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

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.
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PMID:The role of the novel adipocyte-derived hormone adiponectin in human disease. 1261 9

Diabetes mellitus and hypertension are both major public health problems in our country, which co-exist frequently resulting in significant morbidity and mortality. The reported prevalence of hypertension in diabetes varies widely but is probably 1.5-2 times higher than that reported in the general population. In type 2 diabetics many are hypertensives at the time of diagnosis, while in type 1 diabetes, hypertension is predominantly associated with the development of nephropathy. Hypertension in diabetes is due to several pathophysiological mechanisms which include increased volume expansion, altered sodium homeostasis, increased peripheral vascular resistance, hyperinsulinaemia, insulin resistance, etc. The presence of hypertension in diabetic patients increases the mortality 4-5 folds, largely through coronary artery disease and stroke. It may also be an aetiological factor in the development of nephropathy and retinopathy. Treatment of hypertension in a diabetic has considerable therapeutic advantages and should be carried out vigorously. Lifestyle modifications have a useful role in the treatment of mild hypertension and have a beneficial effect on other cardiovascular risk factors. The choice of antihypertensive agents should be based on their potential impact on the metabolic abnormalities observed in diabetics. Amongst the currently available antihypertensive agents, ACE inhibitors and calcium channel blockers are the favoured agents.
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PMID:Hypertension in diabetes. 1284

Type 1 diabetes mellitus (IDDM) is associated with coronary artery disease and microvascular damage. Long-term glycemic control reduces but not fully prevents such complications. Recent evidence suggests that microvascular disease associated to IDDM begins with endothelial dysfunction. In this study, we evaluated changes in levels of nitric oxide (NO) and von Willebrand Factor (vWF) to detect early endothelial dysfunction in IDDM patients recently diagnosed. Subjects were included in one of the following groups: Group 1 (n=14): healthy subjects; Group 2 (n=14): IDDM patients recently diagnosed (<1 year), with no clinical evidence of microvascular disease; Group 3 (n=14): IDDM patients with microvascular disease (retinopathy and nephropathy). Urinary NO metabolites were similar in Group 1 (1.45+/-0.13) and Group 2 (1.6+/-0.2 micromol/mg creatinine) (P>.05), as well as vWF (99.6+/-5.7% and 84.3+/-5.1%, Groups 1 and 2, respectively, P>.05). Plasmatic NO metabolites were lower in Groups 2 and 3 (54.6+/-5.1 and 50.02+/-13.65 nmol/ml, respectively) compared with Group 1 (91.1+/-6.6 nmol/ml) (P=.0005). Also, in Group 3, urinary NO metabolites were lower (0.27+/-0.03 micromol/mg creatinine) and vWF was higher (184+/-25%) than Groups 1 and 2. There is evidence of early endothelial dysfunction even in IDDM patients recently diagnosed, with good glycemic control and without systemic hypertension, dyslipidemia or microvascular disease; this endothelial damage was detected as a decrease in plasmatic NO metabolite levels, before appearance of any clinical evidence of microvascular disease.
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PMID:Plasmatic nitric oxide, but not von Willebrand Factor, is an early marker of endothelial damage, in type 1 diabetes mellitus patients without microvascular complications. 1295 55

The objective of this is study was to examine whether estimated insulin resistance and insulin resistance-related factors are associated with coronary artery calcification (CAC) in 1,420 asymptomatic participants in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. A total of 656 patients with type 1 diabetes and 764 control subjects aged 20-55 years were examined. CAC was assessed by electron-beam computed tomography. Insulin resistance was computed with linear regression based on an equation previously validated in clamp studies on type 1 diabetic adults. Insulin resistance was associated with CAC (OR 1.6 in type 1 diabetes and 1.4 in control subjects, P < 0.001), independent of coronary artery disease risk factors. There was a male excess of CAC in control subjects (OR 2.7, adjusted for age, smoking, and LDL and HDL cholesterol levels) and in type 1 diabetic patients (OR 2.2, adjusted for the same factors and diabetes duration). After adjusting for insulin resistance, the CAC male excess in diabetic patients decreased from OR 2.2 (P < 0.001) to 1.8 (P = 0.04). After adjustment for waist-to-hip ratio, waist circumference, or visceral fat, the gender difference in CAC was not significant in diabetic subjects. In conclusion, gender differences in insulin resistance-associated fat distribution may explain why type 1 diabetes increases coronary calcification in women relatively more than in men.
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PMID:Effect of type 1 diabetes on the gender difference in coronary artery calcification: a role for insulin resistance? The Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. 1457 3

