Impact of Metabolic Surgery on Pancreatic, Renal and Cardiovascular Health in Youth With Type 2 Diabetes

NCT03620773 | Completed Phase 1 FDA Drug

• 1 other identifier: 18-0704
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes (T2D) in youth is increasing in prevalence in parallel with the obesity epidemic. In the US, almost half of patients with renal failure have DKD, and ≥80% have T2D. Compared to adult-onset T2D, youth with T2D have a more aggressive phenotype with greater insulin resistance (IR), more rapid β-cell decline and higher prevalence of diabetic kidney disease (DKD), arguing for separate and dedicated studies in youth-onset T2D. Early DKD is characterized by changes in intrarenal hemodynamic function, including increased renal plasma flow (RPF) and glomerular pressure with resultant hyperfiltration, is common in Y-T2D, and predicts progressive DKD. Studies evaluating the two currently approved medications for treating T2D in youth (metformin and insulin) have shown these medications are not able to improve β-cell function over time in the youth. However, recent evidence suggests that bariatric surgery in adults is associated with improvements in diabetes outcomes, and even T2D remission in many patients. Limited data in youth also supports the benefits of bariatric surgery, regarding weight loss, glycemic control in T2D, and cardio-renal health. While weight loss is important, the acute effect of bariatric surgery on factors such as insulin resistance likely includes weight loss-independent mechanisms. A better understanding of the effects of bariatric surgery on pancreatic function, intrarenal hemodynamics, renal O2 and cardiovascular function in youth with obesity with or without diabetes is critical to help define mechanisms of surgical benefits, to help identify potential novel future non-surgical approaches to prevent pancreatic failure, DKD and cardiovascular disease. The investigators' overarching hypotheses are that: 1) Y-T2D is associated with IR, pancreatic dysfunction, intrarenal hemodynamic dysfunction, elevated renal O2 consumption and cardiovascular dysfunction which improve with bariatric surgery, 2) The early effect of bariatric surgery on intrarenal hemodynamics is mediated by improvement in IR and weight loss, 3) Some aspects of cardio-renal-metabolic complications of T2D are related to obesity and others to T2D independent of obesity. To address these hypotheses, the investigators will measure GFR, RPF, glomerular pressure and renal O2, in addition to aortic stiffness, β-cell function and insulin sensitivity in youth ages 12-21 with T2D (n=40) and in (n=up to 10) youth with similar BMI but without diabetes, before and after vertical sleeve gastrectomy (VSG). To further investigate the mechanisms of renal damage in youth with T2D, two optional procedures are included in the study prior to vertical sleeve gastrectomy: 1) kidney biopsy procedure and 2) induction of induced pluripotent stem cells (iPSCs) to assess morphometrics and genetic expression of renal tissue.

Conditions

Type 2 Diabetes Mellitus; Obesity; Bariatric Surgery Candidate; Nephropathy; Diabetic Kidney Disease; Diabetes Mellitus, Type 2; Diabetes Mellitus; Diabetes Complications; Weight Loss; Diabetic Nephropathies; Adolescent Obesity; Pediatric Obesity

Outcome Measures

Primary Outcomes (4)

• Pancreatic β-cell function

  Measured by Mixed Meal Tolerance Test (MMTT)

  4 hours (MMTT)

• Pancreatic β-cell function

  Measured by blood draws during/after hyperglycemic clamp

  4 hours (hyperglycemic clamp)

• Effective Renal Plasma Flow (ERPF)

  Measured by PAH clearance

  4 hours

• Glomerular Filtration Rate (GFR)

  Measured by iohexol clearance

  4 hours

Secondary Outcomes (3)

• Renal Perfusion

  10 min

• Renal Oxygenation

  60 min

• Aortic Stiffness & Wall Shear Stress

  30 min

Other Outcomes (6)

• Podocyte numerical density and number per glomerulus

  4 hours

• Foot process width of glomeruli

  4 hours

• Detachment and endothelial fenestration of glomeruli

  4 hours

Study Arms (1)

Clinical Investigation

OTHER

Participants will include youth who are scheduled for, and will undergo, vertical sleeve gastrectomy (VSG) surgery at the Bariatric Surgery Clinic at Children's Hospital of Colorado. To understand how bariatric surgery affects renal function, all participants will undergo assessment of Glomerular Filtration Rate, (Iohexol Inj 300 mg/mL) and Effective Renal Plasma Flow (Aminohippurate Sodium Inj 20%). In addition, participants will undergo imaging assessment that includes renal Blood Oxygen Level Dependent (BOLD) and Arterial Spin Labeling (ASL) MRI.

