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| Name | Class |
|---|---|
| Novo Nordisk A/S | INDUSTRY |
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The purpose of this study is to evaluate whether the addition of liraglutide 1.8 mg/day to a high-dose insulin regimen (>1.8 units/kg/day) in patients with uncontrolled (HbA1c >7.5%) type 2 diabetes mellitus will improve blood sugar control.
It also evaluates the effect of liraglutide on liver and pancreatic fat content, explores the mechanism of blood sugar improvement by assessing weight and pancreatic hormone release, and assesses blood pressure, lipid profile, and liver function. Finally it will look at patient quality of life and safety.
Type 2 diabetes is a progressive disease with incessant beta-cell dysfunction that often ultimately requires insulin treatment. Patients requiring high insulin dosages represent a particular treatment challenge and often have uncontrolled glycemia despite progressive dose increases and are especially prone to insulin related lipotoxicity and weight gain.
Glucagon-like peptide agonists (GLP-1) such as liraglutide have many actions that position them to break the vicious cycle in this population through the following mechanisms: (1) weight loss; (2) improved hepatic steatosis; (3) improved pancreatic steatosis; (4) decreased glucagon levels; (5) improved beta-cell function.
The purpose of the study is to demonstrate that liraglutide is both effective and safe when added to a high dose insulin treatment regimen. Liraglutide will improve glycemic control, weight, metabolic parameters, as well as patient satisfaction, with minimal adverse events. The study also proposes to study the mechanisms through which such improvements might occur, especially beta-cell function, glucagon levels, and hepatic and pancreatic fat content.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Liraglutide | Active Comparator |
| |
| Saline injection | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Liraglutide | Drug | Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months |
|
| Measure | Description | Time Frame |
|---|---|---|
| Glycemic Control Measured by HbA1c | HbA1c (%) | 6-months |
| Measure | Description | Time Frame |
|---|---|---|
| Pancreatic and Hepatic Triglyceride Content | Liver Triglyceride and Pancreatic Triglyceride | 6-months |
| Weight | 6-months | |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ildiko Lingvay, MD | UT Southwestern | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT Southwestern | Dallas | Texas | 75390 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27273731 | Derived | Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):939-47. doi: 10.1001/jamainternmed.2016.1540. | |
| 26909799 | Derived | Vanderheiden A, Harrison LB, Warshauer JT, Adams-Huet B, Li X, Yuan Q, Hulsey K, Dimitrov I, Yokoo T, Jaster AW, Pinho DF, Pedrosa I, Lenkinski RE, Pop LM, Lingvay I. Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin. J Clin Endocrinol Metab. 2016 Apr;101(4):1798-806. doi: 10.1210/jc.2015-3906. Epub 2016 Feb 24. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Liraglutide | Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months |
| FG001 | Saline Injection | Saline: Placebo injection of 1.8mg saline once daily for 6-months |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Liraglutide | Liraglutide: Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months |
| BG001 | Saline Injection | Saline: Placebo injection of 1.8mg saline once daily for 6-months |
| 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 | Glycemic Control Measured by HbA1c | HbA1c (%) | Posted | Mean | Standard Deviation | Percent HbA1c | 6-months |
|
|
6 months
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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 | Liraglutide | Liraglutide: Liraglutide 1.8mg injected subcutaneously from pen device once daily for 6-months |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrilation | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ildiko Lingvay | University of Texas Southwestern Medical Center at Dallas | 214-648-2779 | ildiko.lingvay@utsouthwestern.edu |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069450 | Liraglutide |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
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| Saline | Drug | Placebo injection of 1.8mg saline once daily for 6-months |
|
| Beta-Cell Function |
Fasting Glucose as a Measure of Beta-Cell Function |
| 6-months |
| Glucagon | Measured during mixed meal challenge test. | 6-months |
| Total Daily Insulin Dose | The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month. | 6-months |
| Number of Daily Injections | The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month. | 6-months |
| Blood Pressure | 6-months |
| Lipid Profile | 6-months |
| Liver Function Blood Test | 6-months |
| Hypoglycemic Events | Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl | 6-months |
| Quality of Life Survey (QoL) - General Health Perception | General health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor. | 6-months |
| Beta-Cell Function | Fasting C-peptide as a Measure of Beta-Cell Function | 6 months |
| Matsuda Index as a Measure of Beta Cell Function | The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values. Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)). Higher/lower values = better/worse insulin sensitivity. | 6 months |
| Beta-cell Function | AUC c-peptide | 6 Months |
| Ratio (AUC C-peptide/AUC Glucose) | 6 months |
| AUC Glucose | 6 months |
| Quality of Life Survey (QoL) - Current Health Perception | Current health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago. | 6 months |
