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Query: UMLS:C0011854 (type 1 diabetes)
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This paper discusses psychosocial influences of diabetes mellitus type 1 on children and young patients. A group of 21 patients, age 9 to 14 years with Diabetes mellitus type 1 attended a course in "Autogenic Training" for a period of 11 weeks. From the multidimensional questionnaire for children (PFK 9-14, SETZ U. RAUSCHE 1976) 15 dimensions of personality and 5 second rank factors were extracted at the beginning and at the end of training and 5 months later. Additionally HbA1-scores were assessed at the beginning and at the end at a 2 month and a 5 month-follow-up. At the beginning of the course only on one of the 15 scales a significant difference could be observed between experimental group and age related normal population. After training 5 scales and one second rank factor showed significant changes. Significant reduction was observed in: "need for aggressive forms of dominance behaviour" "feeling of submission with respects to other:", "emotional lability" and "tendency for dependence on adults". A significantly increased score was observed in the scale measuring "self confidence regarding one's own meaning, decisions and planning ability". The second rank faktor "neuroticism" was significantly reduced. Against expectations there was no reduction in HbA1 scores. At the end of training HbA1 scores even had increased significantly. But this might have been related to the high frequency of infections during this course. In subjective ratings of training evaluation most of the course members and their parents described fewer problems with attention, less test-anxiety and less aggression and nervousness. The results of this prospective pilot-study are discussed in terms of the psychodynamic influence on diabetes.
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PMID:[Autogenic training in children and adolescents with type 1 diabetes mellitus]. 920 90

Insulin-dependent diabetes mellitus (IDDM) is not a disease of unbridled destruction. The autoimmune attack on pancreatic beta cells has two distinct stages - insulitis and diabetes - and progression of the former to the latter appears to be highly regulated. Identifying the factors controlling this transition has been difficult because it is a complex process that occurs non-universally and asynchronously. We have overcome these difficulties by coupling a simplified TCR transgenic (tg) model of IDDM and the immunosuppressive drug cyclophosphamide (CY). Young BDC2.5 TCR tg mice show insulitis but not diabetes; CY treatment provoked diabetes in 100% of animals with rapid, highly reproducible kinetics. This allowed a detailed temporal analysis of changes in cellular organization and cytokine gene expression within the lesion. The monokines IL-18, IL-12 and TNF-alpha were pivotal, their induction occurring almost immediately and their coordinate action being required for the onset of aggression. Other cytokines with direct toxicity for beta cells, including IL-1 -beta, IL-6 and IFN-gamma, were subsequently induced; in contrast, there was no cellular or molecular evidence of cell contact-mediated mechanisms of beta cell death.
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PMID:Cellular and molecular changes accompanying the progression from insulitis to diabetes. 993 6

Nephropathy may develop in patients with type 1 diabetes because poor glycemic control produces effects that eventually lead to glomerular scarring and renal failure. The worse and more prolonged the hyperglycemia, the greater the risk of diabetic nephropathy. In patients with type 2 diabetes, hyperglycemia, as well as insulin resistance and generalized vascular disease, is involved in the pathogenesis of nephropathy. The glomerular changes of early diabetic nephropathy can be identified only by renal biopsy or by testing for microalbuminuria. Once macroalbuminuria occurs (albumin excretion rate, > 300 mg/day), usually after type 1 diabetes has been present for 10 to 15 postpubertal years, end-stage renal disease is almost inevitable. However, aggressive control of hypertension in diabetic patients without microalbuminuria helps avoid nephropathy, and tight glycemic control in those with microalbuminuria can avoid or delay its onset. Even when macroalbuminuria is present, treatment can prolong renal function. Aggressive antihypertensive therapy, especially with ACE inhibitors, can reduce renal decline by half. Avoiding circumstances that may damage the kidneys (e.g., use of radiocontrast materials or nephrotoxic drugs, dehydration, hyperlipidemia, urinary tract infection, buildup of AGEs) is critical. Some treatment methods are controversial (dietary protein restriction) or still under investigation (use of injected or oral heparin) but may help delay renal transplantation or dialysis.
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PMID:Dealing with diabetic nephropathy. 1002 5

