Extended Data Fig. 2: Glycemic markers, oxidative and non-oxidative glucose disposal as well as adipose tissue GSEA during euglycemic-hyperinsulinemic clamp conditions in homozygous TBC1D4 p.Arg684Ter variant carriers.

a, Basal (Pre-clamp) endogenous glucose rate of appearance (Ra). b, c, Blood glucose levels (b) and plasma insulin concentrations (c) during the insulin clamp. d, Plasma fatty acids during an extended (6-h) oral glucose tolerance test (OGTT). e, RNA Gene Set Enrichment Analysis (GSEA) in adipose tissue obtained at the end of the insulin clamp with number of genes included in the gene set indicated by ‘Size’, Enrichment Score indicated by ‘ES’, Normalized Enrichment Score indicated by ‘NES’, Nominal P Value indicated by ‘NOM p-value’ and False Discovery Rate indicated by ‘FDR q-value’. f, Leg glucose uptake during the 120 min insulin clamp. g, Glucose disappearance rate displayed as oxidative and non-oxidative glucose metabolism during the insulin clamp steady state period (90 min). ‡Different from basal (time = 0) in both groups (line indicates main effect). *Difference between TBC1D4 carriers and Controls. One symbol = P < 0.05, two symbols = P < 0.01 and three symbols = P < 0.001. n = 5 in both groups (a–c, f, g) and n = 8 in Controls and n = 7 in TBC1D4 carriers (d). Data are means ± SEM. Data were analyzed using a two-tailed paired students t-test (a, g) as well as a two-way repeated ANOVA test (one factor repeated (d) and two factor repeated (b, c)) and two-tailed Student-Newman-Keuls post hoc analyses for multiple comparisons (b–d). Statistical analyses were not applied to data in panel f. LLM, leg lean mass. AU, arbitrary units.