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DDW: Gestational diabetes linked to increased NAFLD risk in middle age

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We need to pay attention to all risk factors for NAFLD

Nonalcoholic fatty liver disease is the most common and fastest growing liver disease worldwide. Identifying individuals at high risk for NAFLD remains challenging. Dr. Ajmera and his colleagues highlight the association between gestational diabetes mellitus (GDM) and NAFLD. Their work confirms and extends earlier studies that reported increased hepatic fat content and a substantially increased risk for NAFLD, in women with a prior history of GDM. In the present study, a more racially diverse U.S.-based population was followed for a much longer duration than was previous cohorts. After adjusted multivariate analysis, GDM remained a strong, independent predictor of future NAFLD. Indeed, GDM was a a better NAFLD predictor than the diagnosis of diabetes alone was. It is unclear if prepregnancy NAFLD might have affected the risk for GDM, as subjects were not assessed for hepatic steatosis or liver test elevations at baseline. Also, the percentage of 50-year-old women with NAFLD was much lower in this cohort (7%) than in the general U.S. population (at least 25%), perhaps because the study population was enriched with individuals who are typically at low risk for NAFLD (i.e., African Americans, people with low body mass index, and/or low serum triglycerides).

Additional research is needed to clarify these issues and to investigate how maternal GDM affected the health of their children. Intrauterine exposure to metabolic stresses increases the risk for obesity and other metabolic disorders later in life, suggesting that offspring of mothers with GDM may require specialized surveillance or other precautions during childhood. Given that more young women are entering their reproductive years affected by diabetes and obesity, increased attention to these issues will be required to curb the growing public health burden of NAFLD.

Dr. Cynthia A. Moylan, M.H.S., is assistant professor of medicine, Duke University Medical Center and Veterans Affairs Medical Center, Durham, N.C. She is has no relevant financial conflicts of interests.


AT DDW® 2015


WASHINGTON – Gestational diabetes was identified as a significant, independent risk factor for developing non-alcoholic fatty liver disease later in life, according to a study of more than 1,000 women followed for 25 years.

This study “is the first to show a strong association between gestational diabetes in young adulthood and non-alcoholic fatty liver disease in middle-age,” Dr. Veeral Ajmera of the department of gastroenterology at the University of California, San Francisco, reported at the annual Digestive Disease Week.

Dr. Veeral Ajmera

The study evaluated 1,115 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study, who had at least one delivery, did not have a diabetes diagnosis before pregnancy, and had a CT evaluation for hepatic steatosis at the 25-year visit, in 2010 and 2011. Women were excluded if they did not have a complete CT scan at that time, they had more than 14 drinks of alcohol per week, used medications associated with steatosis, or had chronic viral hepatitis or HIV infections.

At baseline the median age was 25-26 years, about 55%-56% were black, and the prevalence of hypertension (2%-3%) and dyslipidemia were similar. The CARDIA study enrolled about 5,100 men and women aged 18-30 years at four U.S. medical centers in the mid 1980s. Patients had 7 study visits over a 25-year follow-up period.

Of the 1,115 women evaluated, 124 (11%) went on to develop GDM and 75 (7%) met the CT definition for NAFLD (liver attenuation less than or equal to 40 Hounsfield units on CT scan) by the 25-year follow-up, when they were a median age of 50-51 years.

At 25 years, 14% of those with a history of GDM had NAFLD, compared with 5.8% of those who did not have GDM, for an unadjusted odds ratio of 2.56 (p <0.01), Dr. Ajmera said.

In the statistical analysis, the researchers determined that baseline homeostatic model assessment of insulin resistance (HOMA-IR) and baseline triglycerides were also ”strongly associated” with NAFLD at year 25.

“Importantly,” he noted, the measure of the association between GDM and NAFLD remained statistically significant, after adjusting for these covariates (OR, 2.29). At the start of the study, women who went on to develop GDM had significantly higher body mass index (BMI), HOMA-IR, waist circumference, and triglycerides than those who did not develop GDM, but the magnitude of those differences was small.

Additionally, after adjustment for a diagnosis of diabetes at year 25, the association between a history of GDM and NAFLD was stronger (OR, 1.99) than the association between a diagnosis of diabetes at year 25 and NAFLD (OR, 1.5), he said.

The researchers added BMI to their multivariate analysis to determine whether women with a gestational diabetes history gained more weight, and whether that weight explained the increased prevalence of NAFLD, “and found that the association between gestational diabetes and non-alcoholic fatty liver disease remained,” Dr. Ajmera added.

Evaluations of race, baseline BMI, and baseline HOMA-IR as effect modifiers of the relationship between GDM and NAFLD were not significant.

“Gestational diabetes represents insulin resistance unmasked by the stress of pregnancy, and offers the unique opportunity to identify those at risk of NAFLD at a young age,” Dr. Ajmera concluded.

Limitations of the study included not being able to determine if the women had NAFLD before they were diagnosed with GDM. However, based on the participants’ young age at enrollment, that is unlikely, he said. In addition, the researchers had no information on liver biochemistry tests, which, however, are not sensitive or specific for diagnosing NAFLD. The strengths of the study include the length of follow-up of a large biracial population, with measurement of well-characterized metabolic covariates measured, he added.

Dr. Ajmera reported having no relevant financial disclosures. The CARDIA study is supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

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