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, hypoglycemia predicted decreased IS in T1D youth and hyperglycemia, 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.