Elevated Plasma SPARC Levels Are Associated with Insulin Resistance, Dyslipidemia, and Inflammation in Gestational Diabetes Mellitus

Abstract

ObjectiveRecent studies suggested that secreted protein acidic and rich in cysteine (SPARC), a novel adipokine, is a key player in the pathology of obesity and type 2 diabetes. We aimed to determine whether concentrations of SPARC were altered in patients with gestational diabetes mellitus (GDM) compared to normal glucose tolerance (NGT) controls and to investigate the relationships between SPARC and metabolic parameters in pregnant women.Design/MethodsCross-sectional study of 120 pregnant women with GDM and 60 controls with NGT, in a university hospital setting. Plasma levels of SPARC, adiponectin, fibroblast growth factor 21 (FGF21), insulin and proinsulin were determined by ELISA.ResultsGDM women had higher SPARC and lower adiponectin than NGT subjects; no difference was found in FGF21. SPARC levels were the lowest in subjects in the third tertile of insulin sensitivity index (ISIOGTT) and correlated positively with pre-pregnant BMI, insulin and 3 h glucose during 100-g OGTT, HOMA-IR, fasting proinsulin, hsCRP and white blood cells count, and negatively with ISIOGTT, when adjusting for gestational age. Triglyceride (TG), Apolipoprotein A1, apolipoprotein B and lipoprotein (a) correlated with SPARC in partial Pearson correlation. Correlations between SPARC with adiponectin, systolic blood pressure and TG were marginally significant in partial Spearman correlation analysis. In multivariate regression analysis, SPARC was an independent negative indicator of ISIOGTT.ConclusionsSPARC levels are correlated significantly with inflammation and may also be correlated with dyslipidemia and represent an independent determinant of insulin resistance in late pregnancy, indicating a potential role of SPARC in the pathophysiology of GDM.

Secreted protein acidic and rich in cysteine facilitates age-related cardiac inflammation and macrophage M1 polarization

“…Sangaletti et al (47) reported distinct effects on lung inflammation dependent on the expression of SPARC by bone marrow versus stromal cells. Plasma levels of SPARC positively correlate with hypersensitive C-reactive protein and white blood cell numbers in gestational diabetes mellitus (55). These reports support the idea that SPARC may be a key factor to promote inflammation.…”

“…A recent clinical study reports the positive correlation between plasma SPARC and hypersensitive C-reactive protein and white blood cell numbers in gestational diabetes mellitus (55). Another recent report by Ng et al (39) demonstrated that SPARC-null mice showed less inflammatory symptoms in a mouse model of colitis.…”

Novel Role for Matricellular Proteins in the Regulation of Islet β Cell Survival

“…Also known as osteonectin and BM40, SPARC is expressed during tissue remodeling and repair (3) and is also thought to be involved in the development of a number of different cancers (4). There is also evidence that SPARC expression is increased in newly diagnosed type 2 diabetes patients (5) and in gestational diabetes (6). Elevated SPARC is also associated with obesity and BMI (7,8).…”

A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth

“…28). Like SPARC, FSTL-1 has been shown to regulate signalling of the TGF-β superfamily and to regulate growth factor signalling28396061104105. We therefore tested whether FSTL-1 can similarly regulate β cell growth.…”

“…In pancreatic cancer, stromal SPARC over-expression is strongly associated with poor patient prognosis3637. Insulin resistance, diabetes and obesity are also associated with elevated levels of SPARC383940. We have previously shown that SPARC is expressed by pancreatic stromal cells and is localised to the islet basement membrane.…”