We are very sad to share the news that David Dunger FMedSci, Professor Emeritus of Paediatrics, University of Cambridge, passed away on 20th July 2021. Our thoughts are with his family during this difficult time.
Director of Research
Professor of Paediatrics
Academic Symposium for Professor David Dunger
Biography:
David Dunger was 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 (ORPS), 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 worked with Professor Todd identifying critical immune phenotypes associated with these genes in unaffected siblings.
In 2015 Professor Dunger became the Clinic Coordinator of an IMI-2 EU consortium (INNODIA 2012-2022) https://www.innodia.eu/ explores novel methods and new biomarkers for the early identification of T1D development and progression leading to innovative clinical trials.
2) Perinatal origins 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 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 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 was 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 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 was the subject of his continued 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.
Key Publications
Chiesa ST, Charakida M, McLoughlin E, Nguyen HC, Georgiopoulos G, Motran L, Elia Y, Marcovecchio ML, Dunger DB, Dalton RN, Daneman D, Sochett E, Mahmud FH, Deanfield JE. Elevated high-density lipoprotein in adolescents with Type 1 diabetes is associated with endothelial dysfunction in the presence of systemic inflammation. Eur Heart J. 2019 Mar 12. pii: ehz114. doi: 10.1093/eurheartj/ehz114. PMID: 30863865
Marcovecchio ML, Chiesa ST, Bond S, Daneman D, Dawson S, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, Dunger DB; AdDIT Study Group. ACE inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med 2017 Nov 2;377(18):1733-1745. doi: 10.1056/NEJMoa1703518.
Haidar A, Elleri D, Kumareswaran K, Leelarathna L, Allen JM, Caldwell K, Murphy HR, Wilinska ME, Acerini CL, Evans ML, Dunger DB, Nodale M, Hovorka R. Pharmacokinetics of insulin aspart in pump-treated subjects with type 1 diabetes: reproducibility and effect of age, weight, and duration of diabetes. Diabetes Care. 2013 Oct;36(10):e173-4.
De Lucia Rolfe E, Modi N, Uthaya S, Hughes IA, Dunger DB, Acerini C, Stolk RP, Ong KK. Ultrasound estimates of visceral and subcutaneous-abdominal adipose tissues in infancy. J Obes. 2013;951954. Epub 2013 Apr 17. PMC3654330
Ranke MB, Lindberg A, Mullis PE, Geffner ME, Tanaka T, Cutfield WS, Tauber M, Dunger D. Towards optimal treatment with growth hormone in short children and adolescents: evidence and theses. Horm Res Paediatr. 2013; 79(2):51-67. PMID:23446062
Oke J, Farmer A, Neil A, Dalton RN, Dunger D, Stevens R. Monitoring young people with type 1 diabetes for diabetic nephropathy: Potential errors of annual ACR testing. Diabetes Res Clin Pract. 2013; Mar;99(3):307-14. PMID:23312483
Hovorka R, Elleri D, Allen JM, Dunger D. The artificial pancreas for young people with type 1 diabetes: Status and outlook. Diabetes Care for Children & Young People. 2012;1: 49-54.
Elleri D, Allen JM, Harris J, Kumareswaran K, Nodale M, Leelarathna L, Acerini CL, Haidar A, Wilinska ME, Jackson N, Umpleby AM, Evans ML, Dunger DB, Hovorka R. Absorption patterns of meals containing complex carbohydrates in type 1 diabetes. Diabetologia. 2013. 56(5):1108-17.PMID:23435829
Lashen H, Dunger D, Ness A, Ong K. Peripubertal changes in circulating antimullerian hormone levels in girls. Fertil Steril. 2013; 99(7):2071-2075. PMID:23419927
Pekalski ML, Ferreira RC, Coulson RM, Cutler AJ, Guo H, Smyth DJ, Downes K, Dendrou CA, Castro Dopico X, Esposito L, Coleman G, Stevens HE, Nutland S, Walker NM, Guy C, Dunger D, Wallace C, Tree TI, Todd JA, Wicker LS. Postthymic expansion in human CD4 naive T cells defined by expression of functional high-affinity IL-2 receptors. J Immunol. 2013; 190(6):2554-66. PMID:23418630
Williams RM, Ong KK, Dunger DB. Polycystic ovarian syndrome during puberty and adolescence. Mol Cell Endocrinol. 2013; 373(1-2):61-7. PMID:23384539
Leelarathna L, Nodale M, Allen J, Elleri D, Kumareswaran K, Haidar A, Caldwell K, Wilinska M, Acerini C, Evans M, Murphy H, Dunger D, Hovorka R. Evaluating the Accuracy and Large Inaccuracy of Two Continuous Glucose Monitoring Systems. Diabetes Technol Ther. 2013; 15(2):143-9.PMID:23256605
