Browsing by Author "Chen, Zsu-Zsu"

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    Hepatic Fat in Participants With and Without Incident Diabetes in the Diabetes Prevention Program Outcome Study
    (The Endocrine Society, 2021) Goldberg, Ronald B.; Tripputi, Mark T.; Boyko, Edward J.; Budoff, Matthew; Chen, Zsu-Zsu; Clark, Jeanne M.; Dabelea, Dana M.; Edelstein, Sharon L.; Gerszten, Robert E.; Horton, Edward; Mather, Kieren J.; Perreault, Leigh; Temprosa, Marinella; Wallia, Amisha; Watson, Karol; Irfan, Zeb; Medicine, School of Medicine
    Context: There is little information about fatty liver in prediabetes as it transitions to early diabetes. Objective: This study is aimed at evaluating the prevalence and determinants of fatty liver in the Diabetes Prevention Program (DPP). Methods: We measured liver fat as liver attenuation (LA) in Hounsfield units (HU) in 1876 participants at ~14 years following randomization into the DPP, which tested the effects of lifestyle or metformin interventions versus standard care to prevent diabetes. LA was compared among intervention groups and in those with versus without diabetes, and associations with baseline and follow-up measurements of anthropometric and metabolic covariates were assessed. Results: There were no differences in liver fat between treatment groups at 14 years of follow-up. Participants with diabetes had lower LA (mean ± SD: 46 ± 16 vs 51 ± 14 HU; P < 0.001) and a greater prevalence of fatty liver (LA < 40 HU) (34% vs 17%; P < 0.001). Severity of metabolic abnormalities at the time of LA evaluation was associated with lower LA categories in a graded manner and more strongly in those with diabetes. Averaged annual fasting insulin (an index of insulin resistance [OR, 95% CI 1.76, 1.41-2.20]) waist circumference (1.63, 1.17-2.26), and triglyceride (1.42, 1.13-1.78), but not glucose, were independently associated with LA < 40 HU prevalence. Conclusion: Fatty liver is common in the early phases of diabetes development. The association of LA with insulin resistance, waist circumference, and triglyceride levels emphasizes the importance of these markers for hepatic steatosis in this population and that assessment of hepatic fat in early diabetes development is warranted.
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    Metabolite Profiles of Incident Diabetes and Heterogeneity of Treatment Effect in the Diabetes Prevention Program
    (American Diabetes Association, 2019-12) Chen, Zsu-Zsu; Liu, Jinxi; Morningstar, Jordan; Heckman-Stoddard, Brandy M.; Lee, Christine G.; Dagogo-Jack, Samuel; Ferguson, Jane F.; Hamman, Richard F.; Knowler, William C.; Mather, Kieren J.; Perreault, Leigh; Florez, Jose C.; Wang, Thomas J.; Clish, Clary; Temprosa, Marinella; Gerszten, Robert E.; Medicine, School of Medicine
    Novel biomarkers of type 2 diabetes (T2D) and response to preventative treatment in individuals with similar clinical risk may highlight metabolic pathways that are important in disease development. We profiled 331 metabolites in 2,015 baseline plasma samples from the Diabetes Prevention Program (DPP). Cox models were used to determine associations between metabolites and incident T2D, as well as whether associations differed by treatment group (i.e., lifestyle [ILS], metformin [MET], or placebo [PLA]), over an average of 3.2 years of follow-up. We found 69 metabolites associated with incident T2D regardless of treatment randomization. In particular, cytosine was novel and associated with the lowest risk. In an exploratory analysis, 35 baseline metabolite associations with incident T2D differed across the treatment groups. Stratification by baseline levels of several of these metabolites, including specific phospholipids and AMP, modified the effect that ILS or MET had on diabetes development. Our findings highlight novel markers of diabetes risk and preventative treatment effect in individuals who are clinically at high risk and motivate further studies to validate these interactions.