Andrew T Hattersley

Summary

Affiliation: University of Exeter
Country: UK

Publications

  1. ncbi request reprint 'I don't feel like a diabetic any more': the impact of stopping insulin in patients with maturity onset diabetes of the young following genetic testing
    Maggie Shepherd
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, Devon
    Clin Med (Lond) 4:144-7. 2004
  2. pmc Unlocking the secrets of the pancreatic beta cell: man and mouse provide the key
    Andrew T Hattersley
    Diabetes and Vascular Medicine, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    J Clin Invest 114:314-6. 2004
  3. pmc Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk
    Hana Lango
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 57:3129-35. 2008
  4. pmc Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects
    Sian Ellard
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, EX2 5DW, and Wessex Regional Genetics Labs, Salisbury District Hospital, UK
    Am J Hum Genet 81:375-82. 2007
  5. pmc Type 2 diabetes risk alleles are associated with reduced size at birth
    Rachel M Freathy
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 58:1428-33. 2009
  6. pmc Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Rd, Exeter, EX1 2LU, UK
    Diabetes 57:1419-26. 2008
  7. ncbi request reprint Origin of de novo KCNJ11 mutations and risk of neonatal diabetes for subsequent siblings
    Emma L Edghill
    Department of Molecular Genetics, Royal Devon and Exeter National Health Service Foundation Trust, Barrack Road, Exeter, United Kingdom
    J Clin Endocrinol Metab 92:1773-7. 2007
  8. ncbi request reprint A large-scale association analysis of common variation of the HNF1alpha gene with type 2 diabetes in the U.K. Caucasian population
    Michael N Weedon
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 54:2487-91. 2005
  9. pmc Combining information from common type 2 diabetes risk polymorphisms improves disease prediction
    Michael N Weedon
    Department of Diabetes Research and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom
    PLoS Med 3:e374. 2006
  10. pmc A study of association between common variation in the growth hormone-chorionic somatomammotropin hormone gene cluster and adult fasting insulin in a UK Caucasian population
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    J Negat Results Biomed 5:18. 2006

Detail Information

Publications118 found, 100 shown here

  1. ncbi request reprint 'I don't feel like a diabetic any more': the impact of stopping insulin in patients with maturity onset diabetes of the young following genetic testing
    Maggie Shepherd
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, Devon
    Clin Med (Lond) 4:144-7. 2004
    ..Transferring from insulin to sulphonylureas had a positive impact on lifestyle but support was needed for patients to adjust, many having grown up with the belief they would be on insulin for life...
  2. pmc Unlocking the secrets of the pancreatic beta cell: man and mouse provide the key
    Andrew T Hattersley
    Diabetes and Vascular Medicine, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    J Clin Invest 114:314-6. 2004
    ..A new mouse model of transient neonatal diabetes mellitus emphasizes that both the number of beta cells and their function are critical for insulin secretion and may be regulated by imprinted genes...
  3. pmc Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk
    Hana Lango
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 57:3129-35. 2008
    ..Here, we assess the ability of 18 confirmed type 2 diabetes variants to differentiate between type 2 diabetic case and control subjects...
  4. pmc Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects
    Sian Ellard
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, EX2 5DW, and Wessex Regional Genetics Labs, Salisbury District Hospital, UK
    Am J Hum Genet 81:375-82. 2007
    ..A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present...
  5. pmc Type 2 diabetes risk alleles are associated with reduced size at birth
    Rachel M Freathy
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 58:1428-33. 2009
    ..We tested whether common genetic variants that predispose to type 2 diabetes also reduce birth weight...
  6. pmc Common variation in the FTO gene alters diabetes-related metabolic traits to the extent expected given its effect on BMI
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Rd, Exeter, EX1 2LU, UK
    Diabetes 57:1419-26. 2008
    ..Increased BMI is associated with diabetes risk factors, including raised insulin, glucose, and triglycerides. We aimed to test whether FTO genotype is associated with variation in these metabolic traits...
  7. ncbi request reprint Origin of de novo KCNJ11 mutations and risk of neonatal diabetes for subsequent siblings
    Emma L Edghill
    Department of Molecular Genetics, Royal Devon and Exeter National Health Service Foundation Trust, Barrack Road, Exeter, United Kingdom
    J Clin Endocrinol Metab 92:1773-7. 2007
    ..2 subunit of the pancreatic beta-cell K(ATP) channel, result in permanent and transient neonatal diabetes. The majority of KCNJ11 mutations are spontaneous, but the parental origin of these mutations is not known...
