Member Listing

Name

David Dunger

Affiliation

Department of Paediatrics, Metabolic Research Laboratories

Title

Professor

Role

Principal Investigator

Research Summary

David Dunger is a paediatric clinical scientist with over 30 years experience in three key research areas.

1) Pathogenesis of type 1 diabetes and its complications:

In 1986 he initiated the Oxford Regional prospective study of childhood diabetes, recruiting over 500 young people around diagnosis for long term follow up to determine the natural history of microalbuminuria, an early marker of Cardiovascular and nephropathy risk. The results of this 20 year study were reported in the BMJ in 2008. In 2005 he succeeded in securing joint funding from JDRF, DUK, BHF and Pfizer to initiate the first multicentre RCT looking at the effects of Statins and ACE inhibitors in young people with diabetes during adolescence. A further cohort, the Genetic Resource Investigating Diabetes (GRID) collected over 10,000 DNA samples from people with type 1 diabetes in the UK which enabled Professor John Todd’s laboratory to identify key diabetes susceptibility genes. David Dunger is now working with Professor Todd identifying critical immune phenotypes associated with these genes in unaffected siblings.

2) Perinatal orgins of risk for obesity and type 2 diabetes:

This work began with an important collaboration with the ALSPAC study team exploring genetic determinants of size at birth. These studies continue and David Dunger has developed new collaborations with a large intervention pregnancy study group (HAPO) as well as helping to establish the Cambridge Baby Growth Study. Recent novel studies in collaboration with MRC Gambia have identified significant effects of periconceptional nutritional supplementation on methylation of imprinted and nonimprinted genes at birth. He has also identified through animal and more recently human studies that variation in paternally expressed imprinted foetal genes may affect the mothers risk for gestational diabetes (Diabetes, 2011). The work with ALSPAC also identified the critical role of early postnatal weight gain or ‘catch up’ growth in determining later risk for obesity and type 2 diabetes. These studies have identified the ‘road map’ linking early perinatal exposures and the development of insulin resistance, Beta cell dysfunction and ultimately risk for T2D.

3) Experimental Medicine:

David Dunger is an international expert on the growth hormone/insulin like growth factor 1 axis and its effects on metabolism. Using type 1 diabetic subjects and people with growth hormone deficiency as models to explore these relationships he has carried out a series of physiological studies contrasting effects of growth hormone and IGF-1 on glucose metabolism and insulin.

These led to the first experimental studies of rhIGF-1 in type 1 diabetes and subsequently a clinical trial published in the Lancet. Recent studies have examined the roles of GH and IGF-1 during fasting as these have a particular relevance to the study of the foetal origins of adult disease. The importance of the IGF-1 in ensuring normal growth and brain development in preterm and term infants is the subject of his current ongoing studies and his group recently completed a trial of insulin therapy for the preterm infant published in NEJM. Recruitment of a mathematical modeller has driven a number of physiology studies looking at the metabolic effects of GH, insulin and IGF-1 whilst also enabling Cambridge to lead the world in the development of the artificial pancreas.

Expertise

Biochemistry and Molecular Biology, Clinical Trials, Endocrinology, Genetics, Medical Devices and Therapeutics

Selected Publications

Quilter CR, Cooper WN, Cliffe KM, Skinner BM, Prentice PM, Nelson L, Bauer J, Ong KK, Constância M, Lowe WL, Affara NA, Dunger DB. Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk. FASEB J. 2014 Aug 21. pii: fj.14-255240. PMID: 25145626.

Hovorka R, Elleri D, Thabit H, Allen JM, Leelarathna L, El-Khairi R, Kumareswaran K, Caldwell K, Calhoun P, Kollman C, Murphy HR, Acerini CL, Wilinska ME, Nodale M, Dunger DB. Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial. Diabetes Care. 2014 May;37(5):1204-11. PMID: 24757227. PMCID: PMC3994941.

Thankamony A, Capalbo D, Marcovecchio ML, Sleigh A, Wanda Jørgensen S, Hill NR, Mooslehner K, Yeo GS, Bluck L, Juul A, Vaag A, Dunger DB. Low Circulating Levels of IGF-I in Healthy Adults are Associated with Reduced β-cell Function, Increased Intramyocellular Lipid and Enhanced Fat Utilisation During Fasting. J Clin Endocrinol Metab. 2014 Jun;99(6):2198-207. PMID: 24617714.

Beardsall K, Vanhaesebrouck S, Frystyk J, Ogilvy-Stuart AL, Vanhole C, van Weissenbruch M, Midgley P, Thio M, Cornette L, Gill B, Ossuetta I, Iglesias I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB; NIRTURE Study Group. Relationship between Insulin-Like Growth Factor I Levels, Early Insulin Treatment, and Clinical Outcomes of Very Low Birth Weight Infants. J Pediatr. 2014.164(5) :1038-1044. PMID: 24518169.

Marcovecchio ML, Woodside J, Jones T, Daneman D, Neil A, Prevost T, Dalton RN, Deanfield J, Dunger D; on behalf of the AdDIT Investigators. Adolescent Type 1 Diabetes cardio-renal Intervention Trial (AdDIT): Urinary screening and baseline biochemical and cardiovascular assessments. Diabetes Care. 2014;37(3):80513. PMID: 24198300.

Salgin B, Ong KK, Thankamony A, Emmett P, Wareham NJ, Dunger DB. (2012). Higher Fasting Plasma Free Fatty Acid Levels Are Associated with Lower Insulin Secretion in Children and Adult and a Higher Incidence of Type 2 Diabetes. J Clin Endocrin Metab, 2012; 97(9):3303-9. PMID: 22740706.

