Multi-Tracer Pet Quantitation of Insulin Action

Completed

Conditions studied: Diabetes

In brief

We are proposing a clinical investigation of the pathogenesis of insulin resistance (IR) in skeletal muscle and adipose tissue (AT), focusing specifically on the contributions of glucose delivery, transport and phosphorylation. The primary methodology will be dynamic PET imaging, using three tracers that respectively portray the kinetics of glucose delivery, bi-directional trans-membrane glucose transport and glucose phosphorylation. The three tracers are: 1) \[15O\]-H2O for quantifying tissue perfusion, this portrays the kinetics of glucose delivery from plasma to tissue; 2) \[11C\]-3-O-methyl glucose, a tracer constrained to bi-directional trans-membrane glucose transport; and 3) \[18F\]-fluoro-deoxy glucose, which like \[11C\]-3-OMG is transported, but adds the subsequent metabolic step, that of glucose phosphorylation. We propose 2 specific aims to apply this methodology to investigate the pathogenesis of IR. The 1st aim is to quantitatively assess the kinetics of glucose delivery, transport and phosphorylation in skeletal muscle in type 2 DM and as compared to obese and lean non-diabetic men and women. We will appraise the contribution of each step to the to the pathogenesis of IR. We postulate more severe IR in oxidative muscle, with a dual impairment of glucose transport and phosphorylation. The 2nd aim is to implement the triple-tracer dynamic PET imaging protocol in adipose tissue (AT), examining normal insulin action in non-obese volunteers and testing whether differences in AT insulin action are present in obese insulin sensitive volunteers compared to obese IR participants and the relation of AT IR to that of muscle and liver.

Key facts

Study ID

NCT00715221

Run by

University of Pittsburgh

People needed

30

Starts

2007-07-01

Expected to finish

2012-06-01

Last updated by the study team

2017-08-01

Who can join

Age: 30 and older, up to 55. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• Male and Female Normal Weight - non-diabetic (BMI 19-25) Overweight/Obese - non-diabetic (BMI 27-38) Type 2 DM (BMI 27-38)
• Fasting lab glucose < 100 mg/dl (non-diabetic groups) HbA1c < 6.0 (non-diabetic group) HbA1c < 8.5 (diabetic group)
• Ulnar artery patent bilaterally Negative urine pregnancy test Non-smoker Independent in self blood glucose monitoring (diabetic group)

You may not qualify if…

• BP > 150 mmHg systolic or > 95 mmHg diastolic History of any heart disease, including MI, pacemaker History of PVD, (including diminishing pulses) liver disease, kidney disease, pulmonary disease, neuromuscular disease, neurological disease, thyroid disease or any drug or alcohol abuse.
• Current malignancy or history of cancer within the past 5 years Proteinuria 1+ or greater Hematocrit < 34% sTSH >8 ALT > 60; AST > 60; Alk Phos > 150 Total cholesterol > 250 Triglycerides > 300
• MEDICATIONS:
• Chronic medications that can alter glucose homeostasis: oral glucocorticoids, nicotinic acid (Birth control medications are okay and will not exclude) Thiazolidinediones or insulin, previous difficulty with lidocaine (xylocaine) Gained or lost more than 3 kg during the past 3 months Involved in regular exercise > 1 day/week Surgical or vascular implants, any metal in body, claustrophic Currently pregnant OR currently lactating

Where it is running

• University of Pittsburgh — Pittsburgh, Pennsylvania, United States

Full record on ClinicalTrials.gov

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