In our study, prevalence of 12.6% of steatosis was found with US results, and 16.8% of steatosis when we considered only TE results. When we combined hepatic images (US and/or TE), altered results had association with higher rates of MS, FLI and anthropometric measurements. The components of MS associated with steatosis were waist circumference and triglycerides. US was associated mainly with laboratory components of MS, while TE was associated mainly with anthropometric measurements.
The pathogenesis of NAFLD in T1D is controversial. Physiologically, pancreatic insulin is partly cleared in first-pass metabolism on liver, resulting in higher portal insulin levels and lower levels in peripheral circulation(15). Portal hyperinsulinemia is associated with insulin resistance and stimulates lipogenesis and steatosis(3). In T1D, because insulin is administered exogenously, this gradient is lost, which could protect against NAFLD(15). However, alternative pathways have been proposed to explain NAFLD in T1D. ChREBP (Carbohydrate sensitive response element-binding protein) and SREBP-1c (Sterol regulatory element-binding protein 1) are transcription factors that can be activated in the presence of hyperglycemia, independently of hepatic insulin levels, leading to expression of lipogenic genes and promoting fatty liver(3,15). Also, lipoprotein disturbances (such as glycation of apolipoproteins and increased LDL oxidation) may be present in T1D and could result in reduced hepatic exportation of VLDL, leading to NAFLD(15). These metabolic abnormalities can be present even in individuals with T1D and good glycemic control(23). Few studies have investigated the prevalence of NAFLD in T1D, which ranges from 8 to 50%, depending on characteristics of the studied population such as age, frequency of obesity, ethnicity, and method for diagnosis of steatosis (8,10,14,24–26). To our knowledge, this is the first study to access prevalence of NAFLD in a sample of T1D in Brazil, a highly admixed population, with different lifestyle, eating habits and different ethnicity.
NAFLD has a strong association with MS and all of its components(1). Not surprisingly, in our study MS was two times more frequent in the group with altered hepatic image. The most frequent component of MS was hypertension. However, after multivariable adjustment, we found that triglycerides had stronger association with steatosis. Also, when we considered components of FLI, we found risk association with triglycerides levels, even within the normal range. No other factor was associated with steatosis, including glycemic control, transaminases or GGT.
Although FLI was initially developed in comparison to abdominal ultrasound, it has been compared to TE. One study reported that CAP performed better than FLI in detecting steatosis ≥ S2 on liver biopsy(27). This study proposes a CAP cut-off of 310 dB/m to detect steatosis ≥ S2 but it analyzed a population different from ours: only 59% of participants had diabetes and mean BMI was 30 kg/m2. Therefore, this cut-off may not be applicable to our population. TE is widely used for prognosis assessment with fibrosis stage, but it is still lacking validation for steatosis’ diagnosis through CAP. We used cut-off values proposed by de Lédinghen et. al(28) but there is still much discussion regarding optimal cut-off points for CAP(20). Although ultrasound is the preferred initial image for detecting steatosis and TE is usually recommended for fibrosis assessment after steatosis was detected, we chose to perform both methods to see how they would relate to each other(1,29). Although frequency of steatosis found with TE approximates to the frequency found with US, the two imaging methods identified different participants. However, so far, cut-off values of CAP have not been proposed for T1D in comparison to liver biopsy, emphasizing the controversial aspects of this subject in T1D and the need for further studies.
A relevant proportion (31.6%) of our sample had alteration in at least one of the hepatic images and this warrants attention. Some points of our study probably need further investigation, yet to be stablished. Some participants had normal US and altered TE. However, it might be useful to follow prospectively these participants with altered TE, MS and high FLI, analyzing CAP and LSM as continuous variables. Also, we should reinforce metabolic control and weight loss, a real challenge in routine clinical practice.
Our study has some limitations. As previously mentioned, we used two non-invasive methods to detect NAFLD. US is the main tool for screening NAFLD, easily accessible, with low cost, but operator-dependent and with limited sensitivity(19,30). TE, the other method, lacks validation for diagnosis of steatosis. Although we did not have histological confirmation of our findings, the gold-standard exam would be liver biopsy, which is invasive, susceptible to sampling error (30) and inappropriate for screening proposes of our study. Another limitation was the cross-sectional design of the study. Follow-up is necessary to determine how participants with altered hepatic image will evolve.
As strengths of our study we have participants with T1D from an admixed population, which were screened by two methods. The majority of studies with NAFLD in T1D performed only ultrasound(8,10,24–26). Some performed MRI and found lower rates of NAFLD, but this resource is not widely available(7,11,13,14). Also, we did not had access to studies that used TE for steatosis status in T1D so we present novel data. We found two studies that used TE for fibrosis assessment in children and adolescents with T1D, but CAP is not mentioned (31,32).
In conclusion, screening of NAFLD should be considered for T1D with MS and increasing levels of triglycerides, even within the normal range. Diagnosis of NAFLD should be accompanied of measurements to improve metabolic parameters, because of higher cardiovascular risk in this condition. Further prospective studies are necessary to determine the best screening strategy and outcomes in T1D from admixed populations.