Poorly controlled pediatric type 1 diabetes mellitus is a risk factor for metabolic dysfunction associated steatotic liver disease (MASLD): An observational study.

OBJECTIVES: Recent studies have suggested a link between type 1 diabetes mellitus (T1D) and metabolic dysfunction associated steatotic liver disease (MASLD) in children and adolescent, but longitudinal evidence is lacking. This study aimed to investigate the potential association between poorly controlled T1D and elevated alanine aminotransferase (ALT), serving as a proxy for MASLD in children and adolescents over time. METHODS: The study included 32,325 children aged 2-17 years with T1D from Germany, Austria, and Switzerland who had undergone at least one assessment of liver enzyme levels recorded in the Diabetes-Patienten- Verlaufsdokumentation registry. Multivariable logistic and Cox regression models were calculated to show possible associations between T1D and elevated ALT values (>26 U/L in males, >22 U/L in females) as a proxy for MASLD. RESULTS: Children with poorly controlled T1D (HbA1c > 11%) exhibited increased odds of elevated ALT values, after adjustment for age, sex, diabetes duration and overweight (odds ratio [OR] 2.54; 95% confidence interval [CI], 2.10-3.10; p < 0.01). This finding is substantiated by a longitudinal analysis, which reveals that inadequately controlled T1D was associated with a higher hazard ratio (HR) of elevated ALT values compared to children with controlled T1D over an observation period extending up to 5.5 (HR: 1.54; 95% CI, 1.19-2.01; p < 0.01). CONCLUSION: In conclusion, the current study strongly links poorly controlled T1D in children and adolescents to MASLD irrespective of overweight. This association is not only present cross-sectionally but also increases over time. The study underscores the critical role of effective diabetes management in reducing the risk of MASLD in this population.

Prevalence and Characteristics of Metabolic Hyperferritinemia in a Population-Based Central-European Cohort.

BACKGROUND: Hyperferritinemia (HF) is a common finding and can be considered as metabolic HF (MHF) in combination with metabolic diseases. The definition of MHF was heterogenous until a consensus statement was published recently. Our aim was to apply the definition of MHF to provide data on the prevalence and characteristics of MHF in a Central-European cohort. METHODS: This study was a retrospective analysis of the Paracelsus 10,000 study, a population-based cohort study from the region of Salzburg, Austria. We included 8408 participants, aged 40-77. Participants with HF were divided into three categories according to their level of HF and evaluated for metabolic co-morbidities defined by the proposed criteria for MHF. RESULTS: HF was present in 13% (n = 1111) with a clear male preponderance (n = 771, 69% of HF). Within the HF group, 81% (n = 901) of subjects fulfilled the metabolic criteria and were defined as MHF, of which 75% (n = 674) were characterized by a major criterion. In the remaining HF cohort, 52% (n = 227 of 437) of subjects were classified as MHF after application of the minor criteria. CONCLUSION: HF is a common finding in the general middle-aged population and the majority of cases are classified as MHF. The new classification provides useful criteria for defining MHF.

Prevalence of Subclinical Cardiovascular Disease in Patients with Non-Alcoholic-Fatty Liver Disease: Analysis of the Paracelsus 10.000 Cohort Study.

BACKGROUND: In patients with non-alcoholic fatty liver disease (NAFLD) cardiovascular diseases are more often the cause of death than the liver disease itself. However, the prevalence of atherosclerotic manifestations in individuals with NAFLD is still uncertain. This study aimed to explore the association between NAFLD and coronary artery calcification (CAC) in a Central European population. METHODS: A total of 1,743 participants from the Paracelsus 10,000 study were included. The participants underwent CAC scoring and were assessed for fatty liver index (FLI), fibrosing non-alcoholic steatohepatitis Index (FNI) and fibrosis-4 index (FIB-4 score), which are indicators for steatosis and fibrosis. Multivariable logistic regression models were calculated. RESULTS: Results revealed an association between liver steatosis/fibrosis and CAC. A FLI > 60 was associated with higher odds of NAFLD (OR 3.38, 95% CI: 2.61-4.39, p < 0.01) and increased prevalence of CAC-Score >300 compared to FLI <30 (9% vs. 3%, p < 0.01), even after adjusting for traditional cardiometabolic risk factors. While the crude odds ratios of the FIB-4 scores ≥ 1.3 and FNI score were significantly associated with increased odds of CAC, they became non-significant after adjusting for age, sex, and MetS. CONCLUSION: This study reveals a significant association between NAFLD and CAC. The findings suggest that assessing liver fat and fibrosis could enhance assessment of cardiovascular risk, but further research is needed to determine whether hepatic fat plays an independent role in the development of atherosclerosis and whether targeting liver steatosis can mitigate vascular risk.

Relationships between education and non-alcoholic fatty liver disease.

