Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults:a nationwide,multi-center,cross-sectional survey in China

Background:Maturity-onset diabetes of the young(MODY)is the most common monogenic diabetes.The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes(T2DM)among Chinese young adults.Methods:From April 2015 to October 2017,this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China,newly diagnosed between 15 years and 45 years,with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory.Sequencing using a custom monogenic diabetes gene panel was performed,and variants of 14 MODY genes were interpreted as per current guidelines.Results:The survey determined 18 patients having genetic variants causing MODY(6 HNF1A,5 GCK,3 HNF4A,2 INS,1 PDX1,and 1 PAX4).The prevalence of MODY was 0.74%(95%confidence interval[CI]:0.40-1.08%).The clinical characteristics of MODY patients were not specific,72.2%(13/18)of them were diagnosed after 35 years,47.1%(8/17)had metabolic syndrome,and only 38.9%(7/18)had a family history of diabetes.No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.Conclusion:The prevalence of MODY in young adults with phenotypic T2DM was 0.74%,among which HNF1A-,GCK-,and HNF4A-MODY were the most common subtypes.Clinical features played a limited role in the recognition of MODY.

Combination therapy with saxagliptin and vitamin D for the preservation ofβ-cell function in adult-onset type 1 diabetes:a multi-center,randomized,controlled trial

Disease modifying therapies aiming to preserveβ-cell function in patients with adult-onset autoimmune type 1 diabetes are lacking.Here,we conducted a multi-centre,randomized,controlled trial to assess theβ-cell preservation effects of saxagliptin alone and saxagliptin combined with vitamin D as adjunctive therapies in adult-onset autoimmune type 1 diabetes.In this 3-arm trial,301 participants were randomly assigned to a 24-month course of the conventional therapy(metformin with or without insulin)or adjunctive saxagliptin or adjunctive saxagliptin plus vitamin D to the conventional therapy.The primary endpoint was the change from baseline to 24 months in the fasting C-peptide.The secondary endpoints included the area under the concentration-time curve(AUC)for C-peptide level in a 2-h mixed-meal tolerance test,glycemic control,total daily insulin use and safety,respectively.The primary endpoint was not achieved in saxagliptin plus vitamin D group(P=0.18)and saxagliptin group(P=0.26).However,compared with the conventional therapy,2-h C-peptide AUC from 24 months to baseline decreased less with saxagliptin plus vitamin D(-276 pmol/L vs.-419 pmol/L;P=0.01),and not to the same degree with saxagliptin alone(-314 pmol/L;P=0.14).Notably,for participants with higher glutamic acid decarboxylase antibody(GADA)levels,the decline ofβ-cell function was much lower in saxagliptin plus vitamin D group than in the conventional therapy group(P=0.001).Insulin dose was significantly reduced in both active treatment groups than in the conventional therapy group despite all groups having similar glycemic control.In conclusion,the combination of saxagliptin and vitamin D preserves pancreaticβ-cell function in adult-onset autoimmune type 1 diabetes,an effect especially efficacious in individuals with higher GADA levels.Our results provide evidence for a novel adjunct to insulin and metformin as potential initial treatment for adult-onset type 1 diabetes.(ClinicalTrials.gov identifier:NCT02407899).

Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes

Background:Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus(T1DM)and type 2 diabetes mellitus(T2DM).However,the potential associations of insulin resistance(IR)and beta-cell function(BCF)with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood.Methods:A cross-sectional survey of 15,928 participants was conducted.Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF.A restricted cubic spline(RCS)nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids.Results:High triglyceride(TG),low high-density lipoprotein cholesterol,and high low-density lipoprotein cholesterol(LDL-C)accounted for 49.7%,47.8%,and 59.2%of the participants,respectively.In multivariable analysis,high IR was associated with an increased risk of high TGs(P for trend<0.001)in T1DM and is associated with an elevated risk of high TG and low HDL-C(all P for trend<0.01)in T2DM.Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders.Conclusion:High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients,suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.