  8. ncbi request reprint A large-scale association analysis of common variation of the HNF1alpha gene with type 2 diabetes in the U.K. Caucasian population
    Michael N Weedon
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 54:2487-91. 2005
    ..31 [1.08-1.59], P = 0.007). Further studies are required to investigate this association, demonstrating the difficulty of defining the role of rare (<5%) alleles in type 2 diabetes risk...
  9. pmc Combining information from common type 2 diabetes risk polymorphisms improves disease prediction
    Michael N Weedon
    Department of Diabetes Research and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom
    PLoS Med 3:e374. 2006
    ..The value of analyzing multiple alleles simultaneously is not well studied. This is often because, for any given disease, very few common risk alleles have been confirmed...
  10. pmc A study of association between common variation in the growth hormone-chorionic somatomammotropin hormone gene cluster and adult fasting insulin in a UK Caucasian population
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    J Negat Results Biomed 5:18. 2006
    ..We genotyped 1396 subjects (fathers, mothers and children) from a consecutive birth study for the CSH1.01 marker and analysed genotypes for association with 1-year weight in boys and fasting insulin in fathers...
  11. ncbi request reprint The Exeter Family Study of Childhood Health (EFSOCH): study protocol and methodology
    Bridget Knight
    Peninsula Medical School, Royal Devon and Exeter NHS Trust, Exeter, UK
    Paediatr Perinat Epidemiol 20:172-9. 2006
    ..This comprehensive data set is available on a disease-free cohort, and detailed preparatory work has ensured high levels of quality control. The study would welcome collaboration within strict confidentiality rules...
  12. ncbi request reprint Relapsing diabetes can result from moderately activating mutations in KCNJ11
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, USA
    Hum Mol Genet 14:925-34. 2005
    ..This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro...
  13. ncbi request reprint Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene
    Michael N Weedon
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5AX, U K
    Diabetes 54:576-81. 2005
    ..This study establishes that common genetic variation, in addition to rare mutations and environmental factors, can affect both FPG and birth weight...
  14. ncbi request reprint Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood
    Sarah E Flanagan
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 56:1930-7. 2007
    ..Remitting neonatal diabetes was observed in two of three mutation carriers, and permanent diabetes occurred after 6 months of age in subjects without an initial diagnosis of neonatal diabetes...
  15. ncbi request reprint Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations
    Meena Rafiq
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes Care 31:204-9. 2008
    ..2 mutations is well described, but less is known about changing therapy in patients with SUR1 mutations. We aimed to describe the response to sulfonylurea therapy in patients with SUR1 mutations and to compare it with Kir6.2 mutations...
  16. pmc The functional "KL-VS" variant of KLOTHO is not associated with type 2 diabetes in 5028 UK Caucasians
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    BMC Med Genet 7:51. 2006
    ..We performed a large case-control and family-based study to test the hypothesis that KL-VS is associated with type 2 diabetes in a UK Caucasian population...
  17. ncbi request reprint The impact of maternal glycemia and obesity on early postnatal growth in a nondiabetic Caucasian population
    Bridget Knight
    Peninsula Medical School, Exeter, UK
    Diabetes Care 30:777-83. 2007
    ..The relative role of maternal glycemia and maternal obesity is uncertain. We therefore studied the impact of maternal glycemia and maternal obesity on offspring birth measures and early postnatal growth in nondiabetic pregnancies...
  18. pmc A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity
    Timothy M Frayling
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK
    Science 316:889-94. 2007
    ..67-fold increased odds of obesity when compared with those not inheriting a risk allele. This association was observed from age 7 years upward and reflects a specific increase in fat mass...
  19. pmc Five-year follow-up for women with subclinical hypothyroidism in pregnancy
    Beverley M Shields
    Department of Endocrinology, Royal Devon and Exeter Hospital, Exeter, EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 98:E1941-5. 2013
    ..However, there are limited data to indicate whether treatment should be continued outside of pregnancy...
  20. pmc Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families
    Oscar Rubio-Cabezas
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 94:4162-70. 2009
    ..We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present and study the overall frequency of WRS among patients with permanent neonatal diabetes...
  21. doi request reprint The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development
    Lorna W Harries
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, UK
    Diabetes 57:1745-52. 2008
    ..We characterized the spatial and developmental expression patterns of HNF4A transcripts in human tissues and investigated their role as potential moderators of the MODY phenotype...
  22. ncbi request reprint Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population
    Michael N Weedon
    Department of Diabetes Research and Vascular Medicine, Peninsula Medical School, Barrack Road, Exeter, UK
    Diabetes 53:3002-6. 2004
    ..1-linked cases. In conclusion, we have replicated the association of the HNF4alpha P2 promoter haplotype with type 2 diabetes in a U.K. Caucasian population where there is no evidence of linkage to 20q...
