23 research outputs found
Sequence variants associating with urinary biomarkers
Urine dipstick tests are widely used in routine medical care to diagnose kidney and urinary tract and metabolic diseases. Several environmental factors are known to affect the test results, whereas the effects of genetic diversity are largely unknown. We tested 32.5 million sequence variants for association with urinary biomarkers in a set of 150 274 Icelanders with urine dipstick measurements. We detected 20 association signals, of which 14 are novel, associating with at least one of five clinical entities defined by the urine dipstick: glucosuria, ketonuria, proteinuria, hematuria and urine pH. These include three independent glucosuria variants at SLC5A2, the gene encoding the sodium-dependent glucose transporter (SGLT2), a protein targeted pharmacologically to increase urinary glucose excretion in the treatment of diabetes. Two variants associating with proteinuria are in LRP2 and CUBN, encoding the co-transporters megalin and cubilin, respectively, that mediate proximal tubule protein uptake. One of the hematuria-associated variants is a rare, previously unreported 2.5 kb exonic deletion in COL4A3. Of the four signals associated with urine pH, we note that the pH-increasing alleles of two variants (POU2AF1, WDR72) associate significantly with increased risk of kidney stones. Our results reveal that genetic factors affect variability in urinary biomarkers, in both a disease dependent and independent context
Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenLoss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.US National Institutes of Health (NIH) Training
5-T32-GM007748-33
Doris Duke Charitable Foundation
2006087
Fulbright Diabetes UK Fellowship
BDA 11/0004348
Broad Institute from Pfizer, Inc.
NIH
U01 DK085501
U01 DK085524
U01 DK085545
U01 DK085584
Swedish Research Council
Dnr 521-2010-3490
Dnr 349-2006-237
European Research Council (ERC)
GENETARGET T2D
GA269045
ENGAGE
2007-201413
CEED3
2008-223211
Sigrid Juselius Foundation
Folkh lsan Research Foundation
ERC
AdG 293574
Research Council of Norway
197064/V50
KG Jebsen Foundation
University of Bergen
Western Norway Health Authority
Lundbeck Foundation
Novo Nordisk Foundation
Wellcome Trust
WT098017
WT064890
WT090532
WT090367
WT098381
Uppsala University
Swedish Research Council and the Swedish Heart- Lung Foundation
Academy of Finland
124243
102318
123885
139635
Finnish Heart Foundation
Finnish Diabetes Foundation, Tekes
1510/31/06
Commission of the European Community
HEALTH-F2-2007-201681
Ministry of Education and Culture of Finland
European Commission Framework Programme 6 Integrated Project
LSHM-CT-2004-005272
City of Kuopio and Social Insurance Institution of Finland
Finnish Foundation for Cardiovascular Disease
NIH/NIDDK
U01-DK085545
National Heart, Lung, and Blood Institute (NHLBI)
National Institute on Minority Health and Health Disparities
N01 HC-95170
N01 HC-95171
N01 HC-95172
European Union Seventh Framework Programme, DIAPREPP
Swedish Child Diabetes Foundation (Barndiabetesfonden)
5U01DK085526
DK088389
U54HG003067
R01DK072193
R01DK062370
Z01HG000024info:eu-repo/grantAgreement/EC/FP7/20201
Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats
Screening compliance and visual outcome in diabetes
To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPURPOSE: To study the relationship between screening compliance and visual outcome in a screening programme for diabetic eye disease. METHODS: A retrospective case control study. The screening compliance of all the diabetes patients (n = 22) listed at the Icelandic National Registry for the Blind (visual acuity or =0.3) who participated in the same screening programme for diabetic retinopathy. Glycaemic control (HbA1c), office blood pressure and cholesterol levels were assessed. RESULTS: The study group had a significantly lower level of compliance with the screening programme (27% +/- 38% [mean +/- SD] versus 77% +/- 26% [mean +/- SD]; p < 0.0001). Macular oedema or proliferative diabetic retinopathy was found in 60% (13/22) of the study group when entering the screening programme, compared to 7% (3/44) in the control group. Blood pressure (except diastolic BP among type 1 diabetes mellitus), blood glucose and cholesterol levels were identical. The prevalence of blindness and low vision amongst diabetes patients in Iceland is about 0.5%. CONCLUSIONS: There was a significant relationship between screening compliance and visual outcome in diabetes patients in our screening programme
Portable infrared pupillometry using Pupilscan: Relation to somatic and autonomic nerve function in diabetes mellitus
Evaluating iodine deficiency in pregnant women and young infants.:Complex physiology with a risk of misinterpretation
To access publisher full version of this article. Please click on the hyperlink in Additional Links fieldOBJECTIVE: To review methods for evaluating iodine deficiency in pregnant women and young infants and to discuss factors to be considered in the interpretation of their results. DESIGN: Review of the literature regarding the various methods available for assessing iodine status.Setting: Population surveys and research studies. SUBJECTS: Pregnant women and young infants. RESULTS: Several factors to consider when assessing iodine status in pregnant women and young infants include: 1) the urinary iodine (UI) concentration (microg l-1) is not interchangeable with 24 h UI excretion (microg per 24 h); 2) the concentration of iodine in a spot or casual urine sample cannot be used to diagnose iodine deficiency in an individual; 3) a moderate fall in the concentration of serum free T4 during pregnancy is not a sign of maternal iodine deficiency; 4) an increase in the concentration of serum thyroglobulin (Tg) during pregnancy is not a sign of maternal iodine deficiency; 5) a higher concentration of TSH and Tg in cord blood than in maternal blood is not a sign of iodine deficiency in the mother or neonate; and 6) thyroid function in a full-term foetus, a neonate or a small child is not more sensitive to a mild iodine deficiency than in the mother. CONCLUSIONS: If the iodine status of pregnant women and small children is not to be misjudged, the above six factors need to be taken into account