Recent reports suggest that the pancreas participates in tumor necrosis factor alpha (TNF-A) production during stress, and that the islets are predominantly responsible for such synthesis. In vitro TNF-A and interleukin 1-beta (IL-1-beta) inhibit insulin release from islet beta-cells. We measured the circulating levels of IL-1-beta, TNF-A and islet cell antibody (ICA) in 30 children with IDDM (10 of them at their first presentation), 30 of their non-diabetic siblings, and 30 normal age-matched children. In the non-diabetic children we investigated the early phase of insulin release after intravenous bolus of glucose and evaluated tolerance to oral glucose (OGTT). IL-1-beta and TNF-A concentrations were significantly higher in IDDM-siblings (31.8 +/- 7.7 pg/ml and 650 +/- 155 pg/ml respectively) versus normal children (21.2 +/- 6.4 pg/ml and 383 +/- 122 pg/ml respectively). IL-1-beta and TNF-A concentrations did not differ significantly between the diabetic children and healthy age-matched controls. ICA were detected in 60% of the recently diagnosed diabetic children vs. 30% of those with longer duration of diabetes (3.1 +/- 1.2 years). Despite the significantly high prevalence of ICA in the recently diagnosed children with IDDM, their IL-1-beta and TNF-A concentrations were lower than those for the normal children. In experimental animals these cytokines can induce round cell infiltration (insulinitis) and inhibit insulin secretion by beta-cell. The presence of significantly higher concentrations of these cytokines in IDDM siblings, with high prevalence of ICA (16%), was associated with normal oral glucose tolerance and normal peak insulin response (60 +/- 10.4 mlU/ml) after i.v. glucose bolus compared to normal children (52.3 +/- 9.5 mlU/ml). However, after 2 years of follow up, one of them developed IDDM and another developed IGT but none of the normal controls developed abnormal glucose tolerance. It appears that the process of autoimmune aggression against beta-cells, and its effect on insulin release and glucose homeostasis, is a slow and chronic process. However, the production of these cytokines and consequently the degree of beta-cell destruction, in a genetically susceptible subject, might be enhanced by several factors including viral infections. In summary, IL-1-beta and TNF-A levels can be used as indicators of continuing autoimmune aggression against beta-cells before the development of extensive beta-cell destruction.
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PMID:Interleukin-1-beta, tumor necrosis factor-alpha, insulin secretion and oral glucose tolerance in non-diabetic siblings of children with IDDM. 1077 98

Multidirectional studies estimating the alterations of cellular immune system in the preclinical phase of type 1 diabetes mellitus create the possibilities for better understanding the mechanisms of the auto-aggression process leading to the pancreatic beta cells destruction and insulin-dependent diabetes mellitus development. In the present review we analyse the recent studies concerning the alterations of the cellular immune markers (ex. peripheral blood lymphocytes subsets, cytokines production or adhesion molecules expression, etc...), which could reflect an early stages of autoimmune process and better identify people at risk of type 1 diabetes mellitus. In summary we suggest that the measurements of new immune markers of prediabetes, together with the estimation of the pancreatic auto-antibodies, genetic risk and age of the studied subjects give the possibility for the better early diagnosis of the people at high risk of type 1 diabetes mellitus development. There is an increasing hope that these markers are useful for the estimation of the efficacy of the preventive therapeutic procedures aiming to type 1 diabetes mellitus protection.
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PMID:[Immune markers in preclinical phases of diabetes type 1. Role of cytokines, adhesion molecules and peripheral blood lymphocyte subpopulations in the pathogenesis and prediction of insulin-dependent diabetes]. 1139 99

The author hopes to convince the reader that the data presented argue for a stage during the development of IDDM when beta-cell destruction can be counteracted and tolerance to beta cells restored, provided the immune aggression is arrested. This argument constitutes a solid rationale for immunointervention in established IDDM, especially by using potent agents such as CD3. The future for the application of monoclonal antibodies not only in autoimmunity but also in transplantation is exiting. With the development of humanized monoclonal antibodies, therapeutic uses for them are likely to expand. Enormous progress has been made in the last 15 years, and it is likely that before a similar time period has elapsed, monoclonal antibodies will have become standard tools that will dispense the need for long-term immunosuppression and its inherent dangers in various clinical arenas.
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PMID:The use of monoclonal antibodies to restore self-tolerance in established autoimmunity. 1209 61