  23. ncbi request reprint No evidence of association of ENPP1 variants with type 2 diabetes or obesity in a study of 8,089 U.K. Caucasians
    Michael N Weedon
    Molecular Genetics, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK
    Diabetes 55:3175-9. 2006
    ..25 [1.10-1.43], P = 0.0007), although there was some evidence of publication bias. In conclusion, we find no evidence that previously associated variants of ENPP1 are associated with type 2 diabetes or obesity in the U.K. population...
  24. ncbi request reprint Functional variation in VEGF is not associated with type 2 diabetes in a United Kingdom Caucasian population
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    JOP 7:295-302. 2006
    ..The single nucleotide polymorphisms C-2578A (rs699947), G-1154A (rs1570360) and G-634C (rs2010963) in the 5'-region of VEGF are associated with altered serum concentrations of the protein...
  25. pmc Type 2 diabetes TCF7L2 risk genotypes alter birth weight: a study of 24,053 individuals
    Rachel M Freathy
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Am J Hum Genet 80:1150-61. 2007
    ..In conclusion, we have identified the first type 2 diabetes-susceptibility allele to be reproducibly associated with birth weight. Common gene variants can substantially influence normal birth-weight variation...
  26. pmc Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases
    John R B Perry
    Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
    PLoS Genet 8:e1002741. 2012
    ..08], P = 2.2×10⁻¹⁶. This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes...
  27. ncbi request reprint Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 Gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel
    Anna L Gloyn
    Diabetes and Vascular Medicine, Peninsula Medical School, Exeter EX2 5AX, United Kingdom
    J Clin Endocrinol Metab 89:3932-5. 2004
    ..The possibility of germline mosaicism should be considered when counseling recurrence risks for the parents of a child with an apparently de novo KCNJ11 activating mutation...
  28. pmc Homozygous mutations in NEUROD1 are responsible for a novel syndrome of permanent neonatal diabetes and neurological abnormalities
    Oscar Rubio-Cabezas
    Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK
    Diabetes 59:2326-31. 2010
    ..Heterozygous mutations have previously been identified as a rare cause of maturity-onset diabetes of the young (MODY). We aimed to explore the potential contribution of NEUROD1 mutations in patients with permanent neonatal diabetes...
  29. ncbi request reprint Sequencing of candidate genes selected by beta cell experts in monogenic diabetes of unknown aetiology
    Emma L Edghill
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    JOP 11:14-7. 2010
    ..Many of the known genes causing MODY and PNDM were identified as being critical for beta cell function before their identification as a cause of monogenic diabetes...
  30. pmc Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene
    Ewan R Pearson
    Peninsula Medical School, Exeter, United Kingdom
    PLoS Med 4:e118. 2007
    ....
  31. ncbi request reprint Beta-cell dysfunction, insulin sensitivity, and glycosuria precede diabetes in hepatocyte nuclear factor-1alpha mutation carriers
    Amanda Stride
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Devon, UK
    Diabetes Care 28:1751-6. 2005
    ..It is uncertain how many of these features precede the development of diabetes. The aim of our study was to test for these characteristics in young nondiabetic HNF-1alpha mutation carriers...
  32. pmc Interrogating type 2 diabetes genome-wide association data using a biological pathway-based approach
    John R B Perry
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter, UK
    Diabetes 58:1463-7. 2009
    ..In a complementary approach to these single-marker studies, we attempted to identify biological pathways associated with type 2 diabetes. This approach could allow us to identify additional risk loci...
  33. pmc Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies
    Anna M Steele
    NIHR Exeter Clinical Research Facility, University of Exeter, Exeter, Devon, United Kingdom
    PLoS ONE 8:e65326. 2013
    ....
  34. ncbi request reprint Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood
    Emma L Edghill
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK
    Diabetes 57:1034-42. 2008
    ..We aimed to determine the prevalence, genetics, and clinical phenotype of INS mutations in large cohorts of patients with neonatal diabetes and permanent diabetes diagnosed in infancy, childhood, or adulthood...
  35. pmc Diabetes susceptibility in the Canadian Oji-Cree population is moderated by abnormal mRNA processing of HNF1A G319S transcripts
    Lorna W Harries
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, U K
    Diabetes 57:1978-82. 2008
    ..We hypothesized that the variant site at the 3' end of exon 4 might influence splicing and characterized mRNA transcripts to investigate the mutational mechanism underlying this susceptibility to diabetes...
