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| ID | Type | Description | Link |
|---|---|---|---|
| K23HL159292 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| University of Colorado, Denver | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin plus automated insulin delivery system | Active Comparator | 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 | Placebo Comparator | 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. |
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| Multiple daily insulin injections or manual insulin pump plus continuous glucose monitor | Other | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin Hcl 1000Mg Tab | Drug | Agent used to modify insulin sensitivity |
|
| Measure | Description | Time Frame |
|---|---|---|
| Renal vascular resistance | Renal plasma flow will be measured by para-aminohippurate clearance and used to calculate renal vascular resistance | 4 months |
| Glomerular filtration rate | Measured by iohexol clearance | 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Arterial stiffness | Measured by SphygmoCor | 4 months |
| Insulin sensitivity | Measured by hyperinsulinemic-euglycemic clamp | 4 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kalie Tommerdahl, MD | Contact | (206) 616-9015 | ktomme@uw.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Colorado/University of Colorado Anschutz Medical Campus | Active, not recruiting | Aurora | Colorado | 80045 | United States |
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| Aminohippurate Sodium 20 % Injection | Drug | Diagnostic aid/agent used to measure renal plasma flow and calculate renal vascular resistance |
|
|
| Iohexol 300 Mg/mL Injectable Solution | Drug | Diagnostic aid/agent used to measure glomerular filtration rate |
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| Placebo | Drug | Identical to Metformin Hcl 1000Mg Tab but without metabolic effects |
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| Seattle Children's Hospital | Recruiting | Seattle | Washington | 98102 | United States |
|
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D003928 | Diabetic Nephropathies |
| D002318 | Cardiovascular Diseases |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D048909 | Diabetes Complications |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| D010130 | p-Aminohippuric Acid |
| D007267 | Injections |
| D007472 | Iohexol |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D000618 | Aminohippuric Acids |
| D006626 | Hippurates |
| D001549 | Benzamides |
| D000577 | Amides |
| D062366 | para-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D007651 | Keto Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D014283 | Triiodobenzoic Acids |
| D007463 | Iodobenzoates |
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