The goal of this clinical trial is to understand how the blood sugar-lowering hormone insulin works in healthy adults versus those who are at risk for type 2 diabetes. The study will use a drug called alpelisib, which interferes with insulin's actions in the body, to answer the study's main question: does the liver continue to respond to insulin's stimulation of fat production even when it loses the ability to stop making glucose (sugar) in response to insulin. Researchers will compare the impact of single doses of both alpelisib and placebo (inert non-drug) in random order (like flipping a coin) in study participants. Participants will be asked to stay twice overnight in the hospital, take single doses of alpelisib and placebo (one or the other on each of the two hospital stays), and receive intravenous (into the vein) infusions of non-radioactive "tracer" molecules that allow researchers to measure the production of glucose (sugar) and fats by the liver. Measurements will be done both overnight, while participants are asleep and fasting (not eating or drinking other than water) and while consuming a standardized diet of nutritional beverages during the following day.
The objective is to evaluate the effect of lowering insulin levels, while maintaining constant mild hyperglycemia, on plasma glucose and lipid levels.
Adults aged 18-70 years
Able to understand written and spoken English and/or Spanish
For Group IS: BMI 18-25 kg/m2
For Group IR: BMI 30-45 kg/m2
Inability to provide informed consent in English or Spanish
Abnormal vital signs: (1) Systolic blood pressure < 90 mm Hg or > 160 mm Hg and/or (2) Diastolic blood pressure < 55 mm Hg or > 100 mm Hg and/or (3) Abnormal resting heart rate < 55 bpm (except at PI's discretion) or ≥ 110 bpm
Abnormal screening serum electrolytes judged by the PI to be potentially clinically significant, including liver function abnormalities (either of the following): (1) Transaminases (AST or ALT) > 3.0 x the upper limit of normal and/or (2) Total bilirubin > 1.25 x the upper limit of normal
Laboratory evidence of diabetes mellitus: (1) Hemoglobin A1c ≥ 6.5%, and/or (2) Fasting plasma glucose ≥ 126 mg/dL
Columbia University
Lead sponsor
University of California, Berkeley
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
Stanford University
Collaborator