  36. ncbi request reprint Activating mutations in the gene encoding Kir6.2 alter fetal and postnatal growth and also cause neonatal diabetes
    Annabelle S Slingerland
    Peninsula Medical School, Barrack Road, Exeter EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 91:2782-8. 2006
    ..Activating mutations in Kir6.2 are the major cause of neonatal diabetes and reduce insulin secretion by altering the closure of the beta-cell ATP-sensitive potassium channel in the presence of ATP...
  37. pmc Allelic drop-out may occur with a primer binding site polymorphism for the commonly used RFLP assay for the -1131T>C polymorphism of the Apolipoprotein AV gene
    Kirsten J Ward
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Lipids Health Dis 5:11. 2006
    ..Our results also emphasise the need for careful quality control in all molecular genetic studies, particularly while transferring genotyping methods between various ethnic groups...
  38. ncbi request reprint Contrasting diabetes phenotypes associated with hepatocyte nuclear factor-1alpha and -1beta mutations
    Ewan R Pearson
    Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK
    Diabetes Care 27:1102-7. 2004
    ..However, physiological assessment of the HNF-1beta phenotype is limited. We aimed to test the hypothesis that the diabetes phenotype due to HNF-1beta mutations is similar to that in HNF-1alpha...
  39. doi request reprint Mutations in the hepatocyte nuclear factor-1β (HNF1B) gene are common with combined uterine and renal malformations but are not found with isolated uterine malformations
    Richard A Oram
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Am J Obstet Gynecol 203:364.e1-5. 2010
    ..Mutations of the hepatocyte nuclear factor-1β (HNF1B) gene are associated with renal and uterine abnormalities. We aimed to study the role of HNF1B mutations in a cohort with congenital uterine abnormalities...
  40. doi request reprint Mutations in the glucokinase gene of the fetus result in reduced placental weight
    Beverley M Shields
    Diabetes Research, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, UK
    Diabetes Care 31:753-7. 2008
    ..It is uncertain whether there is regulation of the placenta by the fetus or vice versa. We aimed to test the hypothesis that placental growth is mediated, either directly or indirectly, by fetal insulin...
  41. doi request reprint Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia
    Anna M Steele
    National Institue for Health Research, Exeter Clinical Research Facility, Exeter Medical School, University of Exeter, Exeter, United Kingdom
    JAMA 311:279-86. 2014
    ..Patients with heterozygous, inactivating glucokinase (GCK) mutations have mild fasting hyperglycemia from birth, resulting in an elevated glycated hemoglobin (HbA1c) level that mimics recommended levels for type 1 and type 2 diabetes...
  42. ncbi request reprint Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations
    Ewan R Pearson
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 355:467-77. 2006
    ..Diabetes results from impaired insulin secretion caused by a failure of the beta-cell K(ATP) channel to close in response to increased intracellular ATP. Sulfonylureas close the K(ATP) channel by an ATP-independent route...
  43. pmc A common genetic variant in the 15q24 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) is associated with a reduced ability of women to quit smoking in pregnancy
    Rachel M Freathy
    Genetics of Complex Traits, Peninsula Medical School, Institute of Biomedical and Clinical Science, Magdalen Road, Exeter EX1 2LU, UK
    Hum Mol Genet 18:2922-7. 2009
    ..Our data support the role of genetic factors in influencing smoking cessation during pregnancy...
  44. pmc A common variant of HMGA2 is associated with adult and childhood height in the general population
    Michael N Weedon
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK
    Nat Genet 39:1245-50. 2007
    ..There are few examples of common genetic variants reproducibly associated with human quantitativetraits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height...
  45. doi request reprint Phosphodiesterase 8B gene polymorphism is associated with subclinical hypothyroidism in pregnancy
    Beverley M Shields
    Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, Exeter University, Exeter EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 94:4608-12. 2009
    ..We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy...
  46. pmc Fetal thyroid hormone level at birth is associated with fetal growth
    Beverley M Shields
    Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 96:E934-8. 2011
    ..Overt maternal and fetal thyroid disorders are associated with reduced birth weight. We hypothesized that, even in the absence of overt thyroid dysfunction, maternal and fetal thyroid function influence fetal growth...
  47. doi request reprint Home urine C-peptide creatinine ratio (UCPCR) testing can identify type 2 and MODY in pediatric diabetes
    Rachel E J Besser
    Peninsula NIHR Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, UK
    Pediatr Diabetes 14:181-8. 2013
    ..We aimed to assess whether UCPCR can discriminate type 1 diabetes from MODY and type 2 in pediatric diabetes...
