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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. [ABSTRACT FROM AUTHOR]

Whole‐exome sequencing is a new technology. We used it to explore the gene responsible for early‐onset diabetes as a result of impaired insulin secretion in a family. In the INS gene, we identified the heterozygous c.188‐31G>A mutation in the proband – a 43‐year‐old woman. The mutation was also identified in her two daughters with diabetes, but not in her son or her parents, all of whom did not have diabetes. The substitution was located 31 bp proximal to exon 3 in intron 2. It was predicted to create an ectopic splice site leading to inserting 29 nucleotides of intron 2 as an exonic sequence in the transcript. The mutation has been reported in White families, and the present case is the first report in an Asian person. The present results would help in understanding the role of the mutation in developing diabetes. [ABSTRACT FROM AUTHOR]

Aims: To investigate the genetic factors contributing to early-onset type 2 diabetes (EOD) in the Chinese Hans populations.Materials and Methods: For 2734 newly diagnosed type 2 diabetes patients and 4041 normal glycemic controls, 25 single nucleotide polymorphisms from 24 genomic loci linked to diabetes were successfully genotyped. Three genetic risk scores (GRSs) were constructed, including the weighted type 2 diabetes-related GRS (wT-GRS), the weighted β-cell function-related GRS (wB-GRS), and the weighted GRS constructed by risk alleles not related to β-cell function (wNB-GRS). For patients with diabetes, EOD, middle-age-onset type 2 diabetes (MOD), and late-onset type 2 diabetes (LOD) were defined by onset ages ≤40, 40 to 60, and ≥60 years, respectively.Results: From single marker analysis, different gene profiles were identified between EOD and LOD patients. EOD patients had greater wT-GRS and wB-GRS values than LOD patients. After adjustment for sex, elevated wT-GRS and wB-GRS values were significantly associated with an increased risk for EOD by 1.11- and 1.21-fold per allele (P = 1.69 × 10-7 ; 6.07 × 10-8 ). The wT-GRS and wNB-GRS were nominally related to an increased risk of LOD by 1.03-fold per allele (P = 1.03 × 10-2 , 1.78 × 10-2 ). In patients with diabetes, higher wT-GRS and wB-GRS were associated with younger onset age [wT-GRS: β (SE) = -0.0033(0.0016), P = 3.74 × 10-2 ; wB-GRS: -0.0076(0.0028), 7.45 × 10-3 ] and decreased insulinogenic index [wT-GRS: -0.0384(0.0098), 9.39 × 10-5 ; wB-GRS: -0.0722(0.0176), 4.21 × 10-5 ].Conclusion: Our findings indicate a strong genetic predisposition for EOD, which can be mainly attributed to genetic variants linked to β-cell function, suggesting the β-cell dysfunction plays a key role in the pathogenesis of EOD in Chinese Han individuals. [ABSTRACT FROM AUTHOR]