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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 is a severe complication of type I diabetes mellitus. About 25% of all new candidates for renal replacement therapy consist of diabetic patients. Glomerular hyperfiltration is an important causative factor in the development of this nephropathy. Microalbuminuria is the clinical first symptom of glomerular hypertension. New information stresses the importance of angiotensin II. Systemic as well as local reduction of angiotensin II formation can reduce glomerular hyperfiltration. Angiotensin-converting enzyme inhibitors should therefore be considered as first anti-hypertensive agents in type I diabetics with microalbuminuria.
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PMID:Effects of ACE inhibition on the course of nephropathy in type I diabetes mellitus. 143 57

We investigated 24-hour ambulatory blood pressure and arterial distensibility, a marker of biophysical vessel wall properties, in 32 normoalbuminuric type I diabetic patients and 32 healthy control subjects on diets containing 50 mmol and 200 mmol sodium per day. The increase in daytime diastolic blood pressure from 50 to 200 mmol sodium was significantly higher in the diabetic patients than in the control subjects (2.3+/-4.9 versus 0.2+/-3.7 mm Hg, P<.05). On a high sodium regimen, femoral artery distensibility was decreased in the diabetic patients compared with the control subjects (19.2+/-7.6 versus 24.1+/-9.3 10[-3]/kPa, P<.05). Angiotensin-converting enzyme inhibition in the diabetic patients on a high sodium diet decreased daytime diastolic blood pressure and increased femoral artery distensibility. The blood pressure decrease in response to angiotensin-converting enzyme inhibition correlated significantly with the blood pressure increase to sodium (for 24-hour systolic and diastolic blood pressure, r=.72, P<.001 and r=.76, P<.001). In addition, we found that in the diabetic patients on a high sodium diet, the renal blood flow response to exogenous angiotensin II was not bimodally distributed, as is the case in essential hypertension, in which a subgroup of the patients are characterized by sodium sensitivity of the blood pressure and an abnormal renal blood flow response to exogenous angiotensin II ("nonmodulator phenotype"). These results show that blood pressure in insulindependent diabetes mellitus is sodium sensitive, but that this is not related to the nonmodulator phenotype, and suggest that in IDDM a relatively high sodium intake may be a factor that predisposes to the development of diabetic vascular disease.
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PMID:Sodium, blood pressure, and arterial distensibility in insulin-dependent diabetes mellitus. 936 71

Recently, deletion (D)/insertion (I) polymorphism in the Angiotensin I-converting enzyme (ACE) gene has been suggested to be related to the development of diabetic nephropathy in type I diabetes mellitus. This hypothesis, however, remains controversial. Differences in clinical states between patients, especially in glycemic control or duration of diabetes, could be responsible for these contradictory results. In this study we examined the relationship between D/I polymorphism of the ACE gene and diabetic nephropathy in type II diabetic patients who had already developed proliferative retinopathy (n = 45), and were thought to have been in a hyperglycemic state for long enough to develop microangiopathy. The patients were divided into two subgroups: 24 with nephropathy (albumin excretion rate: AER > or = 20 micrograms/min) and 21 without (AER < 20 micrograms/min). There was no difference in the duration of diabetes, HbA1c levels or average blood pressure over the previous year between these subgroups and other clinical characteristics were comparable. Patients without nephropathy exhibited allele I more often than those with nephropathy (p = .025). AER was lowest in genotype II and highest in genotype DD patients but the difference was not statistically significant (p = .07). From these findings, it was concluded that genotype II for the ACE gene could be a marker for reduced risk of diabetic nephropathy.
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PMID:Polymorphism of the angiotensin I-converting enzyme gene in diabetic nephropathy in type II diabetic patients with proliferative retinopathy. 950 66

