HAPTOGLOBIN GENOTYPE AND HIGH-SENSITIVITY CARDIAC BIOMARKERS FOR CARDIOVASCULAR AND MICROVASCULAR RISK STRATIFICATION IN TYPE 2 DIABETES: A PILOT CASE–CONTROL STUDY

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a major global health concern and one of the foremost contributors to cardiovascular (CV) illness and death . Circulating biomarkers such as high-sensitivity cardiac troponins (hs-cTnI, hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are established predictors of heart failure and poor CV outcomes. The haptoglobin (Hp) gene exhibits polymorphism, and the Hp2-2 variant in particular is associated with diminished antioxidant activity and has been implicated in diabetic microvascular complications. However, its potential influence on cardiac biomarkers in patients with T2DM has not been clearly defined.

Objective: This study aimed to investigate the relationship between Hp genotype and levels of hs-cTnI, hs-cTnT, and NT-proBNP, and to assess whether their combined evaluation improves prediction of microvascular and macrovascular complications in adults with T2DM.

Methods: We conducted a hospital-based case–control study involving 84 adults with T2DM recruited from a tertiary care centre in India. Patients with at least one microvascular complication were included as cases (n = 42), while those without complications served as controls (n = 42). Clinical details, biochemical parameters, and high-sensitivity cardiac biomarkers were measured. Hp genotyping was carried out using PCR. Associations between Hp genotype, biomarker concentrations, and complications were examined through multivariable logistic regression, and discriminatory performance was assessed using receiver operating characteristic (ROC) analysis.

Results: The frequency of the Hp2-2 genotype was significantly higher in patients with nephropathy (62.5 %), nephropathy plus neuropathy (83.3 %), and nephropathy plus retinopathy (72.7 %), compared with controls. Median values of hs-cTnI and hs-cTnT were approximately 5 ng/L and 10 ng/L, respectively. Individuals carrying the Hp2-2 genotype showed elevated levels of hs-cTnI, hs-cTnT, and NT-proBNP (all p < 0.01). Each log-unit increase in hs-cTnI and hs-cTnT was independently associated with higher odds of microvascular complications, with adjusted odds ratios of 1.12 (95 % CI: 1.09–1.16) and 1.10 (95 % CI: 1.07–1.13), respectively. Incorporating hs-cTnI or NT-proBNP into conventional risk models modestly enhanced discrimination, increasing the area under the curve (AUC) by 0.04–0.06.

Conclusions: The Hp2-2 genotype and high-sensitivity cardiac biomarkers reflect distinct yet complementary aspects of cardio-renal risk in T2DM. Their combined use may help identify individuals at greater risk who would benefit from closer monitoring and targeted preventive interventions. Larger prospective studies are needed to confirm these findings and to determine their therapeutic significance.