Influence of maternal hyperglycaemia on cord blood mononuclear cells in response to diabetes-associated autoantigens.

UNLABELLED: Perfect maternal diabetes compensation is crucial for the outcome of the baby. However, little is known how hyperglycaemia influences the specific immune response. Furthermore, babies of type 1 diabetes (T1D) mothers have less risk of development T1D than babies with a T1D father. This study aimed to analyze the effect of maternal hyperglycaemia on newborns with focus on the response to diabetes-associated autoantigens. POPULATIONS: (1) Newborns of T1D mothers split into groups according to maternal diabetes compensation during the 3rd trimester: perfect (n = 15) or acceptable (n = 25) compensation. (2) newborns with T1D father (n = 12) (3) newborns with a mother treated for either gestational or type 2 diabetes (n = 10) (4) control newborns (n = 25). Spontaneous as well as diabetes-associated autoantigen-stimulated production of 23 cytokines and chemokines were tested using protein microarray. In addition, the influence of glucose on cytokine and chemokine responsiveness was analyzed in vitro. The study groups differed in their spontaneous as well as stimulated cytokine and chemokine spectra. A prominent Th1 response (high IFN-gamma) from autoantigen stimulation was observed especially in babies of T1D fathers (P = 0.001) and also in mothers with perfect diabetes compensation during the 3rd trimester (P = 0.016) in comparison with control newborns. By contrast, cord blood mononuclear cells cultivated in vitro in high glucose concentration decreased the diabetogenic stimulated Th1 cytokine response. Maternal 'sweet' as well as 'autoimmune environment' may both lead to lower occurrence of T1D within their offspring. Further studies will reveal the exact immunological mechanism of this observation.

[Costs of type II diabetes in the conditions of the Czech Republic's medical care system]. / Náklady na diabetes 2. typu v podmínkách zdravotního systému Ceské republiky.

The analysis of direct medical care costs in the conditions of the Czech Republic has demonstrated that the average annual costs per type II diabetic patient amounts to 25,858 CZK. Thanks to its high prevalence and incidence, it represents 10% of total medical care costs. The hospital treatment of diabetic complications takes up the major share in these costs, similarly as in other advanced European countries. It is therefore evident that type II diabetes has not only health but also economic and social impacts and from this point of view, preventative and therapeutical strategies need to be evaluated.

Cord blood cytokine profile detection in neonates with T1D parents -- monitoring of cellular auto-reactivity using protein microarray.

Type 1 diabetes (T1D) is a great medical challenge and its incidence rises rapidly. T lymphocytes and their cytokine production are supposed to play a major role in T1D development. So far, there is no potent tool to recognize the early signs of cellular auto-reactivity which leads to beta-cell damage. The naïve immune system of the newborn (not yet influenced by external factors) can be used as an important model for T1D pathogenesis studies. Cord blood samples of 22 healthy neonates born at term to a diabetic parent (T1DR) and 15 newborns with no family history of any autoimmune disease (controls) were collected. Determination of 23 cytokines was performed before and after the stimulation with diabetogenic autoantigens using protein microarray. We observed lower basal production of all detected cytokines in the T1DR group - granulocyte/macrophage colony-stimulating factor (GM-CSF) (P = 0.025), growth regulated protein (GRO) (P = 0.002), GRO-alpha (P = 0.027), interleukin (IL)-1-alpha (P = 0.051), IL-3 (P = 0.008), IL-7 (P = 0.027), IL-8 (P = 0.042), monocyte chemoattractant proteins (MCP)-3 (P = 0.022), monokine-induced by IFN-gamma (MIG) (P = 0.034) and regulated upon activation normal T-cell express sequence (RANTES) (P = 0.004). Exclusively lower post-stimulative levels of G-CSF (P = 0.030) and GRO-alpha (P = 0.04) were observed in controls in comparison with the basal levels. A significant post-stimulative decrease in G-CSF (P = 0.030) and MCP-2 (P = 0.009) levels was observed in controls in comparison with T1DR neonates. We also observed the interesting impact of the risky genotype on the protein microarray results. Protein microarray seems to be a useful tool to characterize a risk pattern of the immune response for T1D also in newborns.

Pregnancy in a woman suffering from type 1 diabetes associated with Addison's disease and Hashimoto's thyroiditis (fully developed Autoimmune Polyglandular Syndrome Type 2).

In this article the pregnancy of a woman suffering from the complete triad typical of Autoimmune Polyglandular Syndrome Type 2 (Addison's disease + type 1 diabetes + Hashimoto's thyroiditis) is reported. By using insulin pump therapy with insulin lispro, it was possible to balance diabetes control with changes of steroid replacement therapy. Pregnancy was uneventful until week 27, when signs of preeclampsia occurred. The boy was born without difficulty at gestational age 37 weeks by planned cesarean section but signs of diabetic fetopathy (macrosomia, hypoglycaemia and hypocalcaemia) were expressed. He required a short course of hydrocortisone therapy. He made a good and rapid recovery. The mother made a good post-operative recovery too, but 4 months after the delivery microalbuminuria as well as mild hyperuricemia are still present. Interdisciplinary approach and very careful observation of the mother as well as of the child enabled successful outcome of this highly risky pregnancy.

