RESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) is a prevalent condition with an unclear pathogenesis. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are potential key players in GDM. PARTICIPANTS, MATERIALS, AND METHODS: In a longitudinal observational study, we monitored women from the first trimester through 24-28 weeks of gestation, focusing on the development of GDM. Serum levels of BAFF and APRIL, as well as their mRNA expression, were evaluated in both the first and third trimesters. Furthermore, we assessed cytokines, adipokines, and placental hormones in the serum. RESULTS: In the first trimester, participants who later developed GDM exhibited elevated serum BAFF and reduced serum APRIL levels, although the mRNA expression of these molecules was similar to controls. Serum BAFF exhibited significant positive correlations with metabolic markers and placental hormones. Conversely, serum APRIL was negatively correlated with insulin resistance and inflammatory markers but positively correlated with adiponectin. In the early third trimester, GDM participants continued to display higher serum BAFF levels and lower serum APRIL levels than controls. There was no significant difference in mRNA expression of BAFF between GDM and control groups. Conversely, APRIL mRNA expression was significantly lower in the GDM group. The predictive potential of first-trimester BAFF and APRIL levels for future GDM development was explored, with both molecules demonstrating strong predictive capability. DISCUSSION AND CONCLUSION: This study suggests that elevated serum BAFF and reduced serum APRIL levels during pregnancy may be associated with the development of GDM. These biomarkers can serve as potential early predictors for GDM.
Assuntos
Fator Ativador de Células B , Biomarcadores , Diabetes Gestacional , Primeiro Trimestre da Gravidez , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Humanos , Fator Ativador de Células B/sangue , Feminino , Gravidez , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adulto , Primeiro Trimestre da Gravidez/sangue , Biomarcadores/sangue , Estudos Longitudinais , Prognóstico , Seguimentos , Estudos de Casos e ControlesRESUMO
OBJECTIVE: Non-obese type 2 diabetes seems to be common in India; hence the current study tried to understand the pathogenesis of diabetes in this group focusing on the role of adipocytes especially abdominal fat compartment. Comparison was made between non-obese subjects with newly detected diabetes and those without diabetes, in relation to levels of adipogenic factor and adipokines in pre-adipocytes and mature adipocytes respectively. RESEARCH DESIGN METHODS: Non-obese subjects (BMI-18-25 Kg/m2) were consecutively selected of whom 15 had newly-detected, treatment naïve type 2 diabetes (HbA1% ≥6.5) while 25 were control (HbA1c% ≤5.6). We examined the expression of adipocyte differentiation factor - SREBP-1c from preadipocytes and adipocyte specific adipokines- HMW isoform and total adiponectin, leptin, FABP-4, TNF-α and IL-6 from adipocytesisolated from abdominal visceral and subcutaneous adipose tissues (VAT and SCAT) by RT-PCR and as well as from serum by ELISA. Size of cultured adipocytes was measured in a fully automated imaging system microscope. RESULT: Both in SCAT and VAT, SREBP-1c and adiponectin had significantly lower expression along with increased mRNA level of inflammatory adipokinesdiabetes.Average adipocyte size and frequency of large(hypertrophied) adipocytes were comparatively higher in T2DM subjects and had significant negative correlation with SREBP-1c. HMW adiponectin level significantly reduced in the secretion from VAT and SCAT of T2DM subjects compared to control. CONCLUSION: Reduced expression of SREBP-1c in preadipocytes may lead to increased number of hypertrophied adipocytes in T2DM. Therefore, these dysfunctional hypertrophied adipocytes could cause imbalanced expression of insulin resistant and insulin sensitive adipokines.
Assuntos
Adiponectina , Diabetes Mellitus Tipo 2 , Humanos , Adipócitos/metabolismo , Adipocinas , Tecido Adiposo/metabolismo , Hipertrofia/metabolismo , Insulina/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Gordura SubcutâneaRESUMO
The pathogenesis of gestational diabetes mellitus (GDM) is multifactorial and it shares many features with type 2 diabetes mellitus. Growth differentiation factor 15 (GDF-15), a member of transforming growth factor-ß superfamily, is expressed in a high amount in the placenta in addition to other organs. This cross-sectional study was performed to assess the difference of GDF-15 and pro-inflammatory cytokines between pregnant women with or without GDM, and to explore the possible association of GDF-15 with the parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60 min, and 120 min post-75 gm oral glucose plasma glucose levels) and inflammation (IL-6 and TNF-α) in women with GDM at 24-28 weeks of gestation. Thirty-five women with GDM and 30 age-matched non-diabetic pregnant control (NDPC) subjects were recruited for the study. Mean serum GDF-15, IL-6, and TNF-α levels were significantly higher in GDM in comparison to the NDPC population. These differences persisted even after adjusting for the possible confounders like maternal age and BMI. GDF-15 level showed a positive correlation with parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60 min, and 120 min post-75 gm oral glucose plasma glucose levels) but a variable correlation with the markers of inflammation. In conclusion, our study provides evidence that, in Indian women, serum GDF-15 level is higher in GDM in comparison to age-matched pregnant subjects without GDM in the early third trimester pregnancy. Moreover, in third trimester, GDF-15 level increases with increase in plasma glucose and insulin resistance.