Gene/Protein Disease Symptom Drug Enzyme Compound
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 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately 30% of patients with type 1 and type 2 diabetes develop diabetic nephropathy. Apart from metabolic control, genetic predisposition plays an important role in its genesis. Analysis of intermediate phenotypic markers showed that the activity of Na/Li- and Na+/H(+)-countertransport is increased in patients with diabetic nephropathy. The renin-angiotensin system is of crucial importance as a system for therapeutic intervention and as genetic marker for susceptibility to renal disease. Consequently, the analysis of molecular genetic markers has focused on a polymorphism in the gene for the angiotensin II converting enzyme (ACE). However, the analysis of the I/D-polymorphism with respect to development of diabetic nephropathy in type 1 and type 2 diabetes has yielded conflicting results, at least in type 1 diabetes. These discrepant results may be due to differences in definition, sample size and ethnic background of the patients. In IgA glomerulonephritis it has been shown that the DD genotype (which is correlated with higher serum and tissue ACE activity compared to II genotype) is associated with a more rapid deterioration of renal function. The same adverse effect of the DD genotype could also be demonstrated in patients with diabetic nephropathy. Two studies examined the response to treatment according to the different genotypes, with contradictory results. A Japanese study showed a more pronounced reduction in proteinuria under ACE inhibitor treatment in patients with DD genotype, whereas a Danish study showed that patients with the DD genotype exhibited a steeper decline in renal function despite ACE inhibitor treatment. The data available for other candidate genes are fragmentary and negative throughout.
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PMID:Genetic determinants of diabetic renal disease and their impact on therapeutic interventions. 940 16

The clinical features and quantitative renal morphometry, including the index of mesangial expansion (IME), the index of arteriolar hyalinous change (IAHC), the percentage of globally sclerosed glomeruli (%GS), and interstitial volume fraction for total renal cortex (Vv int/T) of 67 Japanese non-insulin dependent diabetes mellitus (NIDDM) patients were examined. For the total subject population, Vv int/T correlated with urine protein, creatinine clearance, blood pressure, IME, IAHC and %GS, but not with duration of NIDDM. No significant difference in interstitial expansion between normo- and microalbuminuric patients was observed, and Vv int/T did not correlate with urine albumin excretion rate in those patients. However, in the area without hyalinized glomeruli and atrophic tubules, we found significant interstitial expansion and thickening of the tubular basement membrane (TBM) in patients without overt proteinuria as compared with those in the age-matched minimal change control group. This study confirmed that interstitial expansion in NIDDM progresses in parallel with glomerular and arteriolar lesions and that the expansion occurs concurrently with TBM thickening before the appearance of proteinuria.
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PMID:Tubulointerstitial lesions in non-insulin dependent diabetes mellitus. 940 56

Our objective was to assess mean transit time (MTT) and initial uptake, both parameters derived from the renal retention function (RRF), in the study of renal function in patients with diabetic nephropathy. We studied 25 patients, 7 with type I diabetes mellitus and 18 with type II diabetes mellitus, all of whom fulfilled the criteria for diabetic nephropathy with proteinuria and/or retinopathy. We found a statistically significant correlation between initial uptake and the other biochemical and renographic parameters studied except proteinuria: serum creatinine (r = 0.66, P < 0.002), creatinine clearance (r = 0.61, P < 0.003), glomerular filtration rate (r = 0.74, P < 0.003) and effective renal plasma flow (r = 0.66, P < 0.003). The other renographic parameters studied (maximal activity of the conventional renogram and MTT of the deconvoluted renogram) did not show any correlation. Initial uptake is a semi-quantitative renographic parameter that can provide complementary information to biochemical data and it may be useful in the management of diabetic nephropathy, especially in patients with high serum creatinine or creatinine clearance.
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PMID:Renogram deconvolution in the management of diabetic nephropathy: utility of the measurement of initial tracer uptake. 942 2

This study was undertaken to investigate the prevalence of diabetes complications and level of glycaemic and blood pressure control in Black African patients at the primary care level in the public sector Cape Town, South Africa. A stratified random sample of 300 patients attending the three largest ambulatory diabetes clinics in community health centres in Black African residential areas of Cape Town (100 patients from each) during the last 6 months of 1992 was selected. Each patient had a clinical examination, interview, and 1 year retrospective record review. Eighty-one per cent of the sampled patients were reviewed, 90% were non-insulin-dependent (NIDDM) and 10% were treated with insulin. The mean duration of diabetes was 8 (range 0-28) years. Acceptable glycaemic control was present in 49.4% (95% Confidence Intervals 45.6-53.5) of patients while 38.5% (CI 24.8-52.2) of hypertensive patients had acceptable blood pressure control. The prevalence of any grade of retinopathy was 55.4% (CI 48.90-62.9), proliferative and preproliferative retinopathy 15.6% (CI 8.5-22.8), cataracts 7.9% (CI 4.4-11.4), peripheral neuropathy 27.6% (CI 15.2-39.4), absent foot pulses 8.2% (CI 5.2-12.6), amputations 1.4% (CI 0.4-2.4), persistent proteinuria 5.3% (CI 2.5-8.1) and an elevated albumin-creatinine ratio 36.7% (CI 29.0-44.4). The complications were not documented in the clinic records of the preceding year with the exception of 1 patient with absent foot pulses and the 12 patients with proteinuria. The high prevalence of suboptimal glycaemic and blood pressure control as well as complications of diabetes, largely unrecorded in the preceding years' clinic notes, demonstrates the deficiency of and need for preventative diabetes care at the primary care level. The design, institution, and evaluation of effective intervention programmes are a priority to improve the quality of care provided and the health of diabetic patients.
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PMID:Audit of public sector primary diabetes care in Cape Town, South Africa: high prevalence of complications, uncontrolled hyperglycaemia, and hypertension. 945 36

