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)

Kidney disease is a primary cause of morbidity and mortality in diabetic patients. Factors that predetermine development of nephropathy remain unknown. Poor glycemic control, insulin requirement, duration of diabetes and family history of hypertension appear to be associated with an increased risk. Arterial hypertension, which is twice as common in diabetic patients as in the normal population, accelerates the progression of diabetic nephropathy. The pathophysiologic mechanisms responsible for hypertension appear to be different in IDDM and NIDDM. In IDDM, hypertension occurs usually as a consequence of diabetic renal disease. Conversely, the pathogenesis in NIDDM appears to be multifactorial. In either condition, aggressive blood pressure control is the single most important intervention proven to retard the progression of nephropathy. A stepped-care approach similar to that for essential hypertension with slight modifications is indicated in the treatment of the hypertensive diabetic patient with nephropathy. Nonpharmacological therapy, including dietary protein restriction, should be used as first step. Selection of the ideal antihypertensive must be based not only on efficacy but also on its side effect profile. Angiotensin converting enzyme inhibitors and calcium antagonists have a low incidence of side effects and do not induce metabolic disturbances. Therefore, they are the agents of choice for patients who do not respond to nonpharmacological therapy alone. Thiazide diuretics and beta-blockers should be used as first line therapy only for specific indications. Antihypertensive therapy combined with good glycemic control and dietary protein restriction constitute the standard of care for diabetic patients with hypertension and renal disease.
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PMID:Hypertension and kidney disease of diabetes mellitus. 176 55

We examined ten patients with type I diabetes mellitus and ten age- and sex-matched healthy controls. Median duration of diabetes was 7 years (range 0.5-24). None of the diabetic patients had hypertension, microalbuminuria, or proliferative retinopathy. Maximal specific binding capacity for angiotensin II to thrombocytes was significantly increased in diabetics (Bmax 11.9 +/- 1.6 sites per cell vs 7.0 +/- 0.9 in controls; P less than 0.01). In contrast, maximal binding for atrial natriuretic factor tended to be lower in type I diabetics (8.84 +/- 1.25 sites per cell vs 16.8 +/- 2.97; P less than 0.07). There was no difference of apparent dissociation constant (KD) for either receptor. Angiotensin II values (RIA) were greater in diabetics (16.2 +/- 1.5 pg/ml vs 8.5 +/- 1.4 in controls; P less than 0.02) and concentrations of atrial natriuretic factor (RIA) were not significantly different. The data suggest increased angiotensin II binding despite high angiotensin II concentrations in non-nephropathic type I diabetic patients. These findings may be relevant when considering the evolution of hypertension and microangiopathy lesions.
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PMID:Specific binding of angiotensin II and atrial natriuretic factor in non-nephropathic type I diabetes mellitus. 252 55

Angiotensin II receptors on platelets were studied in 13 patients with uncomplicated type I diabetes mellitus and in 15 age-matched normal subjects. Receptor density on cells from the diabetic patients was 15% lower than the normal subjects (5.2 +/- 0.8 SD sites/platelet in diabetic patients and 6.4 +/- 0.8 in normals, P less than 0.001), but there were no differences in receptor affinity as measured by Kd (4.9 +/- 1.5 X 10(-10) mol/l in diabetic patients and 5.4 +/- 1.4 X 10(-10) mol/l in normals). Plasma concentrations of renin and angiotensin II were similar in both groups. The reduced density of angiotensin II receptors on platelets from patients with insulin-dependent diabetes may reflect a generalized abnormality of angiotensin II receptor regulation.
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PMID:Reduced number of angiotensin II receptors on platelets in insulin-dependent diabetes. 301 90

At present we are able to disclose diabetic nephropathy in the very early stages, i.e. when urinary albumin excretion is only slightly increased (20-200 micrograms/min = microalbuminuria). Good blood glucose control and active antihypertensive treatment may stop or retard the further development towards renal failure. Angiotensin-converting-enzyme (ACE)-inhibitors seem to have a renoprotective effect. In this article we suggest guidelines for the use of ACE-inhibitors in patients with type 1 diabetes and early diabetic nephropathy. Special concerns are included in respect of adolescents, pregnant women and persons with type 2 diabetes.
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PMID:[ACE inhibitors and early diabetic nephropathy]. 757 May 36

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p < 0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE I/D genotype was similar in subjects with IDDM, NIDDM, and controls (chi 2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (chi 2 = 3.42, df = 2, p = ns) or NIDDM (chi 2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (chi 2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.
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PMID:Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and diabetic retinopathy in subjects with IDDM and NIDDM. 858 33

