Stem cell transplantation for type 1 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>The use of stem cells to treat type 1 diabetes mellitus has been proposed for many years, both to downregulate the immune system and to provide β cell regeneration.</p> <p>Conclusion</p> <p>High dose immunosuppression followed by autologous hematopoietic stem cell transplantation is able to induce complete remission (insulin independence) in most patients with early onset type 1 diabetes mellitus.</p

Association of the CpG Methylation Pattern of the Proximal Insulin Gene Promoter with Type 1 Diabetes

The insulin (INS) region is the second most important locus associated with Type 1 Diabetes (T1D). The study of the DNA methylation pattern of the 7 CpGs proximal to the TSS in the INS gene promoter revealed that T1D patients have a lower level of methylation of CpG -19, -135 and -234 (p = 2.10−16) and a higher methylation of CpG -180 than controls, while methylation was comparable for CpG -69, -102, -206. The magnitude of the hypomethylation relative to a control population was 8–15% of the corresponding levels in controls and was correlated in CpGs -19 and -135 (r = 0.77) and CpG -135 and -234 (r = 0.65). 70/485 (14%) of T1D patients had a simultaneous decrease in methylation of CpG -19, -135, -234 versus none in 317 controls. CpG methylation did not correlate with glycated hemoglobin or with T1D duration. The methylation of CpG -69, -102, -180, -206, but not CpG -19, -135, -234 was strongly influenced by the cis-genotype at rs689, a SNP known to show a strong association with T1D. We hypothesize that part of this genetic association could in fact be mediated at the statistical and functional level by the underlying changes in neighboring CpG methylation. Our observation of a CpG-specific, locus-specific methylation pattern, although it can provide an epigenetic biomarker of a multifactorial disease, does not indicate whether the reported epigenetic pattern preexists or follows the establishment of T1D. To explore the effect of chronic hyperglycemia on CpG methylation, we studied non obese patients with type 2 diabetes (T2D) who were found to have decreased CpG-19 methylation versus age-matched controls, similar to T1D (p = 2.10−6) but increased CpG-234 methylation (p = 5.10−8), the opposite of T1D. The causality and natural history of the different epigenetic changes associated with T1D or T2D remain to be determined

[Localization of B-cell Adenoma By Transhepatic Portal Catheterization]

Background. The procedures used to locate pancreatic endocrine tumors have only limited success in infants and children in whom the nodules may be small. Portal catheterization may therefore be useful. Cass report. A child aged 6 yrs 4 months was admitted because of several recent episodes of pallor and sweating associated with hypoglycemia. Further investigation showed moderate hyperinsulinemia and low blood levels of ketone bodies and branched amino-acids after a 15 hr fast. Celiac angiography was normal. The hypoglycemic episodes recurred despite treatment with diazoxide for 6 months. A transparietal portal catheterization was therefore performed. Selective pancreatic venous sampling showed high concentrations of insulin in two small veins draining one part of the head of the pancreas (117 and 89 mu U/ml). The head of pancreas was removed 16 months later. Extemporaneous examination revealed an adenoma 0.8 cm in diameter. This patient has completely recovered, 8 months after surgery. Conclusion. Transparietal portal catheterization can detect pancreatic areas with high insulin secretion. It may also help the interpretation of celiac angiographs in children, as diagnosis may be obscured by the normal rich vascularity of the pancreas in these patients

Localisation d'un adénome langerhansien par cathétérisme portal transhépatique.

BACKGROUND. The procedures used to locate pancreatic endocrine tumors have only limited success in infants and children in whom the nodules may be small. Portal catheterization may therefore be useful. CASE REPORT. A child aged 6 yrs 4 months was admitted because of several recent episodes of pallor and sweating associated with hypoglycemia. Further investigation showed moderate hyperinsulinemia and low blood levels of ketone bodies and branched amino-acids after a 15 hr fast. Celiac angiography was normal. The hypoglycemic episodes recurred despite treatment with diazoxide for 6 months. A transparietal portal catheterization was therefore performed. Selective pancreatic venous sampling showed high concentrations of insulin in two small veins draining one part of the head of the pancreas (117 and 89 microU/ml). The head of pancreas was removed 16 months later. Extemporaneous examination revealed an adenoma 0.8 cm in diameter. This patient has completely recovered, 8 months after surgery. CONCLUSION. Transparietal portal catheterization can detect pancreatic areas with high insulin secretion. It may also help the interpretation of celiac angiographs in children, as diagnosis may be obscured by the normal rich vascularity of the pancreas in these patients