Bjornstad Lab
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current studies

Our studies assess several related research questions from different angles, as we comprehensively evaluate established and novel markers of kidney function and early predictors of DKD and CVD in youth and adults with Type 1 and Type 2 Diabetes

+ 1. Renal-HEIR

Full Title: Renal HEIR Study: Renal Hemodynamics, Energetics and Insulin Resistance in Youth Onset Type 2 Diabetes Study

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Principal Investigator: Petter Bjornstad, M.D. Co-investigators: Kristen J. Nadeau, M.D., M.S., Richard J. Johnson, M.D., Lorna Browne, M.D., Uyen Truong, M.D., Pottumarthi V Prasad, Ph.D., David Cherney, M.D., Ph.D., Robert G. Nelson, M.D., Ph.D.

A better understanding of the pathophysiology underlying hyperfiltration and its relationship with insulin resistance is critical to inform development of new therapeutics. The investigators' overarching hypotheses are that: 1) hyperfiltration in youth-onset T2D is associated with changes in intrarenal hemodynamics, resulting in increased renal oxygen demand, 2) the demand is unmet by the inefficient fuel profile associated with IR (decreased glucose oxidation and increase free fatty acid [FFA] oxidation), resulting in renal hypoxia and ultimately renal damage. To address these hypotheses, the investigators will measure peripheral insulin sensitivity, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and renal oxygenation and perfusion by MRI in youth (12-21 years of age) with T2D (n=30), obesity (n=20) and in lean (n=20) controls.

Sponsor: NIH/NIDDK, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 2.IMPROVE-T2D

Full Title: IMPROVE-T2D Study: Impact of Metabolic Surgery on Pancreatic, Renal and CardiOVascular HEalth in Youth with Type 2 Diabetes

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Principal Investigators: Petter Bjornstad, M.D., Kristen Nadeau, M.D., M.S., and Thomas Inge, M.D., Ph.D. Co-Investigators: Lorna Browne, M.D., Uyen Truong, M.D., Pottumarthi V Prasad, Ph.D., David Cherney, M.D., Ph.D., Robert G. Nelson, M.D. Ph.D., Megan Kelsey, M.D., M.S., Melanie Cree Green, M.D., Ph.D., Michal Schafer, M.S., Philip S. Zeitler, M.D., Ph.D.

A better understanding of the effects of bariatric surgery on pancreatic function, intrarenal hemodynamics, renal oxygenation and cardiovascular function is critical to help define mechanisms of surgical benefits, to help identify potential novel future non-surgical approaches to prevent pancreatic failure, DKD and CVD. Our overarching hypotheses are that: 1) Youth-onset T2D is associated with IR, pancreatic dysfunction, intrarenal hemodynamic dysfunction, and cardiovascular dysfunction which improve with bariatric surgery, 2) The early effect of bariatric surgery on cardiorenal health is mediated by improvement in IR and weight loss. To address these hypotheses, we will measure cardio-renal health, in addition to aortic stiffness, β-cell function and insulin sensitivity and central adiposity in youth-onset T2D (n=15) before and 3 and 12 months after vertical sleeve gastrectomy (VSG).

Sponsor: NIH/NIDDK, Children’s Hospital Colorado Research Institute, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 3.CASPER

Full Title: CASPER Study: Copeptin in Adolescent Participants with Type 1 Diabetes and Early Renal Hemodynamic Function

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Principal Investigators: Petter Bjornstad, M.D. Co-Investigators: Kristen Nadeau, M.D., M.S., Marian Rewers, M.D., Ph.D., David Z. Cherney, M.D., Ph.D., Bruce A. Perkins, M.D., M.P.H.

Animal research demonstrates that arginine vasopressin (AVP) acts directly at the V2 receptor (V2R) to modify intrarenal hemodynamic function, but also indirectly by activating RAAS (Tamaki et al. Kidney Int 1996). Our preliminary data suggest that elevated copeptin, a marker of AVP, predicts DKD in T1D adults, independently of other risk factors (Bjornstad et al. J Diabetes Complications 2016 and 2017). However, no human studies to date have examined how copeptin relates to intrarenal hemodynamic function in early DKD in T1D. A better understanding of this relationship is critical to inform development of new therapies targeting the AVP system in T1D. Accordingly, in this study, we propose to define the relationship between copeptin and intrarenal hemodynamics in early stages of DKD, by studying youth aged 12-21 years with T1D duration < 10 years. We will compare our findings with mechanistic data already collected in adults with longstanding T1D (≥ 50 years), with and without DKD (DKD and DKD Resistors) from the JDRF-funded Canadian Study of Longevity in Diabetes.

Sponsor: JDRF, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 4.DKA Study

Full Title: Diabetic Kidney Alarm Study

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Principal Investigators: Petter Bjornstad, M.D. Co-Investigators: Kristen Nadeau, M.D., M.S., Richard J. Johnson, M.D., David M. Maahs, M.D., Ph.D. and Arleta Rewers, M.D., Ph.D.

The overarching goals of this study are to determine whether tubular dysfunction and injury is present in new onset diabetic ketoacidosis (age 3-18), whether it is reversible and whether it is related to uricosuria and copeptin. The investigators propose to study a cohort of youth (ages 3-18, n=40) with new onset T1D who have serum and urine collection at DKA diagnosis and 3-month follow-up.

Sponsor: Thrasher Research Fund, JDRF-ISPAD Research Fellowship, Diabetes Guild, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 5.Renal blood flow Study

Full Title: Renal blood flow and glomerular filtration rate by phase-contrast MRI

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NCT (if applicable): N/A

Principal Investigators: Petter Bjornstad, M.D. and Michal Schafer, M.S., Ph.D. Co-investigators: John Strain, M.D.; Nicholas Stence, M.D.; Lorna Browne, M.D., Kristen J. Nadeau, M.D. M.S.; Uyen Truong, M.D.; Jens Goebel M.D.; John Craddock, M.D.; Amy Keating, M.D.; Michael Verneris, M.D.; Hesham Eissa, M.D.; Roger Giller, M.D.; Alisa Lee Sherick, M.D.; Chris McKinney, M.D.; Ralph Quinones, M.D.

To improve the availability, convenience and safety of ERPF and GFR assessments in youth, we propose adding phase-contrast (PC) MRI in 10 pediatric patients who are status pre-bone marrow transplant (BMT) and scheduled for iothalamate renography. We hypothesize that ERPF quantified by PC-MRI will strongly correlate with GFR derived by iothalamate clearance, and that GFR calculated by PC-MRI (GFR-MRI) will strongly correlate with GFR by iothalamate clearance. Our proposed study is significant in that a major gap in the field of kidney disease surveillance and research is to easily, safely and economically measure ERPF and GFR.

Sponsor: Children’s Hospital Colorado Radiology Funds, Colorado Clinical and Translational Sciences Institute (CCTSI)

+ 6.Alk-UA Study

Full Title: Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults with Type 1 Diabetes

Principal Investigators: Petter Bjornstad, M.D. Co-Investigators: Satish Garg, M.D., Marian Rewers, M.D., Ph.D., Janet K. Snell-Bergeon, Ph.D., David Maahs, M.D., Ph.D., Viral Shah, M.D. Sam Ellis, Pharm.D, Carlos Roncal, M.S., Richard J. Johnson, M.D.

Uricosuria and uric acid crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO3) on uric acid crystals in adults with T1D.

Sponsor: Colorado Clinical and Translational Sciences Institute (CCTSI) Publication: https://www.ncbi.nlm.nih.gov/pubmed/29498467