THE EFFECT OF LUMBRICUS RUBELLUS DLBS1033 EXTRACT ON LEVELS OF HIGH-SENSITIVITY C-REACTIVE PROTEIN, VASCULAR ENDOTHELIAL GROWTH FACTOR, AND QUALITY OF LIFE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Type 2 Diabetes Mellitus (T2DM) is a major global health problem characterized by chronic hyperglycemia, persistent low-grade systemic inflammation, and vascular endothelial dysfunction. These pathological processes are central to the development of micro- and macrovascular complications, which are the leading causes of morbidity, mortality, and reduced quality of life in patients with T2DM.

Chronic hyperglycemia activates multiple pathophysiological pathways, including mitochondrial oxidative stress, the Advanced Glycation End Products (AGEs)-RAGE signaling axis, and impaired insulin signaling, collectively creating sustained systemic microinflammation and progressive endothelial damage. This endothelial dysfunction underlies the development of atherosclerosis, microcirculatory impairment, and pathological angiogenesis in T2DM patients.

High-sensitivity C-Reactive Protein (hs-CRP), a sensitive marker of systemic inflammation, is significantly elevated in T2DM and correlates with increased cardiovascular complication risk. Concurrently, Vascular Endothelial Growth Factor (VEGF), the primary mediator of endothelial cell proliferation and survival, exhibits the so-called 'VEGF paradox' in T2DM, whereby systemically elevated VEGF fails to produce functional neovascularization and instead promotes dysangiogenesis and pathological vascular permeability. These two pathways-hs-CRP-mediated inflammation and VEGF-mediated angiogenesis-interact in a mutually reinforcing pathological cycle that accelerates vascular complication progression.

Current T2DM management primarily targets glycemic control, which, while effective in reducing long-term complications, is insufficient to fully suppress chronic inflammation and correct vascular dysfunction. Adjuvant therapeutic strategies targeting non-glycemic pathogenic pathways, particularly inflammation and endothelial dysfunction, are therefore needed.

Lumbricus Rubellus extract (DLBS1033), produced by PT Dexa Medica through the Dexa Laboratories of Biomolecular Sciences (DLBS) in compliance with Good Manufacturing Practice (GMP) standards, contains low molecular weight proteins (Lumbricus Low Molecular Weight Proteins/LLP), including lumbrokinase-a serine protease enzyme with fibrinolytic, antithrombotic, and anti-inflammatory activities. Previous studies have demonstrated that lumbrokinase can suppress inflammatory mediators such as TNF-α and NF-κB, inhibit platelet aggregation, degrade fibrinogen, and improve microcirculatory function. However, its simultaneous effects on both hs-CRP and VEGF in T2DM patients remain insufficiently studied.