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Query: UMLS:C0011849 (diabetes)
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Proteinuria in diabetes is associated with progressive glomerular damage. We studied the effects of 3-wk dietary protein restriction on proteinuria and renal function in 10 insulin-dependent diabetic men with diabetic nephropathy. Patients were randomly assigned by a crossover design to 40-g low-protein diet (LPD) or usual-protein diet (UPD). Glomerular filtration rate and renal plasma flow were measured by inulin and p-aminohippurate clearance at the end of each period under conditions of sustained euglycemia. Total calorie intake, body weight, serum albumin and total protein concentrations, hematocrit, blood pressure, and glucose control were similar during the two diets. Achieved protein intake was 46 +/- 3 g/day during LPD and 81 +/- 4 g/day during UPD (P less than .001). Urinary urea appearance and plasma urea were significantly lower on LPD. Median total urinary protein was reduced from 3.9 g/day (range 0.5-12.3) on UPD to 2.4 (range 0.2-9.0) on LPD (P less than .006), and there was a significant fall in the median fractional clearance of albumin from 2.0 x 10(-4) (range 0.1-90.9) on UPD to 1.0 x 10(-4) (range 0.1-51.4) on LPD and IgG from 2.1 x 10(-5) (range 0.2-238) to 1.5 x 10(-5) (range 0.1-77) (P less than .006 and P less than .02, respectively). The reabsorption rate of beta 2-microglobulin was similar on the two diets and glomerular filtration rate, renal plasma flow, and filtration fraction remained unchanged. Thus, short-term dietary protein restriction reduces diabetic proteinuria independently of blood glucose or systemic blood pressure changes by improving glomerular permselectivity.
Diabetes 1988 Dec
PMID:Renal response to restricted protein intake in diabetic nephropathy. 319 38

In a population-based study in southern Wisconsin, 1370 diabetic persons diagnosed after 29 years of age were examined using standard protocols to determine the prevalence of proteinuria and associated risk variables. Proteinuria (greater than or equal to 0.30 g/L) was present in 18.0% of persons taking insulin and 12.2% of the persons not taking insulin. Proliferative retinopathy and proteinuria were associated with each other. Proteinuria was also associated with increasing duration of diabetes, high systolic blood pressure, use of digoxin, and being male, but not with a history of cigarette smoking or metabolic control as measured by glycosylated hemoglobin.
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PMID:Proteinuria in diabetes. 333 93

Proteinuria, a complication of both diabetes mellitus and hypertension, was compared in 2 genetically induced models: insulin-dependent diabetic BB rat (BB), and Okamoto-Aoki spontaneously hypertensive Wistar rats (SHR). Both disease states were clearly distinguished from each other and their respective age-matched controls by analysis of 24-hour urine samples for glucose, urobilinogen, bilirubin and total protein. Then individual protein components between 15,000 and 120,000 daltons were separated by molecular weight and quantitated by laser densitometric analysis. The results indicated that insulin-dependent diabetic BB rats excreted urine having elevation of glucose (100-250 mg/dl), bilirubin (0.05 +/- 0.03 mg/dl) and urobilinogen (6.6 +/- 3.8 Ehrlich units/dl) in contrast to all age-matched SHR and normotensive Wistar-Kyoto (WKY) and nondiabetic controls, which excreted urine having normal urobilinogen and no detectable glucose or bilirubin. Both SHR and insulin-dependent BB rats exhibited proteinuria, urinary protein excretion being increased approximately 4-5 times that of their age-matched controls. BB rats excreted 18.80 +/- 2.62 mg protein/day attributed to an increase in albumin and an entire array of proteins between 30,000 and 120,000 daltons not present in controls which primarily excreted proteins below 20,000 daltons. In the SHR, proteinuria did not include an array of proteins; the increase in excreted protein (39.20 +/- 16 mg/day) was primarily attributed to albumin and another protein having a higher molecular weight. The SHR urinary proteins were similar to proteins excreted by streptozocin-induced, noninsulin-dependent diabetic rats treated with the aldose reductase inhibitor sorbinil. If hypertension is associated with diabetic nephropathy, our preclinical results suggest that coadministration of sorbinil with antihypertensive therapy may promote a positive synergistic effect further diminishing proteinuria.
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PMID:Proteinuria associated with hypertension and diabetes mellitus. 336 5

