Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between 1988 and 1992, 565 type 2 diabetic patients were examined for nephropathy and diabetes-associated diseases during hospital treatment. Stages of nephropathy were defined as no clinical sign of nephropathy (N = 280), microalbuminuria (N = 38), overt proteinuria (N = 105), impaired renal function (N = 55), and chronic dialysis therapy (N = 87). In dialyzed patients, HbA1c averaged 6.8%, and, in the other groups, HbA1c was between 7.6% and 8.3% (normal range, 3.8%-6.1%). Cataract was not associated with the severity of nephropathy. Stroke was most common in the stage of renal insufficiency (34%). The following complications, as found in medical history or as current event, showed a significant association with the stage of nephropathy and occurred most frequently in dialysis patients (percentage is displayed for patients with nephropathy in comparison to diabetic dialysis patients): hypertension (53%-89%), left ventricular hypertrophy (39%-81%), myocardial infarction (14%-36%), peripheral vascular disease (27%-77%), foot lesions (7%-75%), minor or major amputations (3%-23%), proliferative retinopathy (6%-46%), blindness (2.9%-16.1%), and internal carotid artery stenosis (15%-36%). In this preselected cohort of diabetic patients, a high morbidity was found already without nephropathy that increased several-fold in the course of the development of nephropathy. Our data identify patients with diabetic nephropathy as a high-risk group for excess morbidity.
 ...
PMID:Morbidity in 565 type 2 diabetic patients according to stage of nephropathy. 955 88

The study was done to assess whether there was a familial aggregation of diabetic kidney disease (DKD) in Type 2 diabetic subjects. The profile of associated complications was also studied. Two groups of diabetic siblings of Type 2 diabetic patients, matched for age, body mass index (BMI) and duration of diabetes mellitus were studied. The siblings also had Type 2 diabetes. Group A comprised of siblings of probands with diabetic nephropathy and retinopathy (n = 30, M:F = 20:10) and Group B were siblings of probands without diabetic nephropathy or microalbuminuria (MAU) (n = 30, M:F = 14:16). Anthropometry, measurement of blood pressure and tests for proteinuria, MAU and retinopathy and ECG and biothesiometry were carried out for all study subjects. Persistent proteinuria was present in 15 (50%) siblings in group A and none in group B. MAU was detected in 26.7% (n = 7) in Group A and 3.3% (n = 1) in Group B (P = 0.057). Thus a total of 22 out of 30 cases in Group A had albuminuria. In Group A, seven (23.3%) had proteinuria and hypertension. Hypertension was present in nine (30.0%) in group A, and in five (16.7%) in group B (NS). Occurrence of retinopathy was found to be significantly higher in group A than in group B (33.3 vs 6.7%, chi2 = 5.1, P = 0.023). Abnormal ECG changes were present in 10% and 6.7% in Group A and Group B, respectively. In Group A, one patient had peripheral vascular disease (PVD) while in Group B none had PVD. A comparison of sib pairs, matched for age, duration of diabetes and the level of metabolic control showed that there was strong familial clustering of diabetic kidney disease in south Indians with Type 2 diabetes. This was independent of the familial clustering of diabetes. Prevalence of other vascular complications were also higher in Group A.
 ...
PMID:Familial aggregation of diabetic kidney disease in Type 2 diabetes in south India. 1036 25

