Gene/Protein Disease Symptom Drug Enzyme Compound
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The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Results of a 2-year prospective, randomized study. 774 19

The development of kidney disease in diabetes mellitus can be viewed as a two-stage process: (1) the development of proteinuria, and (2) its progression to chronic renal failure. Determinants of the latter were examined in 439 IDDM patients who had nephropathy and participated in the Diabetic Retinopathy Study. Using serum creatinine levels obtained during the follow-up period to assess the rate of loss of renal function, we found that only one-third of these patients experienced a rapid loss of function, while the others had slowly declining or unchanging renal function despite the presence of proteinuria and severe diabetic retinopathy. Among the many baseline variables examined, only elevated cholesterol and elevated systemic blood pressure were predictors of a rapid loss of renal function. Patients with this rapid loss of renal function also had the highest risk of death due to cardiovascular causes, as well as all causes. Once again, hypercholesterolemia was the major predictor of these deaths. In conclusion, efforts should be undertaken early to identify patients who are rapidly losing renal function so that interventions to modify systemic blood pressure and hypercholesterolemia may prevent or postpone the development of renal failure and death in patients with IDDM.
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PMID:Hypercholesterolemia--a determinant of renal function loss and deaths in IDDM patients with nephropathy. 815 81

In IDDM or NIDDM, the total plasma cholesterol and triglycerides are usually within normal limits when the blood glucose is controlled. Marked hypertriglyceridemia can develop with loss of glycemic control and is often due to superimposed genetic abnormalities in lipoprotein metabolism. Tight control in IDDM usually reduces LDL and VLDL to normal levels and may raise HDL above the normal range. Low HDL cholesterol and mild to moderate elevations of VLDL triglyceride are common in NIDDM if obesity or proteinuria is also present. Both HDL and LDL may be smaller and more dense and may be enriched with triglyceride as compared with cholesterol. These abnormalities may require weight loss for control. The increased incidence of cardiovascular disease in diabetes is unexplained but is amplified by the well-defined cardiovascular risk factors. The new American Diabetes Association guidelines call for treatment of high triglycerides and LDL cholesterol to be aggressively reduced. Triglycerides should be under 200 mg/dL, are considered borderline high between 200 and 400 mg/dL, and high when above 400 mg/dL. Low HDL is defined as less than 35 mg/dL. Control of obesity with diet and exercise and reduced intake of saturated fat and cholesterol are important first steps. If needed, drug therapy is appropriate to reduce LDL to levels below 130 mg/dL in all adult diabetics and below 100 mg/dL in those with cardiovascular disease.
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PMID:Lipoprotein disorders in diabetes mellitus. 828 28

On the whole, diabetic microangiopathy can be understood as the clinical renal-retinal syndrome. About 10% of all diabetics die of end-stage renal failure, more frequent in IDDM. With an incidence of 14% diabetic retinopathy is one of the major causes of blindness in adulthood. In the non-proliferative state, the pathological changes are limited to the retina, whereas the alterations affect both retina and vitreous in the proliferative state. Photocoagulation is the treatment of choice. If photocoagulatory treatment is not possible because of cataract, vitreous surgery (pars-plana vitrectomy) could improve visual prognosis. The clinical features hypertension, proteinuria and finally renal failure define the term "diabetic nephropathy". The increased intraglomerular pressure is the main pathological alteration of incipient nephropathy. Microalbuminuria essentially determines the prognosis: in IDDM it concerns the incidence of a manifest nephropathy, in NIDDM the excessively increased incidence of cardiovascular mortality. Sonographically, the kidneys are large with bright and wide parenchyma. Along with the development of end-stage renal disease the kidney size diminishes. According to Mogensen, nephropathy is divided into five stages: Stage 1, the early stage, is defined by hypertrophy and hyperfiltration. Stage 2 shows incipient structural changes without any clinical findings. Stage 3 is characterised by persistent microalbuminuria. Stage 4 leads to increasing renal failure and stage 5 to end-stage renal disease and the necessity of dialysis treatment. Incipient nephropathy demands a strict treatment of both hypertension and diabetes. In the meantime, ACE inhibitors are the treatment of choice. In case of dialysis treatment continuous ambulant peritoneal dialysis (CAPD) is usually preferred.
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PMID:[Diabetic microangiopathy]. 847 38

