[Stem-cell therapy, ß-cell- and islet cell-neogenesis: possible treatments of type 1 diabetes in the future?]. / Ossejtterápia, ß-sejt- és Langerhans-sziget-neogenezis: a jövo lehetséges terápiái 1-es típusú diabetesben?

In type 1 diabetic patients perfect normoglycaemia can only be achieved by successful transplantation of the pancreas or Langerhans' islets. Surgical transplantation of the whole pancreas is an invasive operation exerting great burden on the patients. Transplantation of the islets of Langerhans does not burden the patients but the survival of the islet grafts is limited. Both interventions are hampered by the lack of donor organs. However, much of these difficulties could be overcome by the use of "artificial ß-cells" which ought to have an ultrastructure identical with that of natural ß-cells and produce and secrete insulin in a glucose dependent manner. At present three such methods are at our disposal: transformation of the ductal cells of the exocrine pancreas into ß-cells, development of ß-cells from stem-cells, and neogenesis of Langerhans' islets induced by viral delivery of transcription factors. The author summarises the experience and experimental results obtained with the use of the three methods.

Diabetes-related dysfunction of the small intestine and the colon: focus on motility.

In contrast to gastric dysfunction, diabetes-related functional impairments of the small and large intestine have been studied less intensively. The gastrointestinal tract accomplishes several functions, such as mixing and propulsion of luminal content, absorption and secretion of ions, water, and nutrients, defense against pathogens, and elimination of waste products. Diverse functions of the gut are regulated by complex interactions among its functional elements, including gut microbiota. The network-forming tissues, the enteric nervous system) and the interstitial cells of Cajal, are definitely impaired in diabetic patients, and their loss of function is closely related to the symptoms in diabetes, but changes of other elements could also play a role in the development of diabetes mellitus-related motility disorders. The development of our understanding over the recent years of the diabetes-induced dysfunctions in the small and large intestine are reviewed in this article.

[Factors limiting glycaemic control in insulin-treated type 2 diabetes]. / A normoglykaemia elérésének korlátai inzulinkezelt 2-es típusú cukorbetegekben.

Insulin therapy is the most effective treatment of diabetes. It is proven to prevent microvascular disease and likely to decrease the risk of cardiovascular complications. However, these benefits are associated with a 2-3 times increased risk of hypoglycaemia and a faster weight gain compared to other antidiabetic medications. In addition, one study found elevated all-cause mortality among patients on intensive therapy (requiring more frequent insulinisation). Insulin has growth factor properties that may translate to increased mitogenicity. These factors could prevent the medical team or the patient from initiation or intensification of insulin therapy. The authors describe evidence on long-term remission related to transient intensified insulin therapy at diabetes diagnosis. The currently recommended method of insulin initiation is once daily basal insulin treatment that offers different schedules for intensification. The authors review the pharmacokinetics of analogue insulins that translate to similar efficacy to human insulins with a 20-30% lower risk of hypoglycaemia.

[Pharmacogenetics of insulin secretagogue antidiabetics]. / Az inzulinszekretagóg antidiabetikumok farmakogenetikai vonatkozásai.

Type 2 diabetes is making up to 90% of the all diabetic cases. In addition to insulin resistance, insufficient B-cell function also plays an important role in the pathogenesis of the disease. The insufficient production and secretion of insulin can be increased by secretagogue drugs, like sulfonylureas and incretin mimetics/enhancers. In recent years growing number of genetic failures of the B-cells has been detected. These genetic variants can influence the efficacy of secretagogue drugs. Some of these gene polymorphisms were identified in the genes encoding the KATP channel (KCNJ11 and ABCC8). These mutations are able either to reduce or increase the insulin secretion and can modify the insulin response to sulfonylurea treatment. Other polymorphisms were found on genes encoding enzymes or transcription factors. In recent years, the genetic variants of TCF7L2 and its clinical importance have been intensely studied. Authors give a summary of the above gene polymorphisms and their role in insulin secretion.

[Type 1 diabetes mellitus: pathogenesis, symptoms and therapy]. / Az 1-es típusú diabetes mellitus kialakulásának patomechanizmusa, tünettana és kezelési lehetoségei.

Type 1 diabetes is responsible for approximately 10% of the whole diabetic morbidity. The cause of the disease is an autoimmune process directed against the B-cells leading to progressive and irreversible destruction of these cells, and, consequently, the complete and definitive cessation of endogenous insulin production. Accordingly, these patients should be treated with insulin since the beginning of the disease. The author describes the pathogenesis, epidemiology and symptoms of type 1 diabetes and summarizes the possible ways of therapy and care of type 1 diabetic patients.

[Improvement in glycemic control, cardiovascular risk factors and anthropometric data in type 2 diabetic patients after the switch from biphasic human insulin to biphasic premix analog insulin aspart]. / 2-es típusú cukorbetegek szénhidrát-anyagcseréjének, cardiovascularis és alkati paramétereinek változása bifázisos humán inzulinról analóg premix inzulinra történt terápiaváltás után.