The renin-angiotensin system is thought to play an important role in the pathophysiology of kidney disease in diabetes. Previous studies have shown a possible association between the D allele of the angiotensin converting enzyme (ACE) gene, known to be associated with higher circulating levels of ACE, and increased risk of developing nephropathy in NIDDM. The present study investigated the distribution of ACE gene genotypes in the general population and patients with NIDDM, the association between the D allele and diabetic nephropathy, and the association between the ACE genotype and involvement of other target organs in NIDDM. The ACE genotype (insertion/deletion I/D) was determined in all subjects, subsequently divided into 3 groups based on their polymorphism (DD, DI and II). The presence of nephropathy was defined by an albumin-creatinine ratio of 30 mg/g or greater (mean of 2 first morning urine samples). In the general population most had the D allele (DD or ID) and a minority the II genotype. There was no association between genotype and hypertension, ischemic heart disease, hyperlipidemia, and cerebrovascular or peripheral vascular disease. In diabetics the genotype distribution was not different from that in the general population. Within the diabetic group, there was no association between genotype and hypertension, hyperlipidemia, duration of diabetes, or HbA1C levels. Nephropathy, found in 81 of the 156 with NIDDM, was not associated with genotype. Diabetic nephropathy was not associated with retinopathy, neuropathy, or ischemic heart, cerebrovascular or peripheral vascular disease. We conclude that in the population sampled, there was no association between the D allele of the ACE gene and the risk of developing nephropathy in NIDDM.
 ...
PMID:[Angiotensin converting enzyme (ACE) gene polymorphism in a diabetic cohort and diabetic nephropathy]. 1095 9

This study examined the association between urinary markers of early diabetic nephropathy and non-renal diabetic complications in 946 patients with type 2 diabetes mellitus. The association with hypertension was also studied. Data on macrovascular complications (ischaemic heart disease, stroke, peripheral vascular disease) and microvascular complications (retinopathy, peripheral neuropathy) were obtained from case records and clinical examination. Urine samples collected were analysed for albumin, beta(2)-microglobulin, retinol-binding protein (RBP), and N-acetyl-beta-D-glucosaminidase (NAG). Results showed that urinary albumin, RBP and beta(2)-microglobulin levels were higher in patients with macro- and/or microvascular complications, compared to those without. NAG levels were higher only in patients with both types of complications. A higher proportion of patients with complications had abnormally raised urinary protein and enzyme levels, compared to those without. Patients with associated hypertension had higher urinary levels of albumin and beta(2)-microglobulin, regardless of whether complications were present or not. RBP excretion was, however, markedly higher only in patients with microvascular complications, whereas hypertension did not influence NAG excretion. Urine albumin and RBP excretion were predictive of microvascular, as well as both macrovascular and microvascular complications, whereas NAG excretion was predictive of macro- and microvascular complications. These findings could mean that increased urinary protein and enzyme excretion were associated with more severe disease in these patients.
 ...
PMID:Urinary protein excretion in Type 2 diabetes with complications. 1111 88

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD). The United States Renal Data System's report indicates that survival of diabetic patients has improved but continues to be reduced compared with that of nondiabetic patients. Several ways to decrease morbidity and mortality in diabetic patients are discussed: (1) Instructions and treatment in the predialysis period markedly influence compliance of patients, and this plays a determinant role in development and progression of diabetic complications before and during maintenance hemodialysis. (2) After the start of hemodialysis therapy, insulin therapy must be adjusted and respect impaired glucose use and prolongation of insulin half-life. (3) By avoiding of puncture of veins prospectively used for arteriovenous fistulae and timely installation of the fistulae, native arteriovenous fistulae can be achieved in more than 70% of diabetic patients. (4) Hypertension, left ventricular hypertrophy, and cardiovascular problems commonly found in diabetic patients require optimal removal of fluid overload. This is difficult to achieve in the presence of accelerated arteriosclerosis and autonomic polyneuropathy in diabetic patients and requires long and smooth dialysis procedures. (5) Infected necroses caused by diabetic polyneuropathy and peripheral vascular disease require appropriate therapy by experienced nephrologists and surgeons.
 ...
PMID:Attaining long-term survival when treating diabetic patients with ESRD by hemodialysis. 1117 24

