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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01HL088448-05 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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Critically ill children, including children undergoing heart surgery, commonly develop elevated blood glucose (also known as "blood sugar") levels during their illness, which can lead to poor health outcomes and an increased risk of death. This study will examine the effectiveness of maintaining normal blood glucose levels at decreasing infections and improving recovery in young children undergoing heart surgery.
Children undergoing heart surgery are under significant bodily stress, which can lead to higher than normal or lower than normal blood glucose levels. A synthetic form of insulin, a naturally occurring hormone in the body, can be injected into people to normalize blood glucose levels. Insulin is most commonly used to treat people with diabetes, but it is also used in hospitals to control blood glucose levels in patients. Previous studies of adult intensive care unit (ICU) patients have shown that patients whose blood sugar levels are maintained at normal levels with the use of insulin contract fewer infections and are released more quickly from the ICU than patients who do not maintain normal blood glucose levels. This study will use a continuous blood glucose monitoring system to detect changes in blood glucose levels. Intravenous insulin infusions will be used to then safely maintain normal blood glucose levels. The purpose of this study is to determine if maintaining normal blood glucose levels during an ICU stay will help decrease the incidence of infections and improve surgical recovery in young children following heart surgery.
This study will enroll children who are undergoing heart surgery that requires a cardiopulmonary bypass procedure. Participants will be randomly assigned to either a control group or the treatment group. All participants will receive usual care while in the ICU and will undergo continuous glucose monitoring. Participants in the treatment group will receive intravenous insulin infusions to keep their blood glucose within the normal range. While in the ICU, blood will be collected from all participants once a day for the first 3 days and then once a week to monitor glucose levels, hormone levels, and measurements of nutrition and immune function. On days 1 and 5 following surgery, participants who are on a ventilator will have their breath measured to monitor heart function and energy use. Thirty days and 1 year following surgery, study researchers will contact the participant's parent or doctor to collect information on health status and any new infections at the surgical site. Children who enroll in the study will be asked to participate in follow-up neurodevelopmental evaluations at 1 and 3 years of age to assess longer term cognitive effects of tight glycemic control in the ICU.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Insulin | Experimental | Insulin was infused to target a blood glucose concentration of 80-110 mg/dL |
|
| Usual Care | Active Comparator | Insulin was infused according to the discretion of the treating clinical team. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Insulin | Drug | Study drug is continuously infused intravenous insulin. Suggested dose is calculated by a computerized infusion algorithm using the participant's blood sugar concentration. The insulin infusion rate is titrated to maintain normal blood sugar. Participants are eligible to receive insulin while they have an in-dwelling arterial catheter. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Nosocomial Infections in the Cardiac ICU | Nosocomial infections that are attributable to the subject's stay in the Cardiac ICU, according to Center for Disease Control-defined criteria. These definitions are extensive and cannot be accurately condensed to fit within this space. Current CDC/NHSN criteria may be accessed through this URL: https://www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef\_current.pdf. | Measured during participant's ICU stay, a median duration of 3 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiac Index (CI) | Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. | Day 2 (day after cardiopulmonary bypass surgery). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Agus, MD | Boston Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States | ||
| C.S. Mott Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16998362 | Background | Agus MS, Javid PJ, Piper HG, Wypij D, Duggan CP, Ryan DP, Jaksic T. The effect of insulin infusion upon protein metabolism in neonates on extracorporeal life support. Ann Surg. 2006 Oct;244(4):536-44. doi: 10.1097/01.sla.0000237758.93186.c8. | |
| 16951013 | Background | Piper HG, Alexander JL, Shukla A, Pigula F, Costello JM, Laussen PC, Jaksic T, Agus MS. Real-time continuous glucose monitoring in pediatric patients during and after cardiac surgery. Pediatrics. 2006 Sep;118(3):1176-84. doi: 10.1542/peds.2006-0347. |
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Will share with investigators based upon specific requests
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Participants gave consent prior to cardiopulmonary bypass (CPB) surgery, randomization occurred perioperatively and initiation of the protocol occurred postoperatively. 9 subjects were removed from the study between the time of randomization and initiation of the protocol (4 for cancellation of CPB , 3 for physician decision, 2 for death).
Enrollment began in September 2006 and ended in May 2012. All subjects received the study intervention in the Cardiac ICUs at Boston Children's Hospital (Boston, MA) and C.S. Mott Children's Hospital (Ann Arbor, MI).
