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)

To detect early renal involvement in young diabetic patients (IDDM), urinary protein excretion and renal function were examined in 110 patients aged 5.9-25.0 years. Clearances of inulin and PAH were determined as well as albumin (Alb), IgG, N-acetyl-beta-D-glucosaminidase (NAG) and creatinine (Cr) excretion rates (UV). The patients were grouped according to IDDM duration (2- less than 5, 5-10 and greater than 10 years) and albumin excretion rate (non-albuminuria less than 20, microalbuminuria 20-200, and albuminuria greater than 200 micrograms/min per 1.73 m2). Four patients had overt albuminuria, 17 microalbuminuria (equally distributed among the duration groups). Grouped according to albumin excretion rate, the mean GFR was increased in those without albuminuria but 'normalized' in patients with microalbuminuria/albuminuria. Grouped according to albumin excretion rate and the duration of the disease, the non-albuminuric patients with IDDM for greater than 10 years had a lower GFR than those with a shorter duration of IDDM. The patients with microalbuminuria/albuminuria and IDDM for less than 5 years had a reduced GFR. Patients with increased NAG excretion rate had lower Na excretion rate, lower fractional Na excretion and greater creatinine excretion than those with normal NAG excretion. Albumin excretion correlated with IgG excretion, but also with NAG excretion. Our results suggest that early albuminuria in IDDM is of both glomerular and tubular origin. The hyperfiltration declines with increasing albumin excretion but also with the duration of the disease.
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PMID:Urinary protein excretion and renal function in young people with diabetes mellitus. 132 Feb 27

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The aim of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2), referred to here as HF patients; in 10 IDDM patients with normal GFR (greater than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1; Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF, 34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration. 138 91

Not all patients with diabetes develop clinically significant nephropathy and, for this reason, attention has begun to focus on the risk factors for development of this serious complication. These risk factors have not been quantified to the same degree as those factors associated with more common progressive vascular diseases, such as atherosclerosis. However, studies of pathogenesis and clinical and epidemiological surveys of diabetic nephropathy point to numerous risk categories. Glycemic control, genetic and familial predispositions, renal and glomerular enlargement, glomerular hyperfiltration, and capillary and systemic hypertension can be invoked as contributors to this disease process. This review focuses on hemodynamic alterations and their role in the development and progression of diabetic nephropathy. Increases in GFR, largely driven by increases in plasma flow and capillary pressure, appear in early IDDM and NIDDM. This abnormality of renal vascular control probably is derived from alterations in several vasoactive control systems. In addition, the elevations in capillary pressure may be damaging to the glomerular capillaries. Arterial hypertension is not necessarily present before clinical nephropathy appears; however, it is a usual concomitant of progressive diabetic renal disease. The strongest evidences for the roles of altered systemic and renal hemodynamics in the progression of diabetic renal disease are clinical and experimental studies demonstrating attenuation of the disease process by lowering systemic and capillary pressures with antihypertensive agents, and dietary and glycemic modifications. Thus, although multiple factors probably interact to determine risk for the development of diabetic nephropathy, hemodynamic forces are a particularly important contributor and are especially amenable to therapeutic intervention.
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PMID:Diabetic nephropathy. Metabolic versus hemodynamic considerations. 139 17

A placebo-controlled, double-blind clinical trial has been initiated to determine whether angiotensin-converting enzyme inhibitor (ACEI) therapy with captopril (25 mg three times daily) slows the progressive loss of renal function in patients with type 1 diabetes mellitus. Entry criteria include; (1) ages 18 to 50 yr; (2) onset of insulin-dependent diabetes before the age of 30 yr, insulin dependent for at least 7 yr; (3) 24-h urine protein excretion > 500 mg, plus: (a) diabetic retinopathy or (b) if no retinopathy, a renal biopsy diagnosis of diabetic nephropathy; (4) serum creatinine (SCr) < 2.5 mg/dL; (5) informed consent. Patients follow strict medical management protocols. Systemic blood pressure is controlled to predefined goals (< 140-90 mm Hg). The primary outcome of the Study is a doubling of the patients' entry SCr to at least 2 mg/dL confirmed by a > 50% decrease in GFR by radioactive iothalamate clearance technique. Baseline characteristics of the cohort at entry into the Study are (mean +/- SD): male/female, 52%/48%; age, 35 +/- 8 yr; duration of diabetes, 21 +/- 7 yr; duration of proteinuria, 2.8 +/- 3.3 yr; duration of retinopathy, 4.5 +/- 4.1 yr; 50% of cohort presented with hypertension, duration, 4 +/- 4.7 yr; blood pressure, 139/86 +/- 19/12; SCr, 1.35 +/- 0.44 mg/dL; GFR 78 +/- 32 mL/min; BUN, 24 +/- 11 mg/dL; proteinuria, 3.1 +/- 3.3 g/day; cholesterol, 236 +/- 50 mg/dL; total glycosylated hemoglobin, 11.1 +/- 2.1%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A controlled clinical trial of angiotensin-converting enzyme inhibition in type I diabetic nephropathy: study design and patient characteristics. The Collaborative Study Group. 145 67

