Insulin resistance and risk of vascular events, interventions and mortality in type 1 diabetes

2021 ◽  
Author(s):  
Marga A.g. Helmink ◽  
Marieke de Vries ◽  
Frank L.j. Visseren ◽  
Wendela L. de Ranitz ◽  
Harold W. de Valk ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Lower Risk ◽  
Cardiovascular Events ◽  
Additional Risk Factor ◽  
Vascular Events ◽  
All Cause Mortality

Objective: To identify determinants associated with insulin resistance and to assess the association between insulin resistance and cardiovascular events, vascular interventions and mortality in people with type 1 diabetes at high risk of cardiovascular disease . Design: Prospective cohort study. Methods: 195 people with type 1 diabetes from the Secondary Manifestations of ARTerial disease (SMART) cohort were included. Insulin resistance was quantified by the estimated glucose disposal rate (eGDR) with higher eGDR levels indicating higher insulin sensitivity (i.e. lower eGDR levels indicating higher insulin resistance). Linear regression models were used to evaluate determinants associated with eGDR. The effect of eGDR on cardiovascular events, cardiovascular events or vascular interventions (combined endpoint) and on all-cause mortality was analysed using Cox proportional hazards models adjusted for confounders. Results: In 195 individuals (median follow-up 12.9 years, IQR 6.7-17.0), a total of 25 cardiovascular events, 26 vascular interventions and 27 deaths were observed. High eGDR as a marker for preserved insulin sensitivity was independently associated with a lower risk of cardiovascular events (HR 0.75; 95%CI 0.61-0.91), a lower risk of cardiovascular events and vascular interventions (HR 0.74; 95%CI 0.63-0.87), and a lower risk of all-cause mortality (HR 0.81; 95%CI 0.67-0.98). Conclusions: Insulin resistance as measured by eGDR is an additional risk factor for cardiovascular disease in individuals with type 1 diabetes. Modification of insulin resistance by lifestyle interventions or pharmacological treatment could be a viable therapeutic target to lower the risk of cardiovascular disease.

scholarly journals Comment on Garofolo et al. Insulin Resistance and Risk of Major Vascular Events and All-Cause Mortality in Type 1 Diabetes: A 10-Year Follow-up Study. Diabetes Care 2020;43:e139–e141

Diabetes Care ◽  
2021 ◽  
Vol 44 (4) ◽  
pp. e79-e80
Author(s):  
José-Miguel González-Clemente ◽  
Gemma Llauradó ◽  
Lara Albert ◽  
Olga Giménez-Palop ◽  
Eugenia Berlanga ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Diabetes Care ◽  
Vascular Events ◽  
Follow Up Study ◽  
All Cause Mortality

scholarly journals Insulin Resistance and Risk of Major Vascular Events and All-Cause Mortality in Type 1 Diabetes: A 10-Year Follow-up Study

Diabetes Care ◽  
2020 ◽  
Vol 43 (10) ◽  
pp. e139-e141 ◽  
Author(s):  
Monia Garofolo ◽  
Elisa Gualdani ◽  
Maria Giovanna Scarale ◽  
Cristina Bianchi ◽  
Michele Aragona ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Vascular Events ◽  
Follow Up Study ◽  
All Cause Mortality

scholarly journals Serum Insulin Bioassay Reflects Insulin Sensitivity and Requirements in Type 1 Diabetes

2017 ◽  
Vol 102 (10) ◽  
pp. 3814-3821 ◽  
Author(s):  
Joseph A M J L Janssen ◽  
Gemma Llauradó ◽  
Aimee J Varewijck ◽  
Per-Henrik Groop ◽  
Carol Forsblom ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Serum Insulin ◽  
Glycosylated Hemoglobin ◽  
Insulin Dose ◽  
Biologically Active ◽  
Insulin Analogs ◽  
Insulin Requirements