  48. pmc A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses
    Michael N Weedon
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, EX1 2LU, UK
    Am J Hum Genet 79:991-1001. 2006
    ..In conclusion, a comprehensive analysis of common variation of the glucokinase gene shows that this is the first gene to be reproducibly associated with fasting glucose and fetal growth...
  49. pmc Genome-wide association analysis identifies 20 loci that influence adult height
    Michael N Weedon
    Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK
    Nat Genet 40:575-83. 2008
    ..Finally, our results provide insights into the genetic architecture of a classic quantitative trait...
  50. pmc GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency
    Elisa De Franco
    Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
    Diabetes 62:993-7. 2013
    ..Heterozygous GATA6 mutations cause a wide spectrum of diabetes manifestations, ranging from pancreatic agenesis to adult-onset diabetes with subclinical or no exocrine insufficiency...
  51. pmc Permanent Neonatal Diabetes and Enteric Anendocrinosis Associated With Biallelic Mutations in NEUROG3
    Oscar Rubio-Cabezas
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 60:1349-53. 2011
    ..We hypothesized that null mutations in NEUROG3 might be responsible for the disease in a patient with permanent neonatal diabetes and severe congenital malabsorptive diarrhea...
  52. doi request reprint KATP channel mutations in infants with permanent diabetes diagnosed after 6 months of life
    Oscar Rubio-Cabezas
    Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, EX2 5DW Exeter, UK
    Pediatr Diabetes 13:322-5. 2012
    ..Genetic testing is currently recommended for all infants diagnosed before 6 months of age. We aimed to explore the prevalence of K(ATP) channel diabetes in infants presenting between 6 and 12 months...
  53. doi request reprint Amino acid properties may be useful in predicting clinical outcome in patients with Kir6.2 neonatal diabetes
    Clementine S Fraser
    Department of Molecular Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Barrack Road, Exeter EX2 5DW, UK
    Eur J Endocrinol 167:417-21. 2012
    ....
  54. doi request reprint Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia
    Charles Shaw-Smith
    Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter EX2 5DW, UK
    Pediatr Diabetes 13:314-21. 2012
    ..TRMA should be considered in the differential diagnosis of diabetes presenting in the neonatal period...
  55. ncbi request reprint Messenger RNA transcripts of the hepatocyte nuclear factor-1alpha gene containing premature termination codons are subject to nonsense-mediated decay
    Lorna W Harries
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U K
    Diabetes 53:500-4. 2004
    ..Haploinsufficiency is therefore likely to be the most important mutational mechanism of HNF-1alpha mutations causing MODY...
  56. ncbi request reprint Activating mutations in the KCNJ11 gene encoding the ATP-sensitive K+ channel subunit Kir6.2 are rare in clinically defined type 1 diabetes diagnosed before 2 years
    Emma L Edghill
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5AX, UK
    Diabetes 53:2998-3001. 2004
    ..Although activating KCNJ11 mutations are rare in patients diagnosed with type 1 diabetes, the identification of a KCNJ11 mutation may have important treatment implications...
  57. ncbi request reprint Measurement of cord insulin and insulin-related peptides suggests that girls are more insulin resistant than boys at birth
    Beverley M Shields
    Diabetes Research, Peninsula Medical School, Exeter, UK
    Diabetes Care 30:2661-6. 2007
    ..We aimed to examine sex differences in insulin and insulin propeptide concentrations at birth using validated cord blood collection...
  58. ncbi request reprint Genetic cause of hyperglycaemia and response to treatment in diabetes
    Ewan R Pearson
    Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK
    Lancet 362:1275-81. 2003
    ....
  59. doi request reprint Cigarette smoking during pregnancy is associated with alterations in maternal and fetal thyroid function
    Beverley Shields
    Department of Endocrinology, Peninsula Medical School, Royal Devon, Exeter Hospital, Exeter EX2 5DW, United Kingdom
    J Clin Endocrinol Metab 94:570-4. 2009
    ..Studies in the general population have shown lower serum TSH levels in smokers as compared with nonsmokers...
  60. doi request reprint Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes
    Rinki Murphy
    Peninsula Medical School, Exeter, UK
    Nat Clin Pract Endocrinol Metab 4:200-13. 2008
    ..Finally, extrapancreatic features, such as renal disease (caused by mutations in HNF-1beta) or deafness (caused by a mitochondrial m.3243A>G mutation), usually require early treatment with insulin...
  61. ncbi request reprint HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months
    Emma L Edghill
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Diabetes 55:1895-8. 2006
    ..0001). We conclude that infants diagnosed with diabetes before 6 months of age are unlikely to have autoimmune type 1 diabetes and are most likely to have a monogenic etiology...