Long-term studies involving large number of type 2 diabetic patients supplied evidence that constant adequate metabolic control may prevent the late (micro- and macrovascular) diabetic complications. In the present non-interventional, retrospective study, authors performed an analysis of type 2 diabetic patients who had been previously treated with biphasic human insulin (BHI) and their therapy was changed to biphasic analog insulin aspart 30/70 (BIAsp = NovoMix 30). The switch of the insulin therapy was carried out in years 2007 and 2008 with the cooperation of 50 accredited diabetes centers. Data were obtained at the time of therapeutical change and six months later. The number of suitable patients was 2898 with an age of 66.20 +/- 10.10 year, and the duration of diabetes was >10 years in 43% of the patients. After the six-month therapy with NovoMix 30, the mean HbA 1c level decreased statistically significantly from the initial value of 9.10 +/- 1.44% to 7.62 +/- 1.00% ( p < 0.001). The lipid profile also improved although target values were not always attained. A reduction was also observed in both systolic and diastolic blood pressure. Mean body weight decreased from 84.2 +/- 14.9 kg to 82.6 +/- 13.9 kg ( p < 0.01). All these changes occurred in spite of a significantly reduced daily insulin dose (48.4 +/- 17.6 IU) as compared with the initial value (49.0 +/- 17.4 IU, p < 0.001). A marked decrement was also observed in the frequency of hypoglycemic reactions. These results confirm that treatment with NovoMix 30 insulin leads to a significant amelioration of glycemic control as reflected by the decreased level of HbA 1c and the higher proportion of patients attaining the target value, as well as the lower frequency of hypoglycemic episodes. The significant improvements in cardiovascular risk factors are also important, but the explanation is still missing and would require the accomplishment of prospective, controlled studies.

Large increase in the prevalence of self-reported diabetes based on a nationally representative survey in Hungary.

AIMS: To estimate and compare the prevalence of self-reported diabetes based on nationally representative surveys of the Hungarian adult population in 2002 (published data - Hungarostudy) and a survey in 2012. METHODS: A cross-sectional computer-assisted telephone interview survey on a stratified representative sample of community-dwelling adults (n=1000) in 2012. To describe self-reported diabetes prevalence and its temporal changes generalized linear models were used and results were compared to figures from Hungarostudy. RESULTS: Age standardized prevalence of self-reported type 2 diabetes was 11.7% (95%CI 10.0-13.8%) without gender or rural-urban differences in 2012. People with self-reported diabetes were older than controls (mean [SE]: 63.9 [0.9] vs. 45.9 [0.3] years, p<0.0001). The prevalence of diabetes sharply increased after 40 years of age and peaked at age 70 (27.7% [2.5], page*age<0.0001). The prevalence of self-reported diabetes increased by 89% (OR 1.89, 95%CI 1.53-2.32) from 6.2 to 11.7% between the two surveys with the most pronounced increase in the age group 55-64 years (from 11.6 to 24.4%). CONCLUSIONS: We reported an alarming increase in the prevalence of self-reported type 2 diabetes in the last decade that mostly affects working age people. If this trend continues, a major public health crisis in Hungary can be envisaged.

[Treatment of nephrotic syndrome in the adult]. / A felnottkori nephrosis szindróma kezelése.

Approximately two-third of the cases of the adult nephrotic syndrome is caused by a primary glomerular disease, while the remaining one-third is caused by diabetes mellitus, autoimmune diseases, or amyloidosis. There are two different therapies to treat the syndrome: a general and a special treatment. The general treatment includes administering an appropriate diet (reduced intake of proteins and salt), use of diuretics and lipid-lowering drugs (primarily statins) and initiation of anticoagulant treatment, if required. It is generally necessary to administer angiotensin-convertase-enzyme inhibitors and angiotensin receptor blockers as well as initiate a symptomatic treatment to mitigate the loss of special binding-proteins. The special treatment involves the administration of immunosuppressive and cytostatic drugs. This therapy can be initiated only after the evaluation of renal histology and the overall risk status of the patient. Steroids are still the basic immunosuppressive drugs. Their use can be supplemented with other immunosuppressive or cytostatic treatment. In therapy resistant cases, however, new drugs like mycophenolate mofetil or rituximab can also be applied.

Similar genetic features and different islet cell autoantibody pattern of latent autoimmune diabetes in adults (LADA) compared with adult-onset type 1 diabetes with rapid progression.

OBJECTIVE: To compare the clinical parameters, C-peptide levels, pattern of islet cell-specific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression. RESEARCH DESIGN AND METHODS: We evaluated the clinical parameters, C-peptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population. RESULTS: There were no differences in the clinical parameters between LADA and adult-onset type 1 diabetes. Patients with LADA had lower BMI (P < 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P = 0.001), and triglycerides (P = 0.001); higher HDL cholesterol levels (P < 0.0001); and lower prevalence of hypertension (P = 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P = 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P = 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P = 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups. CONCLUSIONS: Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.