High density lipoprotein modulates osteocalcin expression in circulating monocytes: a potential protective mechanism for cardiovascular disease in type 1 diabetes

Abstract

BackgroundCardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes (T1D). A pro-calcific drift of circulating monocytes has been linked to vascular calcification and is marked by the surface expression of osteocalcin (OCN). We studied OCN+ monocytes in a unique population with ≥50 years of T1D, the 50-Year Joslin Medalists (J50M).MethodsCD45 bright/CD14+/OCN+ cells in the circulating mononuclear blood cell fraction were quantified by flow cytometry and reported as percentage of CD45 bright cells. Mechanisms were studied by inducing OCN expression in human monocytes in vitro.ResultsSubjects without history of CVD (n = 16) showed lower levels of OCN+ monocytes than subjects with CVD (n = 14) (13.1 ± 8.4% vs 19.9 ± 6.4%, p = 0.02). OCN+ monocytes level was inversely related to total high density lipoprotein (HDL) cholesterol levels (r = −0.424, p = 0.02), large (r = −0.413, p = 0.02) and intermediate (r = −0.445, p = 0.01) HDL sub-fractions, but not to small HDL. In vitro, incubation with OxLDL significantly increased the number of OCN+ monocytes (p < 0.01). This action of OxLDL was significantly reduced by the addition of HDL in a concentration dependent manner (p < 0.001). Inhibition of the scavenger receptor B1 reduced the effects of both OxLDL and HDL (p < 0.05).ConclusionsLow OCN+ monocytes levels are associated with lack of CVD in people with long duration T1D. A possible mechanism for the increased OCN+ monocytes could be the elevated levels of oxidized lipids due to diabetes which may be inhibited by HDL. These findings suggest that circulating OCN+ monocytes could be a marker for vascular disease in diabetic patients and possibly modified by HDL elevation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0599-2) contains supplementary material, which is available to authorized users.

Risk of cardiac autonomic neuropathy in latent autoimmune diabetes in adults is similar to type 1 diabetes and lower compared to type 2 diabetes: A cross‐sectional study

“…34 On the contrary, high levels of HDL cholesterol may prevent nerve damage in diabetes thanks to the well-known anti-inflammatory and anti-oxidative properties of HDL. 19,35 Our data further stress the importance of a multifactorial treatment in people affected by diabetes, 36 which may also result in a decreased risk of cardiac autonomic neuropathy as suggested by clinical trials 37 We did not find differences between participants with and without cardiac autonomic neuropathy in other well-recognized risk factors for diabetes autonomic neuropathy such as glycaemic control, disease duration and eGFR. 9 This finding may be however explained by the overall good glycaemic control, the relatively short mean disease duration and the preserved kidney function of our population.…”

“…In this regard, dyslipidaemia has been hypothesized contributing to diabetic neuropathy pathogenesis through several pathways, including increased formation of reactive oxygen species and of oxysterols, activation of the toll‐like receptor and of the advanced glycation end product receptor, all of which mediate local inflammation, causing progressive nerve injury 34 . On the contrary, high levels of HDL cholesterol may prevent nerve damage in diabetes thanks to the well‐known anti‐inflammatory and anti‐oxidative properties of HDL 19,35 . Our data further stress the importance of a multifactorial treatment in people affected by diabetes, 36 which may also result in a decreased risk of cardiac autonomic neuropathy as suggested by clinical trials 37 …”

Correlations between serum concentration of three bone-derived factors and obesity and visceral fat accumulation in a cohort of middle aged men and women

“…The roles of serum OCN and FGF23 levels in regulating energy metabolism have led to new insights into the physiological functions of bone [ 8 , 19 , 20 ]. Maddaloni et al suggested that circulating OCN + monocytes could be a marker for vascular disease in diabetic patients [ 21 ]. Our previous studies found that a decreasing trend in serum OCN levels accompanied an increase in VFA, and VFA was inversely correlated with serum OCN levels [ 11 , 12 ].…”

Bone markers and cardiovascular risk in type 2 diabetes patients

“…Those studies reporting an association between osteocalcin and CVD risk, only detected an association in elderly (> 70 year); however, these associations were in opposite directions [ 9 , 11 ]. Additionally, one previous study indicated that osteocalcin may be a marker of vascular disease in patients with type 1 diabetes [ 30 ]. Osteonectin was detected in atherosclerotic plaques, but cohort studies focusing on osteonectin and incident CVD risk are lacking, although one study suggested that osteonectin may predict CVD events [ 14 ].…”