OBJECTIVE--To assess kidney function and AER in patients with PD. RESEARCH DESIGN AND METHODS--Thirty-three patients with PD (age 52 +/- 7 yr, duration of disease 11 +/- 6 yr, BMI 24 +/- 3 kg/m2) and 33 patients with IDDM were matched for sex, BMI, and duration of disease. GFR and RPF were determined by single injection of [51Cr]EDTA and [125I]hippurate. AER was measured by radioimmunoassay in a single timed overnight urine collection. RESULTS--GFR and RPF were, respectively, 113 +/- 35 and 441 +/- 145 ml.min-1.73 m2 in patients with PD and 123 +/- 30 and 549 +/- 94 (P < 0.001) in IDDM. FF was significantly higher in patients with PD (0.26 +/- 0.05 vs. 0.22 +/- 0.03; P < 0.001). Prevalence of hyperfiltration (GFR > 135 ml.min-1.1.73 m2) was similar in both groups (30% in patients with PD vs. 28% in those with IDDM). Geometric mean of urinary AER was 10.4 micrograms/min (range 1-186) in patients with PD and 11.2 (1-198) in IDDM patients. Some 30.3% of patients with PD and 18% of those with IDDM were microalbuminuric (AER > 20 micrograms/min). By multiple regression analysis, AER was significantly related to systolic (P < 0.04) and diastolic blood pressure (P < 0.01) and to BMI (P < 0.03) in patients with PD. Retinopathy was more frequent in microalbuminuric patients with PD than in those without elevated AER. CONCLUSIONS--We suggest that early renal abnormalities occur similarly in patients with PD and IDDM.
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PMID:Renal hemodynamics and albumin excretion rate in patients with diabetes secondary to acquired pancreatic disease. 146 90

Glomerular hyperfiltration has been claimed to be a risk factor for the development of diabetic nephropathy. Protein intake and hyperglycemia can both increase GFR in diabetic and normal subjects. Our study was designed to explore the relative importance of short-term changes in protein intake and glycemia on the modulation of renal hemodynamics in insulin-dependent diabetic (IDDM) patients with and without glomerular hyperfiltration. The renal hemodynamic response to a protein challenge was studied in eight hyperfiltering (HF) and eight normofiltering (NF) patients after a three week period of low or normal protein diet (LPD, NPD), each study being conducted twice, in random order, under conditions of prevailing hyperglycemia (H) and euglycemia (E). In HF patients GFR failed to increase significantly in response to protein challenge during NPD under conditions of either H or E (Baseline vs. 2 hr H: 151 +/- 4 vs. 155 +/- 6, NS; E 147 +/- 4 vs. 157 +/- 7 ml/min/1.73 m2, NS). A more normal response was restored following LPD with GFR increasing in all but one patient after challenge during H and in all patients during E (Baseline vs. 2 hr H: 130 +/- 7 vs. 145 +/- 8, P less than 0.07; E: 127 +/- 7 vs. 143 +/- 7 ml/min/1.73 m2, P less than 0.01). Changes in RPF paralleled the changes in GFR and filtration fraction remained stable under all study conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein intake and blood glucose as modulators of GFR in hyperfiltering diabetic patients. 150 18

To clarify the problem in the measurement of renal plasma flow and glomerular filtration rates in diabetes, the effect of glucose on the determination of para-aminohippuric acid (PAH) and inulin was examined. The concentration of urinary PAH in glucosuric diabetic subjects decreased after the storage of urine samples because of the glycation of PAH. Therefore, glucose must be removed by the acid treatment before the determination of the concentrations of urinary PAH. Since glucose can interfere with the assay of inulin, the sample must be treated with NaOH prior to the determination of the inulin concentration. GFR of the subjects with type 2 diabetes was next examined. GFR in the subjects with a duration of diabetes less than 10 years was significantly higher than that in the subjects with a duration of diabetes more than 10 years. Thus, the subjects with short-term type 2 diabetes may present with hyperfiltration similar to the subjects with short-term type 1 diabetes.
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PMID:[Measurement of renal plasma flow and glomerular filtration rates in diabetic subjects]. 150 86

