Publication Description
Objective
In treatment options for type 2 diabetes in adolescents and youth (TODAY), 4.5% of obese youth clinically diagnosed with type 2 diabetes (T2D) had genetic variants consistent with maturity onset diabetes of youth (MODY) diagnosis. The course of IS and β‐cell function in obese youth with MODY remains unknown. In this secondary analysis, we examined IS and β‐cell function in MODY vs. non‐MODY obese youth at randomization and over time.
Methods
Genetic data in TODAY included 426 non‐MODY (T2D) and 22 MODY youth (7 glucokinase MODY mutation positive [GCK‐MODY], 12 hepatocyte nuclear factor MODY mutation positive [HNF‐MODY], 2 Insulin gene mutation [insulin (INS)‐MODY], and 1 Kruppel‐like factor 11 [KLF11‐MODY]). Oral glucose tolerance test (OGTT)‐derived IS, C‐peptide index, and β‐cell function relative to IS oral disposition index (oDI) was measured at randomization, and over 24 months in addition to total and high‐molecular‐weight adiponectin (HMWA).
Results
At randomization, IS, total adiponectin, and HMWA were significantly higher in the two MODY groups than in non‐MODY. β‐cell function measured by C‐peptide oDI was 3‐fold higher in GCK‐MODY than in HNF‐MODY and 1.5‐fold higher than non‐MODY (P for both <.05 glycemic="" failure="" rate="" was="" in="" hnf="" non="" and="" zero="" gck="" youth.="" while="" the="" changes="" is="" odi="" were="" not="" different="" among="" three="" groups="" first="" improved="" from="" to="" months="" vs="" conclusions="" today="" function="" at="" randomization="" worse="" obese="" youth="" compared="" with="" insulin="" sensitivity="" other="" two="" mody="" groups.="" over="" time="" showed="" greatest="" improvement="" this="" raises="" possibility="" that="" therapeutic="" modalities="" of="" sensitization="" these="" may="" have="" played="" a="" beneficial="" role.="">