Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is unknown whether glucose screening for Type 2 diabetes mellitus (DM2) reduces the risk of diabetic complications. We conducted a case-control study using 303 cases with DM2 and at least one symptomatic microvascular diabetic complication, matched 1:1 to control subjects. All subjects' blood glucose tests for the decade before the first clinical suspicion of DM2 were categorized as screening or not based on the presence of symptoms suggestive of DM2. Approximately 90% of case subjects and control subjects had been screened for diabetes. After adjusting for multiple covariates in a logistic regression model, the odds ratio of developing a complication associated with screening was 0.87 (95% confidence interval 0.38-1.98), suggesting that screening may be associated with a modest reduction in the risk of certain diabetic complications. However, the confidence limits were wide and consistent with no true benefit. Further studies are needed to establish whether the small reduction we observed is genuine.
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PMID:Glucose screening and the risk of complications in Type 2 diabetes mellitus. 1258 73

Two substrates of insulin-degrading enzyme (IDE), amyloid beta-protein (Abeta) and insulin, are critically important in the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2), respectively. We previously identified IDE as a principal regulator of Abeta levels in neuronal and microglial cells. A small chromosomal region containing a mutant IDE allele has been associated with hyperinsulinemia and glucose intolerance in a rat model of DM2. Human genetic studies have implicated the IDE region of chromosome 10 in both AD and DM2. To establish whether IDE hypofunction decreases Abeta and insulin degradation in vivo and chronically increases their levels, we characterized mice with homozygous deletions of the IDE gene (IDE --). IDE deficiency resulted in a >50% decrease in Abeta degradation in both brain membrane fractions and primary neuronal cultures and a similar deficit in insulin degradation in liver. The IDE -- mice showed increased cerebral accumulation of endogenous Abeta, a hallmark of AD, and had hyperinsulinemia and glucose intolerance, hallmarks of DM2. Moreover, the mice had elevated levels of the intracellular signaling domain of the beta-amyloid precursor protein, which was recently found to be degraded by IDE in vitro. Together with emerging genetic evidence, our in vivo findings suggest that IDE hypofunction may underlie or contribute to some forms of AD and DM2 and provide a mechanism for the recently recognized association among hyperinsulinemia, diabetes, and AD.
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PMID:Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. 1263 21

The objective of the work was to assess, based on the results of studies conducted abroad and the author's own results from the Prague register of diabetic patients, whether there exist differences in the epidemiology, clinical course of diabetes mellitus (DM) and its complications between female and male diabetics. As far as type 1 DM is concerned there are significant differences in the clinical course of diabetes, i.e. deteriorated compensation of DM in girls and women in conjunction with menstruation and the menopause. As compared with men, young women have a higher mortality on account of diabetic nephropathy, and at any age they have as higher incidence of hypertension. In DM2 they have also a high incidence of hypertension and risk of compensation of DM during menstruation and later during the menopause. A significantly less frequent complication in women is ischaemia of the lower extremities. From the epidemiological aspect a higher prevalence of DM2 was proved in women after the age of 65 years.
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PMID:[Women and diabetes]. 1264 20

The number of subjects with Type 2 diabetes (DM2) has risen significantly in the last ten years. Obtaining sufficient human tissue to study this disease process as well as many other diseases is generally difficult. T lymphocytes offer a unique opportunity for these studies. Although resting human peripheral T-lymphocytes are devoid of insulin receptors, these receptors emerge upon activation of cells by specific antigens or mitogens. Concomitant with the insulin receptors, two other growth factor receptors (IGF-1 and IL-2) also emerge on the T lymphocyte cell surface along with intracellular signal transduction mechanisms and insulin degrading enzyme (IDE). After binding to its receptor, insulin has been shown to exert its classical effects on carbohydrate metabolism in the stimulated T- cell; thereby, validating the use of activated T-lymphocytes for studying the pathogenesis of metabolic and immune disorders and the mechanism(s) by which insulin exerts its effects. In activated T-lymphocytes, insulin stimulates glucose uptake, glucose oxidation, pyruvate flux and pyruvate dehydrogenase activity, amino acid transport, lipid metabolism and protein synthesis. Through its ability to enhance nutrient uptake and raise the levels of intermediary cellular metabolism, insulin is believed to maintain the allo-activated state of lymphocytes, enhance T-Lymphocyte responsiveness, and support or possibly promote the actions of immuno-derived regulatory growth and differential factors. Since insulin enhances energy requirements and protein synthesis necessary for appropriate T-cell functions, defects in insulin action may lead to inappropriate immunoresponses in various metabolic states such as in diabetes. Studies from our lab have found insulin binding, processing, and responsiveness in phytohemagglutinin(PHA)-activated T-cells are reflective of the donor's glycemic status and ambient insulin levels in subjects with Type 1 and Type 2 diabetes (DM2) and other insulin resistant states. Our studies show that patients with diabetic ketoacidosis and hyperglycemia have increased proinflammatory cytokines and activated CD4+ and CD8+ T lymphocytes. The diabetic state, where effective insulin concentrations are low and both glucose and free fatty acids are high, provides an environment of oxidative stress and activation of the inflammatory pathways. The mechanisms underlying insulin action, in general, or in the CD4+ and CD8+ T-lymphocytes, in particular, have not been clearly elucidated. Due to the accessibility of obtaining these cells from patients, activated T-lymphocytes offer the potential of studying diabetes and other disease in human subjects.
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PMID:Activated T lymphocytes in Type 2 diabetes: implications from in vitro studies. 1286 64