Diabetic nephropathy, clinically defined by overt albuminuria, hypertension and declining GFR, affects 25-35% of IDDM patients. The risk of nephropathy peaks during the second decade of IDDM and declines thereafter, suggesting that only a subset of IDDM patients is at risk for nephropathy. A role for hypertension in the progression of established renal damage in IDDM is now accepted; however the role of hypertension in the genesis of diabetic nephropathy is not yet clear. Mesangial expansion is a characteristic lesion of diabetic nephropathology and correlates with renal function. Functional studies are not indicative of underlying renal pathology except relatively late, when glomerular injury is advanced. Microalbuminuria in the 'predictive' range (greater than 30 micrograms/min) and associated with hypertension and/or declining GFR is a marker of established diabetic glomerulopathy. Only carefully designed longitudinal studies of renal morphology and function with accurate blood pressure monitoring beginning early in the course of IDDM will clarify the relationships between blood pressure and renal damage in IDDM. In NIDDM the frequent presence of non-diabetic renal lesions, of hypertension at or before the onset of diabetes, and the relative paucity of clinical-pathological correlations currently make it difficult to understand the role of hypertension in the genesis and progression of nephropathy. Again, longitudinal studies of blood pressure and renal structure and function are required in NIDDM patients. Finally, animal models of hypertension and diabetes may aid progress in these areas.
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PMID:Hypertension and diabetic renal disease. 179 13

The short-term effects of prostaglandin synthesis inhibition (PGSI; single dose 500 mg of naproxen) on renal function were studied in six women (age: 21.9 +/- 2.4 yrs) with insulin dependent diabetes mellitus (IDDM) of 14.3 +/- 2.8 yrs' duration, and in nine age- and sex-matched controls. The diabetics had no overt signs of nephropathy (Albustix neg, normal serum creatinine, and blood pressure). The clearance of inulin (CIn) and PAH; the filtration fraction (FF); and the excretion of Na, albumin and PGE2 were studied under water diuresis on two separate mornings, first without and then with PGSI. With PGSI all individuals has lower PGE2 excretion. The CIn and FF were significantly (p less than 0.05) higher in the diabetics than in the controls both without (129.4 +/- 23.9 ml/min/1.73 m 2 and 23.4 +/- 2.8% vs. 107.6 +/- 10.3 and 19.7 +/- 1.6) and with (133.7 +/- 29.4 and 22.6 +/- 2.1, vs. 106.8 +/- 10.3 and 20.1 +/- 1.5) PGSI. The diuresis and Na excretion were significantly lower with PGSI, than without, in both groups. The albumin excretion was significantly higher in the diabetics under both conditions (29.9 +/- 16.6 and 34.2 +/- 19.9 micrograms/min/100 ml GFR, vs. 14.5 +/- 10.6 and 12.9 +/- 8.3 in controls). We conclude that the hyperfiltration in this stage of IDDM does not appear to be PG dependent, and that PGSI does not give any immediate effects on the albumin excretion.
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PMID:Renal functional effects of prostaglandin synthesis inhibition in patients with insulin-dependent diabetes mellitus of long duration without nephropathy. 179 42

The effect of strict metabolic control for 5 years on renal function and retinal morphology was estimated in 24 insulin-dependent diabetic individuals (age 29 +/- 8 years, diabetes duration 10 +/- 6 years) with albustix negative urine and minimal or no background retinopathy before the study. They were randomized to conventional insulin treatment (CIT) or continuous subcutaneous insulin infusion (CSII) with a portable pump. During CSII treatment the metabolic status was significantly improved. HbA1c fell from 8.9 +/- 2.0 to 7.4 +/- 1.3% (p less than 0.01) whereas HbA1c was unchanged during CIT treatment. The mean value of urinary albumin excretion (UAE) was not statistically significantly changed (from 12 +/- 10 mg/24 h to 13 +/- 5 mg/24 h in CSII patients and from 14 +/- 12 to 11 +/- 6 mg/24 h in CIT patients (p greater than 0.1). On the other hand, the elevated GFR values were significantly reduced in both CSII and CIT patients, 129 +/- 17 to 120 +/- 9 and 129 +/- 18 to 119 +/- 12 ml/min.1,73m2, respectively (p less than 0.05). Both the number of microaneurysms, haemorrhages and exudates tended to increase mor in CIT patients than in CSII patients during the 5 year study period, but the differences did not reach statistically significance (p greater than 0.1). Pump treatment did not induce proliferations or "cotton wool" exudates. We conclude that no statistically significantly differences between GFR values, UAE rates, and progression of background retinopathy was observed between normoalbuminuric IDDM patients treated for 5 years with CIT and CSII, respectively. However, due to the size of the material a type II error must be taken into consideration.
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PMID:Effect of near normoglycemia for 5 years on progression of early diabetic retinopathy and renal involvement. 213 7


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