Lipoprotein insulin resistance score and risk of incident diabetes during extended follow-up of 20 years: The Women's Health Study

Abstract

Background Type 2 diabetes (T2D) is preceded by prolonged insulin resistance and relative insulin deficiency incompletely captured by glucose metabolism parameters, HDL-c and triglycerides. Objective Whether lipoprotein insulin resistance score (LPIR), a metabolomic marker, is associated with incident diabetes and improve risk reclassification over traditional markers on extended follow up. Methods Among 25,925 non-diabetic women aged 45 years or older, LPIR was measured by nuclear magnetic resonance spectroscopy as a weighted score of VLDL, LDL and HDL particle sizes, and their subsets concentrations. We run adjusted cox regression models for LPIR with incident T2D (20.4 years median follow-up). Results Adjusting for demographics, body mass index (BMI), life style factors, blood pressure and T2D family history, the LPIR hazard ratio for T2D (HR per SD, 95% confidence interval [CI]) was 1.95 (1.85, 2.06). Further adjusting for HbA1c, C-reactive protein, triglycerides, HDL and LDL cholesterol, LPIR HR was attenuated to 1.41 (1.31, 1.53) and had the strongest association with T2D after HbA1C in mutually adjusted models. The association persisted even in those with optimal clinical profiles, adjusted HR per SD 1.91 (1.17, 3.13). In participants deemed at intermediate T2D risk by the Framingham Offspring T2D score, LPIR led to a net reclassification of 0.145 (0.117, 0.175). Conclusion In middle aged or older healthy women followed prospectively over 20 years, LPIR was robustly associated with incident T2D, including among those with an optimal clinical metabolic profile. LPIR improved T2D risk classification and may guide early and targeted prevention strategies.

Impact of Subclinical Hypothyroidism on Cardiometabolic Biomarkers in Women

“…This is due to the very broad generalizability of our findings as euthyroid and SCT women comprise 97.3% of middle aged women in the United States (1). Previous studies have found strong associations for LPIR with incident T2D (20, 21), and also in the current WHS study population (22). The robust association between thyroid and LPIR may be a pathophysiological pathway of its hypofunction towards T2D.…”

Mechanisms underlying the cardiometabolic protective effect of walnut consumption in obese people: A cross‐over, randomized, double‐blind, controlled inpatient physiology study

“…The post-smoothie VLDL particle AUC showed a tendency towards decreased triglyceride-enriched large VLDL particle AUC (P < 0.06; Table 3), balanced by an increase of the fewer triglyceriderich, medium VLDL particle AUC (P < 0.04, Table 3). A significant decrease in the lipoprotein insulin resistance score AUC, an NMR lipid analysis-based and validated method to assess insulin resistance, 17 was observed with walnuts (P < 0.01; Table 3). The large HDL particle AUC significantly increased in the walnut diet (P < 0.01; Table 3 and Figure S2).…”

Lipoprotein insulin resistance score and branched-chain amino acids increase after adrenalectomy for unilateral aldosterone-producing adenoma: a preliminary study

“…Of further note, we observed a hitherto unreported rise in total plasma BCAA after ADX. Given that the LP-IR scores [16][17][18] and BCAA concentrations [20] have been shown to predict incident diabetes in population-based cohort studies, our present findings suggest that the risk of future diabetes development is not ameliorated and could even be worsened in PA patients without T2D initially despite remission of hyperaldosteronism after unilateral ADX.…”

“…LP-IR scores are closely related to glucose disposal measured with the hyperinsulinemic-euglycemic clamp technique and are strongly correlated with homeostasis model assessment of insulin resistance (HOMA-IR) [15,16]. Both the LP-IR and the plasma total BCAA concentration have been found to predict incident T2D in several population studies [16][17][18][19][20].…”