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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Effect of lisinopril on progression of retinopathy and microalbuminuria in normotensive subjects with insulin-dependent diabetes mellitus. Retinopathy and nephropathy are the most important microvascular complications in diabetes with hyperglycaemia and hypertension as important risk factors. Antihypertensive treatment with angiotensin-converting enzyme inhibitors has been shown to delay progression of nephropathy, but the effect on retinopathy has not been established. We, therefore, performed a trial of the effect of the ACE-inhibitor lisinopril on retinopathy and nephropathy in normotensive patients with IDDM. We performed a two year randomized double-blind placebo-controlled trial of the ACE-inhibitor lisinopril on 530 normotensive IDDM patients within the age group 20-59 years from 18 European centres. Patients were either normo- or microalbuminuric. Retinopathy was classified from retinal photographs into five levels (none to proliferative). The primary endpoint of the trial was progression of albuminuria. Mean albumin excretion rate (AER) was 8.0 micrograms/min at baseline in both treatment groups. After two years AER was 2.2. micrograms/min lower in the lisinopril than in the placebo group, a difference of 18.8% (p = 0.03). The difference in AER was 38.5 micrograms/min between treatment groups in patients with microalbuminuria at baseline (p = 0.001), and 0.23 microgram/min in patients with normoalbuminuria at baseline (p = 0.6). Retinopathy was a secondary endpoint. Patients treated with lisinopril had significantly lower Hb-A1c at baseline than the placebo group (6.9%-7.3%). Retinopathy progressed with at least one level in 13.2% of lisinopril treated and 23.4% of placebo treated patients (odds ratio 0.50, p = 0.02). Progression by two levels or progression to proliferative retinopathy were also significantly reduced in the lisinopril group compared to the placebo group (odds ratio 0.27 and 0.18, respectively). In conclusion, lisinopril delays progression of retinopathy and nephropathy in normotensive IDDM patients with micro- or normoalbuminuria.
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PMID:[Effect of lisinopril on progression of retinopathy and microalbuminuria in normotensive subjects with insulin-dependent diabetes mellitus]. 1005 4

Diabetes is a chronic condition which poses a risk for three major complications. They are diabetic retinopathy, nephropathy and neuropathy. Almost one third of diabetic patients (IDDM or NIDDM) develop diabetic nephropathy in their life time. Because of increased vascular permeability in chronic conditions increased urinary albumin excretion in the range of 30-200 mg/L (microalbuminuria) gives an early signal of incipient diabetic nephropathy. The prevalence of microalbuminuria was found to be 41% in diabetic patients with duration of more than 5 years. Seventy percent of diabetic patients with microalbuminuria were hypertensive. ACE inhibitors are shown to have significant effects on microalbuminuria and hypertension. We conclude that microalbuminuria is an early feature of excessive capillary leakage and its assessment in diabetic patients with duration of more than 5 years provides a simple non-invasive method of early diagnosis of incipient diabetic nephropathy. An early intervention may retard the progression to end-stage renal disease (ESRD).
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PMID:Diabetes, microalbuminuria and hypertension. 1005 42

Present study analyses nephroprotective effect of various therapeutic interventions at different stages of kidney involvement in diabetes mellitus. A MEDLINE search of past 10 years data on various experimental studies, controlled clinical trials, meta-analysis and editorials pertaining to nephroprotection in diabetes mellitus was made. Effect of various therapeutic interventions such as metabolic glycaemic control, restricted protein diet and antihypertensive drugs (especially ACE inhibitors) has been analysed on the progression of different stages of kidney involvement in diabetes mellitus such as normoalbuminuria, microalbuminuria, diabetic nephropathy and end stage renal disease (ESRD). An attempt has been made to analyse differential long-term impact of various therapeutic interventions in relation to type of diabetes mellitus (i.e., IDDM and NIDDM) and associated hypertension. Progression of IDDM patients having microalbuminuria or diabetic nephropathy with or without hypertension has improved during the past decade largely because of adequate glycaemic control and effective antihypertensive treatment with conventional drugs e.g. beta-blockers and calcium antagonists, and more so due to the use of ACE inhibitors e.g. captopril, enalapril etc. Superiority of ACE inhibitor tends to decline from normotensive stage to the degree of rise in systemic blood pressure. However, data in NIDDM patients suffering from diabetic nephropathy is incomplete and inconclusive.
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PMID:Nephroprotection in diabetes mellitus. 1005 45

