. Blood samples from all mothers in this region are obtained during pregnancy and at the time of delivery. Cord blood is analysed for HLA high-risk alleles and for autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GADA), the protein tyrosine phosphatase,related IA-2 antigen (IA-2A) and insulin (IAA) as a measure of prenatal autoimmune exposure. Identifying high-risk children by genetic, autoimmune and gestational risk factors followed by prospective analyses will make it possible to test the hypothesis that gestational events may trigger beta cell autoimmunity as a prerequisite for childhood type 1 diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source] Gene,gene interactions between HNF4A and KCNJ11 in predicting Type 2 diabetes in womenDIABETIC MEDICINE, Issue 11 2007L. Qi Abstract Aims Recent studies indicate transcription factor hepatocyte nuclear factor 4, (HNF-4,, HNF4A) modulates the transcription of the pancreatic B-cell ATP-sensitive K+ (KATP) channel subunit Kir6.2 gene (KCNJ11). Both HNF4A and KCNJ11 have previously been associated with diabetes risk but little is known whether the variations in these genes interact with each other. Methods We conducted a prospective, nested case,control study of 714 incident cases of Type 2 diabetes and 1120 control subjects from the Nurses' Health Study. Results KCNJ11 E23K was significantly associated with an increased diabetes risk (odds ratio 1.26, 95% CI 1.03,1.53) while HNF4A P2 promoter polymorphisms were associated with a moderately increased risk at borderline significance. By using a logistic regression model, we found significant interactions between HNF4A rs2144908, rs4810424 and rs1884613 and KCNJ11 E23K (P for interaction = 0.017, 0.012 and 0.004, respectively). Carrying the minor alleles of the three HNF4A polymorphisms was associated with significantly greater diabetes risk in women carrying the KCNJ11 allele 23K, but not in those who did not carry this allele. Analyses using the multifactor dimensionality reduction (MDR) method confirmed the gene,gene interaction. We identified that the best interaction model included HNF4A rs2144908 and KCNJ11 E23K. Such a two-locus model showed the maximum cross-validation consistency of 10 out of 10 and a significant prediction accuracy of 54.2% (P = 0.01) on the basis of 1000-fold permutation testing. Conclusions Our data indicate that HNF4A P2 promoter polymorphisms may interact with KCNJ11 E23K in predicting Type 2 diabetes in women. [source] Type 2 diabetes in families and diabetes preventionEUROPEAN DIABETES NURSING, Issue 2 2008FRCP Professor of Diabetic Molecular Medicine, M Walker MD Abstract Type 2 diabetes frequently clusters in families. Non-diabetic first-degree relatives (offspring and siblings) of patients with type 2 diabetes have a three-fold increased lifetime risk of developing diabetes compared with the background population. This increased diabetes risk results from the combined effects of shared genetic and lifestyle factors. Extensive studies of non-diabetic relatives of type 2 diabetic families show that impaired insulin secretion, insulin resistance and an adverse cardiovascular risk factor profile exist well before the development of frank diabetes. Despite this well-documented adverse metabolic predisposition, patients with type 2 diabetes and their non-diabetic relatives generally have a limited understanding of the risks. Several large-scale studies, such as the Finnish Diabetes Prevention and Diabetes Prevention Program studies, indicate unequivocally that lifestyle modification through dietary change and exercise can dramatically decrease risk of progression to diabetes in high-risk subjects. However, such individuals pursue lifestyle changes only if they understand their own risk of developing diabetes. Further work is therefore needed to investigate and develop optimal ways of improving knowledge of diabetes risk in families of patients with type 2 diabetes, so that they can appreciate the potential benefits of diabetes prevention strategies. Copyright © 2008 FEND [source] Parent responses to participation in genetic screening for diabetes riskPEDIATRIC DIABETES, Issue 4 2004Barbro Lernmark Abstract:, Screening for type 1 diabetes (T1DM) risk in newborns has little negative emotional impact on mothers. In this study, the impact on the mother and the father was evaluated both in the general population and in families with diabetes. All parents with a newborn in Skåne, Sweden, were invited to a screening for T1DM risk in their children (the Diabetes Prediction in Skåne (DiPiS)). Blood was obtained at delivery from the mother and the child. When the child was 2 months old, parents gave written consent and filled out questionnaires, but were not informed about the genetic risk. Of the 10 538 invited families, 6831 (64.8%) consented and 806 (7.7%) declined participation. Five questions addressing both parents were filled out by 6676 (63.4%) mothers and 6099 (57.8%) fathers. In 146/6676 (2.2%) families, one family member had diabetes (D-families). Participation in DiPiS did not affect most parents and the majority was satisfied with the information. The majority of parents (28.9%) were reassured and only 1.1% (140/12 670) reported increased worries