Disentangling the impact of alcohol use and hepatitis C on insulin action in Latino individuals

Rebecca G Kim, Jonathan Kramer-Feldman, Peter Bacchetti, Barbara Grimes, Esteban Burchard, Celeste Eng, Donglei Hu, Marc Hellerstein, Mandana Khalili, Rebecca G Kim, Jonathan Kramer-Feldman, Peter Bacchetti, Barbara Grimes, Esteban Burchard, Celeste Eng, Donglei Hu, Marc Hellerstein, Mandana Khalili

Abstract

Background: Alcohol, insulin resistance (IR), and hepatitis C (HCV) are all significant contributors to adverse outcomes of chronic liver disease. Latinos are disproportionately affected by these risk factors. We investigated the relationship between alcohol use and insulin action in a prospective cohort of Latino individuals with and without HCV.

Methods: One hundred fifty-three nondiabetic Latino individuals (60 HCV+, 93 HCV-) underwent clinical evaluation and metabolic testing; 56 had repeat testing over a median follow-up of 1.5 years. Peripheral IR and hepatic IR were measured via steady-state plasma glucose (SSPG) and endogenous glucose production during a two-step, 240-min insulin suppression test. Insulin secretion (IS) was measured using the graded glucose infusion test. Alcohol use was categorized as none, moderate (≤1 drink/day for women and ≤2 drinks/day for men), and heavy (>moderate). Multivariable models including HCV status assessed associations of alcohol use with baseline SSPG, hepatic IR and IS, and changes in these parameters over time.

Results: Overall, the median age was 44 years, 63.4% were male, 66.7% overweight/ obese, and 31.9% had heavy lifetime alcohol use while 60.4% had moderate lifetime alcohol use. SSPG and IS were similar by levels of alcohol use at baseline and alcohol use was not statistically significantly associated with change in these measures over time. However, lifetime daily heavy alcohol use (vs. not heavy, coef 2.4 μU-mg/kg-min-ml, p = 0.04) and HCV status (coef 4.4 μU-mg/kg-min-ml, p = 0.0003) were independently associated with higher baseline hepatic IR, and current heavy alcohol use was associated with greater change in hepatic IR in follow-up (coef 5.8 μU-mg/kg-min-ml, p = 0.03).

Conclusions: In this cohort of Latino individuals, lifetime and current heavy alcohol use influenced hepatic IR and its change over time. Strategies to decrease rates of heavy alcohol use or increase abstinence along with lifestyle modification and anti-HCV therapy to reduce metabolic risk are critical to prevent adverse liver and metabolic outcomes in Latino individuals.

Keywords: Hispanic; alcohol use disorder; hepatic insulin resistance; insulin secretion; steady-state plasma glucose.

© 2021 by the Research Society on Alcoholism.

Figures

Figure 1:. Baseline hepatic insulin resistance by…
Figure 1:. Baseline hepatic insulin resistance by lifetime daily alcohol use and hepatitis C (HCV) status.
Boxplots showing median baseline hepatic IR [(line), interquartile range (box outline), minimum to maximum values (whiskers) and outliers (dots)] in participants by lifetime daily alcohol use category (none/moderate vs heavy) and HCV status (no HCV vs HCV). Hepatic IR was higher with lifetime daily heavy alcohol use irrespective of HCV status. Median hepatic IR for individuals with none or moderate alcohol use without HCV was 13.2 μU-mg/kg-min-ml (range 6.3–33.4) vs with HCV 18.6 μU-mg/kg-min-ml (range 11.3–27.6) (p=0.001). For participants with lifetime daily heavy alcohol use, hepatic IR for those without HCV was 16 μU-mg/kg-min-ml (range 8.3–33.2) versus 20 μU-mg/kg-min-ml (range 8.4–43.4) in those with HCV (p=0.07). IR = insulin resistance; HCV = hepatitis C virus

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