Drug: Aminohippurate Sodium Inj 20%; Drug: Iohexol Inj 300 mg/mL; Procedure: Vertical Sleeve Gastrectomy; Procedure: Renal Biopsy

Interventions

Aminohippurate Sodium Inj 20% DRUG

Diagnostic aid/agent used to measure effective renal plasma flow (ERPF)

Also known as: Aminohippuric acid, Para-aminohippurate, Sodium 4-amino hippurate (PAH) inj 20% 2g/10 mL

Clinical Investigation

Iohexol Inj 300 mg/mL DRUG

Diagnostic aid/agent used to measure glomerular filtration rate (GFR)

Also known as: omnipaque 300

Clinical Investigation

Vertical Sleeve Gastrectomy PROCEDURE

Participants will undergo vertical sleeve gastrectomy surgery, a laparoscopic bariatric surgery procedure designed for weight loss in obese patients

Also known as: Bariatric Surgery

Clinical Investigation

Renal Biopsy PROCEDURE

Minimally invasive outpatient procedure in interventional radiology to obtain renal tissue cores.

Also known as: Kidney Biopsy

Clinical Investigation

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Obese youth with and without T2D (≥50 kg) scheduled for VSG
• Weight \<550 lbs.
• BMI ≥ 35 kg/m2
• Age 12-21 years
• HbA1c ≤ 12% for participants with T2D, HbA1c \< 6.5% for participants with obesity

You may not qualify if:

• Obesity or T2D onset (diagnosis) \> 18 years of age
• Prepubertal
• Anemia
• For participants undergoing the optional Parts 2-4 of visits 2 and 4, seafood or iodine allergy
• Pregnancy or breastfeeding
• Claustrophobia, implantable devices (MRI contraindications)
• Recent diabetic ketoacidosis or hyperosmolar hyperglycemia
• Other causes of diabetes other than T2D
• For participants undergoing the optional Parts 2-4 of visits 2 and 4, diuretics, sodium-glucose co-transport (SGLT) 2 or 1 blockers, daily NSAIDs or aspirin, sulfonamides, procaine, thiazolsulfone or probenecid, atypical antipsychotics or regular use of oral steroids
• Evidence of bleeding disorder or complications from bleeding
• Use of aspirin, NSAIDS or other blood thinner that cannot be safely stopped for a sufficient time period before and after the biopsy so as to add no additional risk of bleeding
• Blood urea nitrogen (BUN) \> 80 gm/dL
• INR \> 1.4
• PTT \> 35 seconds
• Hemoglobin (Hgb) \< 10 mg/dL

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Dobbs TJ, Pyle L, Moore JM, Garrish J, Behn CD, Weissenkampen D, Baumgartner AD, Gross S, Schutte G, Birznieks C, Melena I, Remmers L, Driscoll L, Cree MG, Kelsey MM, Shah AS, Inge TH, Bjornstad P, Nadeau KJ. Impact of Vertical Sleeve Gastrectomy in Youth-Onset Type 2 Diabetes: Changes in Glycemia, Insulin Sensitivity, and Secretion. Obesity (Silver Spring). 2026 Feb 18. doi: 10.1002/oby.70140. Online ahead of print.

  PMID: 41708511 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus; Diabetes Complications; Weight Loss; Pediatric Obesity

Interventions

p-Aminohippuric Acid; Iohexol; Bariatric Surgery

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Body Weight Changes

Intervention Hierarchy (Ancestors)

Aminohippuric Acids; Hippurates; Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Keto Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triiodobenzoic Acids; Iodobenzoates; Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative

Study Officials

• Petter Bjornstad, MD

  University of Colorado School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants in this study will receive the same intervention.

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 8, 2018
• Study Start: October 1, 2018
• Primary Completion: September 25, 2024
• Study Completion: September 25, 2024
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)