because of participation, compared to 2.8% of the mothers in D-families. Parents in D-families more often ascribed diabetes risk to their child as well as the risk being higher. Mothers and fathers differed in their answers on four of the five study questions, with mothers being more satisfied with the information, reporting more knowledge of diabetes, estimating lower risk of their child to get diabetes, but reporting more worries of possible future chronic disease in the child. Parents with lower education, being born abroad, or being younger who reported worries of chronic disease in the child were also reassured by participation in the study. These results confirm that screening for T1DM risk in newborns does not create worries in most parents, but stress that fathers differ from mothers in opinions and reactions, that parents' reactions are affected by diabetes in the family, and that demographic factors might be important for the parents' reports. [source] HLA class II genetic association of type 1 diabetes mellitus in Czech childrenPEDIATRIC DIABETES, Issue 3 2001Ondrej Cinek Abstract:, To examine human leukocyte antigen (HLA) class II association of type 1 diabetes mellitus (DM) in Czech children, we performed a case,control study of 261 patients diagnosed before the age of 15 and 289 non-diabetic control children. Complete HLA-DQA1, DQB1 genotyping and DRB1*04 subtyping were carried out by polymerase chain reactions with sequence-specific primers. The effect of the DRB1*04 subtypes was studied in DRB1*04 alleles carried on DQB1*0302-DQA1*03 haplotypes. The risk was statistically evaluated by testing 2 × 2 tables, considering corrected p-values <,0.05 significant. The DQB1*0302 (odds ratio, OR = 9.0), DQB1*0201 (OR = 3.4) and DQA1*03 (OR = 7.5) alleles were significantly associated with diabetes risk, while the DQB1*0602 (OR = 0.02), DQB1*0301 (OR = 0.08), DQB1*0503 (OR = 0.13), DQB1*0603 (OR = 0.20), DQA1*01 (OR = 0.28) and DQA1*02 (OR = 0.26) alleles were significantly protective. Of the DQA1-DQB1 genotypes, we point out the extremely high risk of OR = 116 conferred by HLA-DQA1*05-DQB1*0201/DQA1*03-DQB1*0302. Among DRB1*04 subtypes, DRB1*0403 was significantly protective (OR = 0.05, CI 95% 0.01,0.45). Since none of the remaining DRB1*04 subtypes was associated with type 1 DM, our study may present another piece of evidence that the DRB1*0401 and DRB1*0404 alleles do not modify type 1 diabetes risk generally in European populations. [source] Glutamic acid decarboxylase and IA-2 autoantibodies in type 1 diabetes: comparing sample substrates for autoantibody determinationsPEDIATRIC DIABETES, Issue 1 2000C Wasserfall Large-scale programs designed to assess risk for type 1 diabetes through serologic assessment of autoantibodies to recombinant ,-cell autoantigens are hampered by several limitations, including the methods for sample collection and assay performance, as well as the volume required for autoantibody determinations. The present study was designed to develop a low sample-volume, primary screening method for autoantibody detection of high specificity and sensitivity, and to determine the feasibility of dried blood spots collected on filter paper in serving as vehicles for such determinations. Autoantibodies to glutamic acid decarboxylase (GAD) and ICA512bdc (IA-2), both individually and in combination, were determined in persons with type 1 diabetes, healthy controls, or individuals with other autoimmune disorders. Autoantibody results for serum, plasma, and dried blood spots were compared. GAD, IA-2, and combined GAD/IA-2 autoantibodies were concordant in their measurement from minimal volumes of serum, plasma, and whole blood extracted from dried filter paper. The autoantibody levels from the dried blood spots were, however, lower than corresponding serum samples, and, as currently designed, failed to detect low-titer autoantibodies. Despite this limitation, screening for diabetes risk can be performed using small volumes of whole blood, serum, or plasma collected onto filter paper. These methodological improvements should simplify matters, reduce costs, and increase the efficacy of screening programs for type 1 diabetes. Further development of better substrates/methods for blood-specimen collection seems necessary to exploit the full potential of this and other autoantibody measurement strategies for screening large populations. [source] Latest news and product developmentsPRESCRIBER, Issue 13-14 2008Article first published online: 29 JUL 200 NSAIDs stroke risk NSAIDs have been linked with an increased risk of stroke in an epidemiological study from The Netherlands (Arch Intern Med 2008;168: 1219-24). Nine years' follow-up of 7636 older persons (mean age 70) identified 807 strokes. The risk of stroke was significantly increased for current use of nonselective NSAIDs (hazard ratio 1.72 for all strokes) and COX-2 selective NSAIDs (HR 2.75 for all strokes; HR 4.54 for ischaemic stroke). Increased risk was found for several individual NSAIDs but was statistically significant only for naproxen (HR 2.63) and the withdrawn rofecoxib (HR 3.38). HPV vaccine chosen The DoH has chosen GlaxoSmithKline's Cervarix HPV vaccine for the national immunisation campaign beginning in