  62. pmc Type 1 Diabetes Genetic Risk Score: A Novel Tool to Discriminate Monogenic and Type 1 Diabetes
    Kashyap A Patel
    Institute for Biomedical and Clinical Science, University of Exeter Medical School, Exeter, U K National Institute for Health Research Exeter Clinical Research Facility, Exeter, U K
    Diabetes 65:2094-9. 2016
    ..The T1D-GRS is a novel tool to improve the use of biomarkers in the discrimination of monogenic diabetes from T1D. ..
  63. pmc An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy
    Michael N Weedon
    Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
    Nat Genet 45:947-50. 2013
    ..This discovery suggests that perturbing the function of the ubiquitously expressed POLD1 polymerase has unexpectedly tissue-specific effects in humans and argues for an important role for POLD1 function in adipose tissue homeostasis. ..
  64. ncbi request reprint Conditional expression of hepatocyte nuclear factor-1beta, the maturity-onset diabetes of the young-5 gene product, influences the viability and functional competence of pancreatic beta-cells
    Hannah J Welters
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Universities of Exeter and Plymouth, Research Way, Plymouth, Devon PL6 8BU, UK
    J Endocrinol 190:171-81. 2006
    ....
  65. ncbi request reprint Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes
    Anna L Gloyn
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    N Engl J Med 350:1838-49. 2004
    ..2 subunit of this channel (KCNJ11) cause neonatal diabetes...
  66. ncbi request reprint Lack of support for a role of the insulin gene variable number of tandem repeats minisatellite (INS-VNTR) locus in fetal growth or type 2 diabetes-related intermediate traits in United Kingdom populations
    Simon M S Mitchell
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom EX2 5AX
    J Clin Endocrinol Metab 89:310-7. 2004
    ..In the largest study to date, we found a lack of support for a role for INS-VNTR in fetal growth and nominal association with type 2 diabetes-related intermediate traits...
  67. pmc Assessing newborn body composition using principal components analysis: differences in the determinants of fat and skeletal size
    Beverley M Shields
    Peninsula Medical School, Barrack Road, Exeter, UK
    BMC Pediatr 6:24. 2006
    ..These components are likely to have different growth patterns. The aim of this paper is to investigate the association between established determinants of birth weight and these separate components...
  68. ncbi request reprint Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes
    Lorna W Harries
    Institute of Biomedical and Clincal Sciences, Peninsula Medical School, Barrack Road, Exeter, Devon, UK
    Hum Mol Genet 15:2216-24. 2006
    ..We conclude that all three isomers may be critical for beta-cell function and could play a role in both the developing and mature beta cell...
  69. pmc GATA6 haploinsufficiency causes pancreatic agenesis in humans
    Hana Lango Allen
    Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
    Nat Genet 44:20-2. 2011
    ..These findings define the most common cause of human pancreatic agenesis and establish a key role for the transcription factor GATA6 in human pancreatic development...
  70. ncbi request reprint Hepatocyte nuclear factor-1beta gene deletions--a common cause of renal disease
    Emma L Edghill
    1Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Nephrol Dial Transplant 23:627-35. 2008
    ..HNF-1beta gene deletions have recently been shown to cause renal malformations and early-onset diabetes...
  71. pmc Prime suspect: the TCF7L2 gene and type 2 diabetes risk
    Andrew T Hattersley
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, United Kingdom
    J Clin Invest 117:2077-9. 2007
    ....
  72. pmc Urine C-peptide creatinine ratio is a noninvasive alternative to the mixed-meal tolerance test in children and adults with type 1 diabetes
    Rachel E J Besser
    Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, UK
    Diabetes Care 34:607-9. 2011
    ..We assessed urine C-peptide creatinine ratio (UCPCR) as an alternative...
  73. pmc Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-{alpha}/hepatocyte nuclear factor 4-{alpha} maturity-onset diabetes of the young from long-duration type 1 diabetes
    Rachel E J Besser
    Peninsula National Institute for Health Research Clinical Research Facility, Peninsula Medical School, University of Exeter, Exeter, UK
    Diabetes Care 34:286-91. 2011
    ..Urinary C-peptide creatinine ratio (UCPCR), a stable measure of endogenous insulin secretion, is a noninvasive alternative. We aimed to compare stimulated UCPCR in adults with HNF1A/4A MODY, type 1 diabetes, and type 2 diabetes...