End-stage renal failure (ESRF) in diabetic patients, mostly type 2, has become the most frequent cause of renal replacement therapy in western Europe. The majority of patients with type 2 diabetes and renal failure suffer from diabetic glomerulosclerosis, but nondiabetic renal disease and atypical presentations, e.g. as irreversible acute renal failure or ischaemic nephropathy, play an increasingly important role. Known risk factors for the onset of diabetic nephropathy include (1) genetic predisposition (indicated by a history of hypertension and cardiovascular events in first-degree relatives), (2) quality of glycaemic control, (3) level of blood pressure, and (4) smoking. At the time when type 2 diabetes is diagnosed, an abnormal blood pressure profile is found in approximately 80%. In patients with established diabetic nephropathy, hypertension is the most important factor which promotes progression, and this is susceptible to intervention. Although less data are available for type 2 diabetes (compared with type 1 diabetes), ACE inhibitors appear to be the antihypertensive agent of first choice, but monotherapy is rarely sufficient to achieve the blood pressure goal. Although, at least in principle, diabetic nephropathy is a preventable condition, currently only a minority of type 2 diabetic patients in western Europe receives adequate medical treatment to prevent onset or progression of diabetic nephropathy. Consequently, novel approaches to patient management and interdisciplinary interaction are necessary to fulfil the postulate of the St Vincent declaration concerning prevention of diabetic complications.
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PMID:Nephropathy in type 2 diabetes. 1008 14

Diabetes mellitus causes profound alterations in many body tissues. Microvascular diabetic complications include diabetic neuropathy, nephropathy and retinopathy. Nephropathy first becomes manifest with hyperfiltration and microalbuminuria. These functional changes evolve over several years to a stage of marked deterioration of renal function. The possible preventive measures are metabolic control, reduction of dietary protein intake and use of ACE-inhibitors. Metabolic control is also important for the prevention of diabetic retinopathy. In fact, patients with HbA1c higher than 10% have an increased risk of progression of retinopathy. Moreover, an accelerated progression of retinopathy has been observed in patients with systemic hypertension following the onset of microalbuminuria. It has been demonstrated that diabetic neuropathy can also be present during childhood; therefore, it is possible to detect electrophysiological abnormalities in children and adolescents with IDDM. Glycaemic and blood pressure control are, so far, the main means for possible prevention or modification of the natural history of diabetic microvascular complications. Tight glycaemic control may have beneficial effects for diabetic neuropathy. In addition, other preventive measures, such as aldose reductase inhibitors, gangliosides, neurotrophic vitamins, etc., have been studied in the last years. However, no conclusive results have been obtained so far.
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PMID:Prevention of microvascular complications in diabetic children and adolescents. 1019 52