Type I diabetes mellitus (IDDM) is associated with an increased cardiovascular risk, and eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) are consequently accurate for preoperative cardiovascular assessment. According to our algorithm, coronary angiography in SPKT candidates is indicated for patients not only experiencing previous cardiac events or symptoms, but also those with long-standing diabetes (more than 25 years) and/or age over 45 years. Furthermore, a basal transthoracic echocardiographic exam (TTE) is performed to assess cardiac volumes, left ventricular mass, systolic function, and kinesis. The aims of this study were to evaluate perioperative cardiac morbidity and mortality in 18 SPKT-eligible patients, divided into two groups on the basis of the presence/absence of angiographically evident coronary artery disease (CAD), as well as to assess the impact of left ventricular hypertrophy (LVH) on cardiac complications. Cardiac intraoperative morbidity and mortality and postoperative mortality and major morbidity were absent; minor cardiac morbidity consisted only of silent ischemic ECG alterations, without significant differences between groups, although the incidence seemed to be higher in the CAD-positive population. LVH detected preoperatively by TTE exam also failed to correlate with the incidence of such complications. Selection of SPKT candidates by coronary angiography may have positive effects on perioperative cardiac morbidity and mortality. A larger sample size is needed to give the study statistical power. Medium- and long-term follow-up studies are warranted to evaluate the effects of preoperative selection on survival rates.
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PMID:Cardiac evaluation for simultaneous pancreas-kidney transplantation and incidence of cardiac perioperative complications: preliminary study. 1511 Jun 1

Diabetic nephropathy represents the most important microvascular complication in long-term diabetes mellitus because chronic renal insufficiency is further aggravated by increased cardiovascular morbidity and mortality in diabetic patients. Although early intensive insulin therapy has led to a significant reduction of incidence and prevalence of end-stage renal failure over the last decades in juvenile type 1 diabetes mellitus, the total number of type 2 diabetic patients with chronic renal insufficiency is dramatically increasing due to the improved life expectancy of the general population and the more effective medical treatment of macrovascular complications such as arterial hypertension, coronary artery disease, and peripheral arterial occlusive disease. Apart from the personal burden for each individual the frightening epidemiologic dimension of diabetic nephropathy represents an outstanding challenge for our social systems.
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PMID:[Diabetic nephropathy - current concepts in early diagnosis and treatment of diabetic microvascular complications]. 1534 Jul 35

Adipose tissue is a hormonally active tissue, producing adipocytokines which may influence activity of other tissues. Adiponectin, abundantly present in the plasma increases insulin sensitivity by stimulating fatty acid oxidation, decreases plasma triglycerides and improves glucose metabolism. Adiponectin levels are inversely related to the degree of adiposity. Anorexia nervosa and type 1 diabetes are associated with increased plasma adiponectin levels and higher insulin sensitivity. Decreased plasma adiponectin levels were reported in insulin-resistant states, such as obesity and type 2 diabetes and in patients with coronary artery disease. Activity of adiponectin is associated with leptin, resistin and with steroid and thyroid hormones, glucocorticoids, NO and others. Adiponectin suppresses expression of extracellular matrix adhesive proteins in endothelial cells and atherosclerosis potentiating cytokines. Anti-atherogenic and anti-inflammatory properties of adiponectin and the ability to stimulate insulin sensitivity have made adiponectin an important object for physiological and pathophysiological studies with the aim of potential therapeutic applications.
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PMID:Adiponectin, an adipocyte-derived protein. 1554 26

