Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Telomeres are the repeat DNA sequences at the end of chromosomes necessary for successful DNA replication and chromosomal integrity. Telomeres shorten at cell division at a rate determined by oxidative DNA damage, and cells are triggered into replicative senescence once telomeres shorten to a critical length. Telomere-related chromosomal maintenance also has a role in carcinogenesis. Type 2 diabetes is characterised by increased oxidative stress, increased oxidative DNA damage, senescent retinal and renal phenotypes, and an increased risk of epithelial malignancy. We suggest that increased oxidative DNA damage and telomere attrition in type 2 diabetes leads to: (1) carcinogenic telomere-dependent chromosomal non-reciprocal translocations, genomic instability, and the development of epithelial cancers; (2) senescent retinal and renal phenotypes (expressed as diabetic retinopathy and nephropathy); and (3) senescent vascular endothelial, monocyte-macrophage and vascular smooth muscle cells (expressed as endothelial dysfunction and accelerated atherogenesis). An adverse intrauterine environment leads to increased feto-placental oxidative stress and feto-placental oxidative DNA damage. We also suggest that intrauterine oxidative DNA damage and telomere shortening is another point at which increased oxidative stress could contribute to a pre-programmed increased risk of senescent phenotypes in adult offspring, characterised by type 2 diabetes and epithelial malignancy. These suggestions can be used to understand early glucose intolerance in the young children of type 1 diabetes pregnancies, poor cancer outcomes in type 2 diabetes, beta cell fatigue in type 2 diabetes and the absence of increased epithelial cancer risk in type 1 diabetes.
 ...
PMID:Chromosomal telomere attrition as a mechanism for the increased risk of epithelial cancers and senescent phenotypes in type 2 diabetes. 1679 17

Up to now, the studies involving diabetes mellitus and malignancies show controversial results: Many of them have found incidences of malignancies that were comparable or even lower than those in nondiabetic subjects; others conclude that diabetes mellitus is linked to a higher incidence of malignancies and/or a predictor of mortality from cancer. Insulin and its precursors, pro- and pre-proinsulin, have been shown to have some homology to the insulin-like growth factors, but, moreover they have some affinity to bind at receptors of the tumor growth factor and some hybrids too. Hence, an association between diabetes mellitus, insulin, hyperinsulinaemia, and carcinogenesis appears plausible. On the other hand, diabetes mellitus can influence different hormone levels. In some tumor entities, such as prostate carcinoma, this effect can somewhat counterbalance the direct mitogene effect of insulin and its precursors. All in all, as a result of the complexity of these mechanisms and the differences between the tumor entities, the question whether diabetes mellitus is associated with an increased or a reduced risk for the development and in respect of the prognosis of cancer cannot be answered. The only way to give some answer is to focus on specific tumor entities: It seems that diabetes mellitus and/or hyperglycaemia are independent risk factors and/or predictors at least in respect of cancer of the colon, pancreas, female breast, endometrium, and, in men, of the liver and bladder. However, most of these data were assessed in patients with type 2 diabetes mellitus. This makes it highly questionable whether the data can easily be transferred to patients with type 1 diabetes. Moreover, additional potential limitations are that most of the studies do not focus on the treatment modality or the race of participants. In conclusion, up to the present, we have an increased risk for some and a reduced risk for other tumor entities, but still, we cannot give the general answer.
 ...
PMID:Diabetes, insulin, and risk of cancer. 1681 Mar 43

Since insulin is the unique and life-long therapy in type 1 diabetes and classical insulin preparations have certain limitations due to their pharmacokinetic and pharmacodynamic properties, the new insulin analogues aim to eliminate these limitations. Five insulin analogues are commercially available and approved for individuals with type 1 diabetes: three rapid-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting insulin analogues (insulin glargine and insulin detemir). According to several studies conducted in children with type 1 diabetes, insulin analogues, due to their structural alterations, offer flexibility, reduction of nocturnal hypoglycemic episodes and decrease in postprandial hyperglycemic events, resulting in improved quality of life for diabetic children and their families. However, diabetes control measured with glycosylated hemoglobin A1c has been reported to be similar to conventional insulin preparations. Evidence-based medical reports indicate that insulin analogues are safe and effective, and therefore approved for children even from the age of 2 years. Moreover, suspicions and reports on the association of insulin analogues with carcinogenesis have not been established, requiring further investigation. This review reports the properties and characteristics of insulin analogues, as well as the results of current studies concerning pediatric patients with type 1 diabetes.
 ...
PMID:Insulin analogues for type 1 diabetes in children and adolescents. 2324 36

Ever since its discovery (1924) the Warburg effect (aerobic glycolysis) remains an unresolved puzzle: why the aggressive cancer cells "prefer" to use the energetically highly inefficient method of burning the glucose at the cellular level? While in the course of the last 90 years several hypotheses have been suggested, to this date there is no clear explanation of this rather unusual effect. Even though it is commonly assumed that Warburg effect is a consequence of carcinogenesis, yet another hypothesis could be brought up that the cellular switch to aerobic glycolysis may represent the very point in time when a normal cell becomes cancerous. Furthermore, this switch may happen at the point where the fate of pyruvic acid is determined, caused by the inadequate supply of enzymes that promote citric as opposed to lactic acid cycle. Currently, few clinical observations, like low cancer incidence in Type 1 diabetes mellitus and increased cancer incidence in people on high carbohydrate diets might be called upon to support such hypothesis.
...
PMID:Warburg Effect - a Consequence or the Cause of Carcinogenesis? 2716 40

Metabolic syndrome (MS) is a worldwide healthcare issue and a dominant risk factor for the development of incurable diseases affecting the entire body. The hepatic manifestations of MS include nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH). NASH is known to progress to liver cirrhosis and hepatocellular carcinoma (HCC). Excellent animal models for determining the mechanism of pathogenesis and establishing therapeutic treatment of NASH/HCC are strongly required worldwide. We recently reported that two previously established mouse models of obesity and diabetes mellitus, namely, Tsumura-Suzuki Obese Diabetes (TSOD) mice and MSG mice, developed MS-associated NASH and that their clinical course and pathological characteristics closely mimicked those of human MS-NASH patients. Interestingly, most of the mice developed HCC with advancing age, and the pathological and functional characteristics of this condition were identical to those of human HCC. We further established a novel mouse model of HCC based on type 1 diabetes (DIAR-nSTZ mice) and reported its histopathological features. By comparing various aspects of these mouse models, specific and useful characteristics in a suitable model of MS-associated liver diseases, including hepato-carcinogenesis, can be highlighted.
 ...
PMID:Animal models for analyzing metabolic syndrome-associated liver diseases. 2902 8