Diabetic nephropathy (DN) appears in about 30% of patients with type 1 diabetes (D1) and 15 to 60% of patients with type 2 diabetes (D2). It is preceded by microalbuminuria. Microalbuminuria is defined as an albumin excretion rate between 30 and 300 mg/24 h (on a 24-hour urine collection) or between 20 and 200 micrograms/min (on an overnight collection) in at least two out of three consecutive collections made within a 6-month period. Alternative screening techniques use either dipstick (Micral-Test II) or the albumin to creatinine ratio on an early morning urine sample (30-300 mg/g creatinine). Once persistent microalbuminuria is confirmed, 80% of type 1 diabetic patients and 20 to 50% of type 2 diabetic patients will progress to DN. In D2, microalbuminuria also represents a powerful predictor of early mortality from cardiovascular disease. Macroalbuminuria (AER > 300 mg/24 h, corresponding to a total protein excretion > 500 mg/24 h) will eventually lead to a end-stage renal insufficiency within 10 to 20 years. In D2, numerous patients will die from cardiovascular disease before reaching end-stage renal failure. Angiotensin-converting enzyme inhibitors can slow down the evolution toward DN when prescribed when microalbuminuria appears. Screening for microalbuminuria should therefore be a part of the annual clinical assessment in every diabetic patient.
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PMID:[How I evaluate...diabetic nephropathy. First part: micro- and macroalbuminuria]. 981 Feb 12

Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia ( approximately 5 mmol/L) and hyperglycemia ( approximately 15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145+/-22 mL/min per 1.73 m2) and ERPF (636+/-69 mL/min per 1.73 m2) of II subjects declined by 8+/-10% and 10+/-9%, respectively, during hyperglycemia; whereas baseline GFR (138+/-16 mL/min per 1.73 m2) and ERPF (607+/-93 mL/min per 1.73 m2) increased by 4+/-7% and 6+/-11%, respectively, in ID and DD subjects (II versus ID or DD subjects: P=0.0007 and P=0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration (P=0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy.
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PMID:Renal changes on hyperglycemia and angiotensin-converting enzyme in type 1 diabetes. 1008 86

The enzyme 11 beta HSD catalyzes the interconversion of the biologically active cortisol and the biologically inactive cortisone. There are two distinct isozymes: 11 beta HSD type 1 is mainly expressed in liver and is a bidirectional enzyme, with both dehydrogenase and reductase activity. 11 beta HSD type 2 is mainly expressed in kidney and is a unidirectional enzyme with only dehydrogenase activity. 11 beta HSD type 2 protects the mineralocorticoid receptor from being activated by cortisol. Thus, specificity of this receptor in vivo is enzyme and not receptor mediated. The syndrome of apparent mineralocorticoid excess is caused by a congenital deficiency of 11 beta HSD type 2. Liquorice-induced hypertension is an example of an acquired defect in dehydrogenase activity of 11 beta HSD, caused by glycyrrhetinic acid. 11 beta HSD may play a role in the pathogenesis of 'essential' hypertension, obesity and type 1 diabetes mellitus. Angiotensin-converting enzyme inhibitors enhance dehydrogenase activity of 11 beta HSD, which may contribute to their natriuretic effect.
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PMID:[11 beta-hydroxysteroid-dehydrogenase: characteristics and the clinical significance of a key enzyme in cortisol metabolism]. 1032 Dec 59

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

In Australia the number of patients developing end-stage kidney disease is growing. Almost 70% of new cases of treated end-stage kidney disease are due to diabetes, hypertension or glomerulonephritis. The majority of these patients have a chronic decline of renal function over many years before dialysis is required, even when the initial insult is no longer present. Hypertension and the degree of proteinuria are the most important determinants for this progression and ample evidence suggests that angiotensin II is the key player in sustaining both hypertension and proteinuria. Angiotensin II mediates not only haemodynamic changes but also profibrotic and pro-inflammatory processes. Blockade of the renin-angiotensin system decreases proteinuria and slows the progression of both diabetic and non-diabetic proteinuric renal disease. Angiotensin-converting enzyme (ACE) inhibitors are first-line therapy in patients with type 1 diabetes mellitus and nephropathy, whereas angiotensin receptor blockers (ARB) are first-line therapy in patients with type 2 diabetes mellitus and microalbuminuria or overt nephropathy. Finally, treatment with ACE inhibitors delays the progression of proteinuric nephropathy in non-diabetic patients. Combination therapy with ACE inhibitors and ARB may allow a more complete blockade of the renin-angiotensin system and clinical trials show that ACE inhibitor-ARB combinations have an additive antiproteinuric effect of up to 40% compared with ACE inhibitor or ARB alone, without additional blood pressure-lowering effect. Finally, it is important to emphasize that progressive lowering of blood pressure to 120 mmHg is associated with improved renal outcome and that this effect is independent of baseline renal function.
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PMID:Prescribing angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic kidney disease. 1729 66