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| ID | Title | Description |
|---|---|---|
| FG000 | Tight Glycemic Control | Insulin : Study drug is continuously infused intravenous insulin. Suggested dose is calculated by a computerized infusion algorithm using the participant's blood sugar concentration. The insulin infusion rate is titrated to maintain normal blood sugar. Participants are eligible to receive insulin while they have an in-dwelling arterial catheter. |
| FG001 | Standard Care | Usual Care : Participants receive standard Cardiac ICU care without tight blood glucose control. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tight Glycemic Control | Insulin : Study drug is continuously infused intravenous insulin. Suggested dose is calculated by a computerized infusion algorithm using the participant's blood sugar concentration. The insulin infusion rate is titrated to maintain normal blood sugar. Participants are eligible to receive insulin while they have an in-dwelling arterial catheter. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Incidence of Nosocomial Infections in the Cardiac ICU | Nosocomial infections that are attributable to the subject's stay in the Cardiac ICU, according to Center for Disease Control-defined criteria. These definitions are extensive and cannot be accurately condensed to fit within this space. Current CDC/NHSN criteria may be accessed through this URL: https://www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef\_current.pdf. | Posted | Number | infections / 1000 pt days | Measured during participant's ICU stay, a median duration of 3 days. |
|
Entire course of protocol, up to 28 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Insulin | Insulin: Study drug is continuously infused intravenous insulin. Suggested dose is calculated by a computerized infusion algorithm using the participant's blood sugar concentration. The insulin infusion rate is titrated to maintain normal blood sugar. Participants are eligible to receive insulin while they have an in-dwelling arterial catheter. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe hypoglycemia (BG < 40 mg/dL) | Endocrine disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypokalemia (K < 2.0 mmol/L) | Endocrine disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Michael Agus | Boston Children's Hospital | 617-355-5849 | michael.agus@childrens.harvard.edu |
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| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D006943 | Hyperglycemia |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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|
|
| Usual Care | Other | Participants receive standard Cardiac ICU care without tight blood glucose control. |
|
| Duration of ICU Stay | Duration of ICU stay spans from post-operative cardiac ICU admission to cardiac ICU discharge. | The duration of cardiac ICU stay was evaluated from the date of postoperative cardiac ICU admission until the date of cardiac ICU discharge or date of death from any cause, whichever came first, assessed up to 30 days. |
| Duration of Hospital Stay | Duration of hospital stay spans from post-operative cardiac ICU admission to hospital discharge. | The duration of hospital stay was evaluated from the day of postoperative cardiac ICU admission until the day of hospital discharge or day of death from any cause, whichever came first, assessed up to 30 days. |
| Duration of Endotracheal Intubation | Duration of endotracheal intubation spans from endotracheal tube intubation/initiation of mechanical ventilation to endotracheal tube extubation. | The duration of endotracheal intubation (mechanical ventilation) was evaluated from the day of postoperative cardiac ICU admission until the day of extubation or day of death from any cause, whichever came first, assessed up to 30 days. |
| Mortality at Hospital Discharge. | Mortality is assessed at hospital discharge and at 30 days. | Mortality at hospital discharge (In-hospital mortality) was evaluated on the day of hospital discharge or day of death from any cause, whichever came first (no upper limit). |
| Mortality at 30 Days. | Mortality is assessed at hospital discharge and at 30 days. If the participant is discharged from the hospital prior to 30 days, status is determined by a follow-up phone call to the family. | Measured at 30 days. |
| Cardiac Function | Cardiac function is assessed by duration of vasoactive support. | The duration of vasoactive support was evaluated from the day of postoperative cardiac ICU admission until the last day of vasoactive support or day of death from any cause, whichever came first, assessed up to 30 days. |
| Immune Function | Immune function is assessed by C-reactive protein (CRP) on post-operative day 7. | Post-operative day 7. |
| Endocrine Function | Endocrine function is assessed by total triiodothyronine (T3) on post-operative day 7. | Measured during participant's ICU stay on Day 7. |
| Nutritional Status | Nutritional status assessed by percentage of total caloric intake as enteral nutrition during critical illness period. | The percentage of total caloric intake was evaluated from the day of postoperative cardiac ICU admission until the last day of the critical illness period, as defined by the presence of the arterial catheter, assessed up to 30 days. |
| Neurodevelopmental Evaluation, Cognitive | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age.
| Measured at one year of age. |
| Neurodevelopmental Evaluation, Language | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age.
| Measured at one year of age. |
| Neurodevelopmental Evaluation, Motor | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age.