September. Cervarix is a bivalent vaccine conferring immunity against HPV16 and 18, which account for 70 per cent of cervical cancers worldwide. Its competitor, Gardasil, is a quadrivalent vaccine additionally protecting against HPV6 and 11, which cause 90 per cent of genital warts. The procurement process assessed the vaccines against ,a wide range of criteria such as their scientific qualities and cost effectiveness'. The DoH has not revealed what it will pay for Cervarix. Melatonin for insomnia Lundbeck has introduced melatonin (Circadin) as monotherapy for the short-term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over. The dose is 2mg once daily two hours before bed-time and after food for three weeks. A course costs £10.77. Fesoterodine launched Pfizer has introduced feso-terodine (Toviaz), a prodrug for tolterodine (Detrusitol), for the treatment of symptoms of overactive bladder. Treatment is initiated at a dose of 4mg per day and increased to 8mg per day according to response. The full therapeutic effect may not occur until after two to eight weeks; treatment should be re-evaluated after eight weeks. A month's treatment at either dose costs £29.03, the same as sustained-release tolterodine (Detrusitol XL). Intensive glycaemic control for T2D? Two large trials of intensive glycaemic control in patients with type 2 diabetes have conflicting implications for clinical practice. The ACCORD study (N Engl J Med 2008;358:2545-9) found that treating patients at high CVD risk to a target HbA1c of <6.0 per cent was associated with a 22 per cent increased risk of death and no reduction in macrovascular end-points compared with a target of 7.0-7.9 per cent. The ADVANCE study compared treating to a standard (HbA1c 7.3 per cent) or low (HBA1c 6.5 per cent) target. More intensive glycaemic control significantly reduced microvascular end-points, primarily due to a reduction in nephropathy. There was no difference in the risk of retinopathy or macrovascular end-points. Nicorandil as ulcer cause The potassium-channel activator nicorandil (Ikorel) may be associated with gastro-intestinal ulceration but is frequently overlooked as a possible cause, warns the MHRA in its latest Drug Safety Update (2008;1:Issue 11). Ulceration may affect any portion of the gastro-intestinal tract from the mouth to the perianal area, and it is frequently severe and may cause perforation. Ulcers due to nicorandil are refractory to treatment and only resolve on withdrawal of the drug. Withdrawal should be carried out under the supervision of a cardiologist. , This issue of Drug Safety Update also includes an overview of safety issues with natalizumab (Tysabri) for multiple sclerosis. Atypical antipsychotics diabetes risk ,small' The excess risk of diabetes due to treatment with an atypical antipsychotic is small compared with older anti-psychotics, say UK researchers (Br J Psychiatry 2008;192:406-11). Their meta-analysis of 11 studies found that, compared with the use of first-generation antipsychotics in patients with schizophrenia, the over-all increased risk of diabetes with atypicals was 32 per cent. Risperidone was associated with lowest excess risk (16 per cent), followed by quetiapine (Seroquel) and olanzapine (Zyprexa; 28 per cent) then clozapine (39 per cent). Most studies had method-ological limitations. Copyright © 2008 Wiley Interface Ltd [source] Ethnicity and gestational diabetes in New York City, 1995,2003BJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 8 2008DA Savitz Objective, To characterise the patterns of occurrence of gestational diabetes among a wide range of ethnic groups that reside in New York City. Design, Birth records and hospital discharge data were linked to more accurately assess the risk of gestational diabetes by ethnicity, compare risk in US-born to foreign-born women, and assess time trends. Setting, New York City. Population, All singleton live births occurring between 1995 and 2003. Methods, Multivariable binomial regression analysis of ethnicity and gestational diabetes, yielding adjusted risk ratios with non-Hispanic white women as the referent. Main outcome measure, Diagnosis of gestational diabetes on birth certificate or in hospital discharge. Results, Adjusted relative risks (aRRs) were modestly elevated for African-Americans and sub-Saharan Africans and somewhat higher (<2.0) for non-Hispanic Caribbeans, Hispanic Caribbeans, Central Americans, and South Americans. The aRR was 4.7 (95% CI = 4.6,4.9) for South Central Asians (with an absolute gestational diabetes risk of 14.3%), 2.8 (95% CI = 2.7,3.0) among South-East Asian and Pacific Islanders, and 2.3 (95% CI = 2.2,2.4) among East Asians. Among South Central Asians, the greatest risks were found for women from Bangladesh (aRR = 7.1, 95% CI = 6.8,7.3). Foreign-born women consistently had higher risk than US-born women. Risk for gestational diabetes increased over time among South Central Asians, some Hispanic groups, and African-Americans. Conclusions, Risk of gestational diabetes appears to vary markedly among ethnic groups, subject to potential artefacts associated with screening and diagnosis. These differences would have direct implications for health care and may suggest aetiologic hypotheses. [source] | ||||||||||