Insulin resistance is associated with a hyperglycemic glucotype in people with type 1 and type 2 diabetes mellitus.

Background and aims: The gold standard for determining insulin resistance remains the hyperinsulinemic-euglycemic clamp test. The routine use of this test is limited. The estimated glucose disposal rate (eGDR) has been introduced to determine insulin resistance (IR) in patients with type 1 (T1) and type 2 (T2) diabetes mellitus. Continuous glucose monitoring (CGM) is accepted for follow up of glycemic status in people with T1 and T2 diabetes. We investigated the impact of IR on parameters of short- and long-term glycemic control.

Methods: Intermittent CGM-profiles were from a non-interventional, retrospective cross-sectional study of 251 participants (T1: n=148, T2: n=103). IR was determined as follow: eGDR=19.02 – (0.22×BMI) – (3.26×hypertension) – (0.61×HbA1c). Participants were divided in quintiles (Q) based on eGDR calculated separately for T1 and T2 diabetes. In addition to time in range 3.9 – 10 mmol/L (TIR), the composite metrics comprehensive Glucose Pentagon (CGP), Glycemic Risk Index (GRI) and Quality-Score (Q-Score) were calculated to determine overall glycemic quality. Glycation gap (GGap) was determined using the equation predicted HbA1c=0.0143*fructosamine+3.546. Laboratory parameters analysed were fructosamine µmol/L, HbA1c%, C-peptide pmol/l, CRP mg/L, glomerular filtration rate (GFR) ml/min/1.73m2 and Fib-4 index. Statistical analyses were performed using PASW Statistics for Windows [1] [2] [3] [4].

Results: Participants were separated in eGDR-quintiles representing different levels of IR with quintile 1 (Q1) the highest IR (T1: 2.6±0.9; T2: 0.5±1.3) and quintile 5 (Q5) (T1: 8.9±0.9; T2: 6.2±1.4) the lowest. In both diabetes types participants with high IR had significantly increased HbA1c values (Q1 T1: 8.9±0.9%; T2: 9.2±1.5%) compared to those with low IR (Q5 T1: 7.9±1.2%; T2: 7.6±1.2%. Accordingly, TIR decreased with rising IR (Q5 T1: 58.1±19.3%; T2: 68.5±26.0% vs. Q1 T1: 38.2±16.6%; T2: 38.1±26.6%). GGap (Q5 T1: -0.9±0.9; T2: 0.1±0.6 vs. Q1 T1: 0.6±0.8; T2: 0.8±0.9;), GRI and Q-Score increased with rising IR in both diabetes types. CGP increased with IR in T2. Fructosamine, CRP, Fib-4 index and microalbumin were not significant different between eGDR quintiles. GFR was lower in Q1 with high IR (T1: 82.1±17.2; T2: 63.9±21.29) compared to Q5 with low IR (T1: 99.5.1±20.9; T2: 84.1±18.8). The prevalence of peripheral polyneuropathy was increased in quintiles representing increased IR.

Conclusion: Insulin resistance impacts short- and long-term glycemic control in people with type 1 and type diabetes indicated by increased HbA1c, reduced TIR and elevated GRI and Q-Score. Our results implicate that high insulin resistance promotes a hyperglycemic glucotype.

Publication History

Article published online:
28 May 2025

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