Increased plasma D-dimer levels may be a promising indicator for diabetic peripheral neuropathy in type 2 diabetes

Abstract

BackgroundIncreased plasma D-dimer levels have been reported to be associated with a range of adverse health outcomes. This study aimed to determine whether plasma D-dimer is connected to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsThis study was part of a series exploring the potential risks for DPN. All patients were questioned for neurologic symptoms, examined for neurologic signs, and received nerve conduction studies to collect nerve action potential onset latency, amplitude, and nerve conduction velocity (NCV). Composite Z scores of latency, amplitude, and NCV were calculated. DPN was confirmed as both at least a neurologic symptom/sign and an abnormality of nerve conduction studies. Coagulation function indices, such as plasma D-dimer levels, were also synchronously detected.ResultsWe finally recruited 393 eligible patients for this study, of whom 24.7% (n = 97) were determined to have DPN. The plasma D-dimer level was found to be closely associated with the composite Z score of latency, amplitude, and NCV after adjusting for other coagulation function indices and clinical covariates (latency: β = 0.134, t = 2.299, p = 0.022; amplitude: β = –0.138, t = –2.286, p = 0.023; NCV: β = –0.139, t = –2.433, p = 0.016). Moreover, the prevalence of DPN in the first, second, third, and fourth quartiles (Q1, Q2, Q3, and Q4) of the D-dimer level was 15.2%, 15.9%, 26.4%, and 42.7%, respectively (p for trend < 0.001). The corresponding adjusted odds ratios and 95% CIs for DPN in D-dimer quartiles were 1, 0.79 (0.21–2.99), 1.75 (0.49–6.26), and 5.17 (1.38–19.42), respectively. Furthermore, the optimal cutoff value of the plasma D-dimer level to discriminate DPN was ≥0.22 mg/L (sensitivity = 67.01%, specificity = 58.78%, and Youden index = 0.26) after analysis by the receiver operating characteristic curve.ConclusionsIncreased plasma D-dimer levels may be a promising indicator for DPN in patients with T2D.

Comparative Analysis of Biomarkers in Type 2 Diabetes Patients with and without Comorbidities: Insights into the Role of Hypertension and Cardiovascular Disease

“…D-Dimer has not been investigated extensively. However, previous work of ours has shown a relationship between diabetes progression in the presence of macrovascular disease and more recently D-dimer has been shown to be a promising marker for peripheral neuropathy 61,62 . GSSG is a sensitive oxidative stress marker, which reflects possible decreasing synthesis of GSH and increased irreversible utilization by reactive oxygen species reactions 42 .…”

“…The current study extends our understanding of the role of C5a as direct associations of this biomarker was observed with disease progression and presence of comorbidities, providing a useful timeline in terms of the biochemical milieu changes associated with disease progression. D-dimer has previously been reported to be already elevated in prediabetes and diabetic peripheral neuropathy has recently been associated with increased levels of D-dimer alongside fluctuations in HbA1c 61,86 .…”

“…Complement component 5a (C5a) is an inflammatory marker and increases in diabetic patients 41 . However, plasma D-dimer levels have not been discussed extensively but higher levels may be a positive sign of diabetic peripheral neuropathy (DPN) in T2DM patients and correlate with disease progression in pre-diabetes to cardiovascular complications associated with T2DM 61,62 . Typical ranges of the afore mentioned biomarkers from the literature in control (NC), prediabetes (PreDM), and T2DM (T2DM) groups are shown in Table 1.…”

Associations Between Mean Platelet Volume and Various Factors in Type 2 Diabetes Patients: A Single-Center Study from Poland

“…Recent studies show there is a relationship between D-dimer levels and MPV, indicating that in type 2 diabetes patients, increased platelet activation can reflect increased fibrinolytic activity [ 41 , 42 ]. D-dimers are small protein fragments produced during fibrinolysis and are well-established markers of venous thrombosis formation in the general population [ 42 ].…”

“…Recent studies show there is a relationship between D-dimer levels and MPV, indicating that in type 2 diabetes patients, increased platelet activation can reflect increased fibrinolytic activity [ 41 , 42 ]. D-dimers are small protein fragments produced during fibrinolysis and are well-established markers of venous thrombosis formation in the general population [ 42 ]. Previous studies indicated that increased D-dimer concentration was found in individuals with prediabetes [ 43 ], type 2 diabetes patients [ 42 ], or even first-degree relatives of type 2 diabetes patients [ 44 ].…”