  74. pmc Tooth discoloration in patients with neonatal diabetes after transfer onto glibenclamide: a previously unreported side effect
    Janani Kumaraguru
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U K
    Diabetes Care 32:1428-30. 2009
    ..Given the multiple benefits of sulfonylurea treatment for patients with activating KCNJ11 mutations, this association warrants further investigation but should not preclude such treatment...
  75. ncbi request reprint Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene
    Katharine R Owen
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Barrack Road, Exeter EX2 5AX, UK
    Diabet Med 20:823-7. 2003
    ..Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome...
  76. ncbi request reprint Mesangiocapillary glomerulonephritis type 2 associated with familial partial lipodystrophy (Dunnigan-Kobberling syndrome)
    Katharine R Owen
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK
    Nephron Clin Pract 96:c35-8. 2004
    ....
  77. ncbi request reprint Etiological investigation of diabetes in young adults presenting with apparent type 2 diabetes
    Katharine R Owen
    Peninsula Medical School, Department of Diabetes and Vascular Medicine, Exeter, Devon, UK
    Diabetes Care 26:2088-93. 2003
    ..The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial...
  78. ncbi request reprint Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes
    Anna L Gloyn
    Centre for Molecular Genetics, Peninsula Medical School, Exeter, UK
    Diabetes 52:568-72. 2003
    ..000002); but the ABCC8 variants were not associated. Our results confirm that E23K increases risk of type 2 diabetes and show that large-scale association studies are important for the identification of diabetes susceptibility alleles...
  79. ncbi request reprint Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes
    Andrew T Hattersley
    Peninsula Medical School, Exeter EX2 5DW, United Kingdom
    Endocrinology 147:2657-63. 2006
    ..In conclusion, the defining of molecular genetic etiology in monogenic diabetes has identified several specific beta-cell defects, and these are critical in determining the response to treatment...
  80. ncbi request reprint Genetics and type 2 diabetes in youth
    Olivia Gill-Carey
    Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Barrack Road, Exeter, UK
    Pediatr Diabetes 8:42-7. 2007
    ....
  81. ncbi request reprint Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation
    Coralie Bingham
    Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, United Kingdom
    Kidney Int 63:1645-51. 2003
    ....
  82. ncbi request reprint Young-onset type 2 diabetes families are the major contributors to genetic loci in the Diabetes UK Warren 2 genome scan and identify putative novel loci on chromosomes 8q21, 21q22, and 22q11
    Timothy M Frayling
    Department of Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK
    Diabetes 52:1857-63. 2003
    ..Our data confirm our hypothesis that families segregating young-onset type 2 diabetes represent a more powerful resource for defining susceptibility genes by linkage...
  83. ncbi request reprint Mutations in the Kir6.2 subunit of the KATP channel and permanent neonatal diabetes: new insights and new treatment
    Annabelle S Slingerland
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
    Ann Med 37:186-95. 2005
    ..In this article we discuss the work that established Kir6.2 mutations as a common cause of neonatal diabetes, the clinical features, the underlying mechanism and the impact on patient treatment...
  84. ncbi request reprint Maturity-onset diabetes of the young caused by a balanced translocation where the 20q12 break point results in disruption upstream of the coding region of hepatocyte nuclear factor-4alpha (HNF4A) gene
    Anna L Gloyn
    Department of Diabetes and Vascular Medicine, School of Postgraduate Medical and Health Sciences, University of Exeter, Barrack Road, Exeter EX2 5AX, U K
    Diabetes 51:2329-33. 2002
    ..This is the first case of MODY due to a balanced translocation, and it provides evidence to confirm the crucial role of an upstream regulator of HNF4A gene expression in the beta-cell...
  85. ncbi request reprint Different genes, different diabetes: lessons from maturity-onset diabetes of the young
    Amanda Stride
    Department of Diabetes, University of Exeter, Devon, UK
    Ann Med 34:207-16. 2002
    ..This allows confirmation of a diagnosis of MODYand defines the subgroup. Differences in prognosis and treatment strongly support the increased use of molecular genetic testing in diabetes...
  86. ncbi request reprint Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function
    Laura Pascoe
    Diabetes Research Group, Newcastle University, Newcastle upon Tyne, UK
    Diabetes 56:3101-4. 2007
    ..Our objective was to explore the relationships between the diabetes-associated alleles and measures of beta-cell function and whole-body insulin sensitivity...
  87. ncbi request reprint No deterioration in glycemic control in HNF-1alpha maturity-onset diabetes of the young following transfer from long-term insulin to sulphonylureas
    Maggie Shepherd
    Diabetes Care 26:3191-2. 2003
  88. pmc Understanding cystic-fibrosis-related diabetes: best thought of as insulin deficiency?