INTRODUCTION: Individuals with lower levels of education are at a higher risk of developing various health conditions due to limited access to healthcare and unhealthy lifestyle choices. However, the association between non-alcoholic fatty liver disease (NAFLD) and educational level remains unclear. Therefore, the aim of this study was to investigate whether there is an independent relationship between NAFLD and educational level as a surrogate marker for socioeconomic status (SES). METHODS: This cross-sectional study included 8,727 participants from the Paracelsus 10,000 study. The association between NAFLD and educational level was assessed using multivariable logistic regression models and multivariable linear regression. The primary endpoints were NAFLD (FLI score > 60) and liver fibrosis (FIB-4 score > 1.29). Further subgroup analysis with liver stiffness measurement was done. RESULTS: In the study, NAFLD prevalence was 23% among participants with high education, 33% among intermediate, and 40% among those with low education (p<0.01). Importantly, a significantly reduced risk of NAFLD was observed in individuals with higher education, as indicated by an adjusted relative risk of 0.52 (p < 0.01). Furthermore, higher education level was associated with significantly lower odds of NAFLD and fibrosis. Additionally, a subgroup analysis revealed that higher liver stiffness measurements were independently associated with lower levels of education. CONCLUSION: The study's findings indicate that a lower education level increases the risk of NAFLD independent of confounding factors. Therefore, these findings highlight the potential impact of educational attainment on NAFLD risk and emphasize the need for targeted interventions in vulnerable populations.

Single Point Insulin Sensitivity Estimator (SPISE) As a Prognostic Marker for Emerging Dysglycemia in Children with Overweight or Obesity.

The single point insulin sensitivity estimator (SPISE) is a recently developed fasting index for insulin sensitivity based on triglycerides, high density lipoprotein cholesterol, and body mass index. SPISE has been validated in juveniles and adults; still, its role during childhood remains unclear. To evaluate the age- and sex-specific distribution of SPISE, its correlation with established fasting indexes and its application as a prognostic marker for future dysglycemia during childhood and adolescence were assessed. We performed linear modeling and correlation analyses on a cross-sectional cohort of 2107 children and adolescents (age 5 to 18.4 years) with overweight or obesity. Furthermore, survival analyses were conducted upon a longitudinal cohort of 591 children with overweight/obesity (1712 observations) with a maximum follow-up time of nearly 20 years, targeting prediabetes/dysglycemia as the end point. The SPISE index decreased significantly with age (−0.34 units per year, p < 0.001) among children and adolescents with overweight and obesity. Sex did not have an influence on SPISE. There was a modest correlation between SPISE and established fasting markers of insulin resistance (R = −0.49 for HOMA-IR, R = −0.55 for QUICKI-IR). SPISE is a better prognostic marker for future dysglycemia (hazard ratio (HR) 3.47, 95% confidence interval (CI) 1.60−7.51, p < 0.01) than HOMA-IR and QUICKI-IR (HR 2.44, 95% CI 1.24−4.81, p < 0.05). The SPISE index is a surrogate marker for insulin resistance predicting emerging dysglycemia in children with overweight or obesity, and could, therefore, be applied to pediatric cohorts that lack direct insulin assessment.

Elevated transaminases potentiate the risk for emerging dysglycemia in children with overweight and obesity.

BACKGROUND: There is evidence that nonalcoholic fatty liver disease (NAFLD) increases the risk for dysglycemia in children in cross-sectional studies. However, the extent to which NAFLD may confer the risk for dysglycemia in longitudinal studies remains uncertain. OBJECTIVES: We investigated whether elevated levels of alanine aminotransferase (ALT) as a proxy for NAFLD can serve as a predictor for future dysglycemia among children. METHODS: We performed survival analysis up to 11 years of follow-up on longitudinal data of 510 children with overweight and obesity from the Leipzig Childhood Cohort. RESULTS: Children with overweight/obesity and elevated ALT values had a more than 2-fold increased risk (hazard ratio 2.59, 95% confidence interval 1.49 to 4.50; P < 0.01) for future dysglycemia independent of age, sex and BMI-SDS. CONCLUSIONS: Elevated transaminases are an early predictor for glycemic deterioration. Hence, NAFLD should further be addressed as a risk factor and therapeutic target for the early prevention of type 2 diabetes.

Prevalence of prediabetes and type 2 diabetes in children with obesity and increased transaminases in European German-speaking countries. Analysis of the APV initiative.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes mellitus are known to be closely linked with obesity as early as during childhood. OBJECTIVES: The study aimed to determine the prevalence of prediabetes and T2DM in children with obesity with or without increased transaminases. METHODS: Data from the observational multicentre (n = 51), cross-sectional Adipositas Patienten Verlaufsbeobachtung registry were analyzed. Mild increase (mild group) was defined by alanine transaminase (ALT) >24 to ≤50 U/L and moderate to severe increase (advanced group) by ALT > 50 U/L. Prediabetes and T2DM were defined according to recent IDF/ISPAD guidelines. RESULTS: The prevalence of prediabetes and T2DM was 11.9% (95% CI: 11.0-12.8) and 1.4% (95% CI: 1.1-1.7) among all participants (n = 4932; male = 2481; mean age 12.9 ± 2.7 years; BMI-SDS 2.1 ± 0.5; Tanner stage 3.2 ± 1.5). The prevalence of impaired glucose metabolism (prediabetes and T2DM) was 13.8% (95% CI: 12.1-15.4) in the mild, 21.9% (95% CI: 18.8-25.1) in the advanced group, 10.7% (95% CI: 9.4-11.9) in the control group. Mild and advanced groups had greater odds ratios for prediabetes [1.42; 95% CI: 1.17-1.72, 2.26-fold; (1.78-2.86), respectively], the advanced group also for T2DM [2.39 (1.36-4.21)] compared to controls. While an increase in transaminases predominantly affected boys, girls within the advanced group had a higher T2DM prevalence than males (5.4 vs. male 2.1%). CONCLUSIONS: Children with obesity and increased liver transaminases as surrogates of NAFLD should be screened for T2DM.