Abstract
PurposeElevated copeptin, a vasopressin marker, is linked to metabolic disease, and obese rats with low-vasopressin concentration had a decreased risk of liver steatosis. We here investigated the association between copeptin and nonalcoholic fatty liver disease (NAFLD) and possible differences in copeptin concentration between ethnicities.MethodsIn this cross-sectional study of 361 South Africans (n = 172 African black, 189 = Caucasian) with a mean age of 45 years and 45% men, plasma copeptin was measured and associated with NAFLD according to a validated fatty liver index accounting for measures of BMI, waist, triglycerides, and gamma-glutamyltransferase.ResultsThere was no significant difference in copeptin concentrations between ethnicities after age and gender adjustment (p = 0.24). Increasing copeptin tertile levels were significantly associated with obesity, overweight, and abdominal obesity, respectively, after multivariate adjustment for age, gender, ethnicity, and high HOMA-IR (p = 0.02 for all). Individuals in the second and third copeptin tertile had an increased odds (95% CI) of NAFLD of 1.77 (1.04–3.02) and 2.97 (1.74–5.06), respectively, compared to the bottom tertile (p < 0.001). The association between increasing copeptin tertile and NAFLD remained significant after adjustment for age, gender, ethnicity, high HOMA-IR, self-reported current alcohol intake, and statin treatment (p = 0.01).ConclusionsElevated plasma copeptin is independently associated with NAFLD in a population with mixed ethnicities, pointing at the pharmacologically modifiable vasopressin system as a new mechanism behind NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease in Western countries [1], with a prevalence that has increased in parallel with increasing burden of metabolic diseases [2]
This study aims at for the first time investigating the links between copeptin concentration and fatty liver disease, as knowledge of the underlying causes of NAFLD is a prerequisite for the identification of more specific lifestyle and pharmacological treatment
As the risk of developing NAFLD is suggested to differ by ethnicity [16, 17], this study aims at for the first time investigating copeptin concentration as well as links between fatty liver disease and plasma copeptin concentrations in different ethnic groups
Summary
Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease in Western countries [1], with a prevalence that has increased in parallel with increasing burden of metabolic diseases [2]. Experimental work show that obese rats with water induced reduction of VP concentration in plasma have decreased liver steatosis compared with control obese rats [14]. It is not yet known whether the link between high levels of circulating VP (copeptin) and metabolic disturbances is causal, both an experimental study in rats [14] and a human Mendelian randomization study [15] point at a causal relationship
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