Changes in T-cell phenotype and cytokines profile in maternal blood, cord blood and colostrum of diabetic mothers.

OBJECTIVE: The present study evaluated the cells and cytokine of maternal blood, cord blood and colostrum of diabetic mothers. METHODS: The women evaluated were divided according to their body mass index (BMI) and glycemic status into non-diabetic (ND - N = 15), mild gestational hyperglycemic (MGH - N = 15), diabetes mellitus gestational (DMG - N = 13) and type-2 diabetes mellitus (DM2 - N = 15) groups. The subsets of cells and cytokine profile were determined by flow cytometry. RESULTS: Maternal blood from MGH group had increase percentage of CD3(+)T cells, and DM-2 group had decrease percentage of CD4(+) T cells. The cord blood from hyperglycemic groups showed lower percentage of CD3(+) T cells expressing CD45RO(+) and higher of CD4(+) T cells and CD4(+) T cells expressing CD45RA(+). In the colostrum, the CD4(+) T cells and CD4(+) T cells expressed CD45RA(+) increase in hyperglycemic groups. The DM2 group exhibited higher IL17 levels in maternal blood. IFN-γ was lower in cord blood from MGH and DMG groups with overweight/obese. Irrespective of the glycemic status, IL6 was higher in colostrum. CONCLUSION: The results obtained suggest that maternal hyperglycemia modifies the phenotypes of T cells and cytokines profile in maternal, cord blood and colostrum.

Beneficial effects of omega-3 polyunsaturated Fatty acids in gestational diabetes: consequences in macrosomia and adulthood obesity.

Omega-3 polyunsaturated fatty acids (PUFAs) are increasingly being used to prevent cardiovascular diseases, including diabetes and obesity. In this paper, we report data on the observed effects of omega-3 PUFA on major metabolic disorders and immune system disruption during gestational diabetes and their consequences on macrosomia. While controversies still exist about omega-3 PUFA effects on antioxidant status regarding the level of omega-3 PUFA in diet supplementation, their lipid-lowering effects are unanimously recognized by researchers. Animal studies have shown that omega-3 PUFA contributes to the maintenance of the immune defense system by promoting the differentiation of T helper (Th) cell to a Th2 phenotype in diabetic pregnancy and by shifting the Th1/Th2 ratio from a deleterious proinflammatory Th1 phenotype to a protective anti-inflammatory Th2 phenotype in macrosomia and in adulthood obesity that results from macrosomia at birth. Based on the available evidence, international nutritional and food agencies recommend administration of omega-3 PUFA as triglyceride-lowering agents, for the prevention of cardiovascular disease risk and during human pregnancy and lactation. Furthermore, studies targeting humans are still required to explore application of the fatty acids as supplement in the management of gestational diabetes and inflammatory and immune diseases.

Vitamin D rescues dysfunction of fetal endothelial colony forming cells from individuals with gestational diabetes.

INTRODUCTION: Gestational diabetes (GDM) is associated with long-term cardiovascular and metabolic diseases in offspring. However, the mechanisms are not well understood. We explored whether fetal exposure to a diabetic environment is associated with fetal endothelial progenitor cell dysfunction, and whether vitamin D can reverse the impairment. METHODS: Nineteen women with uncomplicated pregnancies and 18 women with GDM were recruited before delivery. Time to first appearance of endothelial colony forming cell (ECFC) colonies and number of ECFC colonies formed from culture of cord peripheral blood mononuclear cells were determined. Angiogenesis-related functions of ECFCs in vitro were tested in the presence or absence of vitamin D. RESULTS: Fetal ECFCs from GDM pregnancies formed fewer colonies in culture (P = 0.04) and displayed reduced proliferation (P = 0.02), migration (P = 0.04) and tubule formation (P = 0.03) compared to uncomplicated pregnancies. Fetal ECFCs exposed to hyperglycemia in vitro exhibited less migration (P < 0.05) and less tubule formation (P < 0.05) than normoglycemic control. Vitamin D significantly improved the dysfunction of fetal ECFCs from pregnancies complicated by GDM or after exposure of healthy ECFCs to hyperglycemia. DISCUSSION: Fetal ECFCs from GDM pregnancies or ECFCs exposed to hyperglycemia in vitro exhibit reduced quantity and impaired angiogenesis-related functions. Vitamin D significantly rescues these functions. These findings may have implications for vascular function of infants exposed to a diabetic intrauterine environment.

