Objective Women with a history of gestational diabetes mellitus (GDM) have an elevated risk of ultimately developing pre-diabetes and diabetes later in life. They also have an increased prevalence of fatty liver, but recent studies have reported conflicting findings on whether hepatic fat affects their risk of pre-diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with glucose homeostasis and determinants thereof in women with and without recent gestational dysglycemia.
Methods Two hundred and fifty-seven women underwent an antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40 with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or moderate (n=27).
Results Liver fat was more prevalent in women with previous GDM than in those with GIGT or NGT (p=0.009) and in women with current pre-diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat increased, there was a progressive worsening of insulin sensitivity and beta-cell function, coupled with rising fasting and 2-hour glucose (all p<0.0001). On multiple linear regression analyses, moderate liver fat was independently associated with lower insulin sensitivity (p=0.0002) and higher 2-hour glucose (p=0.009). Moreover, moderate liver fat emerged as an independent predictor of pre-diabetes/diabetes (OR=3.66, 95% CI 1.1 to 12.5).
Conclusion The higher prevalence of liver fat in women with previous GDM is associated with their increased risk of pre-diabetes/diabetes.
- liver fat
- fatty liver
- gestational diabetes
- insulin sensitivity
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Contributors SM and RR wrote the first draft. MM interpreted all ultrasound scans. CY and RR designed the analysis plan and CY performed the statistical analyses. MM, LM-B, AJH, PWC, MS, BZ, and RR designed/implemented the study. All authors critically revised the manuscript for important intellectual content. All authors approved the final manuscript.
Funding This study was supported by operating grants from the Canadian Diabetes Association (CDA)(CDA-OG-3-15-4924-RR) and Canadian Institutes of Health Research (CIHR)(MOP-84206). LM-B is supported by an Australian National Health and Medical Research Council Fellowship (#605837 and #1078477). AJH holds a Tier-II Canada Research Chair in Diabetes Epidemiology. RR is supported by a Heart and Stroke Foundation of Ontario Mid-Career Investigator Award and holds the Boehringer Ingelheim Chair in Beta-Cell Preservation, Function and Regeneration at Mount Sinai Hospital. RR is guarantor, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Competing interests None declared.
Patient consent Not required.
Ethics approval The liver study protocol has been approved by the Mount Sinai Hospital Research Ethics Board.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data may be requested from the corresponding author.
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