As angiotensin-converting enzyme inhibition is accompanied by a marked decrease in glomerular protein loss, the hypothesis was tested that an increase of the glomerular transcapillary hydraulic pressure difference by exogenous angiotensin II would increase microalbuminuria in patients with insulin (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Acute effects of increasing doses of angiotensin II (1, 3 and 6 ng/kg/min) were studied on mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), filtration fraction (FF), total renal vascular resistance (TRVR), and urinary albumin excretion rate (UAER) in 11 IDDM and 11 NIDDM microalbuminuric patients. Angiotensin II infusion changed MAP from 100 +/- 3 mmHg at baseline to 105 +/- 3, 111 +/- 3, and 116 +/- 3 mmHg (P < 0.001), ERPF from 542 +/- 29 to 478 +/- 24, 429 +/- 23, and 382 +/- 19 ml/min (P < 0.001), FF from 20.2 +/- 0.06 to 23.1 +/- 0.7, 27.1 +/- 1.1, and 29.8 +/- 1.2% (P < 0.001), and TRVR from 9454 +/- 809 to 11,158 +/- 930, 13,310 +/- 1206, and 15,538 +/- 1362 dyne s cm-5 (P < 0.001). GFR and UAER, however, did not change significantly. Therefore, during angiotensin II infusion ERPF decreased, while FF and TRVR increased. As UAER and GFR remained unchanged, the presumed rise in intraglomerular capillary pressure by exogenous angiotensin II did not increase UAER. We suggest that during manipulation of the renin-angiotensin system, as in other renal diseases with proteinuria, factors other than glomerular transcapillary hydraulic pressure determine the degree of urinary albumin loss in microalbuminuric IDDM and NIDDM patients.
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PMID:Urinary albumin excretion rate during angiotensin II infusion in microalbuminuric patients with insulin and non-insulin-dependent diabetes mellitus. 913 45

In adult diabetic patients microalbuminuria is a marker of early vascular damage in the micro- and macrocirculation. Microalbuminuria is a powerful predictor of renal and cardiovascular disease outcome and is associated with other, potentially modifiable, risk factors of vascular damage. Studies of secondary prevention have shown that blood pressure lowering drugs effectively reduce albumin excretion rate. Angiotensin converting enzyme (ACE) inhibitors seem particularly effective in reducing the risk of progression to clinical albuminuria in both insulin dependent and non-insulin dependent diabetic patients and this beneficial effect appears to be long-lasting. Whether this postpones the onset of end-stage renal failure and/or reduces early mortality in these patients remains to be established. Recent studies of primary prevention in insulin-dependent diabetic patients predominantly with normoalbuminuria demonstrate that ACE inhibition reduces significantly the rate of progression of albumin excretion rate and, of great interest, seems to affect beneficially the progression of retinopathy. These results compare favorably with the beneficial effect of intensified insulin therapy and strict blood glucose control in this same group of patients. Thus, ACE inhibitors are a powerful tool to prevent progression of microalbuminuria in diabetes and may prove useful as an adjunct therapy to intensified insulin therapy in the prevention of development of microalbuminuria and of retinopathy progression in insulin dependent diabetes.
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PMID:Angiotensin converting enzyme inhibitors in diabetic patients with microalbuminuria or normoalbuminuria. 940 17

The presence of persistent microalbuminuria in IDDM is strongly predictive of the future development of end stage renal failure and of cardiovascular disease to a lesser extent. Screening for microalbuminuria is an essential component of modern diabetes practice, as effective antihypertensive therapy, and particularly, the use of angiotensin converting enzyme inhibitors is of proven benefit in retarding progression of renal disease. Cost benefit analysis justifies the expense of microalbuminuria screening programmes and early intervention. It has been estimated that the use of angiotensin converting enzyme inhibitors in microalbuminuric IDDM will save 5200 Pounds-11,000 Pounds per year of life saved. Angiotensin converting enzyme inhibitors are not free of side-effects, and it is therefore essential, given the intrinsic variability of the albumin excretion rate, and the regression to normoalbuminuria of a significant proportion of patients, to confirm the diagnosis of microalbuminuria by repeated measurements prior to the commencement of treatment. The value of intensive glycaemic control is unproven, and further prospective studies are required. There are no proven therapies for the prevention of macrovascular disease in IDDM, although the value of cessation of smoking and aggressive blood pressure control are undoubted in the non-diabetic population. Controversy persists about the value of lipid lowering therapy, especially in young patients, although even in this group there is an increased risk of cardiovascular disease. Microalbuminuria is the strongest known predictor of cardiovascular disease in NIDDM; in contrast to the situation in the non-diabetic population, active lipid lowering therapy is not of proven cardiac benefit, but intervention seems justifiable when taken in the context of the very high prevalence of cardiovascular disease. Microalbuminuria is also predictive of end stage renal disease in NIDDM. Although intervention with angiotensin converting enzyme inhibitors has not been proven to prevent end stage renal disease, stabilisation of albumin excretion rate and creatinine clearance have been demonstrated in normotensive NIDDM, and it seems likely that longer term follow-up studies will confirm the benefit of angiotensin converting enzyme inhibitors in the prevention of end-stage renal disease. The observed predictive power of microalbuminuria as regards both cardiac and renal risk in NIDDM when considered in conjunction with the preliminary results of the benefits of angiotensin converting enzyme inhibition lend further support to the employment of microalbuminuria screening in NIDDM.
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PMID:Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. 950 84