Proteinuria is the clinical hallmark of diabetic nephropathy and the harbinger of progressive renal disease. Therefore, the present study was designed to examine the effect of phosphate restriction on the proteinuria of streptozotocin-induced diabetes mellitus in the rat. Uninephrectomy was performed in experimental and control groups to worsen the degree of diabetic nephropathy. Proteinuria was prevented in Sprague-Dawley rats treated with the intestinal phosphate binder, dihydroxyaluminum aminoacetate (DHAAA) (24.75 +/- 20.35 mg/d at 3 months v control, 77.45 +/- 44.72 mg/d, P less than 0.001); an effect that was independent of protein and caloric intake, plasma albumin and lipids, severity of diabetes, mean arterial pressures, cardiac output, and renal calcium accumulation. The effect of DHAAA on protein excretion and glomerular hemodynamics was examined in similarly prepared Munich-Wistar rats; these rats did not tolerate long-term studies. Three weeks of DHAAA again caused a consistent fall in proteinuria (5.98 +/- 7.28 v 34.94 +/- 24.28 mg/d) and in transmembrane hydraulic pressure difference (41.1 +/- 1.2 v 46.4 +/- 2.8 mm Hg, P less than 0.005). In conclusion, phosphate restriction significantly decreases the proteinuria of Sprague-Dawley and Munich-Wistar uninephrectomized rats with streptozotocin-induced diabetes mellitus. Micropuncture of Munich-Wistar rats suggests that a reduction of intraglomerular pressure may be at least partially responsible for such an effect.
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PMID:Phosphate restriction reduces proteinuria of the uninephrectomized, diabetic rat. 337 33

Calcium and vitamin D metabolism were studied in streptozotocin-treated rats up to 10 days after the induction of diabetes. Proteinuria, hypercalciuria, and hyperphosphaturia appeared as early as 3 days after diabetes induction and were reversed by insulin. The serum proteins and fasting calcium concentrations were decreased in untreated diabetic rats. The concentration of serum vitamin D binding protein (DBP) was higher in male than in female control rats (mean +/- SD; 555 +/- 73 vs. 348 +/- 28 mg/liter, P less than 0.001). When sequentially measured in male untreated diabetic rats, DBP concentration steadily decreased. Compared with control values, DBP was reduced 19%, 28%, and 32% on days 3, 6, and 10, respectively, after induction of diabetes in male rats. In female animals, DBP was reduced 22% on day 10 of diabetes. DBP concentration was corrected by insulin treatment of diabetic rats and remained normal in streptozotocin-treated animals that did not develop diabetes. The serum concentration of 25-hydroxyvitamin D3 was similar in both sexes and was not affected by diabetes. Like DBP, the concentration of total 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] was higher in male than in female control rats (120 +/- 24 vs. 96 +/- 17 ng/liter, P less than 0.001), but 10 days after induction of diabetes this concentration decreased by 37% and 29% in male and female rats, respectively. The free 1,25-(OH)2D3 concentration, estimated from the molar 1,25-(OH)2D3/DBP ratio, was similar in both sexes and was not decreased by diabetes. We conclude that experimental diabetes in the rat induces a decrease in DBP concentration and a concomitant decrease in total but not in free 1,25-(OH)2D3 concentrations. This may indicate that diabetes decreases circulating 1,25-(OH)2D3 concentrations through alterations in DBP levels.
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PMID:1,25-Dihydroxyvitamin D and vitamin D-binding protein are both decreased in streptozotocin-diabetic rats. 383 33

This study was undertaken to document clinical features and presentation of Type I diabetes and to study beta cell response in these patients. It provides data on 30 insulin treated patients. Type I diabetes presents most commonly in the 20-40 year age group. A positive family history in first degree relatives was noted in 40%. The commonest complications were retinopathy (63%) and peripheral neuropathy (53%). Proteinuria (10%), ischaemic heart disease (13%) and peripheral vascular disease (13%) were less common. Three kinds of response to C-peptide were noted: 1) no response 2) blunted response (below the normal range) and 3) peak response to glucose within the low normal range. Group 3 probably represents Type II insulin treated diabetes. There was poor correlation between fasting blood glucose and basal or peak C-peptide response, or with duration or complications of diabetes. C-peptide response may be used to differentiate Type I from Type II diabetes.
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PMID:C-peptide response in patients on insulin therapy. 392 68