Our study examined the results of coronary artery bypass (CAB) before simultaneous pancreas-kidney (SPK) transplant in type 1 diabetics in renal failure. Of 588 pancreas transplant patients from 1992 to 2002, 77 (24 females, 53 males) were candidates for SPK transplant. All 77 had coronary evaluation and were referred for pretransplant CAB. Among the 77 CAB patients, the mean age was 42 years (range: 30- 63 years), and the duration of diabetes was 28.52 years (range: 9-51 years). All had neuropathy, retinopathy, and nephropathy; 12.9% (n = 10) had angina; and 76% (n = 59) were on dialysis at the time of CAB. The creatinine level of the 18 nondialysis patients was 3.7 mg%; 42.8% (n = 33) had suffered myocardial infarction. The left ventricular ejection fraction (LVEF) was 49% (30-65%). At CAB surgery, 88% (n = 68) triple, 9% (n = 7) double, and 2.5% (n = 2) single arterial grafts were implanted. All 77 CAB patients had severe coronary artery disease (CAD); some vessels could not be bypassed in 9.8%. At surgery, 3.4 grafts/patient were implanted (range: 1-6 grafts). All 59 dialysis patients continued dialysis after CAB; 6 nondialysis patients required dialysis after CAB. The intensive care stay averaged 1.86 days (range: 1-10 days); the hospital stay averaged 10.5 days (range 6-28 days). There was no operative mortality. Eventually, 68 patients underwent SPK transplant; 9 await organs. The waiting period for 68 CAB patients who had SPK was 2 years, 5 months (range: 2 months to 10 years). The SPK operative mortality was 3.9% (n = 3). Significant CAD exists in patients > 30 years of age with type 1 diabetes and renal failure. Pretransplant CAB can be done safely and may reduce posttransplant mortality associated with cardiac events.
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PMID:Coronary bypass before simultaneous pancreas-kidney transplants for type 1 diabetics in renal failure. 1557 61

Diabetes mellitus is a worldwide epidemic. Cardiovascular disease remains the major cause of morbidity and mortality in people with diabetes. Studies have suggested that increased risk of cardiovascular disease is not restricted to type II or type I diabetes mellitus, but extends to prediabetic stages such as impaired fasting glucose, impaired glucose tolerance, metabolic syndrome, and obesity. Insulin resistance, impaired fasting glucose, impaired glucose tolerance, and diabetes mellitus form a continuous sequence of risk for cardiovascular disease. Therefore, cardiovascular disease mortality and morbidity within the diabetes epidemic grow into vast proportions. Evidence also exists that diabetic patients have a high prevalence of heart failure or impaired diastolic and systolic cardiac function subsequent to the combination of coronary artery disease, hypertension, and diabetic cardiomyopathy. In view of the proportions of this new epidemic, prevention of diabetes and its prediabetic states is likely to be the most effective strategy to prevent serious cardiovascular events.
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PMID:Epidemiology of the diabetic heart. 1634 Apr 2

It is well known that subjects with type 1 diabetes are at an increased risk of death from coronary heart disease in comparison to non-diabetic age-matched individuals because hyperglycaemia is believed to be a key risk factor for the development of micro- and macrovascular complications. On the other hand there is increasing evidence about the role of inflammatory mediators in the pathogenesis of atherosclerosis and the development of acute coronary syndromes. It has been recently suggested that IL-18 and sICAM-1 have a strong predictive value for cardiovascular diseases and deaths in patients with coronary artery disease and/or in apparently healthy men. The aim of our study was to estimate the serum levels of IL-18 and sICAM-1 in subjects with type 1 diabetes and their relatives, who share HLA diabetic susceptibility genes (with or without pancreatic autoantibodies), but still without glucose level disturbances, as an evaluation of the possible role of genetic predisposition to the presence of IL-18 in diabetic families. The study was carried out in 35 type 1 diabetic subjects, their 101 healthy first-degree relatives: 36 siblings and 65 parents and the control group consisted of 31 healthy volunteers. We have found increased IL-18 and sICAM-1 levels in subjects with type 1 diabetes and their first degree relatives, who share diabetic HLA haplotypes: DRB1*03/DRB1*04 or DRB1*03/*04/DQB1*02 independently of their autoimmune status. There was a strong positive correlation between IL-18 and sICAM-1 levels in diabetic subjects and their first degree relatives without glucose level disturbances. To our knowledge this is the first study, which suggests that sICAM-1 elevations could be a result of IL-18 overproduction in type 1 diabetic subjects and their first degree relatives. Since in previous studies IL-18 and sICAM-1 were found to be predictors of death in subjects with CHD, one could speculate that high levels of IL-18 observed in subjects with genetic predisposition, but still with normal glucose levels, are an in addition to hyperglycaemia, pathogenic factors responsible for a higher risk of acute coronary events in subjects with diabetes type 1.
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PMID:Interleukin 18 and sICAM-1 serum levels in families with type 1 diabetes mellitus. 1635 56


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