Insulin Resistance in T1D with Diabetic Kidney Disease
Johan R Simonsen, Daniel Gordin, Andrzej S Januszewski, Alicia J Jenkins, Daniël H van Raalte, Michael JB van Baar, Petter Bjornstad, Lena M Thorn, Per-Henrik Groop
A pilot study on measured insulin sensitivity and estimated glucose disposal rates in adults with type 1 diabetes and diabetic kidney disease. Endocrine. 2026;91:61. Epub 2026 Feb 3.
Insulin resistance is increasingly recognised as a feature of type 1 diabetes (T1D), not just type 2. Diabetic kidney disease (DKD) has previously been linked to insulin resistance through observational data, but whether this relationship holds up under direct, gold-standard measurement had never been tested in people with T1D and DKD. This pilot study, co-authored by Diabeter Center Amsterdam/Amsterdam UMC's author Daniël van Raalte, set out to address that gap using the euglycemic-hyperinsulinemic clamp — the most rigorous method available for measuring insulin sensitivity — and also to evaluate how well existing estimated glucose disposal rate (eGDR) formulas perform in this population.
Seventeen adults with T1D from the Finnish Diabetic Nephropathy (FinnDiane) cohort participated: ten with DKD (most with severe albuminuria and reduced kidney function) and seven with preserved kidney function. All underwent a 240-minute euglycemic-hyperinsulinemic clamp. Measured glucose disposal rates (mGDR) were compared with values from three published eGDR formulas (Williams, Duca, and Januszewski).
Key findings:
- Insulin sensitivity was markedly lower in the DKD group: M/I-values — the ratio of glucose disposal rate to plasma insulin, a direct measure of insulin sensitivity — were 62.5% lower in individuals with DKD compared to those without, although this difference did not reach statistical significance in this small pilot (p=0.154).
- The direction of the finding is clinically meaningful: Despite the lack of statistical significance, the magnitude of the difference is substantial and the authors consider it clinically relevant. The small sample size (n=17) almost certainly limited statistical power rather than reflecting a true absence of effect.
- All three eGDR formulas predicted significantly lower insulin sensitivity in DKD: Interestingly, while none of the formulas correlated strongly with measured GDR values, all three successfully detected the between-group difference — suggesting they may still have utility as screening tools even if they do not precisely track clamp values.
- The Williams formula performed best overall (r=0.35 across the whole group), while the Januszewski formula showed the strongest correlation specifically within the DKD group (r=0.46).
- Existing eGDR formulas have limitations in this population: The formulas were derived from younger cohorts with better-preserved kidney function and different glycaemic profiles, limiting their direct applicability to older individuals with advanced DKD.
- A larger study is warranted: Based on their pilot data, the authors estimate that at least 21 participants per group would be needed to demonstrate a statistically significant difference with 90% power.
This study provides the first direct clamp-based evidence suggesting increased insulin resistance in people with T1D and DKD, and highlights the need for larger confirmatory studies. Understanding insulin resistance in this group may have important implications for cardiovascular risk management and the potential role of insulin-sensitising therapies in people with T1D and kidney disease.
Concluding, the authors state
"Our study implies that there is a likely increased insulin resistance in adult individuals with type 1 diabetes and DKD relative to those without DKD. Euglycemic clamps in larger cohorts are needed to confirm this, and to elucidate which eGDR-formulas may best predict insulin sensitivity in these individuals."
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