Diabetic nephropathy is a leading cause of end-stage renal disease, and its prevalence and incidence vary greatly from country to country, being highest in the United States and Japan. In the United States, diabetic nephropathy accounts for approximately 40% of patients beginning renal replacement therapy. Type 2 diabetes is the largest and fastest-growing single disease that requires dialytic therapy. Most patients succumb to cardiovascular causes, including coronary artery disease and myocardial infarction, sudden death, cardiac failure, and stroke. The survival from cardiovascular complications is relatively better in East Asian countries and to a lesser extent in Mediterranean countries compared with countries that traditionally have higher cardiovascular death rates. Peripheral vascular disease and sepsis contribute to increased morbidity and mortality. Amputation of limbs secondary to peripheral vascular disease in particular has adverse effects on rehabilitation. Asymptomatic hypoglycemia may develop in hemodialysis patients. Such hypoglycemia is not associated with a hormonal balance but is postulated to be due to blunted hormonal response to hypoglycemia. Diabetic muscle infarction is another rare complication attributable to diabetic microangiopathy; magnetic resonance imaging may help in the diagnosis. Risk factors for increased mortality include advanced age, poor glycemic control before starting dialysis, smoking, left ventricular hypertrophy, hypoalbuminemia, and neuropathy, in particular, autonomic dysfunction. In addition to adequate dialysis, it is advisable to achieve tight blood pressure control (at least <140/90 mm Hg and preferably much lower), better blood glucose control (hemoglobin A(1c), <7%), correction of nutritional status, and appropriate foot care.
 ...
PMID:Hemodialysis in diabetic patients. 1157 54

Diabetic nephropathy is one of the major causes of end-stage renal disease and is often associated with other macrovascular complications such as ischemic heart disease and peripheral vascular disease. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (AIIR) have both been shown to have a protective effect on the progression of diabetic nephropathy and have thus become the first choice for treatment of hypertension and/or renal involvement in patients with diabetes. However, most of these patients, especially those with type 2 diabetes, require two of more medications in order to reduce their blood pressure to the levels, which have been proposed in recently published consensus papers. These target blood pressure levels are 130/80 mm Hg in diabetic subjects with proteinuria of up to 1 g/day and 125/75 mm Hg in those with proteinuria in excess of 1 g/day. Combinations of different medications may have a synergistic effect. Some of the early studies using a combination of either a nondihydropyridine or a dihydropyridine calcium channel blocker with ACE-I demonstrated a synergistic effect on proteinuria in patients with diabetic nephropathy. However, these studies have not been substantiated, but calcium channel blockers, with their proven ability to reduce blood pressure, play an important role in the treatment of patients with diabetic nephropathy and hypertension. The combination of ACE-I with AIIR may have several theoretical advantages. Many studies using this combination have been performed in animal models of diabetes and in patients with diabetic and nondiabetic renal disease. Some of these studies have demonstrated a synergistic effect of the combination on proteinuria or hypertension, but the results have not been consistent in all studies. It may be concluded that, until additional studies provide more convincing evidence, this combination could be used in patients whose proteinuria or hypertension has not responded to either one of the agents as monotherapy or to a combination of other medications.
 ...
PMID:Combination antihypertensive therapy in the treatment of diabetic nephropathy. 1216 70

Here we report the utility of a molecular epidemiologic approach for common, polygenic diseases. Since 1992, the angiotensin I-converting enzyme (ACE) deletion/deletion (D/D) genotype has been linked to several cardiovascular diseases, including diabetic nephropathy. Earlier, the ACE D/D genotype had been associated with excess tissue ACE activity. We have observed an association of the ACE D/D genotype with a large number of common diseases, including chronic renal failure due to non-insulin-dependent diabetes mellitus or hypertension, hypertensive peripheral vascular disease, and emphysema [chronic obstructive pulmonary disease (COPD)]. ACE inhibitors have been in clinical use since 1977 and have a well-known safety record. Armed with the knowledge that ACE overactivity was associated with their disease, we gave what was intended to be a tissue ACE-inhibitory dose of a hydrophobic ACE inhibitor to 800 Caucasian and African-American male patients with hypertension and 200 Caucasian and African-American male patients with chronic renal failure, over a period of 3 years. We here report their outcomes, which include those of two patients with end-stage hypertensive peripheral vascular disease and one patient with end-stage emphysema (COPD). As a group, the outcomes are superior to what is available in the literature. This experience suggests the power of pharmacogenomics to improve clinical outcomes for common diseases safely, quickly, and inexpensively, if effective drugs already exist.
 ...
PMID:From pharmacogenomics to improved patient outcomes: angiotensin I-converting enzyme as an example. 1239 47

