Immunoablation and autologous hematopoietic stem cell transplantation in the treatment of new-onset type 1 diabetes mellitus: long-term observations.

The activity of the autoimmune mechanism underlying type 1 diabetes mellitus (T1DM) can be suppressed when immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) are applied early in the course of the disease. We report here a single centre experience with this treatment modality. Twenty-four patients underwent a AHSCT preceded by immunoablative conditioning with high-dose cyclophosphamide and anti-thymocyte globulin. During the 52-month median time of follow-up 20 out of 23 patients (87%) remained for at least 9.5 months without the use of exogenous insulin. The median time of T1DM remission for these patients was 31 months (range of 9.5-80 months). Among the patients available for follow-up (n=20), four remain insulin free (for 80, 61, 42 and 34 months). The average glycated hemoglobin (HbA1c) concentrations were 10.9% at diagnosis, 5.9% at 1 year, 6.4% at 2 years, 6.8% at 3 years and 7.1% at 4 years after AHSCT. No severe complications of diabetes were seen, however one of the patients died of pseudomonas sepsis in the course of neutropenia after AHSCT. AHSCT leads to a remission of T1DM with good glycemic control in the vast majority of patients, with the period of remission lasting over 5 years in some patients.

Independence of exogenous insulin following immunoablation and stem cell reconstitution in newly diagnosed diabetes type I.

Type I diabetes mellitus is a metabolic disease caused by chronic immune attack against the insulin-producing cells of the pancreas. It has recently been shown that the clinical course of this disease can be interrupted by immune ablation and PBSCT. In this report, we describe our experience with this treatment modality in a series of eight cases. Patients with newly diagnosed type I diabetes were received treatment consisting of two to three plasmaphereses, hematopoietic stem cell mobilization with CY and G-CSF, collection of at least 3 × 10(6) per kg of CD34+ cells, and conditioning with CY and anti-thymocyte globulin followed by stem cell infusion. All patients became independent of exogenous insulin after the transplantation. One patient resumed low-dose insulin 7 months after transplantation. Six out of eight patients were given acarbose for better glycemic control after transplantation. All patients exhibited good glycemic control: the average HbA1c concentrations were 12.3% at diagnosis, and 5.6 and 6.2% at 3 and 6 months after transplantation, respectively. We conclude that at least temporary independence of exogenous insulin can be achieved in type I diabetes patients following immunoablation and reconstitution of the immune system with autologous PBSCs.

[Strategies for early detection of the risk of type II (non-insulin-dependent) diabetes in 1st degree relatives of patients with this disease]. / Model postepowania umozliwiajacego wczesne wykrywanie zagrozenia cukrzyca typu 2 (insulinoniezalezna) u krewnych I stopnia osób ze znana postacia tej choroby.

UNLABELLED: The present study included two groups of subjects: I. the adult offspring of parents with conjugal type 2 diabetes (n = 77; age range 18-59 yrs and mean age 38 +/- 0.8 yrs; BMI range 18.9-40.3 kg/m2 and mean value 26.6 +/- 0.6 kg/m2); and II. the adult offspring having one parent with type 2 diabetes: either father (n = 83-53%) or mother (n = 74-47%). The age range of the latter group was 21-64 yrs, mean age 41 +/- 0.8 yrs; BMI range was 17.6-46.4 kg/m2, and mean value 26.8 +/- 0.4 kg/m2. The normal glucose tolerance of the "healthy" parent was verified with the OGGT evaluated by the WHO and ADA criteria. In all offspring the same test (75 g) was performed, and glucose in venous blood and insulin (IRI) in serum were determined on fasting and at 30, 60 and 120 min of the test. In fasting state the levels of serum lipids (triglycerides, total and LDL and HDL cholesterol and apolipoprotein AI and B) were also measured. In the group I unknown diabetes mellitus was discovered in 4 cases (4%): in 3 according to the WHO/ADA criteria and in one case evaluated by the ADA criteria), in 19 subjects (25%) IGT was found in 16 isolated and in 3 associated with isolated fasting glycaemia (IFG), and only in one case (1%) the isolated IFG was ascertained. In the group II diabetes was discovered according to the ADA criteria in 4 persons (2.5%), IGT in 29 subjects (18.5%), of whom 8 had also IFG. In this subgroup 16 subjects had diabetic father and 13 diabetic mother. The isolated IFG had 7 offspring (4.4%), of whom 2 had diabetic father and 5 diabetic mother. Apart from glycaemia, other parameters didn't disclose difference between the offspring of diabetic father and diabetic mother. However, considering these parameters together for the whole group II, it was found that the offspring with IGT, isolated and associated with IFG, differed from the remaining ones with significantly higher BMI, higher systolic blood pressure, higher 2-h serum IRI, and higher levels of serum triglycerides, total cholesterol and ApoB. CONCLUSION: Measurement of isolated fasting glycaemia and its interpretation by the ADA criteria is inadequate in studies aiming at early detection of glucose intolerance in subjects with familial increased risk of type 2 diabetes and should include also the determination of the 2-h glycemia of the OGTT evaluated according to the WHO criteria. On the other hand, the determination of fasting glycaemia and its evaluation by the ADA criteria is a valuable in diabetes screening, as its elevated level may identify other metabolic disorders associated with diabetes, and unfavorable risk of cardiovascular complications of this disease.