Background: An increasing number of people with type 1 diabetes (TlD) have co-existing insulin resistance (IR). Our goal was to investigate whether IR is associated with continuous glucose monitor (CGM)-derived parameters (glucometrics) such as time in range (TIR), time above range (TAR), time below range (TBR) and glycaemic variability (CV).
Methods: This is a retrospective analysis of two separate clinical studies (NCT04664036, NCT04623320). In the first database, IR was quantified according to the estimated glucose disposal rate (eGDR) formula: 21.158 + (-0.09 x waist circumference, cm)+ (-3.407 x hypertension)+ (-0.551 x HbAlc, %) and in the second, by performing a hyperinsulinaemic-euglycaemic clamp (HEC). All glucometrics were calculated over 28 days.
Results: A total of 287 subjects were included. The mean age was 46 ± 17 years, 55 % were male, median diabetes duration was 26 [14- 36] years, TIR equalled 57 ± 14 % and the median eGDR was 7.6 (5.6 - 9.3) mg/kg min. The cohort was divided in tertiles based on the eGDR. The tertile of people with the lowest eGDR (highest level of IR) had a higher TAR compared to the tertile with the highest eGDR (33 ± 14 vs 39 ± 15 %, P< 0.05). ). Using linear regression, eGDR was independently associated with TIR and TAR ( = 0.016 and -0.021 respectively, P< 0.001), and this adjusted for age, gender, diabetes duration, smoking status and alcohol intake. Logistic regression analyses showed that an increasing eGDR was independently associated with a higher TIR (OR 1.251, 95% Cl 1.120 - 1.399, P< 0.001), lower TAR (OR 1.281, 95% Cl 1.146 - 1.443 P< 0.001) and a higher TBR (OR 0.801, 95% Cl 0.801 - 0.994, P< 0.05). In the 48 people undergoing a HEC, a higher TBR with increasing insulin sensitivity was present when analysing IR by the HEC-determined glucose disposal rate (M-value), but did not reach statistical significance.
Discussion and conclusion: Only a limited number of studies investigated the link between IR and glucometrics in TlD (1, 2). The strengths of our study are the detailed characterization of the patient population, the reasonably large number of HEC tests and the high-quality CGM data. To conclude, our study found that a lower IR, measured by eGDR, was independently associated with a higher TIR, lower TAR and a higher TBR. No significant association between glucometrics and the M-value was observed, probably due to a lack of power. These data suggest that measuring and targeting IR might benefit individuals with TlD in optimizing their glycaemic control.
References: 1. Chan CL, Pyle L, Morehead R, Baumgartner A, Cree-Green M, Nadeau KJ. The role of glycemia in insulin resistance in youth with type 1 and type 2 diabetes. Pediatr Diabetes. 2017;18(6):470-7.2. Guo K, Zhang L, Ye J, Niu X, Jiang H, Gan S, et al. Metabolic syndrome associated with higher glycemic variability in type 1 diabetes: A multicenter cross-sectional study in china. Front Endocrinol (Lausanne). 2022;13:972785.