Association of β-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children

BACKGROUND In addition to insulin resistance,impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Scarce clinical data exist for pediatric T2DM.AIM To investigate the association ofβ-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study.METHODS This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019.Children with normal glycemic levels(n=1935)were included as healthy control subjects.The homeostasis models(HOMAs)were used to assess theβ-cell function(HOMA2-%B)and insulin resistance(HOMA2-IR)levels.The HOMA index was standardized by sex and age.We performed logistic regression analysis to obtain odds ratios(ORs)for T2DM risk using the standardized HOMA index,adjusted for confounding factors including sex,Tanner stage,T2DM family history,body mass index z-score,and lipid profile.RESULTS The male-female ratio of newly diagnosed T2DM patients was 1.37:1(OR=2.20,P=0.011),and the mean ages of onset for boys and girls were 12.5±1.9 years and 12.3±1.7 years,respectively.The prevalence of related comorbidities including obesity,elevated blood pressure,and dyslipidemia was 58.2%,53.2%,and 80.0%,respectively.The T2DM group had lower HOMA2-%B levels(P<0.001)and higher HOMA2-IR levels(P<0.001)than the control group.Both the decrease in HOMA2-%B z-score(OR=8.40,95%CI:6.40-11.02,P<0.001)and the increase in HOMA2-IR z-score(OR=1.79,95%CI:1.60-2.02,P<0.001)were associated with a higher risk of T2DM,and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors.CONCLUSION Besides insulin resistance,β-cell function impairment is also strongly associated with Chinese pediatric T2DM.Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.

Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader–Willi syndrome

Background Recombinant human growth hormone(rhGH)therapy has shown to improve height and body composition in children with Prader–Willi syndrome(PWS),the evidence of early rhGH treatment on motor and mental development is still accumulating.This study explored the time effect on psychomotor development,anthropometric indexes,and safety for infants and young children with PWS.Methods A phase 3,single-arm,multicenter,self-controlled study was conducted in six sites.Patients received rhGH at 0.5 mg/m2/day for first four weeks,and 1 mg/m2/day thereafter for up to 52 weeks.Motor development was measured using Peabody Developmental Motor Scales-second edition,mental development using Griffiths Development Scales-Chinese(GDS-C).Height standard deviation score(SDS),body weight SDS,and body mass index(BMI)SDS were also assessed.Results Thirty-five patients were enrolled totally.Significant improvements were observed in height,body weight,and BMI SDS at week 52;GDS-C score showed significant improvement in general quotient(GQ)and sub-quotients.In a linear regression analysis,total motor quotient(TMQ),gross motor quotient(GMQ),and fine motor quotient were negatively correlated with age;however,treatment may attenuate deterioration of TMQ and GMQ.Changes in GQ and locomotor sub-quotient in<9-month group were significantly higher than≥9-month group.Mild to moderate severity adverse drug reactions were reported in six patients.Conclusion Fifty-two-week treatment with rhGH improved growth,BMI,mental development,and lessened the deterioration of motor function in infants and young children with PWS.Improved mental development was more pronounced when instituted in patients<9 months old.

Clinical characteristics and beta-cell function of Chinese children and adolescents with type 2 diabetes from 2009 to 2018

Background The limited available studies have unveiled different natural histories and prognosis associated with pediatric type 2 diabetes (T2D) and adult T2D.To date,data on the clinical features,metabolic profiles and beta-cell function characteristics are still limited in the Chinese pediatric T2D population.Methods A total of 56 children with T2D,31 with prediabetes and 159 with obesity were recruited.Clinical characteristics,metabolic profiles,beta-cell function and insulin resistance were analyzed.Results The mean onset age of T2D was 12.35 ± 1.99 (7.9-17.8) years,and 7% of children were younger than 10 years;55% of them were male,57% had a family history of diabetes and 64% had classic symptoms,and 25% had a low or high birth weight.89% of T2D patients were obese or overweight.A total of 58% of the patients with prediabetes were male.The fast serum C-peptide level was highest in the obesity group (P < 0.001),and there was no significant difference between the T2D and prediabetes groups.The mean homeostatic model of assessment of beta-cell function was the highest in the obesity group and was lowest in the T2D group (P < 0.00 1).The T2D group had the most serious lipid metabolism disorder,with the highest levels of total triglycerides,total cholesterol,and low density lipoprotein and the lowest high density lipoprotein level among the three groups.Conclusions A younger onset age and greater male susceptibility were found in Chinese pediatric T2D patients,and there was a stepwise deterioration trend in beta-cell function among patients with obesity,prediabetes and T2D.Based on our results,together with the SEARCH study results,an early screening and intervention program for T2D is recommended in high-risk or obese Chinese pediatric populations starting at 7 years.

Association between new onset type 1 diabetes and real-world antibiotics and neonicotinoids’exposure-related gut microbiota perturbation

Background The real-world exposure levels of non-therapeutic antibiotics and neonicotinoids in type 1 diabetes(T1D)children and their associations as environmental triggers through gut microbiota shifts remained unknown.We thus investigated the antibiotics and neonicotinoids’exposure levels and their associations with gut microbiota in pediatric T1D.Methods Fifty-one newly onset T1D children along with 67 age-matched healthy controls were recruited.Urine concentrations of 28 antibiotics and 12 neonicotinoids were measured by mass spectrometry.Children were grouped according to the kinds of antibiotics’and neonicotinoids’exposures,respectively.The 16S rRNA of fecal gut microbiota was sequenced,and the correlation with urine antibiotics and neonicotinoids’concentrations was analyzed.Results The overall detection rates of antibiotics were 72.5%and 61.2%among T1D and healthy children,whereas the neonicotinoids detection rates were 70.6%and 52.2%(P=0.044).Children exposed to one kind of antibiotic or two or more kinds of neonicotinoids had higher risk of T1D,with the odd ratios of 2.579 and 3.911.Furthermore,co-exposure to antibiotics and neonicotinoids was associated with T1D,with the odd ratio of 4.924.Antibiotics or neonicotinoids exposure did not affect overall richness and diversity of gut microbiota.However,children who were exposed to neither antibiotics nor neonicotinoids had higher abundance of Lachnospiraceae than children who were exposed to antibiotics and neonicotinoids alone or together.Conclusion High antibiotics and neonicotinoids exposures were found in T1D children,and they were associated with changes in gut microbiota featured with lower abundance of butyrate-producing genera,which might increase the risk of T1D.