Diabetes mellitus increases the risk for hypertension and associated cardiovascular diseases, including coronary, cerebrovascular, renal and peripheral vascular disease. The risk for developing cardiovascular disease is increased when both diabetes and hypertension co-exist; in fact, over 11 million Americans have both diabetes and hypertension. These numbers will continue to climb, internationally, since the leading associated risk for diabetes development, obesity, has reached epidemic proportions, globally. Moreover, the frequent association of diabetes with dyslipidemia, as well as coagulation, endothelial, and metabolic abnormalities also aggravates the underlying vascular disease process in patients who possess these comorbid conditions. The renin-angiotensin-aldosterone system (RAS) and arginine vasopressin (AVP) are overactivated in both hypertension and diabetes. Drugs that inhibit this system, such as ACE inhibitors and more recently angiotensin receptor antagonists (ARBs), have proven beneficial effects on the micro- and macrovascular complications of diabetes, especially the kidney. The BRILLIANT study showed that lisinopril reduces microalbuminuria better than CCB therapy. Numerous other long-term studies confirm this association with ACE inhibitors including the HOPE trial. Furthermore, the European Controlled trial of Lisinopril in Insulin-dependent Diabetes (EUCLID) study, showed that lisinopril slowed the progression of renal disease, even in individuals with mild albuminuria. In fact, there are now five appropriately powered randomized placebo-controlled trials to show that both ACE inhibitors and ARBs slow progression of diabetic nephropathy in people with type 2 diabetes. These effects were shown to be better than conventional blood pressure lowering therapy, including dihydropyridine CCBs. In patients with microalbuminuria, ACE inhibitors and ARBs reduce the progression of microalbuminuria to proteinuria and provide a risk reduction of between 38 and 60% for progression to proteinuria. This is important since microalbuminuria is known to be associated with increased vascular permeability and decreased responsiveness to vasodilatory stimuli. Recently, increased AVP levels have been lined to microalbuminuria and hyperfiltration in diabetes. The microvascular and macrovascular benefits of ACE inhibition, ARBs and possible role of AVP antagonists in diabetic patients will be discussed, as will be recommendations for its clinical use.
 ...
PMID:Treatment of the diabetic patient: focus on cardiovascular and renal risk reduction. 1243 44

The hyperglycemic milieu in diabetes results in the formation of advanced glycation end products (AGEs) that predominantly act through specific receptors, particularly the receptor for AGEs (RAGE). Two functional polymorphisms in the promoter of the RAGE gene (-429 T/C and -374 T/A) and one in the AGE binding domain in exon 3 (G82S) were studied in 996 Finnish type 1 diabetic patients. In patients with poor metabolic control (HbA(1c) >9.5%), the AA genotype of the -374 T/A polymorphism was more common in those with a normal albumin excretion rate than in those with proteinuria (30 vs. 10%, P = 0.01). We observed less coronary heart disease (6 vs. 14%, P < 0.05), acute myocardial infarction (2 vs. 14%, P = 0.01), and peripheral vascular disease (2 vs. 14%, P < 0.05) in patients with the AA genotype of the -374 T/A polymorphism than in those with the TT + TA genotype. Thus, the association between the RAGE -374 T/A homozygous AA genotype and cardiovascular disease as well as albumin excretion in type 1 diabetic patients with poor metabolic control suggests a gene-environment interaction in the development of diabetic nephropathy and cardiovascular complications.
 ...
PMID:The functional -374 T/A RAGE gene polymorphism is associated with proteinuria and cardiovascular disease in type 1 diabetic patients. 1260 36


<< Previous 1 2 3 4 5 6 Next >>