| Measured at one year of age. |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| 15929674 | Background | Javid PJ, Halwick DR, Betit P, Thompson JE, Long K, Zhang Y, Jaksic T, Agus MS. The first use of live continuous glucose monitoring in patients on extracorporeal life support. Diabetes Technol Ther. 2005 Jun;7(3):431-9. doi: 10.1089/dia.2005.7.431. |
| 15185208 | Background | Agus MS, Javid PJ, Ryan DP, Jaksic T. Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation. J Pediatr Surg. 2004 Jun;39(6):839-44; discussion 839-44. doi: 10.1016/j.jpedsurg.2004.02.013. |
| 22805161 | Background | Gaies MG, Langer M, Alexander J, Steil GM, Ware J, Wypij D, Laussen PC, Newburger JW, Goldberg CS, Pigula FA, Shukla AC, Duggan CP, Agus MS; Safe Pediatric Euglycemia after Cardiac Surgery Study Group. Design and rationale of safe pediatric euglycemia after cardiac surgery: a randomized controlled trial of tight glycemic control after pediatric cardiac surgery. Pediatr Crit Care Med. 2013 Feb;14(2):148-56. doi: 10.1097/PCC.0b013e31825b549a. |
| 22957521 | Result | Agus MS, Steil GM, Wypij D, Costello JM, Laussen PC, Langer M, Alexander JL, Scoppettuolo LA, Pigula FA, Charpie JR, Ohye RG, Gaies MG; SPECS Study Investigators. Tight glycemic control versus standard care after pediatric cardiac surgery. N Engl J Med. 2012 Sep 27;367(13):1208-19. doi: 10.1056/NEJMoa1206044. Epub 2012 Sep 7. |
| 37526194 | Derived | Bellon F, Sola I, Gimenez-Perez G, Hernandez M, Metzendorf MI, Rubinat E, Mauricio D. Perioperative glycaemic control for people with diabetes undergoing surgery. Cochrane Database Syst Rev. 2023 Aug 1;8(8):CD007315. doi: 10.1002/14651858.CD007315.pub3. |
| 36071424 | Derived | Sadhwani A, Asaro LA, Goldberg CS, Ware J, Butcher J, Gaies M, Smith C, Alexander JL, Wypij D, Agus MSD. Impact of tight glycemic control and hypoglycemia after pediatric cardiac surgery on neurodevelopmental outcomes at three years of age: Findings from a randomized clinical trial. BMC Pediatr. 2022 Sep 7;22(1):531. doi: 10.1186/s12887-022-03556-z. |
| 27112038 | Derived | Sadhwani A, Asaro LA, Goldberg C, Ware J, Butcher J, Gaies M, Smith C, Alexander JL, Wypij D, Agus MS. Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial. J Pediatr. 2016 Jul;174:193-198.e2. doi: 10.1016/j.jpeds.2016.03.048. Epub 2016 Apr 23. |
| 25850865 | Derived | Fisher JG, Sparks EA, Khan FA, Alexander JL, Asaro LA, Wypij D, Gaies M, Modi BP, Duggan C, Agus MS, Yu YM, Jaksic T. Tight Glycemic Control With Insulin Does Not Affect Skeletal Muscle Degradation During the Early Postoperative Period Following Pediatric Cardiac Surgery. Pediatr Crit Care Med. 2015 Jul;16(6):515-21. doi: 10.1097/PCC.0000000000000413. |
| 24671945 | Derived | Agus MS, Asaro LA, Steil GM, Alexander JL, Silverman M, Wypij D, Gaies MG; SPECS Investigators. Tight glycemic control after pediatric cardiac surgery in high-risk patient populations: a secondary analysis of the safe pediatric euglycemia after cardiac surgery trial. Circulation. 2014 Jun 3;129(22):2297-304. doi: 10.1161/CIRCULATIONAHA.113.008124. Epub 2014 Mar 26. |
| Cardiopulmonary bypass canceled |
|
| BG001 |
| Standard Care |
Usual Care : Participants receive standard Cardiac ICU care without tight blood glucose control. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Standard Care | Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control. |
|
|
| Secondary | Cardiac Index (CI) | Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. | This outcome (using indirect calorimetry) was not available at the Michigan site, and not captured in Boston participants A) who had been extubated or were receiving only pressure support ventilation, B) without a properly placed catheter allowing for a true mixed venous sample or C) for whom equipment malfunction precluded an accurate measurement. | Posted | Median | Inter-Quartile Range | liters/min/m^2 | Day 2 (day after cardiopulmonary bypass surgery). |
|
|
|
| Secondary | Duration of ICU Stay | Duration of ICU stay spans from post-operative cardiac ICU admission to cardiac ICU discharge. | Posted | Median | Inter-Quartile Range | Days | The duration of cardiac ICU stay was evaluated from the date of postoperative cardiac ICU admission until the date of cardiac ICU discharge or date of death from any cause, whichever came first, assessed up to 30 days. |
|
|
|
| Secondary | Duration of Hospital Stay | Duration of hospital stay spans from post-operative cardiac ICU admission to hospital discharge. | Posted | Median | Inter-Quartile Range | Days | The duration of hospital stay was evaluated from the day of postoperative cardiac ICU admission until the day of hospital discharge or day of death from any cause, whichever came first, assessed up to 30 days. |
|
|
|