A total of 412 Hong Kong Chinese diabetic patients were studied on at least two occasions 8-16 weeks apart. Although 28% were insulin-treated, only 3.6% had insulin-dependent diabetes (IDDM). In the remaining 397 patients with non-insulin-dependent diabetes (NIDDM), the mean (s.d.) body mass index (BMI) was 24.4 +/- 3.2 kg/m2 in females and 24.2 +/- 3.2 kg/m2 in males. Obesity was present in 17% of males (BMI > 27 kg/m2) and 40% of females (BMI > 25 kg/m2). Established hypertension was present in 49%. Abnormal albuminuria, defined as a mean urinary albumin/creatinine (UA/Cr) ratio greater than 5.4 mg/mmol based on two random spot urine samples, was present in 47%. On stepwise multiple regression analysis, UA/Cr ratio (R2 = 0.34, F = 65.4, P < 0.001) showed significant associations with systolic blood pressure (standardized regression coefficient beta = 0.40, P < 0.001), plasma creatinine concentration (beta = 0.27, P < 0.001) and glycosylated haemoglobin (beta = 0.20, P < 0.001). While the prevalence of hypertension increased with increasing severity of proteinuria, 40% of normoalbuminuric patients had hypertension. Among patients diagnosed before the age of 35 (n = 67), 52% were insulin-treated although only 10% were insulin-dependent. Among these NIDDM patients of young onset (n = 59), obesity was present in 25% of males and 56% of females. Overall, 18% of these patients had a blood pressure greater than 140/90 mmHg and 27% had abnormal albuminuria. In Hong Kong Chinese, diabetes mellitus is predominantly non-insulin-dependent even in the young. Obesity is more prevalent among females. Abnormal albuminuria is relatively common and is closely associated with hypertension and glycaemic control. In the light of increasing prevalence of diabetes among overseas Chinese, our findings may have important implications in the management of Chinese diabetic patients.
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PMID:Obesity, albuminuria and hypertension among Hong Kong Chinese with non-insulin-dependent diabetes mellitus (NIDDM). 849 35

Increased susceptibility of LDL to oxidation has been shown to be associated with the presence of coronary heart disease and may account for the accelerated vascular disease seen in diabetes. The response of LDL to in vitro oxidative stress has been proposed as a measure of the predisposition of LDL to the in vivo subendothelial oxidative stress. Increased susceptibility to oxidation has been demonstrated recently in diabetic patients with poorly controlled IDDM. Thus, we conducted studies to determine whether the increased susceptibility of LDL to oxidation was secondary to diabetes per se or to the level of glycemic control. Fifteen IDDM patients with good glycemic control and with no evidence of macrovascular disease or proteinuria were compared with healthy age-, sex-, race-, and BMI-matched nondiabetic subjects. Fasting blood glucose levels averaged 12.1 +/- 1.1 (mean +/- SE) vs. 4.9 +/- 0.1 mmol/l in the diabetic versus the control groups, respectively. HbA1c levels averaged 7.7 +/- 0.5 vs. 4.4 +/- 0.2%, reflecting well-controlled diabetes (P < 0.0001). Total, LDL, VLDL, and HDL cholesterol, triglyceride, and lipoprotein(a) levels did not differ between the groups. The particle size, lipid composition, fatty acid content, antioxidant content, and glycation were similar for LDL isolated from both groups. A rapid LDL preparation technique was used to compare LDL susceptibility to oxidation under the following conditions: final LDL cholesterol concentration of 100 microg/ml, 5 micromol/l of CuCl2 at 25 degrees C. There was no difference in the susceptibility to in vitro oxidation of LDL isolated from IDDM patients compared with control subjects. There was no correlation of glycemic control with any of the parameters of the in vitro oxidation of LDL. LDL from patients with well-controlled IDDM does not differ in composition or in susceptibility to in vitro oxidative stress compared with LDL from nondiabetic subjects.
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PMID:LDL from patients with well-controlled IDDM is not more susceptible to in vitro oxidation. 863 50

Elevated serum sialic acid (SSA) predicts cardiovascular disease in the non-diabetic population and is also associated with the presence of microalbuminuria and clinical proteinuria in patients with insulin-dependent diabetes (IDDM). We have studied 121 patients with IDDM of long duration (mean duration 25.2 years) to investigate the relationship of SSA concentrations to the presence of retinopathy, nephropathy, and neuropathy. SSA levels were elevated in patients with retinopathy (0.578 +/- 0.161 gl-1, n = 98) when compared with those without retinopathy (0.468 +/- 0.145 gl-1, n = 23, p = 0.002). Patients with nephropathy (urinary albumin:creatinine ratio of > 3 mg mmol-1 in all of three early morning specimens of urine) also had raised SSA levels (0.625 +/- 0.169 gl-1, n = 30) compared with those without nephropathy (0.533 +/- 0.160 gl-1, n = 91, p = 0.006). There was a significant correlation of SSA with urinary albumin:creatinine ratio (correlation coefficient 0.33, p < 0.001). SSA levels were not related to the presence or absence of neuropathy (0.567 +/- 0.181 gl-1, n = 28, vs 0.533 +/- 0.160 gl-1, n = 93, p = 0.92, respectively). In conclusion, retinopathy and nephropathy but not neuropathy are associated with increased SSA levels in patients with IDDM. The significance of this is not yet clear but it is possible that sialic acid is involved in the pathophysiology of microvascular disease in IDDM.
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PMID:Serum sialic acid and the long-term complications of insulin-dependent diabetes mellitus. 868 44

