BENITIONSClinical Trial Intelligence

Skeletal Muscle Diacylglycerol and Sphingolipids - Impact of Localization and Species on Insulin Resistance in Humans

단계 해당 없음 완료 NCT03077360

대상 질환Diabetes Mellitus, Type 2, Pre-diabetes, Obesity
임상 단계단계 해당 없음
스폰서University of Colorado, Denver
상태완료
참여자 수62 명
중재(약물)Lifestyle
시작일2017년 2월 1일
완료일2020년 11월 19일
결과 공개일2022년 6월 21일

요약

The rationale for the proposed research is that elucidating changes in localized diacylglycerol (DAG) and sphingolipid species that predict insulin sensitivity will reveal specific localized lipids to target in therapeutics for type 2 diabetes. To attain the overall objective, the investigators propose three specific aims: 1. Identify the influence of sarcolemmal DAG and sphingolipids on cell signaling and insulin sensitivity before and after insulin sensitizing lifestyle interventions. Strong preliminary data shape the hypothesis that sarcolemmal 1,2-disaturated DAG and C18:0 ceramide species will decrease after insulin sensitizing lifestyle interventions, leading to less Protein kinase C (PKC) and Protein phosphatase 2A (PP2A) activation, and enhanced insulin signaling. Skeletal muscle DAG and sphingolipid isomers, species, localization, and de novo synthesis will be measured before and after diet-induced weight loss or exercise training interventions in obese men and women. Insulin sensitivity will be measured using insulin clamps, and muscle lipids using Liquid Chromatography Mass Spectrometry (LC/MS). 2. Determine the impact of mitochondrial/ER (endoplasmic reticulum) DAG and

Percent Change in Insulin Sensitivity Compared to Baseline Measurement.

Baseline and 12 weeks · Percent change

Weight Loss Only31.8 ± 8.8 Percent change
Exercise Only17.4 ± 8.7 Percent change
Delayed Intervention Control-4.8 ± 9.3 Percent change

Percent Change in Localized Muscle Lipids Compared to Baseline

Baseline and 12 weeks · percentage change

Weight Loss Only-25 ± 6 percentage change
Exercise Only-30 ± 7 percentage change
Delayed Intervention Control5 ± 6 percentage change
Weight Loss Only-20 ± 5 percentage change
Exercise Only-25 ± 5 percentage change
Delayed Intervention Control10 ± 3 percentage change

Percent Change in Body Weight Compared to Baseline Measurement

Baseline, 3 Months · Percent Change

Weight Loss Only-10.5 ± 0.9 Percent Change
Exercise Only-0.5 ± 0.5 Percent Change
Delayed Intervention Control0.5 ± 0.4 Percent Change

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