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Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

ABSTRACT: AIMS/HYPOTHESIS:Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP. METHODS:198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) ?6. Plasma levels of dp-ucMGP were measured by ELISA. RESULTS:In this cohort, the mean age was 64+/-8.4 years old, and 80% of patients were men. Peripheral neuropathy was present in 15.7% of the patients and was significantly associated (r = 0.51, p<0.0001) with dp-ucMGP levels (? = -0.26, p = 0.045) after integrating effects of height (? = -0.38, p = 0.01), insulin treatment (? = 0.42, p = 0.002), retinopathy treated by laser (? = 0.26, p = 0.02), and total cholesterol levels (? = 0.3, p = 0.03) by multivariable analysis. CONCLUSIONS:The association between diabetic neuropathy and the inactive form of MGP suggests the existence of new pathophysiological pathways to explore. Further studies are needed to determine if dp-ucMGP may be used as a biomarker of sensitive neuropathy. Since dp-ucMGP is a marker of poor vitamin K status, clinical studies are warranted to explore the potential protective effect of high vitamin K intake on diabetic peripheral neuropathy.

SUBMITTER: Jeannin AC

PROVIDER: S-EPMC7039520 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

Jeannin Anne-Caroline AC Salem Joe-Elie JE Massy Ziad Z Aubert Carole Elodie CE Vermeer Cees C Amouyal Chloé C Phan Franck F Halbron Marine M Funck-Brentano Christian C Hartemann Agnès A Bourron Olivier O

PloS one 20200224 2

<h4>Aims/hypothesis</h4>Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrix-gla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP.< ...[more]

PMID: 32092076

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Project description:Aims/introductionNon-alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of diabetic peripheral neuropathy, resulting in intolerable pain and extremity amputation that reduces the quality of life. However, the role of non-alcoholic fatty liver disease in the pathogenesis of diabetic peripheral neuropathy remains unclear. Thus, we evaluated the correlation of liver fibrosis and steatosis, which are representative histological morphologies of non-alcoholic fatty liver disease, with diabetic peripheral neuropathy in type 2 diabetes patients.Materials and methodsFive hundred twenty individuals with type 2 diabetes were recruited. All the patients were detected nerve conduction study for diabetic peripheral neuropathy and fibro touch for liver steatosis and fibrosis. Correlation of DPN with liver steatosis and fibrosis were analysed with binary logistic analysis.ResultsAmong the 520 patients, the prevalence of liver steatosis, fibrosis and diabetic peripheral neuropathy was 63.0% (n = 328), 18.1% (n = 94) and 52.1% (n = 271), respectively. The prevalence of diabetic peripheral neuropathy was significantly elevated in patients with liver steatosis (55.7 vs 44.9%, P = 0.03) and fibrosis (61.5 vs 50%, P = 0.04), and it increased as liver stiffness measurement increased. Additionally, both hepatic steatosis (odds ratio 1.48, 95% confidence interval 1.04-2.11, P = 0.03) and fibrosis (odds ratio 1.60, 95% confidence interval 1.02-2.51, P = 0.04) were correlated with diabetic peripheral neuropathy. After adjusting for age, sex, weight, height, body mass index, waist hip ratio, duration of type 2 diabetes, blood glucose, homeostatic model assessment of insulin resistance, blood pressure, serum lipid, liver enzyme, urea, uric acid, creatinine and inflammatory factors, liver fibrosis remained associated with diabetic peripheral neuropathy (odds ratio 2.24, 95% confidence interval 1.11-4.53, P = 0.02).ConclusionsThe prevalence of diabetic peripheral neuropathy was elevated in patients with liver steatosis and fibrosis. Liver fibrosis was also independently associated with an increased risk of diabetic peripheral neuropathy.