Cooper WN, Khulan B, Owens S, Elks CE, Seidel V, Prentice AM, Belteki G, Ong KK, Affara NA, Constancia M, Dunger DB. (2012). DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomised controlled trial. FASEB J, 2012;26(5):1782-90. PMID: 22267336.

Petry CJ, Seear RV, Wingate DL, Manico L, Acerini CL, Ong KK, Hughes IA, Dunger DB. (2011). Associations Between Paternally Transmitted Fetal IGF2 Variants and Maternal Circulating Glucose Concentrations in Pregnancy. Diabetes, 2011 60(11);3090-6. PMID: 21926269. PMCID: PMC3198064.

Marcovecchio ML, Dalton RN, Chiarelli F, Dunger DB. (2011). A1C Variability as an Independent Risk Factor for Microalbuminuria in Young People with Type 1 Diabetes. Diabetes Care, 2011: 34(4):1011-3. PMID: 21335371. PMCID: PMC3064014.

Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodal M, De Palma A, Wilinska ME, Acerini CL, Dunger DB. (2010). Manual closed-loop insulin in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet, 357(9716):743-51. PMID: 20138357.

Elks CE, Loos RJ, Sharp SJ, Langenberg C, Ring SM, Timpson NJ, Ness AR, Davey Smith G, Dunger DB, Wareham NJ. Ong KK. (2010). Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. PLoS Med, 7(5):e1000284. PMID: 20520848. PMCID: PMC2876048.

Marcovecchio ML, Tossavainen PH, Acerini CL, Barrett TG, Edge J, Neil A, Shield J, Widmer B, Dalton RN, Dunger DB. (2010). Maternal but not paternal association of ambulatory blood pressure with albumin excretion in young offspring with type 1 diabetes. Diabetes Care, 33(2):366-71. PMID: 19918004. PMCID: PMC2809284.

Regan FM, Williams RM, McDonald A, Umpleby AM, Acerini CL, O’Rahilly S, Hovorka R, Semple RK, Dunger DB. (2010). Treatment with recombinant human insulin-like growth factor (rhlGF)-l/rhlGF binding protein-3 complex improves metabolic control in subjects with severe insulin resistance. J Clin Endocrinol Metab, 95(5):2113-22. PMID: 20233784.

Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, Ong K, vanWeissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Osuetta I, Iglesias I, Theyskens C, de Jong M, Gill B, Ahluwalia JS, de Zegher F, Dunger DB. (2010). Prevalence and determinants of hyperglycemia in very low birth weight infants: cohort analysis of the NIRTURE study. J Paediatr, 157(5):715-9. PMID: 20570286.

Marcovecchio ML, Dalton RN, Schwarze CP, Prevost AT, Neil HA, Acerini CL, Barrett T, Cooper JD, Edge J, Shield J, Widmer B, Todd JA, Dunger DB. (2009). Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes. Diabetologia, 52(6):1173-81. PMID: 19305965.

Ong KK, Emmett P, Northstone K, Golding J, Rogers I, Ness AR, Wells JC, Dunger DB. (2009). Infancy weight gain predicts childhood body fat and age at menarche in girls. J Clin Endocrinol Metab, 94(5):1527-32. PMID: 19240149.

Marcovecchio ML, Dalton RN, Prevost AT, Acerini CL, Barrett TG, Cooper JD, Edge J, Neil A, Shield J, Widmer B, Todd JA, Dunger DB. (2009). Prevalence Of Abnormal Lipid Profiles And The Relationship With The Development Of Microalbuminuria In Adolescents With Type 1 Diabetes. Diabetes Care, 32(4):658-63. PMID: 19171721. PMCID: PMC2660471.

Salgin B, Marcovecchio ML, Humphreys SM, Hill N, Chassin LJ, Lunn DJ, Hovorka R, Dunger DB. (2009). Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects. Am J Physiol Endocrinol Metab, 296(3):E454-61. PMID: 19106250. PMCID: PMC2660143.

Ong KK, Langkamp M, Ranke MB, Whitehead K, Hughes IA, Acerini CL, Dunger DB. (2009). Insulin-like growth factor I concentrations in infancy predict differential gains in body length and adiposity: the Cambridge Baby Growth Study. Am J Clin Nutr, 90(1):156-61. PMID: 19474142.

Beardsall K, Ong KK, Murphy N, Ahmed ML, Zhao JH, Peeters MW, Dunger DB. (2009). Heritability of childhood weight gain from birth and risk markers for adult metabolic disease in prepubertal twins. J Clin Endocrinol Metab, 94(10):3708-13. PMID: 19723754.

Salgin B, Marcovecchio ML, Williams RM, Jackson SJ, Bluck LJ, Humphreys SM, Acerini CL, Dunger DB. (2009). Effects of growth hormone and free fatty acids on insulin sensitivity in patients with type 1 diabetes. J Clin Endocrinol Metab, 94(9):3297-305. PMID: 19567515. PMCID: PMCI2846959.

Ong KK, Diderholm B, Salanzo G, Wingate D, Hughes IA, MacDougall J, Acerini CL, Dunger DB. (2008). Pregnancy, insulin, glucose and BMI contribute to birth outcomes in nondiabetic mothers. Diabetes Care, 31(11):2193-7. PMID: 18697902. PMCID: PMC2571044.

Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Ossuetta I, Iglesias I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB. (2008). Early insulin therapy in very-low-birth-weight infants. N Engl J Med, 359(18):1873-84. PMID: 18971490.

Amin R, Widmer B, Prevost AT, Schwarze P, Cooper J, Edge J, Marcovecchio L, Neil A, Dalton RN, Dunger DB. (2008). Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ, 336(7646):697-701. PMID: 18349042. PMCID: PMC2276285.