Abstract Context Insulin resistance could increase insulin requirements in type 1 diabetes (T1D). Current insulin immunoassays do not detect insulin analogs. Kinase insulin receptor (IR) activation (KIRA) bioassays specific for human IR isoforms A (IR-A) and B (IR-B) permit assessment of all circulating insulin bioactivity. We studied whether IR-A and IR-B KIRA assays are related to direct measures of insulin sensitivity or insulin doses in T1D. Design We evaluated 31 adult patients with T1D (age 45.7 ± 1.6 years, body mass index 28.8 ± 0.7 kg/m2). Serum IR-A and IR-B bioactivities were measured by KIRA bioassays. Insulin sensitivity of glucose production (Ra) was measured by the euglycemic hyperinsulinemic clamp technique in which a low insulin dose (0.4 mU/kg/min for 240 minutes) was combined with D-[3-3H] glucose infusion to measure rates of Ra and utilization and insulin action on antilipolysis from suppression of serum free fatty acids. Results Baseline circulating IR-A bioactivity was 53 ± 7 pmol/L, and IR-B bioactivity was 81 ± 11 pmol/L. Compared with baseline, insulin infusion significantly increased IR-A (P < 0.001) and IR-B (P < 0.001) bioactivities. Fasting IR-A and IR-B bioactivities were positively related to endogenous Ra (r = 0.44, P = 0.01 and r = 0.38, P < 0.05). Fasting IR-A (r = 0.43, P = 0.02) and IR-B (r = 0.47, P = 0.01) bioactivities were significantly correlated with insulin requirements and glycosylated hemoglobin (IR-A: r = 0.52, P = 0.002; IR-B: r = 0.48, P = 0.006). Conclusions Circulating IR-A and IR-B bioactivities are associated with insulin resistance, high insulin requirements, and poor glycemic control in T1D. Measurement of IR bioactivity by KIRA assays provides a tool to assess the amount of biologically active insulin in groups of T1D patients treated with insulin analogs.

scholarly journals Utility of Insulin Resistance in Estimating Cardiovascular Risk in Subjects with Type 1 Diabetes According to the Scores of the Steno Type 1 Risk Engine

2020 ◽  
Vol 9 (7) ◽  
pp. 2192 ◽  
Author(s):  
Albert Cano ◽  
Gemma Llauradó ◽  
Lara Albert ◽  
Isabel Mazarico ◽  
Brenno Astiarraga ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Clinical Practice ◽  
Insulin Sensitivity ◽  
High Risk ◽  
Cvd Risk ◽  
C Statistic ◽  
Potential Applicability ◽  
Risk Engine

Background: We sought to assess the potential of insulin resistance (IR) for estimating cardiovascular disease (CVD) risk in adults with type 1 diabetes (T1DM) according to the scores of the Steno Type 1 Risk Engine (ST1RE). Methods: A total of 179 adults with T1DM (50.8% men, age 41.2 ± 13.1 years, duration of T1DM 16 (12–23) years) without established CVD were evaluated. IR was assessed by the estimation of insulin sensitivity (eIS) using two validated prediction equations: the estimated insulin sensitivity developed from the Pittsburgh Epidemiology of Diabetes Complications Study (eIS-EDC) and the estimated insulin sensitivity developed from Coronary Artery Calcification in T1DM Study (eIS-CACTI) ST1RE was used to estimate 10-year CVD risk and to classify subjects into three groups according to their risk: low (<10%; n = 105), moderate (10–20%; n = 53), and high (≥20%; n = 21). Results: Both eIS-EDC and eIS-CACTI correlated negatively with ST1RE scores (eIS-EDC: r = −0.636, p < 0.001; eIS-CACTI: r = −0.291, p < 0.001). The C-statistic for predicting moderate/high risk and high risk was 0.816 (95% confidence interval (CI): 0.754–0.878) and 0.843 (95% CI: 0.772–0.913), respectively, for the eIS-EDC equation, and was 0.686 (95% CI: 0.609–0.763) and 0.646 (95% CI: 0.513–0.778), respectively, for the eIS-CACTI equation. The eIS-EDC equation had a significantly higher C-statistic both for moderate-/high-risk (p = 0.001) and high-risk (p = 0.007) subjects. Two cut-off points of eIS-EDC were identified for detecting moderate/high risk (8.52 mg·kg−1·min−1; sensitivity 74% and specificity 76%) and high risk (8.08 mg·kg−1·min−1; sensitivity 65% and specificity 95%) with potential applicability in clinical practice. Conclusions: eIS negatively correlates with the score of CVD risk in the ST1RE. Two cut-off points of eIS are reported with potential utility in clinical practice for detecting adults with T1DM with the highest CVD risk.

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