Association of estimated glucose disposal rate and chronic diabetic complications in patients with type 1 diabetes

Abstract Introduction The role of insulin resistance in diabetic chronic complications among individuals with type 1 diabetes (T1D) has not been clearly defined. The aim of this study was to examine the performance of insulin resistance, evaluated using the estimated glucose disposal rate (eGDR) for the identification of metabolic syndrome (MS) and diabetic chronic complications. Methods Cross‐sectional study in a tertiary care centre. We included patients of 18 years and older, with at least 6 months of T1D duration. Anthropometric, clinical and biochemical data were collected. Results Seventy patients, 41 (58.6%) women, with a median age of 36.6 years (range 18–65). Mean age of onset and duration of diabetes was 13.5 ± 6.5 and 23.6 ± 12.2 years, respectively. Twenty‐one (30%) patients met the metabolic syndrome (MS) criteria. Patients with MS had lower eGDR compared to patients without (5.17 [3.10–8.65] vs. 8.86 [6.82–9.85] mg/kg/min, respectively, p = .003). Median eGDR in patients with nephropathy, retinopathy and neuropathy compared with those without was 6.75 (4.60–8.20) versus 9.53 (8.57–10.3); p < .001, 6.45 (4.60–7.09) versus 9.50 (8.60–10.14); p < .001, 5.56 (4.51–6.81) versus 9.49 [8.19–10.26] mg/kg/min; p < .001, respectively. The eGDR showed an area under the curve of 0.909, 0.879, 0.897 and 0.836 for the discrimination of MS, retinopathy, neuropathy and nephropathy, respectively. Conclusions Patients with T1D diabetic complications have higher insulin resistance. The eGDR discriminates patients with chronic diabetic complications and MS. While more ethnic‐specific studies are required, this study suggests the possibility to incorporate eGDR into routine diabetes care.


| INTRODUC TI ON
Metabolic syndrome (MS) can be seen as the coexistence of multiple risk factors that predispose to type 2 diabetes and cardiovascular disease being insulin resistance an important causative factor. 1,2 The prevalence of metabolic syndrome (MS) in type 1 diabetes (T1D) patients has been widely studied in numerous large cohorts considering different definitions. Depending on the age, the studied population and the definition, its prevalence ranges from 8% to 45%. [3][4][5] Regardless of the definition, the use of the MS concept in T1D has limitations, since the hyperglycaemia criterion is inevitably fulfilled which potentially overestimates its prevalence. Moreover, raised blood pressure and elevated triglycerides or its treatment criteria represent a problem since the indications for its therapy can be other than the aforementioned. 6 Since insulin resistance is implicated in the pathophysiology of MS, 7 a more suitable measurement for insulin resistance in T1D population is required.
The eugylcaemic-hyperinsulinaemic clamp, which is the gold standard for insulin resistance measurement, is not practical in clinical settings. 8 The difficult situation for assessing insulin resistance in patients with T1D is not new. As a result, several insulin sensitivity estimation formulas have been developed and validated against the euglycaemic-hyperinsulinaemic clamp. [9][10][11] The estimated glucose disposal rate (eGDR) is an equation that includes clinical parameters measured in clinical practice to determine the degree of insulin sensitivity. 9 In addition, it has been associated and considered as a good discriminator of diabetic complications in T1D. 4,[12][13][14] As the frequency for macro-and microvascular complications from diabetes is expected to rise, 15 effective and practical cardiovascular risk assessment and treatment is needed for T1D population. The aim of this study is to evaluate insulin resistance using the eGDR among adults with T1D with and without MS and to examine the performance of the eGDR for the identification of diabetic chronic complications.

| MATERIAL S AND ME THODS
A cross-sectional study was carried out in T1D patients treated at the Diabetic Outpatient Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán over a period of 1 year (March 2020 through December 2020). Subjects of at least 18 years old and with T1D of at least 6 months of duration were included. The study protocol was approved by the Local Ethics Committees, and informed consent was obtained from all participants.
T1D was defined as receiving insulin regimen (≥3 injections per day) before 25 years of age and either absence of C-peptide (below the level of detection limit) and/or past or present positive autoantibodies.

| Statistical methods
Data are presented as mean ± SD or median and interquartile range.
To evaluate intergroup differences, we used Student's t test and Mann-Whitney U where appropriate. Frequency distribution of categorical variables is reported as frequencies and percentages and was compared between groups using chi-square tests. To assess the ability of the eGDR to discriminate the presence of metabolic syndrome and/or chronic diabetic complications, receiver operating characteristic (ROC) curves were used. Statistical analyses were conducted using Statistical Package for the Social Sciences (SPSS for Windows, version 24.0).

| RE SULTS
Seventy patients with T1D were included, 41 (58.6%) were women with a mean age of 36.6 years (range 18-65). The mean age of onset and duration of diabetes was 13.5 ± 6.5 years and 23.6 ± 12.2 years, respectively. Diabetic nephropathy, neuropathy and retinopathy were present in 35.7%, 37.1% and 35.7%, respectively. The clinical and biochemical characteristics of the studied population are summarized in Table 1.

| DISCUSS ION
These results show that eGDR, a surrogate of insulin resistance, was lower in patients with T1D with MS. Moreover, patients with diabetic chronic complications had also a lower eGDR compared to those without. The current results are consistent with previous research assessing insulin resistance in T1D patients. 4 Note: Data expressed as frequencies (%), mean (SD) or median (IQR), as appropriate.
The identification of an eGDR cut-off point associated with MS has been explored before. 23

| CON CLUS ION
This study supports that eGDR is useful for the identification of MS and chronic diabetic complications in patients with T1D. While more ethnic-specific studies are required, this report also suggests that integration of the eGDR into routine T1D care would be useful.

Support journal submission publication fee was financially by Novo
Nordisk.

AUTH O R CO NTR I B UTI O N S
All authors have contributed to the realization and improvement of the article, also agreed on the content of the manuscript. César Ernesto Lam-Chung contributed to study design, data collection, data analyses and writing of the report. Néstor Martínez Zavala, contributed to data analyses and writing of the report. The final version has been read and approved by all authors.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author, [PAV], upon reasonable request.