Insulin Receptor Substrate 1 (IRS-1) Regulation in Insulin Resistance

NCT01240252 | Completed Phase 1

• 2 other identifiers: 10-003382R01DK047936
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The study is being conducted to find out why too much fat in your blood stream may cause insulin resistance in your muscles. Insulin is the hormone, produced normally by your body, which causes your blood sugar to return to normal after you eat.

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes; insulin resistance

Outcome Measures

Primary Outcomes (1)

• Proportion of insulin resistant patients with elevated serine/threonine phosphorylation of IRS-1 in muscle.

  IRS-1 will be immunoprecipitated from percutaneous muscle biopsies, resolved by gel electrophoresis, digested with trypsin, and analyzed by high-performance liquid chromatography nanospray tandem mass spectrometry (MS/MS) analysis

  one month from date of volunteer study

Secondary Outcomes (1)

• Quantitative assay of the ability of insulin to clear glucose from the blood in insulin resistant patients.

  one month from date if volunteer study

Study Arms (3)

Type 2 Diabetes Mellitus Subjects

EXPERIMENTAL

Two hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m\^2 surface area per minute one time over 4 hours.

Drug: Human insulin

Overweight or Obese Subjects with Normal Glucose Tolerance

EXPERIMENTAL

Two hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m\^2 surface area per minute one time over 4 hours.

Drug: Human insulin

Non-Obese Control Subjects

PLACEBO COMPARATOR

Two hours after the start of deuterated glucose, subjects will receive human insulin (U100 Humulin) at a rate of 80 mU/m\^2 surface area per minute one time over 4 hours.

Drug: Human insulin

Interventions

Human insulin DRUG

U100 Humulin at a rate of 80 mU/m\^2 surface area per minute one time over 4 hours

Also known as: Humulin

Non-Obese Control Subjects; Overweight or Obese Subjects with Normal Glucose Tolerance; Type 2 Diabetes Mellitus Subjects

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 30-65 y
• Healthy lean, obese, or known type 2 diabetic
• Body Mass Index (BMI) less than 36
• All nondiabetic subjects must have normal oral glucose tolerance
• Subjects must have the following laboratory values:
• Hematocrit ≥ 35 vol%
• Serum creatinine ≤ 1.6 mg/dl
• Aspartate aminotransferase (AST) (SGOT)\< 2 times upper limit of normal
• Alanine aminotransferase (ALT) (SGPT)\< 2 times upper limit of normal
• Alkaline phosphatase \< 2 times upper limit of normal
• Triglycerides \< 150 mg/dl
• Prothrombin time (PT) 11.7 -14.3 seconds
• Partial thromboplastin time 23.0-37.0 seconds

You may not qualify if:

• No diseases known to affect glucose metabolism other than healthy type 2 diabetes
• Subjects must not be receiving any of the following medications: thiazide or furosemide diuretics, beta-blockers, or other chronic medications with known adverse effects on glucose tolerance levels unless the patient has been on stable dose of such agents for the past three months before entry into the study. Subjects may be taking a stable dose of estrogens or other hormonal replacement therapy, if the subject has been on these agents for the prior three months. Subjects taking systemic glucocorticoids are excluded.
• Subjects with a history of clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG), peripheral vascular disease (history of claudication), or pulmonary disease (dyspnea on exertion of one flight or less; abnormal breath sounds on auscultation) will not be studied.
• Recent systemic or pulmonary embolus, untreated high-risk proliferative retinopathy, recent retinal hemorrhage, uncontrolled hypertension, systolic BP\>180, diastolic BP\>105, autonomic neuropathy, resting heart rate \>100, electrolyte abnormalities.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance

Interventions

Insulin; Insulin, Regular, Human

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Lawrence Mandarino, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 29, 2010
• First Posted: November 15, 2010
• Study Start: March 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: June 5, 2013

Record last verified: 2013-06

Locations

US (1)