The prevalence of gestational diabetes mellitus in women diagnosed with non-alcoholic fatty liver disease during pregnancy: A systematic review and meta-analysis

Highlights

• The prevalence of gestational diabetes (GDM) in pregnant women with non-alcoholic fatty liver disease (NAFLD) was 26.0%.

• Pregnant women with NAFLD are at a 3–fold higher odds of developing GDM compared to those without NAFLD.

• However, a high degree of heterogeneity existed between the studies examined in this systematic review and meta-analysis.

• A limited amount of well–conducted studies are currently available when exploring the complex association between NAFLD and GDM.

Abstract

Aims

To further explore the relationship between non–alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM) by determining the prevalence of GDM in women diagnosed with NAFLD antepartum.

Methods

Electronic databases were searched using specific keywords. Original studies of adult women reporting NAFLD (confirmed on imaging) and GDM (confirmed via oral glucose tolerance test) prevalence were included. Studies involving women with pre-gestational pre-diabetes, type 1/type 2 diabetes, chronic liver disease/cirrhosis unrelated to NAFLD were excluded. The prevalence of GDM occurring in women with NAFLD was calculated along with pooled odds ratios and 95% confidence intervals (CI) using the random effects model.

Results

Seven studies (total 2299 participants) were included. The prevalence of GDM in women with NAFLD was 26.0% (95% CI 20.9–31.7%, I² = 48%, τ² = 0.06). The odds of having GDM were 2.9 times higher in pregnant women diagnosed with NAFLD compared with non-NAFLD women, although a high degree of heterogeneity existed (unadjusted OR 2.9, 95% CI 1.0–8.4, I² = 81%, τ² = 0.83, p < 0.05).

Conclusion

Our study provides further insight into the prevalence of GDM in pregnant women diagnosed with NAFLD. There is a current lack of well-conducted studies examining this complex association between NAFLD and GDM.

Introduction

Gestational diabetes mellitus (GDM), characterised by glucose intolerance diagnosed during pregnancy, is increasing in global prevalence, with a reported one in six pregnancies affected by GDM in 2019.¹ Multiple factors are predictive for which women will develop GDM, including advanced maternal age at gestation, susceptible ethnicities, overweight and obesity, a prior history of GDM or a family history of diabetes.1, 2, 3. Women with a prior history of GDM are at a 6-fold increased risk of developing type 2 diabetes mellitus (Type 2 DM), with the steepest increase in incidence occurring in the first 5 years postpartum.^4,5 Given the high risk of early onset Type 2 DM in these women, it is important to avert a public health crisis by further exploring whether other metabolic risk factors associated with Type 2 DM may be shared with GDM.

Non-alcoholic fatty liver disease (NAFLD), defined as excessive liver fat (i.e. hepatic steatosis occurring in >5% of hepatocytes) in the absence of significant alcohol intake or other causes of liver disease, is emerging as a serious public health concern, with the prevalence ranging between 25 and 45% worldwide.⁶ Of concern, over 60% of patients with Type 2 DM have a concomitant diagnosis of NAFLD.⁶ It is speculated that NAFLD shares a similar pathogenic pathway to Type 2 DM via increased insulin resistance, with hepatic steatosis shown to enhance gluconeogenesis, further increasing postprandial hyperinsulinaemia and dysglycaemia.⁷

The close relationship between GDM and Type 2 DM raises the possibility that a relationship could also exist between NAFLD and GDM. Indeed, prior studies have explored this association, particularly on the postpartum development of NAFLD in women with a prior history of GDM.8, 9, 10, 11 The prevalence of ultrasound-detected hepatic steatosis signifying NAFLD in European women with a prior history of GDM was 38% compared to a prevalence of 17% in women without GDM.⁸ In Caucasian and Black American women with a previous history of GDM, a higher rate of NAFLD was detected via ultrasound or computerised tomography.^9,10 Recently, a systematic review in 2019 determined that women with GDM are at increased risk of developing NAFLD postpartum compared to women without GDM.¹¹ Examining the antepartum detection of NAFLD and its association with GDM from the available literature has not yet been performed.

The primary aim of this systematic review and meta-analysis is to determine the prevalence of GDM in women found to have imaging evidence of NAFLD during their pregnancy. A secondary objective is to assess whether a higher occurrence of GDM develops in women with NAFLD compared to those without.