The renal protective effect of antihypertensive drugs is linked to 2 mechanisms. First, reduction in blood pressure (BP) is a fundamental prerequisite common to all antihypertensive drugs. The exact definition of the level to which BP should be reduced remains to be established, although there is some evidence that BP should be reduced below 130/85 mm Hg in patients with diabetic and nondiabetic nephropathies and below 125/75 mm Hg in patients with nondiabetic nephropathies and proteinuria >1 g/day. However, available data suggest that tight BP control (BP<140/80 mm Hg) can reduce the risk of cardiovascular complications in hypertensive patients with type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus; NIDDM). Secondly, intrarenal actions on mechanisms such as glomerular hypertension and hypertrophy, proteinuria, mesangial cell proliferation, mesangial matrix production and probably endothelial dysfunction, which can cause and/or worsen renal failure, are relevant for the renal protective action of some drug classes. ACE inhibitors possess such properties and also seem to lower proteinuria more than other antihypertensive drugs, despite a similar BP lowering effect. Calcium antagonists likewise exert beneficial intrarenal effects, but with some differences among subclasses. It remains to be evaluated whether angiotensin II-receptor antagonists can exert intrarenal effects and antiproteinuric actions similar to those of ACE inhibitors. While primary prevention of diabetic nephropathy is still an unsolved problem. there is convincing evidence that in patients with type 1 (insulin-dependent diabetes mellitus; IDDM) or 2 diabetes mellitus and incipient nephropathy ACE inhibitors reduce urinary albumin excretion and slow the progression to overt nephropathy. Similar effects have been reported with some long-acting dihydropyridine calcium antagonists, although less consistently than with ACE inhibitors. In patients with diabetic overt nephropathy, ACE inhibitors and nondihydropyridine calcium antagonists are particularly effective in reducing proteinuria and both drugs can slow the decline in glomerular filtration rate more successfully than other antihypertensive treatment. Available data in patients with nondiabetic nephropathies indicate that ACE inhibitors can be beneficial, principally in patients with significant proteinuria, in slowing the progression of renal failure. However, it is still unclear whether this beneficial effect of ACE inhibitors is particularly evident in patients with mild and/or more advanced renal failure and whether calcium antagonists possess a similar nephroprotective effect. Overall, data from clinical trials thus seem to indicate that ACE inhibitors and possibly calcium antagonists should be preferred in the treatment of patients with diabetic and nondiabetic nephropathies. However, further information is needed to understand renal protection.
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PMID:Renal protection and antihypertensive drugs: current status. 1035 94

Diabetes mellitus and hypertension is often associated, but with a different type of development in type 1 and type 2 diabetes. Type 1 diabetes, renal disease, starting with microalbuminuria, is associated with increasing blood pressure or hypertension, whereas the patient without renal disease is most often normotensive. Poor metabolic control is a predictor of microalbuminuria or incipient nephropathy, but with microalbuminuria hypertension is an important risk factor for progression along with poor glycemic control. The same is the case for overt renal disease, and metabolic control is important in all stages of renal disease in type 1 diabetes. It has also been shown that good metabolic control as well as antihypertensive treatment, especially with ACE-inhibitors, often combined with other agents is quite effective in preventing progression in renal disease in all its stages. In type 2 diabetes, blood pressure elevation is often found as early as at the actual diagnosis, and blood pressure significantly increases according to the degree of albuminuria, normo-microalbuminuria and clinical proteinuria (macroalbuminuria). Elevated blood pressure is an important risk for renal disease but more importantly so also for cardiovascular disease. Several studies document that antihypertensive treatment in particular with ACE-inhibitors is important in preventing microalbuminuria, in treating microalbuminuria and thus preventing progression, also in overt renal disease. Near-normalization of blood pressure is vital. Regarding cardiovascular disease, a series of studies now document that antihypertensive treatment with various antihypertensive agents is able to significantly reduce a number of major cardiovascular complications in diabetes, such as cardiac disease, stroke, and also microvacular disease, including retinopathy. Several studies show that antihypertensive treatment should be started at a level higher than 140-150/90. The blood pressure to be achieved during treatment is probably around 140/85 mmHg or even 130/80 mmHg as a pragmatic goal. However, there is no sign of a J-shaped curve in any of the studies, and therefore even lower blood pressure could be advantageous. Even mortality, at least from diabetes-related causes can be effected by antihypertensive treatment. With more advanced renal disease, normalization of blood pressure is increasingly difficult, especially systolic blood pressure, and therefore it is recommendable to screen patients much earlier on with focus on blood pressure recordings and measurements of albuminuria, including microalbuminuria, and to treat early.
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PMID:Drug treatment for hypertensive patients in special situations: diabetes and hypertension. 1042 11

