Non‐alcoholic fatty liver disease in pediatric type 2 diabetes: Metabolic and histologic characteristics in 38 subjects

Abstract

Background Obesity and type 2 diabetes (T2D) is risk factors for non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH). In children with T2D and liver biopsies, we investigated correlations between NAFLD/NASH and transaminase activity, A1c, lipids, and histologic changes in repeat biopsies. Methods Liver histology of children with T2D was evaluated using the NASH CRN scoring system and NAFLD Activity Score (NAS). We included results ≤6 months from biopsy and A1c nearest biopsy. Results Thirty‐eight subjects (21 females, 17 males, 63.2% Hispanic, 15.8% Caucasian) had T2D diagnosed at 13.4 ± 2.7 years, 78.9% using metformin and 50% on insulin. Histological diagnosis of NAFLD occurred at mean age 14.3 ± 2.3 years, notable for NASH in 61%. Steatosis grade was higher in children with NASH than those without (mean 2.6 ± 0.7 vs 2.1 ± 0.5 (P < 0.001). Stage 3 fibrosis was noted only in subjects with NASH (26%). ALT was higher in NASH vs those without (112 ± 56 vs 85 ± 112, P = 0.016). NAS correlated with A1c (r = 0.51, P < 0.01) and triglycerides (r = 0.5, P < 0.01), and inversely with high‐density lipoprotein (HDL) (r = −0.42, P = 0.04). Males had lower HDL and higher triglycerides (P < 0.04). In eight subjects with repeat biopsies, NAS was equal (37.5%) or improved (62.5%), and steatosis decreased (68.1% to 32.8%, P = 0.027). Conclusions In children with T2D and NAFLD, NASH is common. Having advanced fibrosis in 26% of NASH cases at this age is concerning. Better control of lipids, weight, and diabetes may help avoid worsening in NAS.

From Nonalcoholic Fatty Liver Disease (NAFLD) to Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)—New Terminology in Pediatric Patients as a Step in Good Scientific Direction?

“…Moreover, children with T2DM had a greater risk of having NASH (43.2%), regarded as a more progressive form of NAFLD, compared with prediabetes (34.2%) or those with normal glucose (22%) [53]. Similar observations were included in other studies, where T2DM was associated with more advanced forms of NAFLD within the studied pediatric and adult population [54,55]. Therefore, as one would expect, early detection of liver steatosis in high-risk populations is important for avoiding further development of severe forms of NAFLD.…”

FTO: a critical role in obesity and obesity-related diseases

“…FTO contributed to obesity susceptibility in Caucasian, Chinese, African American and Hispanic population (44) . FTO rs9939609 A allele and rs1421085 C risk allele increased the risk of obese in Balinese (45) , and the FTO variant rs1421085 CT genotype was associated to raise the risk of overweight/obesity (BMI ≥ 25 kg/m 2 for overweight and BMI ≥ 30 kg/m 2 for obesity) to 1·583 times in Pakistani individuals (46) . The severe obesity in Brazilian population was strongly related to FTO rs9939609 allele (A) (47) .…”

Metformin therapy in pediatric type 2 diabetes mellitus and its comorbidities: A review

“…Several conditions are associated with T2D including obesity, dyslipidemia, hypertension, obstructive sleep apnea, polycystic ovary syndrome, and non-alcoholic fatty liver disease (20)(21)(22)(23)(24). Microvascular complications manifest as nephropathy, neuropathy, and retinopathy and present much earlier than those in children with type 1 diabetes (25).…”