MANATEE-T1D: Metformin and AutomaTEd Insulin Delivery System Effects on Renal Vascular Resistance, Insulin Sensitivity, and Cardiometabolic Function in Youth with Type 1 Diabetes
- Conditions
- Type 1 DiabetesDiabetic Kidney DiseaseCardiovascular DiseasesEndothelial DysfunctionInsulin Sensitivity
- Interventions
- Registration Number
- NCT05065372
- Lead Sponsor
- Kalie Tommerdahl
- Brief Summary
Diabetic kidney disease and cardiovascular disease remain the leading causes of morbidity and mortality in people with type 1 diabetes and are exacerbated with longer duration of diabetes and time outside goal glycemic range. Yet, type 1 diabetes is a complex disease with pathophysiology that extends beyond beta-cell injury and insulin deficiency to include insulin resistance and renal vascular resistance, factors that accelerate cardiovascular disease risk. We have shown that metformin improved peripheral insulin sensitivity and vascular stiffness in youth with type 1 diabetes on multiple daily insulin injections or standard insulin pumps. However, metformin's effect on kidney and endothelial outcomes, and the effects of type 1 diabetes technologies, with or without metformin, on any cardiovascular or kidney outcome, remains unknown. Automated insulin delivery systems combine an insulin pump, continuous glucose monitor, and control algorithm to modulate background insulin delivery and decrease peripheral insulin exposure while improving time in target range and reducing hypoglycemia. We hypothesize that automated insulin delivery systems, particularly when combined with metformin, may modulate renal vascular resistance and insulin sensitivity, thereby impacting cardiometabolic function. MANATEE-T1D is a randomized, double-blind, placebo-controlled trial of 4 months of metformin 2,000 mg daily in 40 youth aged 12-25 years with type 1 diabetes on automated insulin delivery systems vs. 20 control youth with type 1 diabetes on multiple daily injections plus a continuous glucose monitor or an insulin pump in manual mode plus a continuous glucose monitor which will assess for changes in calculated renal vascular resistance and gold standard measures of whole-body and adipose insulin sensitivity, arterial stiffness, and endothelial function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- T1D and using an automated insulin delivery system or multiple daily insulin injections/manual insulin pump plus continuous glucose monitor for > 6 months
- Age 12-25 years
- Use of an automated insulin delivery system or multiple daily insulin injections plus a continuous glucose monitor or an insulin pump in manual mode plus a continuous glucose monitor for > 6 months
- Hemoglobin A1c < 11%
- No recent episodes of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar syndrome (HHS) (within 30 days)
- Pubertal (Tanner stage ≥ 2)
- Weight > 54 kg and BMI > 5th percentile for age and sex
- Blood pressure > 140/90 mm Hg
- Hemoglobin < 9 g/dL
- Estimated glomerular filtration rate < 60 mL/min/1.73 m2 or serum creatinine > 1.2 mg/dL or history of urinary albumin to creatinine ratio ≥ 300mg/g or history of acute kidney injury
- Use of anti-diabetic agents except insulin, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB's), diuretics, daily non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin, sulfonamides, procaine, thiazosulfone or probenecid
- Seafood or iodine allergy
- Pregnancy or breast feeding for females
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Metformin plus automated insulin delivery system Metformin Hcl 1000Mg Tab Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with metformin and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function. Metformin plus automated insulin delivery system Aminohippurate Sodium 20 % Injection Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with metformin and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function. Metformin plus automated insulin delivery system Iohexol 300 Mg/mL Injectable Solution Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with metformin and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function. Placebo plus automated insulin delivery system Aminohippurate Sodium 20 % Injection Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with a placebo pill which is identical in appearance to the metformin pill and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function. Placebo plus automated insulin delivery system Iohexol 300 Mg/mL Injectable Solution Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with a placebo pill which is identical in appearance to the metformin pill and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function. Placebo plus automated insulin delivery system Placebo Some participants with type 1 diabetes using an automated insulin delivery system will be randomized to receive treatment with a placebo pill which is identical in appearance to the metformin pill and will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function. Multiple daily insulin injections or manual insulin pump plus continuous glucose monitor Aminohippurate Sodium 20 % Injection Participants with type 1 diabetes using multiple daily injections or an insulin pump in manual mode plus a continuous glucose monitor will not be randomized to receive medication treatment but will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function. Multiple daily insulin injections or manual insulin pump plus continuous glucose monitor Iohexol 300 Mg/mL Injectable Solution Participants with type 1 diabetes using multiple daily injections or an insulin pump in manual mode plus a continuous glucose monitor will not be randomized to receive medication treatment but will undergo RPF (Aminohippurate Sodium Injections 20%), GFR (Iohexol Inj 300 MG/ML), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) assessments, in addition to assessments of cardiovascular and endothelial function.
- Primary Outcome Measures
Name Time Method Renal vascular resistance 4 months Renal plasma flow will be measured by para-aminohippurate clearance and used to calculate renal vascular resistance
Glomerular filtration rate 4 months Measured by iohexol clearance
- Secondary Outcome Measures
Name Time Method Arterial stiffness 4 months Measured by SphygmoCor
Insulin sensitivity 4 months Measured by hyperinsulinemic-euglycemic clamp
Trial Locations
- Locations (2)
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States