Circulating progranulin levels in women with gestational diabetes mellitus and healthy controls during and after pregnancy

Abstract

Objective: Progranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the role of PGRN in gestational diabetes mellitus (GDM), which is regarded as a model for early type 2 diabetes. Methods: PGRN serum levels were measured in 90 pregnant women (45 GDM and 45 normal glucose tolerance (NGT)). In addition, PGRN was measured during a 2-h, 75 g oral glucose tolerance test in 20 pregnant women (ten GDM and ten NGT) and in 16 of them post partum (ten GDM and six NGT). Results: PGRN concentrations were significantly higher in pregnant women compared with post partum levels (536.79G31.81 vs 241.53G8.86, P!0.001). Multivariate regression analyses showed a strong positive correlation of PGRN with estrogen and progesterone. The insulinogenic index, a marker of early insulin secretion, displayed a positive correlation with PGRN, both during and after pregnancy (RZ0.47, PZ0.034; RZ0.63, PZ0.012). HbA1c and the oral glucose insulin sensitivity index showed significant post partum associations with PGRN (RZ0.43, PZ0.049; RZK0.65, PZ0.009). Conclusions: PGRN concentrations are markedly lower after pregnancy regardless of the gestational glucose tolerance state. PGRN levels per se do not discriminate between mild GDM and NGT in pregnant women. Therefore, the development of GDM appears to be due to impaired b-cell function that is not related to PGRN effect.

Progranulin protein levels are differently regulated in plasma and CSF

“…Given that some patients had converted to MCI or DAT at the time of sample collection, we studied whether diagnosis, PiB uptake scores, or APOE genotypes were associated with PGRN levels. For example, it is known that PGRN levels are elevated due to inflammation or other clinical conditions such as pregnancy or cancer 21,22 ; however, whether these conditions similarly affect plasma and CSF PGRN levels is unknown. Determining PGRN levels in patients with DAT was not the primary objective of this study and the number of affected subjects that we analyzed was low; however, these findings are consistent with previous studies reporting no significant difference in plasma PGRN levels in patients with Alzheimer disease (AD) as compared with controls.…”

Progranulin: at the interface of neurodegenerative and metabolic diseases

“…Circulating progranulin levels are higher in insulin-resistant, compared with insulin-sensitive, obese individuals [58] , and, most recently, increased plasma progranulin levels were reported in individuals with T2D, as well as in obese individuals [2] . Other recent studies reported that circulating progranulin levels are independent of BMI and/or insulin, but these studies included subjects with complicating conditions, such as gestational diabetes [59] , renal failure [60] , or post-nutritional weight loss [61] . Thus, in the absence of specific comorbid conditions, circulating progranulin levels appear to be a useful biomarker for inflammation and T2D related to obesity.…”

Potential Roles of Microglial Cell Progranulin in HIV-Associated CNS Pathologies and Neurocognitive Impairment

“…Elevated serum PGRN levels have also been reported in autoimmune disorders such as systemic lupus erythematosus and certain infectious conditions (Tanaka et al, 2012). Serum PGRN levels are also markedly elevated in mothers during gestation and show strong positive correlation with estrogen and progesterone (Todoric et al, 2012). …”