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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth retardation is a common feature in children with end-stage renal failure (ESRF). Medical management of renal insufficiency rarely normalizes growth and optimistic reports on the effect of rhGH treatment on growth velocity may presage more extensive use of rhGH in pediatric nephrology. Ample evidence has shown beneficial effects of GH replacement therapy in both childhood and adolescent hypopituitarism. However, the remarkably few side effects of treatment reported in these conditions cannot necessarily be extrapolated to children with ESRF. Uremia is associated with a wide range of metabolic and hormonal derangements including decreased glucose tolerance. This is mainly due to impaired insulin-stimulated glucose disposal in peripheral tissues and insufficient insulin-induced suppression of hepatic glucose production. Insulin-stimulated glucose uptake in skeletal muscle in ESRF is reduced by 30-50% as compared to that in healthy subjects, and a reduction may be detected even in subjects with a more moderate reduction in renal function (GFR around 25 ml/min). Dialysis therapy improves the disturbed insulin action significantly. The cause of the insulin resistance in ESRF is multifactorial. Impaired physical fitness, accumulation of uremic toxins, raised levels of GH and glucagon, metabolic acidosis, dyslipidemia and the medication applied may all contribute. If exogenous GH administration is added to the already marked uremic insulin resistance, insulin action may be severely disturbed and the secondary hyperinsulinism further magnified. However, frank diabetes mellitus does not develop unless the beta cells fail to meet the enhanced demands. This will probably occur only in patients with a beta-cell genotype pivotal for the phenotypic expression of non-insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose metabolism in chronic renal failure with reference to GH treatment of uremic children. 837 90

The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxan-induced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA;TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P < 0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (PGC). Treatment with lisinopril lowered the PGC to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated PGC. While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090. Combination therapy of diabetic dogs produced a further significant (P < 0.05) decrement in proteinuria. We conclude that although treatment of diabetic dogs with either lisinopril or TA-3090 results in differential effects on PGC; each produces a similar decrement in proteinuria. Further, combination therapy has a greater effect on proteinuria than either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria. 839 Oct 95

OBJECTIVE--To evaluate the frequency and correlates of glomerular hyperfiltration in NIDDM patients without overt proteinuria. RESEARCH DESIGN AND METHODS--A cross-sectional study was conducted. Seventy-one consecutive NIDDM patients attending an outpatient clinic, with Albustix-tested negative urine and a 24-h AER < 200 micrograms/min, were examined for long-term complications of diabetes. We measured their GFR (51Cr-EDTA single-injection method), 24-h AER (RIA), plasma creatinine, HbA1c, total cholesterol, triglycerides, urinary glucose, and urea. RESULTS--GFR above the upper limit of the normal range for age-matched control subjects (137.1 ml.min-1 x 1.73 m2) was present in 15 of 71 (21%) NIDDM patients. Subjects with normal and hyperfiltration did not differ in terms of age, sex distribution, BMI, duration of NIDDM, BP, AER, or frequency of long-term complications. Plasma glucose was significantly higher in subjects with hyperfiltration (mean [range]: 12.8 [4.3-18.7] vs. 8.7 [2.6-17.5] mM). HbA1c failed to reach statistical significance, although it tended to be higher in the group with hyperfiltration (10.4 [6.7-13.9] vs. 9.4 [4.2-16.5]%, P = 0.10). Age (rS -0.37, P = 0.002), FPG (rS 0.45, P < 0.0005), total cholesterol (rS -0.31, P = 0.008), and glycosuria (rS 0.40, P = 0.001) correlated significantly with GFR. In a stepwise multiple regression analysis, FPG, age, and total cholesterol emerged as significant correlates of the dependent variable GFR. CONCLUSIONS--Hyperfiltration occurred in 21% of NIDDM patients without overt proteinuria. FPG and age significant correlates of the GFR in these patients. Cholesterol is significantly (although only modestly) correlated with the GFR.
Diabetes Care 1993 Jan
PMID:Glomerular hyperfiltration in NIDDM patients without overt proteinuria. 842 64

Diabetic nephropathy develops in approximately 35% of patients with insulin-dependent diabetes mellitus (IDDM) and in a similar proportion of patients with non-insulin-dependent diabetes mellitus (NIDDM). However, we remain at present unable to identify the susceptible subset prior to the development of microalbuminuria. Up to 25% of IDDM patients and a variable proportion of NIDDM patients manifest glomerular hyperfiltration in the first few years of diabetes. It has been debated whether this basal hyperfiltration is predictive of future renal disease and whether better prediction can be achieved by the use of the renal haemodynamic response to a protein meal, defined by some authors as renal reserve. The concept of renal functional reserve in patients with diabetes mellitus is complicated by the dependence of the GFR response on basal GFR, the influence of the prevailing metabolic conditions, and because the response differs to different stimuli. We review the factors affecting renal hemodynamics and renal hemodynamic responses in the context of supranormal, normal, and impaired renal function in diabetes. We conclude that although the measurement of renal functional reserve may help clarify important pathophysiological mechanisms, the assessment of basal GFR in clinical practice is all that is required for predictive and monitoring purposes.
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PMID:Renal functional reserve in subjects with diabetes mellitus. 852 51

