The role of glycemia in insulin resistance in youth with type 1 and type 2 diabetes

Background Hyperglycemia has traditionally been considered a major contributor to insulin resistance ( IR ) in type 1 diabetes ( T1D ), yet studies examining the relationship between HbA1c and IR are conflicting. Glucose measures captured by continuous glucose monitoring ( CGM ) (eg, peak glucose, standard deviation, hypoglycemia) in youth have not been explored as predictors of insulin sensitivity ( IS ). Objective Assess the relationship between IS and glycemia in youth with T1D and type 2 diabetes ( T2D ). Methods Sedentary 12‐19 year olds with diabetes had peripheral IS measured by hyperinsulinemic‐euglycemic clamp. HbA1c and 3 days of CGM data were also collected. Spearman correlation coefficients were calculated to examine the association between variables. Results Participants included 100 youth with T1D [46% male, median body mass index ( BMI ) 74 percentile, HbA1c 8.5%] and 42 with T2D (26% male, BMI 99 percentile, HbA1c 6.9%). Nineteen with T1D and 13 with T2D also wore CGM . In T2D youth, higher HbA1c , average sensor glucose, area under the CGM curve, and metabolic syndrome characteristics correlated with lower IS . In T1D youth, higher BMI percentile, waist circumference, triglycerides, and LDL cholesterol, but not HbA1c , correlated with lower IS . Moreover, higher CGM overnight means glucose correlated with greater IS , and CGM hypoglycemia correlated with lower IS . Conclusions Markers of metabolic syndrome and hyperglycemia predicted decreased IS in T2D youth. Paradoxically, hypo glycemia predicted decreased IS in T1D youth and hyper glycemia, particularly overnight, predicted improved IS . These preliminary results imply different mechanisms underlying IR in T1D vs T2D and suggest a role for non‐insulin therapies in T1D to improve IR .