Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coeliac disease and type 1 diabetes mellitus can frequently coexist, presumably due to a common genetic predisposition. The present study was designed to evaluate the frequency of coeliac disease among Hungarian diabetic children and to study the effect of gluten-free diet on glycaemic control. A total of 205 diabetic children (age range 2.0-17.0 years, median 11.6 years) were screened for coeliac disease by determination of IgA-endomysium (EMA) antibodies. In the positive cases, a jejunal biopsy was performed and, in addition to routine histology, the number of intraepithelial gamma/delta T-cells was also determined. Insulin requirement, glycosylated haemoglobin level and body mass index of diabetic children with coeliac disease were determined before and 3 months after the introduction of gluten-free diet. IgA-EMA was positive in 24 cases, 17 of them (8.3% of all diabetic children) had a subtotal villous atrophy and thus coeliac disease was diagnosed. In all but two of these children, the mean number of gamma/delta T-cells was elevated (above 7 cells/mm). Of the remaining seven patients with positive EMA but normal villous structure, five (2.4%) had elevated number of epithelial gamma/delta T-cells, indicating probable latent coeliac disease. The insulin requirement of the children had significantly increased 3 months after the introduction of gluten-free diet (median values 0.64 versus 0.48 U/kg per day, P<0.05). Median body mass indices also showed significant elevation after this period (16.8 versus 14.2 kg/m(2), P<0.05) CONCLUSION: the frequency of coeliac disease was high in the studied group. Introduction of a gluten-free diet improved the somatic development of these children. A latent form of coeliac disease is also frequent in children with type 1 diabetes mellitus.
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PMID:Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus. 1248

OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
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PMID:Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. 2018 7

Type 2 diabetes is associated with increased risk of cancer. This risk is related to HbA1 increase and this influence is present also in prediabetes and in nondiabetics with HbA1c in upper normal range. In last 2 years, it was concluded that that the specific antidiabetic therapy could influence the cancer risk. In this review we show that reduction of HbA1c does not change cancer risk. Most important is the risk reduction of cancer risk by metformin. Insulin therapy and the use ofsulphonylurea related drugs, increases the risk of cancer. This risk can be eliminated in the combination with metformin. Other published results including the suspected effect related to the use of glargine, pioglitazone, sitagliptine and exenatide are inconsistent and analysis of long term effects of these drugs is necessary. The large discussion in many publications shows the important role of FDA and EMA. This agencies do not suspend drugs without consistent evaluation of results.
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PMID:[Is there any relation between diabetes therapy and cancer risk?]. 2195 71

Insulin secretion has a crucial role in glucose homeostasis, and failure to secrete sufficient insulin is a hallmark of type 2 diabetes. Genome-wide association studies (GWAS) have identified loci contributing to insulin processing and secretion; however, a substantial fraction of the genetic contribution remains undefined. To examine low-frequency (minor allele frequency (MAF) 0.5-5%) and rare (MAF < 0.5%) nonsynonymous variants, we analyzed exome array data in 8,229 nondiabetic Finnish males using the Illumina HumanExome Beadchip. We identified low-frequency coding variants associated with fasting proinsulin concentrations at the SGSM2 and MADD GWAS loci and three new genes with low-frequency variants associated with fasting proinsulin or insulinogenic index: TBC1D30, KANK1 and PAM. We also show that the interpretation of single-variant and gene-based tests needs to consider the effects of noncoding SNPs both nearby and megabases away. This study demonstrates that exome array genotyping is a valuable approach to identify low-frequency variants that contribute to complex traits.
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PMID:Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. 2326 89

Insulin therapy in the management of Type 2 diabetes is often postponed and/or not adequately intensified to maintain glycemic control because of the risk of weight gain and hypoglycemia. A fixed combination of the long-acting insulin degludec and liraglutide has recently been accepted by the EMA for the management of Type 2 diabetes. The incentive for this combination is to exploit the advantages of each of the drugs while counterbalancing the side effects. Insulin degludec effectively reduces fasting plasma glucose, but carries the risk of hypoglycemia and body weight gain. Liraglutide, on the other hand, exerts glycemic control with a minimal risk of hypoglycemia and, at the same time, reduces appetite and body weight.
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PMID:Fixed combination of insulin and a glucagon-like peptide-1 analog for the treatment of type 2 diabetes, exemplified by insulin degludec and liraglutide. 2581 88

Insulin and its analogues have so far and for almost 100 years been the only officially approved treatment for type 1 diabetes in Europe. However, in clinical practice, various drugs against type 2 diabetes have sometimes been used off label as adjuvants to insulin for type 1 diabetes. Recently, the EMA approved the SGLT2 inhibitor dapagliflozin as an adjuvant treatment for type 1 diabetes in adults. This article is a survey of various adjuvant treatments used against type 1 diabetes, focusing on SGLT2 inhibitors and their pros and cons.
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PMID:[A survey of various adjuvant treatments used against type 1 diabetes, focusing on SGLT2 inhibitors]. 3119 6