Pål R. Njølstad
A5012146929- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Birth, Development, and Health
- Genetic Associations and Epidemiology
- Genetics and Neurodevelopmental Disorders
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Pregnancy and preeclampsia studies
- Diabetes Treatment and Management
- Genomics and Rare Diseases
- Endoplasmic Reticulum Stress and Disease
- Obesity, Physical Activity, Diet
- Gestational Diabetes Research and Management
- Pancreatitis Pathology and Treatment
- Adipose Tissue and Metabolism
- Nutrition, Genetics, and Disease
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- Diet and metabolism studies
- Developmental Biology and Gene Regulation
- Child and Adolescent Psychosocial and Emotional Development
- RNA modifications and cancer
- RNA Research and Splicing
University of Bergen
2016-2025
Haukeland University Hospital
2016-2025
Norwegian Institute of Public Health
2020-2025
Broad Institute
2013-2023
Institute for Molecular Medicine Finland
2023
University of Helsinki
2023
Massachusetts General Hospital
2023
Harvard University
2010-2023
Wellcome Sanger Institute
2023
Smerteklinikken
2009-2023
Patients with permanent neonatal diabetes usually present within the first three months of life and require insulin treatment. In most, cause is unknown. Because ATP-sensitive potassium (K(ATP)) channels mediate glucose-stimulated secretion from pancreatic beta cells, we hypothesized that activating mutations in gene encoding Kir6.2 subunit this channel (KCNJ11) diabetes.We sequenced KCNJ11 29 patients diabetes. The secretory response to intravenous glucagon, glucose, sulfonylurea...
Heterozygous activating mutations in KCNJ11, encoding the Kir6.2 subunit of ATP-sensitive potassium (KATP) channel, cause 30 to 58 percent cases diabetes diagnosed patients under six months age. Patients present with ketoacidosis or severe hyperglycemia and are treated insulin. Diabetes results from impaired insulin secretion caused by a failure beta-cell KATP channel close response increased intracellular ATP. Sulfonylureas an ATP-independent route.
Diabetes mellitus is a heterogeneous disorder that can occur at any age.1 Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, rare usually associated with intrauterine growth retardation.2 Like in general, neonatal and be either transient or permanent. Transient abnormalities chromosome 6,2,3 whereas mutations insulin promoter factor 1 result pancreatic agenesis permanent diabetes.4 We describe two patients whom complete deficiency...
M.P. has acted as scientific advisor for the development of glibenclamide-glyburide suspension named AMGLIDIA in European Union. The other authors have declared no conflicts interest.
Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic indirect effects, but large-scale family datasets have been lacking. We combined data 178,086 siblings 19 cohorts to generate population (between-family) within-sibship (within-family) estimates 25...
<h3>Importance</h3> Latino populations have one of the highest prevalences type 2 diabetes worldwide. <h3>Objectives</h3> To investigate association between rare protein-coding genetic variants and prevalence in a large population to explore potential molecular physiological mechanisms for observed relationships. <h3>Design, Setting, Participants</h3> Whole-exome sequencing was performed on DNA samples from 3756 Mexican US individuals (1794 with 1962 without diabetes) recruited 1993 2013....
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role maternal genetic variation. We aimed to identify variants associated with that could highlight potentially relevant determinants growth. meta-analysed data up 8.7 million SNPs in 86 577 women European descent from Early Growth Genetics (EGG) Consortium and UK Biobank. used structural equation modelling (SEM) analyses mother-child pairs quantify separate effects....
Permanent neonatal diabetes (PND) can be caused by mutations in the transcription factors insulin promoter factor (IPF)-1, eukaryotic translation initiation factor-2α kinase 3 (EIF2AK3), and forkhead box-P3 key components of secretion: glucokinase (GCK) ATP-sensitive K+ channel subunit Kir6.2. We sequenced gene encoding Kir6.2 (KCNJ11) 11 probands with GCK-negative PND. Heterozygous were identified seven probands, causing three novel (F35V, Y330C, F333I) two known (V59M R201H) amino acid...
To reevaluate the persistence and stability of previously observed differences between pediatric diabetes centers to investigate influence demography, language communication problems, changes in insulin regimens on metabolic outcome, hypoglycemia, ketoacidosis.This was an observational cross-sectional international study 21 centers, with clinical data obtained from all participants A1C levels assayed one central laboratory. All individuals aged 11-18 years (49.4% female), duration at least 1...
Genome-wide association studies identified noncoding SNPs associated with type 2 diabetes and obesity in linkage disequilibrium (LD) blocks encompassing HHEX-IDE introns of CDKAL1 FTO [Sladek R, et al. (2007) Nature 445:881–885; Steinthorsdottir V, Nat. Genet 39:770–775; Frayling TM, Science 316:889–894]. We show that these LD contain highly conserved elements overlap the genomic regulatory transcription factor genes HHEX , SOX4 IRX3 . report human risk drive expression endoderm or pancreas...
Mutations in the insulin (INS) gene can cause neonatal diabetes. We hypothesized that mutations INS could also maturity-onset diabetes of young (MODY) and autoantibody-negative type 1 diabetes.We screened 62 probands with MODY, 30 suspected 223 subjects from Norwegian Childhood Diabetes Registry selected on basis autoantibody negativity or family history diabetes.Among MODY patients, we identified mutation c.137G>A (R46Q) a proband, his diabetic father, paternal aunt. They were diagnosed at...
Inappropriately elevated insulin secretion is the hallmark of persistent hyperinsulinemic hypoglycemia infancy (PHHI), also denoted congenital hyperinsulinism. Causal mutations have been uncovered in genes coding for β-cell’s ATP-sensitive potassium channel and metabolic enzymes glucokinase glutamate dehydrogenase. In addition, one infant was recently found to a mutation gene encoding short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD), an enzyme participating mitochondrial fatty acid...
Neonatal diabetes can be either permanent or transient. We have recently shown that neonatal result from complete deficiency of glucokinase activity. Here we report three new cases glucokinase-related diabetes. The probands had intrauterine growth retardation (birth weight <1,900 g) and insulin-treated birth (diagnosis within the first week life). One subjects was homozygous for missense mutation Ala378Val (A378V), which is an inactivating with activity index only 0.2% wild-type second...
Abstract Aims To assess the importance of family factors in determining metabolic outcomes adolescents with Type 1 diabetes 19 countries. Methods Adolescents aged 11–18 years, from 21 paediatric care centres, countries, and their parents were invited to participate. Questionnaires administered recording demographic data, details insulin regimens, severe hypoglycaemic events number episodes diabetic ketoacidosis. completed parental involvement scale Diabetes Quality Life for Youth—Short Form...