Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes

Abstract

Background The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up. Methods In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110–125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman’s coefficients. Kaplan–Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models. Results During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan–Meier survival curves also showed that the lower third of plasma apoE levels (< 5.97 mg/dL) was significantly associated with a lower risk of conversion to T2D (log-rank test, p = 0.002) compared to the middle and upper thirds. Conclusions The plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations. Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509

Quartet of APOCs and the Different Roles They Play in Diabetes

“…Some studies have suggested that APOC3 could play a role in development or worsening of insulin resistance because of the links among plasma APOC3, dyslipidemia, insulin resistance, and diabetes. 72,73 Indeed, a small clinical trial investigating the triglyceride-lowering effects of volanesorsen (an APOC3 antisense oligonucleotide therapeutic) in subjects with T2D indicated that suppression of APOC3 resulted in improved insulin sensitivity. 74 However, a larger randomized clinical trial on volanesorsen failed to detect improvements in insulin resistance or HbA1c in subjects with T2D.…”

Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review

“…In a study conducted in a small cohort of subjects of American Indian or Mexican ancestry, a structural polymorphism of apoC1, the T45S variant, which is associated with a higher propensity of the protein to undergo N-terminal truncation, was found to be associated with higher prevalence of diabetes secondarily to the onset of obesity [ 112 ]. In a 5-year prospective study, although plasma levels of apoC1 correlated positively with a high risk of T2D, this link was lost after adjusting for TG levels [ 113 ]. The only genetic study which investigated a most common apoC1 gene polymorphism (rs11568822) in relation with diabetes failed to find a correlation [ 114 ].…”

Prediabetes and insulin resistance in a population of patients with heart failure and reduced or preserved ejection fraction but without diabetes, overweight or hypertension

“…Regarding the risk of HF, in the Multi-Ethnic Study of Atherosclerosis (MESA) HbA 1c and fasting plasma glucose in the diabetes but not in the prediabetes range were each associated with higher risks of incident hospitalization for HF (HFpEF or HFrEF) [ 28 ]. Stratifying the risk of incident type 2 diabetes in prediabetic subjects using new markers [ 29 ] may also be helpful.…”