The aim of this study was to assess the prevalence of long-term complications in a large sample of French NIDDM patients. Therefore, 427 NIDDM patients 35-74 years old were recruited in ten centers. Standardized clinical criteria and central reading for retinal and electrocardiographic changes were used to assess the presence of complications. The prevalence rates of complications were 29.7% and 3.3% for background and proliferative retinopathy; 21.8%, 6.1%, and 2.8% for microalbuminuria, proteinuria, and renal insufficiency; 19.9 and 11.7% for asymptomatic and symptomatic pheripheral neuropathy; 8.2% for orthostatic hypotension; 10.1% and 8.4% for angina pectoris and myocardial infarction; and 13.1% and 6.3% for mild and moderate to severe peripheral vascular disease, respectively. In conclusion, prevalence rates in this study were lower than in most studies from other countries.
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PMID:Low prevalence of long-term complications in non-insulin-dependent diabetes mellitus in France: a multicenter study. CODIAB-INSERM-ZENECA Pharma Study Group. 955 86

The aim of this study was to evaluate the influence of endogenous insulin levels and of insulin administration on coronary heart disease (CHD) and on mortality in a cohort of patients with long-standing non-insulin-dependent diabetes mellitus (type 2). In a cross-sectional study, 93 patients (known duration 17 +/- 8 years, mean+/-SD) with poor metabolic control (glycosylated hemoglobin, HbA1C 9.3%+/-2.09%) were evaluated for CHD, for insulin release (C-peptide), for clinical and metabolic parameters including body mass index (BMI), smoking habits, arterial blood pressure (BP), blood lipids, kidney function, and proteinuria. Life status was ascertained 5 years later by direct examination or through death certificates. At entry, 54 out of 93 patients had CHD; after 5 years, 25 patients had died. Comparisons performed on patients of the same age range showed that patients with CHD (34 vs 24) had a greater BMI, higher diastolic BP, higher creatinine, triglyceride and uric acid levels, and higher fasting and i.v. glucagon-stimulated C-peptide release. By logistic stepwise regression analysis, fasting C-peptide and triglycerides were independently associated with CHD. In the follow-up study, surviving patients (39 vs 19) showed at baseline lower triglyceride and creatinine levels, were less frequently affected by CHD, and received lower doses of insulin; by logistic stepwise regression analysis, presence of CHD, dose of insulin, and creatinine levels were independent risk factors for mortality. These data indicate that in patients with long-standing type 2 diabetes mellitus and poor metabolic control, CHD and overall mortality are related to insulin release and to insulin administration, suggesting that markers of insulin resistance represent additional risk factors for CHD and for mortality. Reduction of insulin resistance, together with achievement of good metabolic control, might prevent morbidity and mortality in long-standing type 2 diabetes mellitus.
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PMID:Markers of insulin resistance are associated with cardiovascular morbidity and predict overall mortality in long-standing non-insulin-dependent diabetes mellitus. 962 90

It has been suggested that hereditary risk for hypertension and cardiovascular disease (CVD) as well as intrauterine growth may be involved in the pathogenesis of diabetic nephropathy. In the present study, we investigated the influence of familial and perinatal risk factors on the occurrence of micro- and macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with > or =5 years' duration of IDDM was screened for microalbuminuria. Data on family history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth weight, gestational age, and duration of breastfeeding; and maternal education, smoking, hypertension, and proteinuria during pregnancy were collected. We identified 75 patients with an albumin excretion rate > or =15 microg/min in more than two overnight urinary samples and compared them in a nested case-control study with three normoalbuminuric control subjects per patient from the same cohort, matched for diabetes duration. Perinatal factors were analyzed in all patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225 control subjects. In univariate analysis, hypertension in parents (odds ratio [OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were significantly associated with the development of micro- and macroalbuminuria. When adjusted for other familial and perinatal factors, current mean blood pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration, using logistic regression analyses, only parental hypertension in all patients and maternal smoking during pregnancy and low level of maternal education in full-term patients were independent risk factors. When patients with poor glycemic control were analyzed separately, familial CVD, poor metabolic control, parental hypertension, maternal smoking during pregnancy, and level of maternal education were independent risk factors, with the adjusted OR markedly increased, compared with the matched subgroup with better HbA1c. In conclusion, familial hypertension and CVD, maternal smoking during pregnancy, and low level of maternal education may independently increase the risk for incipient nephropathy in full-term offspring who later develop IDDM. Current poor glycemic control seemed to increase the effect of these risk factors.
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PMID:Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM patients. 964 37

