This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

ObjectiveThe aim of this study was to assess whether size for gestational age and dehydroepiandrosterone sulfate (DHEAS) are associated with cardiometabolic risk in central precocious puberty (CPP) girls.MethodsThe retrospective study included 443 patients with newly diagnosed CPP. Subjects were categorized by birth weight for gestational age (appropriate [AGA], small [SGA], and large [LGA] for gestational age) and serum DHEAS concentration (high [≥75th percentile] and normal [<75th percentile] DHEAS). Cardiometabolic parameters were examined. Composite cardiometabolic risk (CMR) score was calculated based on BMI, blood pressure, glucose, insulin, triglyceride, and HDL cholesterol. Non-obesity CMR score was computed, omitting the value from BMI. Logistic regression models, general linear models, and partial correlation analyses were used to evaluate associations. Propensity score matching was performed for sensitivity analyses.ResultsOverall, 309 patients (69.8%) were born AGA, 80 (18.1%) were born SGA, and 54 (12.2%) were born LGA. Compared with AGA counterparts, CPP girls born SGA were more prone to have elevated HbA1c (adjusted OR = 4.54; 95% CI, 1.43–14.42) and low HDL cholesterol (adjusted OR = 2.33; 95% CI, 1.18–4.61). In contrast, being born LGA was not associated with increased risk for any glucose or lipid derangements. Despite the fact that elevated CMR score was more common among individuals born LGA than AGA (adjusted OR = 1.84; 95% CI, 1.07–4.35), no significant difference was found on non-obesity CMR score (adjusted OR = 0.75; 95% CI, 0.30–1.88). When controlling for age, birth weight SDS, and current BMI-SDS, individuals with high DHEAS exhibited higher HDL cholesterol and apolipoprotein A-1 concentrations and lower triglyceride level and non-obesity CMR score. Furthermore, DHEAS correlated positively with HDL cholesterol and apolipoprotein A-1 and negatively with triglyceride, prominently in girls born SGA, after adjustments for the three abovementioned confounders. Sensitivity analyses corroborated the findings.ConclusionAmong CPP girls, those born SGA were more likely to possess cardiometabolic risk factors compared to their AGA peers. The difference we observed in cardiometabolic risk between individuals born LGA and AGA was driven by BMI. High DHEAS was associated with favorable lipid profile in CPP girls, even in subjects born SGA.

Objective: The Krüppel-like factor 11 (KLF11) gene causes maturity-onset diabetes of the young 7 (MODY7). There are few reports on the clinical and functional characteristics of KLF11 mutations in patients with MODY7, making diagnosis and treatment complicated.Research Design and Methods: We report a novel KLF11 variant associated with MODY7 in a Chinese family. The proband had hyperglycemia at 9 years of age, and his mother had developed diabetes at age 28 years. Both required insulin injections from the initial phase of the disease. They were negative for islet cell autoantibodies and had normal fasting C-peptide levels. We observed changes in the levels of fasting blood glucose, C-peptide, and islet cell autoantibodies in the proband over 4.5 years.Results: Whole-exon sequencing was used to screen the proband and his family members for KLF11 variants. The heterozygous KLF11 variant (c.1045C>T, p. Pro349Ser) was identified in the proband, his mother, his maternal grandmother, and an elderly aunt, although the latter two individuals were unaffected. In silico analyses indicated that this variant involved a change in the amino acid side chain in the transcriptional regulatory domain 3. Luciferase reporter assays revealed that the variant had impaired insulin promoter regulation activity. Moreover, in vitro analyses showed that this variant impaired insulin secretion from pancreatic beta cells.Conclusions: This study documents a novel heterozygous KLF11 variant (p. Pro349Ser) as a potential monogenic mutation associated with MODY7 in a family. This variant impairs insulin secretion from pancreatic beta cells, possibly by repressing insulin promoter regulation activity.