Diabetes mellitus and arterial hypertension are two common diseases that often coexist. Patients with diabetes have much higher rate of hypertension than that in general population. The co-existence of these disorders appears to accelerate microvascular and macrovascular complications and greatly increases the cardiovascular risk, risk of stroke and end stage renal disease. Arterial hypertension is clearly related to nephropathy in subjects with type 1 diabetes. In patients with type 2 diabetes insulin resistance seems to play a pivotal role in the pathogenesis of hypertension. Several well designed randomized controlled trials have provided evidence that patients with diabetes will benefit from a more aggressive treatment of hypertension. This benefit is seen at blood pressure level<130/80 mmHg. Moreover, most diabetic patients with hypertension require combination therapy to achieve optimal blood pressure goals. Angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, diuretics, beta-adrenoreceptor blockers and calcium- channel blockers are all effective antihypertensive agents in type 2 diabetes mellitus and no comparative trial showed the superiority of any particular class in either lowering blood pressure or reducing cardiovascular morbidity and mortality. On the basis of experimental arguments and clinical observations that have shown their apparent superiority in slowing diabetic nephropathy, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers are preferred as the first choice alone or in combination with diuretics. Second choice should be long-acting calcium-channel blockers or cardioselective beta blockers. Clinicians should be aware of the need for aggressive treatment of hypertension and spend more time in order to provide maximal benefit to the treatment of diabetes mellitus and hypertension.
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PMID:Arterial hypertension in diabetes mellitus: from theory to clinical practice. 1892 53

Angiotensin-converting enzyme-2 (ACE2) enhances the degradation of ANG II and its expression is altered in diabetic kidneys, but the regulation of this enzyme in the urine is unknown. Urinary ACE2 was studied in the db/db model of type 2 diabetes and stretozotocin (STZ)-induced type 1 diabetes during several physiological and pharmacological interventions. ACE2 activity in db/db mice was increased in the serum and to a much greater extent in the urine compared with db/m controls. Neither a specific ANG II blocker, telmisartan, nor an ACE inhibitor, captopril, altered the levels of urinary ACE2 in db/db or db/m control mice. High-salt diet (8%) increased whereas low-salt diet (0.1%) decreased urinary ACE2 activity in the urine of db/db mice. In STZ mice, urinary ACE2 was also increased, and insulin decreased it partly but significantly after several weeks of administration. The increase in urinary ACE2 activity in db/db mice reflected an increase in enzymatically active protein with two bands identified of molecular size at 110 and 75 kDa and was associated with an increase in kidney cortex ACE2 protein at 110 kDa but not at 75 kDa. ACE2 activity was increased in isolated tubular preparations but not in glomeruli from db/db mice. Administration of soluble recombinant ACE2 to db/m and db/db mice resulted in a marked increase in serum ACE2 activity, but no gain in ACE2 activity was detectable in the urine, further demonstrating that urinary ACE2 is of kidney origin. Increased urinary ACE2 was associated with more efficient degradation of exogenous ANG II (10(-9) M) in urine from db/db compared with that from db/m mice. Urinary ACE2 could be a potential biomarker of increased metabolism of ANG II in diabetic kidney disease.
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PMID:Regulation of urinary ACE2 in diabetic mice. 2386 71


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