Elleri D, Allen JM, Kumareswaran K, Leelarathna L, Nodale M, Caldwell K, Cheng P, Kollman C, Haidar A, Murphy H, Wilinska M, Acerini C, Dunger D, Hovorka R. Closed-Loop Basal Insulin Delivery Over 36 Hours in Adolescents With Type 1 Diabetes: Randomized clinical trial. Diabetes Care. 2013;36(4):838-44. PMID:23193217
Elleri D, Allen J, Biagioni M, Kumareswaran K, Leelarathna L, Caldwell K, Nodale M, Wilinska M, Acerini C, Dunger D, Hovorka R. Evaluation of a portable ambulatory prototype for automated overnight closed-loop insulin delivery in young people with type 1 diabetes. Pediatr Diabetes. 2012; 13(6):449-53. PMID:22817340
Beardsall K, Vanhaesebrouck D, Ogilvy-Stuart AL, Vanhole C, Vanweissenbruch M, Midgley P, Thio M, Cornette L, Ossuetta I, Palmer CR, Iglesias I de Jong M, Gill B, de Zegher F, Dunger DB. Validation of the continuous glucose monitoring sensor in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2013;98(2):F136-40. doi: 10.1136/archdischild-2012-301661. PMID: 22791467
Beardsall K, Costeloe K, Dunger DB. Hyperglycemia in the Newborn-Clinical guidelines are needed but must be based on correct reporting of the data. J Parenter Enteral Nutr. 2012; 36(4):378. Author reply 379. PMID:22627186
Ranke MB, Lindberg A, Mullis PE, Geffner ME, Tanaka T, Cutfield WS, Tauber M, Dunger D. Towards Optimal Treatment with Growth Hormone in short children and adolescents: Evidence and Theses. Horm Res Paediatr. 2013; 79(2):51-67. PMID:23446062
Urbanek M, Hayes MG, Lee H, Freathy RM, Lowe LP, Ackerman C, Jafari N, Dyer AR, Cox NJ, Dunger DB, Hattersley AT, Metzger BE, Lowe Wl Jr. The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy. PLoS One. 2012;7(3):e32958. PMID:22479352
Haidar A, Elleri D, Allen J, Harris J, Kumareswaran K, Nodale M, Acerini C, Wilinska M, Jackson N, Umpleby M, Evans ML, Dunger D, Hovorka R. Validity of Triple- and Dual-Tracer Techniques to Estimate Glucose Appearance. Am J Physiol Endocrinol Metab. 2012; 302(12):E1493-501.PMID:22454288
Thankamony A, Ong KK, Ahmed ML, Ness AR, Holly JM, Dunger DB. Higher levels of IGF-1 and Adrenal Androgens at Age 8 Years are Associated with Earlier Age at Menarche in Girls. J Clin Endocrinol Metab. 2012. 97(5):E786-90. PMID:22419724
Cherney DZ, Scholey JW, Daneman D, Dunger DB, Dalton RN, Moineddin R, Mahmud F, Dekker R, Elia Y, Sochett E, Reich HN. Urinary markers of renal inflammation in adolescents with Type 1 diabetes mellitus and normoalbuminuria. Diabet Med. 2012;29(10):1297-302. PMID: 22416821
Salgin B, Marcovecchio ML, Hill N, Dunger DB, Frystyk J. The effect of prolonged fasting on levels of growth hormone-binding protein and free growth hormone. Growth Horm IGF Res. 2012; 22(2):76-81. PMID: 22386777
Marcovecchio LM, Tossavainen PH, Heywood JJ, Dalton NR, Dunger DB. An independent effect of parental lipids on the offspring lipid levels in a cohort of adolescents with type 1 diabetes. Pediatr Diabetes. 2012; Sep;13(6):463-9. PMID:22369206
Khulan B, Cooper WN, Skinner BM, Bauer J, Owens S, Prentice AM, Belteki G, Constancia M, Dunger D, Affara NA. Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Hum Mol Genet. 2012; 1;21(9):2086-101. PMID:22307237
Lauzon-Guillain B, Wijndaele K, Clark M, Acerini CL, Hughes IA, Dunger DB, Wells JC, Ong KK. Breastfeeding and infant temperament at age three months. PLoS One. 2012;7(1):e29326.PMID:22253712
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.
Marcovecchio ML, Giannini C, Widmer B, Dalton RN, Martinotti S, Chiarelli F, Dunger DB. (2008). C-reactive protein in relation to the development of microalbuminuria in type 1 diabetes: the Oxford Regional Prospective Study. Diabetes Care, 31(5):974-6. PMID: 18235049.
Ong KK, Northstone K, Wells JC, Rubin C, Ness AR, Golding J, Dunger DB. (2007).
Earlier mother’s age at menarche predicts rapid infancy growth and childhood obesity. PLoS Med, 4(4):e132. PMID: 17455989. PMCID: PMC1876410.
Saukkonen T, Shojaee-Moradie F, Williams RM, Amin R, Yuen KC, Watts A, Acerini CL, Umpleby AM,Dunger DB. (2006). Effects of recombinant human IGF-I/IGF-binding protein-3 complex on glucose and glycerol metabolism in type 1 diabetes. Diabetes, 55(8):2365-70. PMID: 16873702.