What question did this study set out to answer?

To assess the impact of metabolic syndrome on the relationship between lipoprotein (a) and the incidence of type 2 diabetes.

February 8, 2026

The effect of metabolic syndrome on the relation between lipoprotein (a) and incident type 2 diabetes and outcome: observations from the UK-Biobank.

Key Points

To assess the impact of metabolic syndrome on the relationship between lipoprotein (a) and the incidence of type 2 diabetes.
Analyzed data from the UK-Biobank cohort focusing on lipoprotein (a) levels.
Excluded known and undiagnosed type 2 diabetes cases using baseline HbA1c.
Diagnosed metabolic syndrome using modified NCEP-ATP III criteria, considering HbA1c for prediabetes.
Used Kaplan-Meier method for time-to-event analysis and Cox regression for risk assessment.
Found an inverse relationship between lipoprotein (a) and the risk of incident type 2 diabetes in individuals with metabolic syndrome.
For each increasing quartile of lipoprotein (a), the risk of type 2 diabetes decreased in those with metabolic syndrome.
Major adverse cardiovascular events were positively associated with lipoprotein (a) quartiles in both groups.

Abstract

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

Bookmark

The effect of metabolic syndrome on the relation between lipoprotein (a) and incident type 2 diabetes and outcome: observations from the UK-Biobank.

Key Points

Abstract

Cite This Study