Member Listing

Name

David Dunger

Affiliation

Department of Paediatrics, Metabolic Research Laboratories

Title

Professor

Role

Principal Investigator

Research Summary

Research Interests

daviddunger

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

1) Pathogenesis of type 1 diabetes (T1D) and its complications

In collaboration with Professor J Todd, Professor Dunger established the UK Genetic Resource Investigating Diabetes (UK GRID) collecting over 10,000 DNA samples from people with T1D leading to the identification of key diabetes susceptibility genes. In 2015 Professor Dunger became the Clinic Coordinator of an IMI-2 EU consortium (INNODIA 2012-2022) which will explore novel methods and new biomarkers for the early identification of T1D development and progression leading to innovative clinical trials.

In a subset of UK GRID his group established the Nephropathy Family Study (NFS) which complemented the earlier Oxford Regional Prospective Study of T1D (ORPS). These studies have identified the natural history of microalbuminuria and linked pathophysiology in childhood onset of T1D.  The group also secured funding from JDRF, BHF, DUK and Pfizer to carry out the first RCT of statins/ACE inhibitors in adolescents with T1D (AdDIT website) which was reported in 2017.

2) Perinatal origins of risk for obesity and type 2 diabetes (T2D)

Professor Dunger and his colleague, Dr Ken Ong, have studied genetic and environmental determinants of size at birth and early growth, initially in collaboration with ALSPAC but more recently through the Cambridge Baby Growth Study and collaborations with Mead Johnson. Important discoveries have been the influence of fetal imprinted genes in determining maternal BP and glucose status; the critical role of ‘postnatal’ catch up growth in determining risk for T2D and MS; the role of lipidomics in determining risk for T2D during early pregnancy and identifying metabolic effects of breast/bottle feeding in the newborn.

3) Experimental Medicine

David Dunger is an international expert on the metabolic effects of the growth hormone/insulin like growth factor-1 axis. He led the first studies of rhIGF-1 in T1D and more recently subjects with severe insulin resistance.  His physiological studies in collaboration with Dr K Beardsall also led to the first studies of insulin replacement in the very low birth weight infant (NIRTURE: NEJM 2008) and participation in the FP7 study PREVENTROP exploring the use of rhIGF-1 in this population.

Collaboration with Professor Roman Hovorka (a mathematical modeller) has led to an impressive series of physiological studies exploring the use of pumps and glucose sensors in subjects with T1D and his work has lead to Cambridge becoming a world leader in the development of closed loop insulin delivery systems (the artificial pancreas).

Expertise

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

Selected Publications

Selected Publications

Marcovecchio ML, Chiesa ST, Armitage J, Daneman D, Donaghue KC, Jones TW, Mahmud FH, Marshall SM, Neil HAW, Dalton RN, Deanfield J, Dunger DB; Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) Study Group.   Renal and Cardiovascular Risk According to Tertiles of Urinary Albumin-to-Creatinine Ratio: The Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT).   Diabetes Care. 2018 Sept;41 (9):1963-1969. doi: 10.2337/dc18-1125. PMID: 30026334

Willemsen RH, Burling K, Barker P, Ackland F, Dias RP, Edge J, Smith A, Todd J, Lopez B, Mander AP, Guy C, Dunger DB.   Frequent Monitoring of C-peptide Levels in Newly Diagnosed Type 1 Subjects Using Dried Blood Spots Collected at Home. J Clin Endocrinol Metab. 2018 May 31. doi: 10.1210/jc.2018-00500. [Epub ahead of print].   PMID: 29860430

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. PMID:29091568.

Petry CJ, Ong KK, Hughes IA, Acerini CL, Frystyk J, Dunger DB. Early Pregnancy-Associated Plasma Protein A Concentration are Associate with Third Trimester Insulin Sensitivity. J Clin Endocrinol Metab. 2017. doi: 10.1210/jf.2017-00272. PMID: 28323969. PMCID:PMC5464396

Diderholm B, Beardsall K, Murgatroyd P, Lees C, Gustafsson J, Dunger D. Maternal rates of lipolysis and glucose production in late pregnancy are independently related to fetal weight. Clin Endocrinol (Oxf). 2017. doi: 10.111/cen.13359. PMID:28434207.

Lu L, Koulman A, Petry CJ, Jenkins B, Matthews L, Hughes IA, Acerini CL, Ong KK, Dunger DB.  An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.  Diabetes Care. 2016 Oct 4. pii: dc160863. PMID: 27703025.

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. Nov; 28(11):4868-79. PMID: 25145626.

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.  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.

Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Ossuetta I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB.  Early insulin therapy in very-low-birth-weight-infants. N Engl J Med. 2008; 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.  Risk of microalbuminuria and progression to macroalbuminuria in a cohort with childhood onset type 1 diabetes: prospective observational study. BMJ. 2008; 29;336(7646):697-701.  PMID:18349042PMCID:PMC2276285.

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