In this retrospective study, the prevalence of chronic microangiopathic complications was determined in 474 Chinese patients with non-insulin dependent diabetes mellitus (NIDDM) who presented within 1 year of diagnosis to the diabetes clinic from January 1990 to December 1996. Mean age (+/- S.E.) was 53.6 (+/- 0.6) years. The overall prevalence of retinopathy was 21.9%. A significant increase was observed from 1990 to 1994 (P < 0.005), with the prevalence being 14.8, 13.0, 24.5, 32.3 and 35.4%, respectively, in consecutive years. A decreasing prevalence was seen from 1994 to 1996 (P < 0.001), being 8.2 and 7.4% in 1995 and 1996, respectively. A total of 95% of patients had nonproliferative retinopathy--proliferative retinopathy was found in 5% only. The overall prevalence of clinical nephropathy (proteinuria > 0.5 g/day) was 3.7%. Clinical neuropathy (increased vibration perception threshold) was found in 12.8% of patients. Patients with retinopathy and neuropathy were older (P < 0.0001 and P < 0.005, respectively) than those without the complications and systolic hypertension was more prevalent in patients with retinopathy (P < 0.05). In conclusion, a high prevalence of diabetic microangiopathic complications, especially of retinopathy, is present in newly diagnosed NIDDM patients in our population. It remains to be determined whether the changing prevalence of retinopathy at diagnosis bears any relationship to the increasing public awareness of diabetes and its complications in Hong Kong in recent years. Examination for chronic microangiopathic complications should be carried out in all newly diagnosed NIDDM patients.
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PMID:Changing prevalence of retinopathy in newly diagnosed non-insulin dependent diabetes mellitus patients in Hong Kong. 964 50

Proteinuria is a well known risk factor for cardiovascular morbidity. There has been no report on cardiovascular morbidity in Indian NIDDM patients with proteinuria. Hence this study has been undertaken to estimate the prevalence of cardiovascular diseases (CVD) in South Indian NIDDM with proteinuria. We studied two groups of NIDDM patients with diabetes for > or = 5 years: group PR with persistent proteinuria of > 500 mg/day (n = 297) and group NPR with normoalbuminuria (albuminuria < or = 30 micrograms/mg creatinine)(n = 296), who reported for review during the study period. They were matched for age, duration of diabetes and BMI. The prevalence of cardiovascular diseases, namely myocardial infarction, the presence of ischaemic heart disease and the history of coronary bypass surgery were compared in the two groups. The prevalence of hypertension was higher among the PR than the NPR patients (56.5 vs 24.7%, chi 2 = 61.3, P < 0.01). CVD were detected in 39.2% (n = 116) of the PR and 13.2% (n = 39) of the NPR groups. (chi 2 = 54.85, P < 0.001). The risk was thus three-fold higher in the PR group. Univariate analysis showed that in the proteinuric group, the prevalence of complications was higher in association with hypertension (45.8% vs 30.2%, chi 2 = 6.82, P = 0.009). Multiple logistic regression analysis showed that the factors associated with CVD were proteinuria (odds ratio 5.03), age (OR 1.08) and BMI (OR 1.07) while sex, age at onset of diabetes, duration of diabetes, hypertension, smoking, HbA1, serum creatinine, cholesterol and triglycerides did not show independent contribution. The study, highlights the high risk conferred by macroproteinuria in Indian NIDDM patients. This risk is found to be independent of the presence of associated hypertension.
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PMID:Cardio vascular morbidity in proteinuric south Indian NIDDM patients. 967 70

We evaluated the role of obesity in proteinuria by treadmill exercising of simple obese subjects and non-obese subjects with non-insulin dependent diabetes mellitus in whom the albumin excretion rate at rest was within normal range. Non-obese healthy volunteers were studied as the controls. The fractional renal clearances of four endogenous proteins, albumin, IgG, IgG4, and beta2-microglobulin were measured before, during, and after treadmill exercise in 17 simple obese and 15 non-obese diabetic subjects, and in 21 normal subjects. Exercise increased the fractional albumin clearance in all groups. In diabetic subjects, the fractional IgG4 clearance also increased: fractional beta2-microglobulin clearance increased in normal controls and in diabetics. In obese subjects, the fractional clearances of albumin, IgG, and IgG4 were similar to those in normal controls, but fractional beta2-microglobulin clearance was significantly lower. These results suggest that enhanced microalbuminuria in obese subjects is probably of glomerular origin. In normal subjects and diabetics, exercise-induced microproteinuria is probably of both glomerular and tubular origin. Defect in the charge-selective barrier of the glomerular capillary wall has been implicated in diabetics. Thus some additional factors relevant to obesity must be taken into account in the consideration of the mechanism of microalbuminuria in diabetics with obesity.
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PMID:Do obesity and non-insulin dependent diabetes mellitus aggravate exercise-induced microproteinuria? 972 Oct 70


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