Microalbuminuria is a marker for diabetic nephropathy. It also signifies cardiovascular disease, as well as nephropathy, in type 2 diabetes (DM2). Microalbuminuria may precede DM2, occurring with the insulin resistance syndrome and its components, including obesity and hypertension. Other indicators of cardiovascular risk, such as markers of inflammation, are associated with microalbuminuria in populations of patients with and without diabetes. With the rising prevalence of DM2 in minority youth, especially in Native Americans, a marker for future disease risk would allow earlier prevention strategies to be tested. Before microalbuminuria can be used in a prevention strategy, more needs to be known about the mechanism(s) of the association between elevated excretion, its relationship to glucose intolerance, and its relative contribution to cardiovascular and renal disease. These questions are especially applicable as we begin to observe the long-term complications of diabetes in youth.
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PMID:Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective. 1476 31

Morphological characteristics of bone tissues were studied in the feet of patients with diabetes mellitus type 1 and 2 (DM1 and DM2). Osteoblasts and osteoclasts prevalence, the presence of collagen type III in the composition of newly formed bone were characteristic for DM1. Osteocytes prevalence and abundant granulation tissue in newly formed bone was a feature of DM2. The analysis of bone tissue resorption suggests that lacunar osteoclastic resorpsion is the main type in DM1 while periosteocytic osteolysis and smooth resorption are typical for DM2. Thus, osteolysis genesis and synthesis of bone tissue in DM1 and DM2 may be different.
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PMID:[Osteopathy in diabetic foot syndrome]. 1505 2

Few studies have described the genetics of childhood diabetes mellitus (DM) in US minorities. High-risk DQA1 and DQB1 alleles (DQA1*0301, DQB1*0201, and DQB1*0302 in African Americans and Latinos, and DQA1 *0501 in African Americans) were identified from previous studies and tested in 45 African American and 26 Latino patients from the population-based Chicago Childhood Diabetes Registry, and in 50 healthy race-matched controls. Sixteen of the African American patients and three Latinos had youth-onset type 2 DM and were analyzed separately. In African Americans with type 1 DM, both DQA1*0102 and DQB1*0602 were protective (p < 0.0001), and the susceptibility alleles DQA1*0301 and DQB1*0201 were more frequent than in controls (p < 0.01). In Latinos, DQA1*0301 and DQB1*0302 were marginally increased in patients with DM1 compared to controls; no individual DQA1 or DQB1 allele was protective. Patients with DM1 were significantly more likely to carry one or two high-risk DQA1 alleles in both populations; they were also more likely than controls to carry at least one high-risk DQB1 allele. The odds ratio for the ability to form at least two high-risk DQA1-DQB1 heterodimers (cis and/or trans) was 7.9 (95% CI: 1.7-40.0) for African Americans and 5.7 (1.3-25.6) for Latinos with DM1. African American patients with DM2 were not statistically different from controls, and were less likely to carry four high-risk susceptibility alleles than patients with DM1 (p = 0.002). Many of the HLA-DQ associations previously documented in non-Hispanic White populations also are found in African Americans and Latinos with DM1, although some differences exist.
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PMID:HLA-DQA1 and -DQB1 alleles in Latino and African American children with diabetes mellitus. 1511 6