Patients with diabetic nephropathy face an increased risk of dying due to cardiac causes. The aim of this follow-up trial was to describe the association between the length of the QT interval, as a marker of myocardial electrical stability, and the risk of death in insulin-dependent (IDDM) diabetic patients with overt diabetic nephropathy. A consecutive sample of 85 IDDM patients with overt diabetic nephropathy (i.e. persistent proteinuria > or = 500 mg/24 h) were followed-up until death or for a period of 5-13 years. QT intervals were measured once at baseline in a 12-lead ECG and corrected for heart rate (QTc). During the follow-up period 33 patients (39%) died. In the Cox proportional hazards model independent predictors of death were age (p = 0.0007), the length of the maximum QTc period (p = 0.0049), presence of autonomic neuropathy (p = 0.0068), diabetes duration (p = 0.0163) and RR variation (p = 0.0395). In conclusion, in nephropathic IDDM patients QT prolongation is associated with an increased mortality risk which is independent of the presence of autonomic neuropathy. Further studies are needed to determine whether this risk might be reduced by therapeutic interventions.
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PMID:Prolonged QT interval as a predictor of mortality in diabetic nephropathy. 872 Jun 6

Hypertension is both an exacerbating factor for, and a consequence of, diabetic renal disease. In diabetic patients, hypertension is associated with increased total body sodium secondary to impaired renal excretion, and increased vascular reactivity, notably to catecholamines and angiotensin II. The mechanisms causing these changes are discussed. Control of hypertension will slow the progression of diabetic renal disease and the inexorable decline in GFR. A number of studies now suggest that in proteinuric IDDM and NIDDM patients angiotensin converting enzyme inhibitors (ACE-I) may have additional reno-protective effects in addition to their hypotensive action. In addition ACE-I will reduce proteinuria and delay the onset of diabetic nephropathy in normotensive microalbuminuric IDDM and NIDDM patients. Use of ambulatory blood pressure monitoring indicates that such patients may not be truly 'normotensive'. On-going studies seem to suggest that the most reno-protective blood pressure is the lowest one achievable, as long as the patient remains asymptomatic. Further studies are required to assess the impact of blood pressure control, and especially ACE-I, on the incidence of end-stage renal failure. In addition, more direct comparisons between different pharmacological agents in early diabetic renal disease would be useful.
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PMID:The management of hypertension in diabetes: with special reference to diabetic kidney disease. 873 20

In IDDM, microalbuminuria (urinary albumin excretion rate (AER) of 20-200 micrograms/min) is a predictor of persistent proteinuria and diabetic nephropathy. Early intervention may prevent or reduce the rate of progression of renal complications. The Micral-Test strip can be used to establish a semi-quantitative estimate of AER. We assessed the field performance of the Micral-Test strip in detecting microalbuminuria in the EUCLID study, an European wide, 18 centre study of 530 IDDM participants, aged 20 to 59 years. People with macroalbuminuria were excluded. On entry, all participants had albumin concentrations from two overnight urine collections measured by a central laboratory, and the corresponding Micral-Test performed on the two collections locally. a cut off of > or = mg/l albumin from the first Micral-Test, to detect a centrally measured albumin concentration > or = 20 mg/l, yielded 29 (5.8%) false negative results and 58 (11.6%) false positive results (sensitivity 70%, specificity 87%). The mean AER, from two collections, was compared with the corresponding 'pooled' Micral-Test results (mean of the two readings). Receiver Operating Characteristic (ROC) curves were used to assess if there was a suitable 'pooled' Micral-Test result for screening microalbuminuria. A 'pooled' Micral-Test result (> or = 15 mg/l) was used to detect mean AER > or = 20 micrograms/min (sensitivity 78%, specificity 77%). This 'pooled cut-off' had already been used for screening on to the study and led to an over-estimate (154 vs. 77) of the true number of microalbuminuric participants on the study. In conclusion, our findings suggest that the Micral-Test strip is not an effective screening tool for microalbuminuria, using the 'pooled' result from two measurements did not improve the sensitivity of the test.
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PMID:The use of the Micral-Test strip to identify the presence of microalbuminuria in people with insulin dependent diabetes mellitus (IDDM) participating in the EUCLID study. 879 7


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