The objective of this study was to test the relationship between neurologic and microvascular complications of type 1 diabetes mellitus. It was hypothesized that the mechanisms operative in autonomic dysfunction seen in diabetic patients with microangiopathy play a role in the rapidity of progression to renal failure. Twenty-six type 1 diabetic patients with proteinuria were studied with computerized monitoring of heart rate variation during timed ventilation, assumption of upright posture, and Valsalva maneuver and with 24-h ambulatory blood pressure monitoring at baseline. Renal function was evaluated over the ensuing 12 months of intensive insulin therapy. Blood pressure was treated so as to achieve consistent 24-h readings < 140/90 mm Hg. Angiotensin converting enzyme inhibitors were the preferred antihypertensive agents. Serial serum creatinine concentrations were compared using repeated measures analysis of variance. Over 12 months there were no significant serum creatinine changes for any autonomic test group with normal results at baseline. Groups with abnormal autonomic results at baseline demonstrated statistically significant increases in serum creatinine over 12 months compared to their baseline. Of the tests, Valsalva separated groups of patients with similar degrees of baseline renal impairment. Each of the sympathetic plus Valsalva combinations demonstrated a significant difference in progression of serum creatinine increase over 12 months. In each instance, if both sympathetic and Valsalva results were abnormal, there was a statistically significant increase in serum creatinine over 12 months when compared to groups in which one or both test results were normal. There is a relationship between autonomic function and the progression of renal dysfunction. The inability to vary the heart rate to a Valsalva maneuver identifies a degree of parasympathetic dysfunction that permits unopposed sympathetic tone, heralding more rapid renal destruction. A simple inexpensive bedside laboratory test discerned a relatively low-risk group of diabetic patients with proteinuria that demonstrated no deterioration in renal function over 12 months. When the Valsalva maneuver was markedly abnormal the presence of a mean arterial pressure > 100 mm Hg was associated with a greater likelihood of rapid renal deterioration. This group at higher risk of renal deterioration should undergo aggressive lowering of mean arterial blood pressure to < 95 mm Hg.
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PMID:Relationship between autonomic function and progression of renal disease in diabetic proteinuria: clinical correlations and implications for blood pressure control. 954 70

Diabetic nephropathy is the most common cause of end-stage renal disease in the United States. We undertook a study to assess the impact of assignment to different levels of blood pressure control on the course of type 1 diabetic nephropathy in patients receiving angiotensin-converting enzyme (ACE) inhibitor therapy. We also examined the long-term course of this well-characterized cohort of patients receiving ACE inhibitor therapy. One hundred twenty-nine patients with type 1 diabetes and diabetic nephropathy who had previously participated in the Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy Study who had a serum creatinine level less than 4.0 mg/dL were randomly assigned to a mean arterial blood pressure (MAP) goal of 92 mm Hg or less (group I) or 100 to 107 mm Hg (group II). Patients received varying doses of ramipril as the primary therapeutic antihypertensive agent. All patients were followed for a minimum of 2 years. Outcome measures included iothalamate clearance, 24-hour creatinine clearance, creatinine clearance estimated by the Cockcroft and Gault formula, and urinary protein excretion. The average difference in MAP between groups was 6 mm Hg over the 24-month follow-up. The median iothalamate clearance in group I was 62 mL/min/1.73 m(2) at baseline and 54 mL/min/1.73 m(2) at the end of the study compared with a baseline of 64 mL/min/1.73 m(2) and final 58 mL/min/1.73 m(2) in group II. There were no statistically significant differences in the rate of decline in renal function between groups. There was a significant difference in follow-up total urinary protein excretion between group I (535 mg/24 h) and group II (1,723 mg/24 h; P = 0.02). Thirty-two percent of 126 patients achieved a final total protein excretion less than 500 mg/24 h. Patients from groups I and II had equivalent rates of adverse events. In patients with type 1 diabetes mellitus and diabetic nephropathy, the MAP goal should be 92 mm Hg or less for optimal renoprotection, if defined as including decreased proteinuria. With the combination of ACE inhibition and intensive blood pressure control, many patients can achieve regression or apparent remission of clinical evidence of diabetic nephropathy.
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PMID:Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Collaborative Study Group. 1056 Nov 56


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