In vitro effects of oil's fatty acids on T cell function in gestational diabetic pregnant women and their newborns.

BACKGROUND: The aim of this investigation was to determine the in vitro effects of linseed, olive and Nigel oils on T cell proliferation and function in gestational diabetes. METHODS: Blood samples were collected from 40 control healthy and 32 gestational diabetic mothers and their newborns. Peripheral blood lymphocytes were isolated using a density gradient of Ficoll. T cell proliferation, interleukin-2 and -4 (IL-2, IL-4) secretion, fatty acid composition and intracellular oxidative status were investigated. RESULTS: Mitogen (Concanavalin A) stimulated lymphocyte proliferation, IL-2 secretion, intracellular reduced glutathione levels, superoxide dismutase (SOD) and catalase activities were lower while intracellular malondialdehyde (MDA) and carbonyl proteins were higher in diabetic mothers and in their newborns as compared to their respective controls. Linseed oil induced a reduction in T-lymphocyte proliferation and IL-2 production, and alpha linolenic acid membrane enrichment in both diabetic and control groups. In the presence of Nigel oil, T-lymphocyte proliferation and IL-2 secretion, phospholipid linoleic and oleic acids were enhanced. Olive oil had no effect on lymphocyte proliferation in all groups. Linseed, olive and Nigel oils induced an increase in T cell levels of reduced glutathione levels and in activities of catalase and SOD with a concomitant decrease in MDA and carbonyl protein contents. CONCLUSION: Linseed, olive and Nigel oils had beneficial effects on T cell functions in gestational diabetes.

Nicotinamide supplementation protects gestational diabetic rats by reducing oxidative stress and enhancing immune responses.

Gestational diabetes (GD) is a common complication during pregnancy. Metabolic changes in GD affect fetal development and fetal glucose homeostasis. The present study utilized a rat model of GD to evaluate the effects of nicotinamide on diabetic parameters; antioxidant gene expression viz, superoxide dismutase (SOD) and catalase (CAT); reactive oxygen species (ROS) production by neutrophils and enhancement of lymphocyte mediated immune response. Nicotinamide (50, 100 and 200 mg/kg) was orally supplemented to gestational diabetic rats from days 6 through 20 of gestation. After GD induction, the control group had elevated glucose and reduced insulin while nicotinamide (100 & 200 mg/kg) supplementation reversed these changes. The same doses of nicotinamide upregulated mRNA expressions of SOD and CAT genes in liver but reduced the oxidative burst activity of neutrophils in response to phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP) or E. coli activation. Nicotinamide (100 & 200 mg/kg) supplementation also increased expression of activated T helper (CD4+CD25+) cells and induced proliferation of splenocytes. These findings provide evidence for utilizing nicotinamide as supplement or adjunct to support existing therapeutic agents for gestational diabetes and in pregnant individuals with weakened immune systems.

Role of lipids and fatty acids in macrosomic offspring of diabetic pregnancy.

Diabetic pregnancy frequently results in macrosomia or fetal obesity. It seems that the anomalies in carbohydrate and lipid metabolism in macrosomic infants of diabetic mothers are due to maternal hyperglycemia, which leads to fetal hyperinsulinemia. We have developed a rat model of macrosomic offspring and assessed the onset of obesity in these animals. The macrosomic offspring born to diabetic mothers are prone to the development of glucose intolerance and obesity as a function of age. It seems that in utero programming during diabetic pregnancy creates a "metabolic memory" which is responsible for the development of obesity in macrosomic offspring. We have demonstrated that the metabolism of lipids, and altered anti-oxidant status and immune system are implicated in the etiopathology of obesity in these animals. We have reported beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) in obese animals, born to diabetic dams.