Relationships between cholesterol efflux and high-density lipoprotein particles in patients with type 2 diabetes mellitus.

BACKGROUND: High-density lipoprotein (HDL) encompasses a heterogeneous population of lipoproteins with differences in functionality. The impact of HDL heterogeneity on its ability to support HDL-mediated cholesterol efflux has not been previously studied in patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: To examine the relationships between various HDL subtypes and cholesterol efflux from macrophages in patients with T2DM. METHODS: Lipoprotein molecular profiles of 44 patients were studied by NMR spectroscopy. Cholesterol efflux was expressed as percentage efflux of radioactivity from lipid-laden THP-1 macrophages preincubated with (3)H-cholesterol and then incubated with serum depleted of apolipoprotein B to provide an HDL-enriched acceptor medium. RESULTS: There was a predominance of small HDL particles (59%) and small putatively atherogenic low-density lipoprotein particles (56%). Neither HDL-C nor ApoA-I concentrations showed statistically significant correlations with percentage cholesterol efflux, but a significant positive relationship was found with the total HDL particle concentration (r = 0.41, P = .005) contributed to largely by medium HDL particles (r = 0.41, P = .006). The correlation between medium-sized HDL particle concentration remained significantly associated with cholesterol efflux when assessed with the use of a linear regression model that included all the HDL lipoprotein subclass concentrations as well as apolipoprotein A-I. Importantly, no statistically significant association was observed between the number of small HDL particles and cholesterol efflux. Hemoglobin A1c showed a significant inverse correlation with cholesterol efflux (r = -0.31, P = .04). CONCLUSION: In patients with moderately controlled type 2 diabetes mellitus, cholesterol efflux from macrophages incubated with apolipoprotein B-depleted plasmas correlated significantly and positively with the concentration of total and medium-sized HDL and not with that of the smallest particles.

Severe Graves' ophthalmopathy after retrobulbar anesthesia for cataract extraction in a patient with mild stable thyroid eye disease.

It has been hypothesized that the distinct anatomic localization of the Graves' triad may be partially explained by pressure and trauma. While there are reports of local trauma clearly contributing to the pathogenesis of pretibial myxedema, direct evidence for a similar mechanism in Graves' ophthalmopathy (GO) has been lacking. We describe a 65-year-old male patient with stable mild Graves' ophthalmopathy of 24 years' duration in whom a retrobulbar block was administered prior to cataract removal. Three weeks after the procedure, he complained of rapidly progressive bilateral diplopia. In 6 months, there was moderate exophthalmos, exposure keratitis, almost complete ophthalmoplegia, and decreasing visual acuity requiring surgical decompression. Postdecompression, inflammatory signs and vision improved but there was complete ophthalmoplegia. The eye signs remained unchanged for the next 4 months but there was exacerbation of the disease within a week of receiving radioiodine despite concomitant steroid administration. Orbital irradiation was finally administered with rapid improvement in extraocular eye muscle function. We hypothesize that local inflammatory and immune responses stimulated by trauma and/or pressure in the retrobulbar compartment, triggered the development of severe ophthalmopathy in this patient. Thyroid-stimulating immunoglobulin (TSI) levels remained markedly elevated despite the clinical improvement suggesting that the beneficial effects of radiotherapy in this case were not mediated by suppressing TSI production.