HLA-DR, HLA-DQB1 and PTPN22 gene polymorphism: association with age at onset for autoimmune diabetes.

INTRODUCTION: Autoimmune diabetes has different clinical manifestations related to the age at onset. It is divided into several subtypes, including "classical" type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). The LADA is considered a slowly progressing subtype of autoimmune diabetes, although the clinical picture is more similar to type 2 diabetes. MATERIAL AND METHODS: The aim of this study is to investigate whether genetic predisposition influences age at onset in autoimmune diabetes. We studied rs2476601 PTPN22 gene polymorphism and HLA DR, HLA-DQB1 in 175 patients with classical type 1 diabetes, 80 LADA, and 151 control subjects from north-east Poland. RESULTS: The frequencies of the PTPN22 TT genotype were higher in the group of patients with classical type 1 diabetes (6.3%) and LADA (11.3%) than in control subjects (0.7%) (p = 0.02 and p = 0007, respectively). In patients with classical type 1 diabetes we observed an increasing trend in frequencies of genotype TT dependent on age at onset (3.9% (0-5 year olds), 6.0% (6-15 year-olds), 8.2% (16-25 year olds), p = 0.048). The incidence of predisposing human leukocyte antigen (HLA) genotypes HLA DR3/DQB1*02 and DR4/DQB1*0302 was found to decrease in the group with type 1 diabetes in relation to age at onset and LADA (HLA DR3/DQB1*02 - 69.2% (0-5 year olds), 57.0% (6-15 year olds), 51.0% (16-25 year olds), 46.3% (LADA), p = 0.032; HLA DR4/DQB1*0302 - 80.8% (0-5 year olds), 63.0% (6-15 year olds), 51.0% (16-25 year olds), 43.8% (LADA), p = 0.0003), and to increase for the protective allele DQB1*0602 (0.0% (0-5 year olds), 1.0% (6-15 year olds), 2.0% (16-25 year olds), 6.3% (LADA), p = 0.029). CONCLUSIONS: Thus, age at onset for autoimmune diabetes appears to be related to a combination of predisposing and protective HLA alleles. Against a background of HLA genetic predisposition, other non-HLA loci may influence age at onset for late autoimmune diabetes.

[Scleral necrosis after scleral buckling surgery of the patient with pyoderma gangrenosum]. / Martwica twardówki po operacji wglabiajacej u chorej z pyoderma gangrenosum.

Pyoderma gangrenosum (PG) is a rare skin disease caused by immune dysfunction. The systemic diseases are often associated. The aim of the study was to report necrotic scleritis which developed after scleral buckling procedure in the case of the 64 years old patient suffered from primary retinal detachment and idiopathic PG. The retinal reattachment was achieved. The conjunctival wound dehiscence, necrotising scleritis and marginal keratitis as a manifestation of the patergic reaction were diagnosed. The treatment with corticosteroids locally (Dexamethason) and systematically (Prednison and Sulfasalazine), was administrated. The improvement and stabilisation of the local condition of ocular surface were observed. After reduction of systemic drugs, the exacerbation of local inflammation and vitritis was observed. The prolonged therapy was necessary. The risk of wound healing disturbances of an ocular surface with aggravated necrotic reaction must be expected after ocular surgery of the patient with PG. The adequate immunosupressive prolonged treatment with proper collaboration with the dermatologist is necessary.

[Glucokinase gene mutations in gestational diabetes in Polish population. Prediction of diabetes mellitus development after delivery]. / Mutacje genu glukokinazy w cukrzycy ciezarnych w populacji polskiej. Prognozowanie ryzyka rozwoju cukrzycy po ciazy.

Gestational Diabetes Mellitus (GDM) comprises different forms of glucose metabolism disturbances with first recognition during pregnancy. There are a number of publications that have suggested that diabetes with onset during pregnancy is not a monogeneous disease and apart from "classical" form of GDM, which precedes type 2 diabetes development, MODY 2 diabetes, caused by monogenic defect of glucokinase gene, is relatively frequent "subtype" of gestational diabetes. The aim of our study was to estimate the risk of diabetes mellitus development, including MODY 2 diabetes, between 6 months - 10 years after delivery in 225 women with gestational diabetes. Gucokinase gene mutations and polymorphisms were performed by direct sequencing of DNA. In the present study it was shown that the frequency of glucokinase gene mutation is 6.7% in the Polish population of gestational diabetic women and 17.8% of new onset or persistant diabetes recognised during 5 years after pregnancy could be a result of this mutation. We have also observed that risk of type 2 diabetes development is about 50% in the next 5 years after delivery in women with gestational diabetes and is associated with higher levels of BMI during or after delivery and with clinical and biochemical features of insulin resistance (high values of WHR abd HOMA-R). Moreover, our study suggests that c.1253+8 C-->T polymorphism in intron 9 of glucokinase gene could have a role in predisposition to type 2 diabetes in women with gestational diabetes. In summary, our results suggest that, because of high costs and time-consuming methods of genetic studies, the investigations of glucokinase gene mutations should be concentrated in women with gestational diabetes without clinical and biochemical features of insulin resistance, but with family history of diabetes in two generations.

[The results of wet AMD treatment by intravitreal injections--preliminary report]. / Wyniki leczenia wysiekowej postaci zwyrodnienia plamki zwiazanego z wiekiem iniekcjami doszklistkowymi ranibizumabu--doniesienie wstepne.

Age-related macular degeneration (AMD) is the leading cause of irreversible, severe loss of vision in the developed countries. One of the modern methods of treatment in neovascular form of AMD are repeated intravitreal injections of ranibizumab (Lucentis). Ranibizumab is a recombinant, humanized, monoclonal antibody that neutralizes all biologically active forms of vascular endothelial growth factor A (VEGF-A). The aim of the study was to analyze the results of intravitreal ranibizumab injections in wet AMD patients. There were 57 patients enrolled in the study. 87% of them avoided any loss of visual acuity and 47.3% gained at least one line at visual acuity chart. Authors conclude that treatment with repeated intravitreal injections of ranibizumab is effective in neovascular form of AMD.

[Evaluation of adiponectin and TNFalpha genes expression in women with gestational diabetes. Preliminary results]. / Ocena ekspresji genów adiponektyny i TNFalpha w tkance tluszczowej i lozysku kobiet z cukrzyca ciazowa, badania wstepne.

OBJECTIVES: Recent studies suggest the essential role of different cytokines realised from adipose tissue in pathogenesis of gestational diabetes. The aim of the study was evaluation of adiponectin (diabetes development protective factor) and TNFalpha (one of the most important insulin resistance mediator) genes expression in maternal visceral and subcutaneous adipose tissue as well as placental tissue. MATERIAL AND METHODS: The study group consists of patients with gestational diabetes, healthy pregnant glucose tolerant women represented the control group. Tissue samples--placental tissue, visceral and subcutaneous adipose tissue--were obtained from patients who were undergoing ceasarean section. RT-PCR technique was performed for evaluation of adoponectin and TNF alpha genes expression. RESULTS: Our study showed decreased adiponectin gene expression and increased TNFalpha gene expression in visceral adipose tissue in pregnant women with gestational diabetes. An expression of adiponectin gene in diabetic placental tissue was not observed. We also noticed slight increase of TNF alpha gene expressionin placenta of diabetic cases. CONCLUSIONS: Decreased adiponectin and increased TNFalpha genes expression in adipose tissue of pregnant women with gestational diabetes seems to play a significant role in insulin resistance appearance and can lead to development of diabetes in pregnancy.