Project description:BackgroundPlasma 1,5-anhydro-D-glucitol (1,5-AG) may be a easily accessible marker for glycemic variability under mild-to-moderate hyperglycemia. The present study was to investigate the association of 1,5-AG with peripheral nerve function and diabetic peripheral neuropathy (DPN) in patients with T2D and mild-to-moderate hyperglycemia.MethodsWe recruited 574 T2D patients with mild-to-moderate hyperglycemia (HbA1c < 8.0%) for this cross-sectional study, with plasma 1,5-AG synchronously detected. All patients were questioned for neurologic symptoms, examined for neurologic signs and screened for peripheral nerve function. Nerve function included the latency, amplitude and nerve conduction velocity (NCV) of limbs nerves (median, ulnar nerve, common peroneal, superficial peroneal, tibial and sural nerve). Besides, composite Z-score of latency, amplitude and NCV were calculated. DPN was identified as both at least a neurologic symptom/sign and an abnormality of peripheral nerve function.ResultsAmong the recruited patients, 23.9% (n = 137) were identified to be with DPN, and the prevalence of DPN decreased from 36.6%, 24.5%, 21.2%, 13.3% from first (Q1), second (Q2), and third (Q3) to fourth quartile (Q4) of 1,5-AG. Moreover, multivariable linear regression analysis showed 1,5-AG was associated with composite Z-score of nerve latency (β = - 0.18, t = - 3.84, p < 0.001), amplitude(β = 0.26, t = 5.35, p < 0.001) and NCV (β = 0.24, t = 5.61, p < 0.001), respectively. Furthermore, compared to Q4 of 1,5-AG as reference, the adjusted odds ratios and 95% CIs for DPN of Q3, Q2, and Q1 were 1.29(0.59-2.81), 1.85(0.87-3.97), and 2.72(1.16-6.34), respectively. Additionally, receiver operating characteristic analysis revealed that optimal cutoff value of 1,5-AG to indicate DPN was ≤ 30.8 μmol/L, with sensitivity of 56.20% and specificity of 66.36%.ConclusionsLow plasma 1,5-AG is closely associated with impaired peripheral nerve function and DPN in T2D patients under mild-to-moderate hyperglycemia.

Project description:BackgroundIncreased serum carcinoembryonic antigen (CEA) levels are reported to be associated with various metabolic and inflammatory diseases. This study assessed whether high-normal serum CEA is related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D).MethodsAll subjects received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate composite Z scores of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum CEA levels and other clinical indices were also synchronously detected. Multivariable linear regression analyses were used to determine the independent effects of serum CEA levels on nerve conduction indices, multivariable logistic regression analyses were used to determine the independent impact of CEA levels on the risk of DPN, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of CEA levels to discriminate DPN.ResultsWe ultimately recruited 402 eligible subjects with normal ranges of serum CEA for this study, and 25.4% (n = 102) were determined to have DPN. After adjusting for other clinical covariates, serum CEA levels were independently associated with the composite Z score for latency (β = 0.132, t = 2.330, p = 0.021), amplitude (β = - 0.164, t = - 2.838, p = 0.005) and NCV (β = - 0.210, t = - 3.662, p < 0.001). Moreover, the prevalence of DPN in the first, second, third and fourth quartiles of CEA level was 12.9%, 19.0%, 29.4% and 40.4%, respectively (p for trend < 0.001); the corresponding adjusted odds ratios and 95% CIs for DPN in CEA quartiles were 1, 1.47 (0.45-4.82), 1.72 (0.54-5.53) and 4.58 (1.39-15.06), respectively. Furthermore, the optimal cut-off value of high-normal serum CEA to discriminate DPN was ≥ 2.66 ng/mL, with a Youden index of 0.28, sensitivity of 66.67% and specificity of 61.00%.ConclusionsIncreased serum CEA levels within the normal range are closely linked to dysfunction of peripheral nerve conduction and the risk of DPN, and high-normal serum CEA levels are a potential risk factor for DPN in T2D.

Dataset Information

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

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Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes.

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