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Perturbation of hyaluronan metabolism predisposes patients with type 1 diabetes mellitus to atherosclerosis.

ABSTRACT: AIMS/HYPOTHESIS: Cardiovascular disease contributes to mortality in type 1 diabetes mellitus, but the specific pathophysiological mechanisms remain to be established. We recently showed that the endothelial glycocalyx, a protective layer of proteoglycans covering the endothelium, is severely perturbed in type 1 diabetes, with concomitantly increased plasma levels of hyaluronan and hyaluronidase. In the present study, we evaluated the relationship between hyaluronan and hyaluronidase with carotid intima-media thickness (cIMT), an established surrogate marker for cardiovascular disease. SUBJECTS AND METHODS: Non-smoking type 1 diabetes patients without micro- or macrovascular complications and matched controls were recruited and cIMT of both carotid arteries was measured. To evaluate the relationship between cIMT and hyaluronan and hyaluronidase as well as other parameters, uni- or multivariate regression analyses were performed. RESULTS: We included 99 type 1 diabetes patients (age 10-72 years) and 99 age- and sex-matched controls. Mean cIMT, HbA(1c), high sensitivity C-reactive protein, hyaluronan and hyaluronidase were significantly increased in type 1 diabetes vs controls. Plasma hyaluronan and hyaluronidase were correlated in type 1 diabetes. In univariate regression analyses, mean IMT was associated with plasma hyaluronan, age and male sex, whereas after multivariate analysis only age and sex remained statistically significant. CONCLUSIONS/INTERPRETATION: We conclude that type 1 diabetes patients show structural changes of the arterial wall associated with increased hyaluronan metabolism. These data may lend further support to altered glycosaminoglycan metabolism in type 1 diabetes as a potential mechanism involved in accelerated atherogenesis.

SUBMITTER: Nieuwdorp M

PROVIDER: S-EPMC1914278 | biostudies-other | 2007 Jun

REPOSITORIES: biostudies-other

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Project description:BackgroundShort sleep duration and poor sleep quality are important risk factors for atherosclerosis. The use of smart bracelets that measure sleep parameters, such as sleep stage, can help determine the effect of sleep quality on lower-extremity atherosclerosis in patients with type 2 diabetes.ObjectiveTo investigate the correlation between sleep disorders and lower-extremity atherosclerosis in patients with type 2 diabetes.MethodsAfter admission, all patients were treated with lower-extremity arterial ultrasound and graded as having diabetic lower-extremity vascular lesions according to the results. A smart bracelet was used to obtain the patient sleep data. The correlation between sleep patterns and diabetic lower-extremity atherosclerosis, diabetic foot, and various metabolic indices was verified.ResultsBetween August 2021 and April 2022, we screened 100 patients with type 2 diabetes, with 80 completing sleep monitoring. Univariate ordered logistic regression analysis indicated that patients with a sleep score below 76 (OR = 2.707, 95%CI: 1.127-6.488), shallow sleep duration of 5.3 h or more (OR=3.040, 95 CI: 1.005-9.202), wakefulness at night of 2.6 times or more (OR = 4.112, 95%CI: 1.513-11.174), and a deep sleep continuity score below 70 (OR = 4.141, 95%CI: 2.460-615.674) had greater risk of high-grade lower limb atherosclerosis. Multivariate ordinal logistic regression analysis revealed that the risk of high-grade lower limb atherosclerosis was higher in patients with 2.6 or more instances of nighttime wakefulness (OR = 3.975, 95%CI: 1.297-12.182) compared with those with fewer occurrences. The sleep duration curve of patients with different grades of diabetic lower-extremity atherosclerosis was U-shaped. According to the results of the one-way analysis of variance, the higher the deep sleep continuity score, the lower the Wagner scale score for diabetic foot (P < 0.05).ConclusionsSleep disorders (long, shallow sleep duration, frequent wakefulness at night, and poor continuity of deep sleep) can worsen lower limb atherosclerosis in patients with type 2 diabetes. This finding can provide a new method for medical professionals to prevent and treat diabetic lower-extremity vascular lesions.

Project description:BackgroundCompelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM).ObjectiveThis study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM.MethodsSerum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models.ResultsThis cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05).ConclusionsT2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

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Perturbation of hyaluronan metabolism predisposes patients with type 1 diabetes mellitus to atherosclerosis.

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