Aggressive treatment of hypertension is effective in reducing both microvascular and macrovascular complications in type 2 diabetes, and target BP less than 130/85 or 130/80 mmHg are now recommended. Inhibition of renin angiotensin aldosterone system (RAAS) plays an essential role in the treatment of hypertension and diabetes-related complications. Studies focusing on renal end-points suggest that angiotensin-converting enzyme inhibitors (ACE-I) are more effective than other traditional agents in reducing the onset of clinical proteinuria in both type 1 and type 2 diabetic patients with incipient nephropathy, mainly in normotensive ones (secondary prevention). However, several small trials in type 2 diabetic patients with overt nephropathy (tertiary prevention) failed to demonstrate a specific renoprotective role for ACE-I, at variance with type 1 diabetes. Three recent large trials address the question of whether angiotensin II receptor blockers (ARB) prevent the development of clinical proteinuria or delay the progression of nephropathy in type 2 diabetes. The IRMA study showed that irbesartan is more effective than conventional therapy in preventing the development of clinical proteinuria and in favoring the regression to normoalbuminuria for comparable BP control in patients with incipient nephropathy. The IDNT and RENAAL trials showed that ARB are more effective than traditional antihypertensive therapies in reducing progression toward end-stage renal failure (ESRF) in type 2 diabetic patients with overt nephropathy independently of changes in BP. Moreover, a reduction in hospitalizations for heart failure was demonstrated for ARB-treated patients compared with placebo. Furthermore, the LIFE study showed that losartan is more effective than conventional therapy in reducing cardiovascular morbidity and mortality in a cohort of diabetic patients with hypertension and left ventricular hypertrophy. In conclusion, ARB seem to be effective in both preventing renal damage and reducing progression toward ESRF in type 2 diabetic patients. Thus, the guidelines for the prevention and treatment of diabetic nephropathy are now changed. In type 1 diabetes ACE-I are the first-choice drug; in type 2 diabetes, ARB are considered first-choice drugs in secondary prevention as well as ACE-I and have been now elected the unique first-choice drug in tertiary prevention of ESRF. Finally, ARB should be considered as the first-choice drug in cardiovascular prevention too, as well as ACE-I.
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PMID:Renal and cardiovascular protection in type 2 diabetes mellitus: angiotensin II receptor blockers. 1246 18

Diabetes complications are common and almost triple the annual cost of managing diabetes. Microvascular complications are the major risk in type 1 diabetes, while macrovascular complications are the major cause of morbidity and mortality in type 2 diabetes. Control of hyperglycaemia (target HbA(1c) level < or = 7%) and hypertension (target blood pressure < or = 130/80 mmHg) prevents microvascular complications in both types of diabetes; a multifactorial approach, comprising behaviour modification and pharmacological therapy for all risk factors, reduces the development of micro- and macrovascular complications in type 2 diabetes. The benefit of treating dyslipidaemia is at least as great in the diabetic population as in the non-diabetic population. Angiotensin-converting enzyme inhibitors and low-dose aspirin are indicated in people with diabetes and other cardiovascular risk factors. Regular annual screening for diabetes complications allows treatable disease to be identified. Aggressive management of hyperglycaemia and other risk factors can prevent many complications
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PMID:3: Preventing complications of diabetes. 1458 83

Diabetic nephropathy is the most common cause world-wide of renal failure requiring renal replacement therapy, most patients having type 2 rather than type 1 diabetes. Cardiovascular risk increases progressively as nephropathy develops. In addition to abnormalities in the glomerular endothelium and mesangium, recent data suggest that changes are also seen in the glomerular epithelial cell or podocyte. The foot processes of the podocyte broaden and efface and there is loss of podocyte specific proteins such as nephrin. Eventually there is loss of podocytes themselves. These changes may contribute to proteinuria. The development of nephropathy can be prevented by good glucose and blood pressure control. Once microalbuminuria or proteinuria are present, control of intraglomerular pressure, using inhibitors of the renin-angiotensin system, and control of systemic blood pressure are paramount, and can delay the need for renal replacement therapy by many years. Aggressive management of cardiovascular risk factors also slows the progression of nephropathy and prevents cardiovascular events.
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PMID:Recent advances in diabetic nephropathy. 1524 65

Hypertension occurs in approximately 30% of patients with type 1 diabetes and from 50 to 80% of patients with type 2 diabetes. Although the pathogenesis of hypertension is distinct in each type, hypertension markedly enhances the already high risk of cardiovascular and renal disease in types 1 and 2 and implications for treatment are similar in both. The threshold for blood pressure treatment in diabetic patients is generally agreed to be 140/90 mm/hg with a target BP of < 130/80. So-called "lifestyle modifications" play an important role in therapy, particularly in type 2 patients, by decreasing blood pressure and improving other risk factors for cardiovascular disease. Indeed non-pharmacologic interventions have been demonstrated to prevent the development of type 2 diabetes in patients at high risk to develop the disease. Aggressive anti-hypertensive drug treatment is warranted given the high risk associated with the combination of diabetes and hypertension and the demonstrated effectiveness of anti-hypertensive treatment in reducing cardiovascular morbidity and mortality in this group of patients. ACE inhibitors and ARBs are the cornerstones of pharmacologic management, in no small part because of the renoprotective effects of these agents in antagonizing the development and progression of diabetic renal disease. Multiple agents, including diuretics, will usually be required to attain target blood pressure levels.
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PMID:Diabetes and hypertension: pathogenesis, prevention and treatment. 1570 16


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