| Secondary | Duration of Endotracheal Intubation | Duration of endotracheal intubation spans from endotracheal tube intubation/initiation of mechanical ventilation to endotracheal tube extubation. | Posted | Median | Inter-Quartile Range | Days | The duration of endotracheal intubation (mechanical ventilation) was evaluated from the day of postoperative cardiac ICU admission until the day of extubation or day of death from any cause, whichever came first, assessed up to 30 days. |
|
|
|
| Secondary | Mortality at Hospital Discharge. | Mortality is assessed at hospital discharge and at 30 days. | Posted | Number | Participants | Mortality at hospital discharge (In-hospital mortality) was evaluated on the day of hospital discharge or day of death from any cause, whichever came first (no upper limit). |
|
|
|
| Secondary | Mortality at 30 Days. | Mortality is assessed at hospital discharge and at 30 days. If the participant is discharged from the hospital prior to 30 days, status is determined by a follow-up phone call to the family. | This outcome was not measured for participants lost to follow-up at 30 days post cardiac surgery. | Posted | Number | Participants | Measured at 30 days. |
|
|
|
| Secondary | Cardiac Function | Cardiac function is assessed by duration of vasoactive support. | Posted | Median | Inter-Quartile Range | Days | The duration of vasoactive support was evaluated from the day of postoperative cardiac ICU admission until the last day of vasoactive support or day of death from any cause, whichever came first, assessed up to 30 days. |
|
|
|
| Secondary | Immune Function | Immune function is assessed by C-reactive protein (CRP) on post-operative day 7. | Participants analyzed include those with adequate access for blood sampling, C-reactive protein (CRP) drawn on post-operative day 7 and successful processing and preparation of samples, | Posted | Median | Inter-Quartile Range | mg/dL | Post-operative day 7. |
|
|
|
| Secondary | Endocrine Function | Endocrine function is assessed by total triiodothyronine (T3) on post-operative day 7. | Thyroid hormones were assayed only if the participant remained in the cardiac ICU and there was central venous or arterial access for blood sampling. | Posted | Median | Inter-Quartile Range | ng/dL | Measured during participant's ICU stay on Day 7. |
|
|
|
| Secondary | Nutritional Status | Nutritional status assessed by percentage of total caloric intake as enteral nutrition during critical illness period. | Nutritional intake was tracked during the period of critical illness, as defined by the presence of an arterial catheter. | Posted | Median | Inter-Quartile Range | Percent of total caloric intake | The percentage of total caloric intake was evaluated from the day of postoperative cardiac ICU admission until the last day of the critical illness period, as defined by the presence of the arterial catheter, assessed up to 30 days. |
|
|
|
| Secondary | Neurodevelopmental Evaluation, Cognitive | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age.
| Participants were not eligible if: born before 3/1/2008 (1 year before start of testing); age greater than one year at time of surgery; died; lived abroad; parent/guardian declined; severe disability precluded testing; did not show for testing; testing completed at greater than 18 months post eligibility. | Posted | Mean | Standard Deviation | Scores on a scale | Measured at one year of age. |
|
|
|
| Secondary | Neurodevelopmental Evaluation, Language | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age.
| Participants were not eligible if: born before 3/1/2008 (1 year before start of testing); age greater than one year at time of surgery; died; lived abroad; parent/guardian declined; severe disability precluded testing; did not show for testing; testing was completed at greater than 18 months post eligibility. | Posted | Mean | Standard Deviation | Scores on a scale | Measured at one year of age. |
|
|
|
| Secondary | Neurodevelopmental Evaluation, Motor | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age.
| Participants were not eligible if: born before 3/1/2008 (1 year before start of testing); age greater than one year at time of surgery; died; lived abroad; parent/guardian declined; severe disability precluded testing; did not show for testing; testing completed at greater than 18 months post eligibility. | Posted | Mean | Standard Deviation | Scores on a scale | Measured at one year of age. |
|
|
|
| 16 |
| 490 |
| 15 |
| 490 |
| EG001 | Usual Care | Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control. | 5 | 490 | 19 | 490 |
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| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D006946 | Hyperinsulinism |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |