Summary 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.

Summary 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.

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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.