Myotonic dystrophy (DM) is caused by either an untranslated CTG expansion in the 3' untranslated region of the DMPK gene on chromosome 19 (dystrophia myotonica type 1 [DM1]), or an untranslated CCTG tetranucleotide repeat expansion in intron 1 of the ZNF9 gene on chromosome 3 (dystrophia myotonica type 2 [DM2]). RNA-binding proteins adhere to transcripts of the repeat expansions that accumulate in the nucleus, and a trans-dominant dysregulation of pre-mRNA alternative splicing has been demonstrated for several genes. In muscle from patients with DM1, altered insulin-receptor splicing to the nonmuscle isoform corresponds to the insulin insensitivity and diabetes that are part of the DM phenotype; because of insulin-receptor species differences, this effect is not seen in mouse models of the disease. We now demonstrate that comparable splicing abnormalities occur in DM2 muscle prior to the development of muscle histopathology, thus demonstrating an early pathogenic effect of RNA expansions.
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PMID:Insulin receptor splicing alteration in myotonic dystrophy type 2. 1511 29

Several studies have demonstrated an association between low birth weight and impaired insulin sensitivity or even type 2 diabetes mellitus (DM2) in later life. Growth hormone (GH) is known to increase fasting and postprandial insulin levels. For that reason concern has been expressed regarding possible detrimental effects of GH therapy in children born SGA. In a Dutch trial the possible side effects of GH therapy on carbohydrate metabolism were assessed in short children born SGA after 6 years and at 6 months after discontinuation of GH therapy. This study included 79 prepubertal short children born SGA, participating in a multicenter double-blind, randomized, dose-response GH trial. Inclusion criteria were: 1) birth length SDS below -1.88, 2) age 3-11 years in boys and 3-9 years in girls, 3) height SDS < -1.88, 4) no spontaneous catch-up growth, and 5) an uncomplicated neonatal period. Mean (SD) value for age was 7.3 (2.1) years, birth length SDS -3.6, height SDS -3.0 (0.7) and BMI SDS -1.2 (1.3). All children were randomly assigned to either group A (n = 41) using 1 mg GH/m2/day or group B (n = 38) using 2 mg/m2/ d/ay (approximately 0.1 or 0.2 IU/kg/d, respectively). Standard oral glucose tolerance tests (OGTTs) were performed before and during 6 years of GH therapy and 6 months after discontinuation of GH therapy. Before GH therapy 8% of the children had impaired glucose tolerance (IGT) according to criteria of the WHO. After 6 years of GH therapy, IGT was found in 4% and after stopping GH in 10%. Mean fasting glucose increased significantly with 0.5 mMol/l after 1 year of GH therapy, without a further increase thereafter. GH therapy induced considerably higher fasting and glucose-stimulated insulin levels. None of the observed changes were different between the GH dosage groups. Children who remained prepubertal had similar glucose and insulin levels compared to children who entered puberty. HbA1c levels were always in the normal range and none of the children developed diabetes mellitus. After discontinuation of GH therapy the mean serum glucose levels remained normal and the mean serum insulin levels decreased significantly, to normal age reference values. Before the start of GH the mean systolic blood pressure was significantly higher compared to age-matched peers, whereas during GH therapy a significant decline in mean systolic blood pressure occurred, which remained similar after discontinuation of GH treatment. In conclusion, continuous, long-term GH therapy in short children born SGA has no adverse effects on glucose levels, even with GH dosages up to 2 mg/m2/day. However, as has been reported in other patient groups, GH induced higher fasting and glucose-stimulated insulin levels, indicating insulin resistance. After discontinuation of GH, serum insulin levels declined to normal age-matched reference levels. Since impaired insulin sensitivity and DM2 have been demonstrated in relatively young patients born SGA, long-term follow-up of children born SGA is advised, also after discontinuation of GH therapy.
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PMID:Small for gestational age (SGA): endocrine and metabolic consequences and effects of growth hormone treatment. 1513 8

As type 2 diabetes mellitus (DM2), obesity and sedentary lifestyles are increasing in developing countries, this observational study investigated the role of physical activity on DM2 in Jamaica. Anthropometry, body composition (by bioelectrical impedance analysis) and glucose tolerance status was assessed in 722 adults in 1993 and 1997. Energy expenditure was estimated in a subset using measured resting energy expenditure in combination with self-reported activity recalls. The rates of impaired glucose tolerance (IGT) were 23.7 and 27.3%, and DM2 were 16.3 and 23.7% among men and women, respectively. After adjusting for body composition, a one-unit increase in physical activity significantly reduced the odds of having diabetes (OR = 0.05; 95% CI: 0.004, 0.66), but not IGT. Hence, decreased physical activity is a significant independent contributor to the high rates of glucose intolerance in Jamaica. Efforts must be directed at minimizing obesity and increasing physical activity in developing countries.
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PMID:Energetic determinants of glucose tolerance status in Jamaican adults. 1516 40


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