[Diagnosis and therapy of gestational diabetes mellitus]. / Diagnostika a terapie gestacního diabetes mellitus.

In 1999-2000 at the Medical Clinic Motol Faculty Hospital in collaboration with the Gynaecological Clinic of the Hospital a group of 55 pregnant women with the diagnosis of gestational diabetes (GDM) were followed up. The objective of the investigation was to find out how in the investigated area (detachment area of the Gynaecological and Obstetric Clinic Motol Faculty Hospital) GDM is diagnosed at present, how it is treated and what is the percentage of perinatal morbidity in the investigated group. The mean age of the investigated women was 32.3 +/- 4.5 years. The presence of risk factors for the development of GDM was found in 59.8% of the examined women. 65.7% women had a positive gynaecological case-history. GDM was detected most frequently during the 30th week of pregnancy, in 25% women in the 35th and later week of gestation. In 52% the diagnosis of GDM was established only on hospital admission on account of complications of pregnancy. The mean HbA1C level during detection of gestational diabetes was 6.81 +/- 0.41%. The majority of women -91.1%--were treated by diet, 8.9% women had insulin treatment. The prevalence of diabetic foctopathy was 48.3%. The mean weight of the offspring of diabetic mothers was 3350 g +/- 248 g, the mean length was 49.6 +/- 6.3 cm. No stillbirth was recorded. One infant suffered from an inborn developmental defect (morbus Down). The results provide evidence not only of late diagnosis of GDM (after the 28th week of gestation) but also of inadequate screening in the field, as GDM is frequently detected only during complications of pregnancy.

[Gestational diabetes mellitus]. / Gestacní diabetes mellitus.

Any degree of carbohydrate intolerance which develops for the first time during pregnancy is defined as gestational diabetes mellitus (GDM). GDM is often discovered late, in more than half the cases only during complications associated with pregnancy. Early diagnosis of GDM and early correct therapy of GDM leads to reduction of complications associated with pregnancy, delivery and the perinatal period of the infant. As in our country unequivocal rules for detection of gestational diabetes are still lacking. We feel that introduction of correct routine screening will contribute to the earlier diagnosis of GDM in all women and thus also to appropriate therapy of gestational diabetes.

[Serum levels of sialic acid in patients with type 1 diabetes mellitus in relation to the incidence of late complications]. / Sérové koncentrace kyseliny sialové u nemocných s diabetes mellitus 1. typu ve vztahu k prítomnosti pozdních komplikací.

BACKGROUND: Sialic acid is released from terminal oligosaccharide chain of some proteins of the acute phase (fibrinogen, orosomucoid, haptoglobin, etc.). Its serum concentrations have been commonly increased during acute inflammation. Its relation diabetes mellitus or late complications of the disease have been recently studied as well. The aim of our investigation was to determine serum concentrations of sialic acid in patients with diabetes mellitus Type 1 in relation to presence or absence of late diabetic complications. METHODS AND RESULTS: The authors examined a group of 62 patients treated for diabetes mellitus Type 1, mean age 28.7 +/- 9.8 years, having been treated for this disease for 11.8 +/- 8.7 years on the average. The mean level of glycated hemoglobin HbAlc was 9.08 +/- 1.84%. In 21 patients there were signs of diabetic nephropathy, seven of them already suffering from proteinuria. Retinopathy already developed in 12 patients. The mean concentration of sialic acid in the whole cohort was 1.916 +/- 0.292 mmol/litre. The correlation of serum sialic acid with age, duration of diabetes and glycated hemoglobin was not statistically significant. There was no significant difference between the serum concentration of sialic acid in patients without apparent nephropathy and those who were affected by nephropathy, or the subgroup with proteinuria (1.945 +/- 0.328 against 1.914 +/- 0.302 mmol/litre and 1.943 +/- 0.328 mmol/litre, respectively). Statistically significantly higher concentrations of serum sialic acid were found in the subgroup of patients with present retinopathy (2.085 +/- 0.244 mmol/litre against 1.890 +/- 0.270 mmol/litre, P < 0.018). CONCLUSIONS: Our findings are in agreement with the previously proved increased concentration of proteins of the acute phase in diabetic patients and correspond well to the previously proved finding of elevated serum concentration of sialic acid in diabetic patients of Type 2 with retinopathy against other patients. It may not be excluded that the serum sialic acid could be used as a marked of the risk of late complications of diabetes mellitus.