Diabetes Mellitus, Type 2, Healthy, Non-Alcoholic Fatty Liver Disease, Obesity
Conditions
Brief summary
The goal of this study is to evaluate the role of transcription factor EB (TFEB) in adipose (fat) tissue macrophages (ATM) in regulating adipose tissue and systemic metabolic function in obesity. The investigators will assess the differences in ATM lipid metabolism in people with metabolically abnormal obesity and lean individuals. Both groups will have: * screening visit * imaging (body composition testing - dual-energy x-ray absorptiometry (DEXA) scans, magnetic resonance imaging \[MRI\] and magnetic resonance spectroscopy \[MRS\] scans) * Overnight visit with intravenous infusion (IV), muscle, and fat tissue biopsies
Interventions
None listed
Sponsors
Bettina Mittendorfer
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Washington University School of Medicine
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
: * age: ≥18 but ≤70 years * not pregnant or breastfeeding * weight stable and sedentary before enrollment * no use tobacco products, excessive amounts of alcohol, or dietary supplements, or medications known to or suspected to affect glucose and lipid metabolism (aside from certain medications used to treat diabetes in the metabolically abnormal obesity \[MAO\]-Type 2 Diabetes group) * no evidence of significant organ system dysfunction or disease (e.g. chronic severe kidney disease, cancer) * participants must fulfil all of the following group-specific inclusion criteria below: Lean group: * Body mass index (BMI) ≥18.5 but \<25.0 kg/m2 * Intrahepatic triglyceride (IHTG) content \<5% * fasting blood glucose concentration: \<100 mg/dl * blood glucose concentration 2 h after a 75 g oral glucose challenge: \<140 mg/dl * Hemoglobin A1C (HbA1c) \<5.7 % Metabolically normal obesity (MNO) group: * BMI ≥30.0 but \<45.0 kg/m2 * IHTG content \<5% * fasting blood glucose concentration: \<100 mg/dl * blood glucose concentration 2 h after a 75 g oral glucose challenge: \<140 mg/dl * HbA1c \<5.7 % Metabolically abnormal obesity (MAO)-insulin resistance and non-alcoholic fatty liver disease (NAFLD) group: * BMI ≥30.0 but \<45.0 kg/m2 * IHTG content \>7.5% * fasting blood glucose concentration: ≥100 but \<126 mg/dl * blood glucose concentration 2 h after a 75 g oral glucose challenge: ≥140 but \<200 mg/dl * HbA1c: ≥5.7 but \<6.4 % MAO-type 2 diabetes group: * BMI ≥30.0 but \<45.0 kg/m2 * clinical diagnosis of type 2 diabetes or fasting blood glucose concentration \>126 mg/dl or blood glucose concentration 2 h after a 75 g oral glucose challenge\>200 mg/dl or HbA1c \>6.4 % without medication if not diagnosed and medically treated for diabetes
Exclusion criteria
\- Individuals that do not meet all inclusion Criterion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin sensitivity | Within 2 weeks of Clinical Visit | Sensitivity assessed as insulin-mediated glucose disposal during a hyperinsulinemic-euglycemic clamp procedure |
| 24-hour plasma glucose concentration | Within 2 weeks of Clinical Visit | — |
| Macrophage isolation in adipose tissue biopsy | Within 2 weeks of Clinical Visit | macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS) |
| Macrophage isolation in skeletal muscle tissue | Within 2 weeks of Clinical Visit | macrophage gene expression using RNA sequencing and fluorescent activated cell sorting (FACS) |
Countries
United States
Contacts
CONTACTHeather McHatton
CONTACTAman Pritish Aher
PRINCIPAL_INVESTIGATORBettina Mittendorfer
University of Missouri-Columbia
Outcome results
None listed