Metabolic Heterogeneity Underlying Hypertriglyceridemia: Hepatic Triglyceride Biosynthesis in Humans With Different Insulin Resistance Phenotypes
Insulin Resistance, Hypertriglyceridemia
About this trial
This is an interventional basic science trial for Insulin Resistance
Eligibility Criteria
Inclusion Criteria: Ability to give informed consent Overweight, defined as BMI 25-30 kg/m2 Modest hypertriglyceridemia, defined as fasting plasma triglycerides 1.5-3.0mM High risk of insulin resistance, defined as fasting plasma insulin >64pM Stable weight for at least 3mo prior to participation Exclusion Criteria: Active or chronic liver disease, kidney disease, congestive heart failure, unstable angina, history of acute cardiovascular events within 6mo of screening, history of seizures or syncope, or an active infection requiring antimicrobial therapy; Use of insulin, thiazolidinediones, SGLT2 inhibitors, or sulfonylureas; Use of fibrates, omega 3 (fish oil), niacin, or PCSK9 antagonists; Use of systemic glucocorticoids within 60d prior to participation; Hematocrit <35%; Pregnancy of breastfeeding; Active tobacco use, excessive alcohol intake (>14U/wk), or history of drug abuse.
Sites / Locations
- AMC Amsterdam
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
IR participants with standardized dinner
IR participants with standardized dinner and premeal exercise
Participants with global IR and tissue-specific IR. Participants with global IR (in both skeletal muscle and adipose tissue) and tissue-specific IR (in adipose tissue). Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention. Contribution of DNL to hepatic VLDL will be measured using a deuterated water drink, to be ingested prior to the standardized dinner. Blood will be drawn the following morning for the measurement of deuterium incorporation into triglycerides. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed.
Participants with global IR and tissue-specific IR. Participants with global IR (in both skeletal muscle and adipose tissue) and tissue-specific IR (in adipose tissue). Glucose tolerance, skeletal muscle/whole-body insulin sensitivity and adipose tissue insulin sensitivity will be evaluated prior to intervention. DNL will be assessed in all participants after a single day with short bouts of premeal exercise with a standardized dinner. Contribution of DNL to hepatic VLDL will be measured using a deuterated water drink, to be ingested prior to the standardized dinner. Blood will be drawn the following morning for the measurement of deuterium incorporation into triglycerides. Plasma deuterium will be allowed to wash out over several weeks, and the 2nd deuterated water study will be performed.