A total of 6695 diabetic men and women, aged 35 to 54 years, from 14 centres and representing 13 national groups, participated in a vascular disease prevalence survey. A random sample was drawn after stratification of each centre's diabetic base population by sex, duration of diabetes and age. A common agreed protocol, standardized examination procedures, and centralized laboratory methods were used in the investigation. Within the age range examined there was considerable variation between centres in a number of variables, including degree of obesity (measured as Body Mass Index (BMI)), proportion treated with insulin and proportion of cigarette smokers. The latter also showed considerable sex differences within centres. Subjects with age at onset below 25 years were notably few in Hong Kong, Tokyo and Oklahoma. There was also considerable variation in the apparent prevalence of both large- and small-vessel (macrovascular and microvascular) disease between centres. In pooled data, measures of large-vessel disease were significantly and independently associated with age, blood pressure and BMI in both sexes, and with diabetes duration and plasma cholesterol in men only. Within-centre analyses showed blood pressure to be the most consistently associated variable in both sexes. In pooled data, small-vessel disease of the eye was significantly and independently associated with diabetes duration, blood pressure, BMI and type of treatment in both sexes. In within-centre analyses, diabetes duration was the most consistently associated variable, followed by blood pressure. Proteinuria as an index of small-vessel disease of the kidney was, in pooled data, significantly and independently correlated with diabetes duration, blood pressure and plasma cholesterol in both sexes. In within-centre analyses, blood pressure was the most consistently associated variable, with diabetes duration and plasma cholesterol equal second - significant in 12 of the 28 centre/sex groups. Heterogeneity of large-vessel disease prevalence in diabetic subjects is confirmed by this study, and the possibility of heterogeneity in small-vessel disease prevalence and severity is suggested.
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PMID:Prevalence of small vessel and large vessel disease in diabetic patients from 14 centres. The World Health Organisation Multinational Study of Vascular Disease in Diabetics. Diabetes Drafting Group. 406 55

Screening for urinary tract infection was carried out in 27,722 schoolboys aged 5 to 14 using Uricult to perform urine cultures and Hema-combistix to detect hematuria, proteinuria and glycosuria. Cultures of 10(5) colonies per ml or more on two occasions were found in 40 cases (0.14%), but no case was confirmed by the family physician using standard culture techniques.Proteinuria was found in 136 cases (0.49%) and confirmed in 47 (37%) of the 126 children who were seen by their family physician. In this group 8.8% had evidence of pyelonephritic scarring on intravenous pyelograms without a positive urine culture.Hematuria was found in 19 children and confirmed in 10 (59%) of the 17 children who were seen by their family physician. No abnormalities were detected on intravenous pyelography in any case.Glycosuria was found in 12 cases and confirmed in five. Three of these children had renal glycosuria and two had previously undetected diabetes.
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PMID:City-wide screening for urinary abnormalities in schoolboys. 460 40

Serum alpha 2-macroglobulin (alpha 2m) and total glycosylated haemoglobin (HbA1) concentrations were measured in 110 insulin dependent Type 1 diabetics with minimal or no fundoscopic retinopathy, referred to as non-retinopaths, and in 52 proliferative retinopaths. Proteinuria was recorded in 8 (7%) non-retinopaths and 29 (56%) retinopaths and was accompanied by elevated alpha 2m concentrations in both groups of diabetics but only significantly so in the non-retinopaths. Diabetics without proteinuria showed a significant correlation between alpha 2m concentration and duration of diabetes, HbA1 and age (being higher at extremes of age). Alpha 2m concentrations were significantly higher in retinopaths than in non-retinopaths without proteinuria when allowance was made for the influence of age and duration of diabetes on alpha 2m. This difference may be attributed to the higher HbA, levels found in retinopaths than in non-retinopaths and was no longer evident when account was taken of the prevailing HbA1 concentration in individual patients.
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PMID:Alpha 2-macroglobulin and proliferative retinopathy in type 1 diabetes. 618 82

PRA, active renin, and inactive renin (IR; activated by dialysis to pH 3.3 and 7.4) were measured in the plasma of 53 patients with diabetes mellitus and 32 normal volunteers (group 1). Proteinuria was present in 21 diabetics (group 3; nephropathy) and absent in 32 diabetics (group 2). The mean PRA was lower in group 3 than in groups 1 and 2. PRA less than 0.2 ng/ml . h occurred more frequently and at a younger age in uncomplicated diabetics than in normal controls. Despite very low PRA, plasma aldosterone was normal in most of the diabetics. IR was significantly higher than normal in the uncomplicated diabetics and was greatly increased in diabetics with nephropathy. Since the kidneys are a principal source of IR, and since patients with diabetic nephropathy have consistently elevated plasma IR, it is possible that increased plasma IR in patients without proteinuria or reduced renal function might be an early sign of renal involvement. However, as other explanations of increased plasma IR exist, the hypothesis must be tested by longitudinal studies of diabetic patients.
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PMID:Increased inactive renin in diabetes mellitus without evidence of nephropathy. 633 80


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