Abstract Background Lower genetically predicted Lp(a) is not causally associated with increased T2DM risk. Development of T2DM itself may lower Lp(a). Metabolic syndrome (MetS) increases incident T2DM and insulin resistance (IR). Purpose To assess whether baseline MetS affects the relation between Lp(a) and incident type 2 diabetes and outcome. Methods UK-Biobank cohort whose Lp(a) is available; known and undiagnosed T2DM (from baseline HbA1c) excluded. Major adverse cardiovascular event (MACE) - death, non-fatal myocardial infarction (MI), revascularisation or ischaemic stroke after entry obtained from Death Register and hospital episode statistics data. A modified NCEP-ATP III criteria was used to diagnose MetS (in absence of fasting blood glucose, HbA1c was used to diagnose preDM). Presence of ≥3/5 criteria denoted MetS. Time to incident T2DM and MACE in Lp(a) quartiles analysed by Kaplan-Meier method. Cox regression used to assess risk of incident T2DM/MACE in Lp(a) quartiles. Results 333753 entrants (83892-Q1, 82997-Q2, 83446-Q3, 83438-Q4); 287917 had all the MetS criteria recorded; 45436 (13.61%) preDM, 94459(28.30%) high waist circumference; 131566(39.43%) high triglyceride, 60449(19.80%) low HDL-C, 203025(64.48%) hypertension. MetS present in 69110 (24.0%). Lp(a) and incident T2DM were inversely associated in subjects with MetS but not without (Fig1AB). Risk of T2DM adjusted for its risk factors including MetS decreased with increasing Lp(a) quartile in the whole cohort (Lp(a) Q2: HR 0.93, 0.88-0.99, p=0.016, Q3: HR 0.93, 0.88-0.99, p=0.014; Q4: HR 0.92, 0.87-0.97, p=0.004). This was seen in patients with MetS (Q2: HR 0.91, 0.85-0.98, p=0.012; Q3: 0.91, 0.85-0.98, 0.015; Q4: 0.90, 0.84-0.97, p=0.005) but not without. This relation existed only when all 5 components of MetS is present (Q2:HR 0.91, 0.76-1.07, p=0.252; Q3: HR 0.83, 0.70-0.99, p=0.035; Q4: HR 0.79, 0.66-0.94, p=0.008) and in all individual abnormal traits of MetS (Fig2A-J). MACE was directly related to Lp(a) quartiles in patients with and without MetS (Fig1CD) , after adjustment (Q4: HR 1.15, 1.10-1.19, p0.0001 for no MetS) and (Q3: HR 1.09, 1.03-1.16, p=0.003; Q4: HR 1.15, 1.09-1.22, p0.0001 for MetS). Conclusion Inverse relation of Lp(a) and incident T2DM is seen in patients with MetS, a high IR state. MACE was directly associated with Lp(a) quartiles in both groups.Fig 1 Fig 2
Sangha et al. (Sat,) studied this question.