| Quality of Life Survey (QoL) - Treatment Satisfaction | Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied. | 6 months |
| Quality of Life Survey (QoL) - Treatment Impact | Treatment impact was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied. | 6 months |
| Quality of Life Survey (QoL) - Social or Vocational Worry | Social or vocational worry was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time. | 6 months |
| Quality of Life Survey (QoL) - Hypoglycemia Fear | Hypoglycemia fear was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry. | 6 months |
| Quality of Life Survey (QoL) - Glycemia Control Perception | Glycemia control perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled. | 6 months |
| Quality of Life Survey (QoL) - Lifestyle Flexibility | Lifestyle flexibility was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice. | 6 months |
| Quality of Life Survey (QoL) - Social Stigma | Social stigma was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree. | 6 months |
| Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment | Satisfaction with insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied. | 6 months |
| Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment | Willingness to continue insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing. | 6 months |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Secondary | Pancreatic and Hepatic Triglyceride Content | Liver Triglyceride and Pancreatic Triglyceride | Posted | Mean | Standard Deviation | Percent Triglyceride | 6-months |
|
|
|
| Secondary | Weight | Posted | Mean | Standard Deviation | Kilograms | 6-months |
|
|
|
| Secondary | Beta-Cell Function | Fasting Glucose as a Measure of Beta-Cell Function | Posted | Mean | Standard Deviation | mg/dL | 6-months |
|
|
|
| Secondary | Glucagon | Measured during mixed meal challenge test. | Posted | Mean | Standard Deviation | pg/mL | 6-months |
|
|
|
| Secondary | Total Daily Insulin Dose | The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month. | Posted | Median | Inter-Quartile Range | IU | 6-months |
|
|
|
| Secondary | Number of Daily Injections | The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month. | Posted | Mean | Standard Deviation | number/day | 6-months |
|
|
|
| Secondary | Blood Pressure | Posted | Mean | Standard Deviation | mmHg | 6-months |
|
|
|
| Secondary | Lipid Profile | Posted | Mean | Standard Deviation | mg/dL | 6-months |
|
|
|
| Secondary | Liver Function Blood Test | Posted | Mean | Standard Deviation | U/L | 6-months |
|
|
|
| Secondary | Hypoglycemic Events | Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl | Posted | Median | Inter-Quartile Range | events per month per patient | 6-months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - General Health Perception | General health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor. | Posted | Mean | Standard Deviation | score on a scale | 6-months |
|
|
|
| Secondary | Beta-Cell Function | Fasting C-peptide as a Measure of Beta-Cell Function | Posted | Mean | Standard Deviation | microgram/L | 6 months |
|
|
|
| Secondary | Matsuda Index as a Measure of Beta Cell Function | The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values. Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)). Higher/lower values = better/worse insulin sensitivity. | Posted | Mean | Inter-Quartile Range | index | 6 months |
|
|
|
| Secondary | Beta-cell Function | AUC c-peptide | Posted | Mean | Standard Deviation | ug/(L/min) | 6 Months |
|
|
|
| Secondary | Ratio (AUC C-peptide/AUC Glucose) | Posted | Mean | Standard Deviation | Ratio | 6 months |
|
|
|
| Secondary | AUC Glucose | Posted | Mean | Standard Deviation | mg/(dL/min) | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Current Health Perception | Current health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Treatment Satisfaction | Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Treatment Impact | Treatment impact was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Social or Vocational Worry | Social or vocational worry was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Hypoglycemia Fear | Hypoglycemia fear was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Glycemia Control Perception | Glycemia control perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Lifestyle Flexibility | Lifestyle flexibility was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Social Stigma | Social stigma was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment | Satisfaction with insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| Secondary | Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment | Willingness to continue insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing. | Posted | Mean | Standard Deviation | score on a scale | 6 months |
|
|
|
| 0 |
| 35 |
| 1 |
| 35 |
| 14 |
| 35 |
| EG001 | Saline Injection | Saline: Placebo injection of 1.8mg saline once daily for 6-months | 0 | 36 | 6 | 36 | 14 | 36 |
| COPD exacerbation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Stent placement | Cardiac disorders | Systematic Assessment |
|
| Acute cholecystitis | Gastrointestinal disorders | Systematic Assessment |
|
| Cellulitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Gastroenteritis | Gastrointestinal disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Decreased in apetite | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| Increase of serum amylase | Gastrointestinal disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
Not provided
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| D004700 | Endocrine System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| HDL |
|