Association Between a Novel Metabolic Score for Insulin Resistance and Mortality in People With Diabetes

Abstract

BackgroundGrowing studies have shown that insulin resistance (IR) is associated with poor prognoses among patients with diabetes, whereas the association between IR and mortality has not been determined. Hence we aimed to evaluate the associations between IR and all-cause, cardiovascular diseases (CVDs) and cancer-related mortality in patients with diabetes.MethodsWe enrolled 2,542 participants with diabetes with an average age of 57.12 ± 0.39 years and 52.8% men from the 1999–2014 National Health and Nutrition Examination Survey (NHANES 1999–2014). A novel metabolic score for insulin resistance (METS-IR) was considered as alternative marker of IR. Mortality data were obtained from the National Death Index records and all participants were followed up until December 31, 2015. Cox proportional hazards regression, restricted cubic spline and Kaplan-Meier survival curves were performed to evaluate the associations between METS-IR and all-cause and cause-specific mortality in patients with diabetes.ResultsDuring 17,750 person-years of follow-up [median (months), 95% CI: 90, 87–93], 562 deaths were documented, including 133 CVDs-related deaths and 90 cancer-related deaths. Multivariate Cox regression showed that compared with Quintile 1 (METS-IR ≤ 41), METS-IR in Quintile 2, 3, and 4 was all associated with all-cause mortality (Q2 vs. Q1: HR 0.65, 95% CI 0.49–0.87, P = 0.004; Q3 vs. Q1: HR 0.69, 95% CI 0.50–0.96, P = 0.029; Q4 vs. Q1: HR 0.57, 95% CI 0.36–0.91, P = 0.019; respectively). Restricted cubic spline indicated that METS-IR was non-linearly associated with all-cause and CVDs-related mortality. Threshold effect analyses determined that threshold values of METS-IR for all-cause and CVDs-related mortality were both 33.33. Only METS-IR below the threshold was negatively associated with all-cause and CVDs-related mortality (HR 0.785, 95% CI 0.724–0.850, P < 0.001; HR 0.722, 95% CI 0.654–0.797, P < 0.001; respectively). Sensitivity analyses showed that when excluding participants who died within 1 years of follow-up, the results of threshold effect analyses remained consistent, whereas excluding participants with CVDs, METS-IR below the threshold was only negatively correlated with all-cause mortality. Subgroup analyses indicated that for all-cause mortality, the results were still stable in all subgroups except newly diagnosed diabetes, but for CVDs-related mortality, the association persisted only in participants who were ≤ 65 years, male, White, non-White, already diagnosed diabetes, or uesd oral drugs, insulin, insulin sensitizing drugs.ConclusionMETS-IR was non-linearly associated with all-cause and CVDs-related mortality in patients with diabetes, and METS-IR below the threshold was negatively associated with all-cause and CVDs-related mortality.

Predictive values of metabolic score for insulin resistance on risk of major adverse cardiovascular events and comparison with other insulin resistance indices among Chinese with and without diabetes mellitus: Results from the 4C cohort study

“…Additionally, we found that the METS‐IR index was strongly correlated with the risk of all‐cause death and diabetes among individuals without diabetes, which is in agreement with previous studies 40,41 . A recent study 42 showed that METS‐IR was nonlinearly associated with all‐cause mortality and CVD‐related mortality in patients with diabetes, which is consistent with our findings because, in our study, the number of all‐cause and CVD deaths in the individuals with diabetes also increased with the elevation of METS‐IR, although this change was not statistically significant due to the lower event number. It is noteworthy that a linear relationship between METS‐IR levels and MACEs was observed in individuals with diabetes, whereas a nonlinear relationship was observed in those without diabetes.…”

METS-IR and all-cause mortality in Korean over 60 years old: Korean genome and epidemiology study-health examinees (KoGES-HEXA) cohorts

“…Given these points, it can be inferred that higher IR may lead to increased mortality related to cancer and CVD. Some studies have yielded diverse results regarding the correlation between IR and mortality, encompassing both all-cause and cause-specific outcomes ( 27 , 44 – 53 ). When interpreting our results within the context of previous research, both concordant and discordant findings emerge.…”

“…In the analysis of the association between IR and cause-specific mortality, no study demonstrated a significant association with both cancer-related and CVD-related mortality. Some studies established an association between IR and all-cause mortality ( 44 , 45 ), along with either CVD ( 27 , 46 – 49 ) or cancer-related mortality ( 50 , 51 ), while others failed to find associations with mortality ( 52 , 53 ). This implies that understanding the shared pathophysiology, such as insulin resistance, between CVD and cancer, while simultaneously comprehending the distinct characteristics of each disease, is crucial for formulating tailored strategies for each.…”

Association between MetS-IR and prediabetes risk and sex differences: a cohort study based on the Chinese population

“…The hyperinsulinemic-euglycemic clamp is recognized as the gold standard for evaluating IR, but due to the relatively complicated measurement method, it cannot be widely used in large-scale epidemiological investigations; While MetS-IR, as a simple IR surrogate indicator, is considered to be widely used (16). The MetS-IR is a new score to assess cardiometabolic risk in healthy and high-risk subjects and a promising tool to screen for insulin sensitivity, as described by Bello-ChavollaOY et al The value of this parameter has been confirmed in a large number of subsequent epidemiological investigations, including risk assessment and prediction of diabetes, NAFLD, hyperuricemia, prehypertension, and hypertension, hypertension combined with hyperuricemia, metabolic syndrome, and various chronic diseaserelated complications (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)40). Also, it is worth noting that in a recent study by Li et al, who included 1,205 baseline normoglycemic subjects and evaluated the association between MetS-IR and prediabetes for the first time, their results showed that, MetS-IR was not significantly associated with prediabetes (17).…”