    Lee Dobson
    Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK
    J R Soc Med 97:26-35. 2004
    ..g. relative preservation of fasting glucose) may initially respond to beta cell secretagogues. A large randomized prospective trial in the USA should answer this point in the next few years...
  89. ncbi request reprint Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy
    Jørn V Sagen
    Section of Pediatrics, Department of Clinical Medicine, University of Bergen, N 5021 Bergen, Norway
    Diabetes 53:2713-8. 2004
    ..2 may be managed on an oral sulfonylurea with sustained metabolic control rather than insulin injections, illustrating the principle of pharmacogenetics applied in diabetes treatment...
  90. ncbi request reprint Molecular genetics goes to the diabetes clinic
    Andrew T Hattersley
    Peninsu Medical School, Exeter
    Clin Med (Lond) 5:476-81. 2005
    ..The challenge for diabetologists is to use clinical skills to detect these monogenic patients whose care will be greatly helped by the treatment changes that follow molecular genetic testing...
  91. ncbi request reprint Contrasting insulin sensitivity of endogenous glucose production rate in subjects with hepatocyte nuclear factor-1beta and -1alpha mutations
    Anna Brackenridge
    Department of Diabetes and Endocrinology, Royal Surrey County Hospital, Guildford, UK
    Diabetes 55:405-11. 2006
    ..This is likely to reflect reduced action of HNF-1beta in the liver and possibly the kidney. This may be mediated through regulation by HNF-1beta of the key gluconeogenic enzymes glucose-6-phosphatase or PEPCK...
  92. ncbi request reprint The variable number of tandem repeats upstream of the insulin gene is a susceptibility locus for latent autoimmune diabetes in adults
    Minal Desai
    Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
    Diabetes 55:1890-4. 2006
    ..In conclusion, differences in VNTR-encoded susceptibility do not explain the differences in clinical presentation that distinguish classical type 1 diabetes and LADA...
  93. ncbi request reprint Assessment of the role of common genetic variation in the transient neonatal diabetes mellitus (TNDM) region in type 2 diabetes: a comparative genomic and tagging single nucleotide polymorphism approach
    Anna L Gloyn
    Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK
    Diabetes 55:2272-6. 2006
    ..Using a study sufficiently powered to detect odds ratios of <1.2, we conclude that common variation in the TNDM region does not play an important role in the genetic susceptibility to type 2 diabetes...
  94. ncbi request reprint Beyond the beta cell in diabetes
    Andrew T Hattersley
    Nat Genet 38:12-3. 2006
  95. ncbi request reprint Intrauterine hyperglycemia is associated with an earlier diagnosis of diabetes in HNF-1alpha gene mutation carriers
    Amanda Stride
    Department of Diabetes and Vascular Medicine, University of Exeter, Devon, UK
    Diabetes Care 25:2287-91. 2002
    ....
  96. pmc Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes
    Eleftheria Zeggini
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK
    Science 316:1336-41. 2007
    ..The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes...
  97. ncbi request reprint Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses
    Takafumi Tsuchiya
    Departments of Medicine and Human Genetics, The University of Chicago, 5841 S Maryland Ave, MC1027, Chicago, IL 60637, USA
    Mol Genet Metab 89:174-84. 2006
    ..68 (1.33-2.11), P=0.00001). The pooled and meta-analyses as well as the linkage disequilibrium and haplotype diversity studies suggest a role for genetic variation in CAPN10 affecting risk of T2D in Europeans...
  98. ncbi request reprint Necrobiosis lipodica is a clinical feature of maturity-onset diabetes of the young
    Amanda Stride
    Diabetes Care 25:1249-50. 2002
  99. ncbi request reprint Variation in the calpain-10 gene affects blood glucose levels in the British population
    Stephen Lynn
    School of Clinical Medical Sciences, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK
    Diabetes 51:247-50. 2002
    ..002). We conclude that genetic variation in the CAPN10 gene influences blood glucose levels in nondiabetic British subjects and that this is due, at least in part, to the effects of calpain-10 on the early insulin secretory response...
  100. ncbi request reprint A putative functional polymorphism in the IGF-I gene: association studies with type 2 diabetes, adult height, glucose tolerance, and fetal growth in U.K. populations
    Timothy M Frayling
    Department of Diabetes and Vascular Medicine, University of Exeter, Barrack Road, Exeter EX2 5AX, U K
    Diabetes 51:2313-6. 2002
    ..66). There was no association with measures of fetal growth, including birth weight (P = 0.17). Our results do not support the previous associations and suggest that the promoter microsatellite is unlikely to be functionally important...