CD40 ligand (CD40L) regulates multiple phases of the humoral and cellular immune response through binding to CD40. Previous investigations have suggested that insulin-dependent diabetes (IDDM) in both humans and nonobese diabetic mice may be strongly influenced by similar immunoregulatory molecules. As persons with or at increased risk for the disease are characterized by a number of immunological abnormalities, including that of self-reactive autoantibody production (e.g. islet cell cytoplasmic autoantibodies), we analyzed the expression of CD40L on T lymphocytes (CD3+ cells) in a series of individuals with newly diagnosed IDDM (n = 11), nondiabetic relatives of IDDM probands at increased risk for the disease (n = 21; islet cell cytoplasmic autoantibodies positive; Juvenile Diabetes Foundation titer, > or = 20), and healthy controls (n = 13). Both phorbol myristate acetate (PMA)-stimulated and unstimulated peripheral blood mononuclear cells from study subjects were analyzed by flow cytometry with a series of phenotypic antibody markers (CD3, CD40L, and isotype controls). The kinetics of CD3 and CD40L expression on peripheral blood mononuclear cells under PMA-stimulated and unstimulated conditions were similar in the three study groups (6, 24, and 48 h; all P = NS). Similarly, unstimulated and PMA stimulated CD40L expressions (percentage of positive cells and level) on CD3+ cells from newly diagnosed IDDM patients and persons at increased risk for the disease were similar to those in healthy controls (6, 24, and 48 h; all P = NS). These findings do not support abnormal CD40L expression as the mechanism underlying the functional defect(s) in communication between T lymphocytes and antigen-presenting cells that allows for autoantibody production or the inability of individuals to regulate antiself immunity in IDDM.
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PMID:No alteration in T lymphocyte expression of CD40 ligand (CD154) in individuals with or at increased risk for insulin-dependent diabetes mellitus. 1056 51

We have evaluated the suitability of different rat models for the study of effects of antihypertensives on cardiovascular and metabolic complications of diabetes mellitus and hypertension. IDDM was induced in Wistar and spontaneously hypertensive (SH) rats by single tail vein injection of STZ (45 mg/kg, i.v.). Neonatal STZ-diabetes (nSTZ) was induced by administering STZ, 70 mg/kg (i.p.) to 5 day old Wistar rat pups. DOCA-hypertension was induced in Wistar and STZ-diabetic rats using deoxycorticosterone acetate (DOCA, 5 mg/kg, s.c.) and NaCl (2%) in drinking water. Intravenous injection of STZ produced cardinal signs of diabetes mellitus including hyperglycemia, loss of body weight, polyphagia and polydipsia. STZ-diabetic rats also showed hyperlipidemia and hypoinsulinemia. STZ-treated rats developed hypertension and bradycardia. nSTZ rats were found to have mild hyperglycemia and were hypertensive and hyperinsulinemic. The OGTT and ITT revealed that nSTZ rats are insulin resistant. SH rats were also found to be hyperinsulinemic and hypertensive. Although, these rats were found to be insulin resistant, they did not demonstrate hyperglycemia. DOCA-treated STZ-diabetic rats were found to have milder hyperglycemia when compared to STZ-diabetic rats not treated with DOCA. Although, DOCA treatment was not found to alter serum levels of glucose and insulin, results of OGTT revealed enhanced glucose disposal in DOCA-treated Wistar rats, suggesting that DOCA probably produces some effect on glucose homeostasis in rats. The present data also suggest that STZ-diabetic rat may be considered a suitable model for IDDM. On the other hand, nSTZ and SH rats were hyperinsulinemic and insulin resistant and may be used as models to study insulin sensitivity. DOCA-hypertensive rat may not be a suitable model for studying the effects of various drug interventions on glucose homeostasis and insulin sensitivity as DOCA itself appears to influence these factors.
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PMID:Comparative evaluation of different rat models with co-existing diabetes-mellitus and hypertension. 1084 25


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