Our single channel work has characterized two ion channels capable of depolarizing mesangial cells and activating classic, voltage-activated Ca2+ channels in response to growth-stimulatory peptides (such as Ang II, ET and insulin): (1) Ca(2+)-dependent, 4 pS Cl- channel promoting Cl- efflux; and (2) Ca(2+)-dependent, 27 pS nonselective cation channels promoting cation influx. We have also characterized a third channel which provides an alternative, receptor-operated pathway for Ca2+ entry in response to the growth factor, PDGF: (3) Ca(2+)-permeable, 1 pS cation channel. Consistent with our model of mesangial cell signal transduction (Fig. 1), these three mesangial cell ion channels are activated by binding of growth factors to membrane receptors (Fig. 8). Defective channel regulation, such as occurs in early diabetes mellitus, would promote mesangial cell relaxation and pathogenic glomerular hyperfiltration. Glomerular hyperfiltration and hypertension have been proposed to be major pathogenic factors in renal disease progression [4, 29, 38, 39]. Compensatory renal growth factor responses initially provide adaptive changes in glomerular hemodynamics after loss of functional renal mass. However, chronic stimulation of these mesangial cell ion channels by renal growth factors would promote sustained extracellular Ca2+ entry, resulting in mesangial cell contraction and growth, and progressive decreases in Kf and GFR. Eventually, this process leads to irreversible renal damage due to the development of glomerulosclerosis and interstitial fibrosis.
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PMID:Role of growth factors in mesangial cell ion channel regulation. 856 77

The macula densa, a plaque of specialized tubular epithelial cells located in the distal tubule, monitors the NaCl concentration of the tubular fluid and sends an as of yet unidentified signal to control glomerular hemodynamics. In this mechanism, called tubuloglomerular feedback (TGF), an increase in NaCl concentration at the macula densa constricts the glomerular afferent arteriole and thus decreases the single-nephron GFR. Along with the myogenic response, TGF significantly contributes to renal autoregulation. In addition, the macula densa also controls the rate of renin release, and hence the level of angiotensin II. Studies indicate that an appropriate interaction between TGF and the renin-angiotensin system is essential for body fluid and electrolyte homeostasis in the face of rather big variations in daily salt intake. Thus, alterations in TGF may play an important role in the pathogenesis/pathophysiology of various diseases such as hypertension, diabetes mellitus and congestive heart failure.
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PMID:Tubuloglomerular feedback. 867 42

The outcome of kidney transplantation was evaluated in 246 nondiabetic, CsA-treated recipients of primary cadaver transplant, divided into 4 groups according to length of time on dialysis: group < or = 2, 0-24 months; group 2-5, 25-60 months; group 5-15, 61-180 months; group > 15, over 180 months. The 4 groups did not differ in graft survival, proteinuria (g/die), or estimated GFR values at 1, 2, 3, 4, and 5 years after grafting. They did not differ in the frequency of cataract, hip osteonecrosis, tumors, or posttransplant diabetes mellitus at 3 years after grafting. Ocular hypertone (p < 0.02), tendon ruptures (p < 0.001), arterial occlusive disease of lower limbs (p < 0.01), cholelithiasis (p < 0.05), and chronic hepatitis--which occurred only in anti-HCV and/or HBs Ag-positive patients--(p < 0.001), were more frequent in group > 15, and in all these cases but ocular hypertone a linear trend of increasing frequencies with increasing dialytic age was statistically significant. Group 5-15 had the lowest patient survival (p < 0.02). Moreover, a progressive decline of patient survival with increasing dialytic age was noted in groups < or = 2, 2-5, and 5-15. Unexpectedly, group > 15 had remarkably good survival, and this finding denies the hypothesis of a purely linear decline of patient survival after transplantation with increasing dialytic age.
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PMID:Influence of length of time on dialysis before grafting on kidney transplant results. 872 66

The goal of this study was to determine what extent nitric oxide (NO) and/or angiotensin II (AngII) are involved in the hyperfiltration observed in rats with streptozotocin-induced diabetes mellitus. Studies were performed on anesthetized rats 7 to 10 days after the induction of diabetes. Nitro-L-arginine (LNA) was used to inhibit NO synthesis, and losartan was used to block AngII receptors. Three protocols were utilized: (i) control and diabetic rats treated with a constant infusion of LNA; (ii) control and diabetic rats treated first with a constant infusion of losartan and then LNA plus losartan; and (iii) nephrectomized control and diabetic rats treated with LNA (to evaluate the involvement of renal vasoactive factors other than AngII in the systemic response to LNA). Compared with controls, diabetics had a significantly elevated baseline GFR but the same mean arterial pressure (MAP). In Protocol i, LNA caused the same increase in MAP in both groups but only decreased the GFR in controls. In Protocol ii, losartan caused a significant increase in the GFR only in controls. The coinfusion of LNA and losartan caused no change in the GFR in controls but induced a large GFR decrease in diabetics. Losartan had no effect on MAP in either group and did not affect the LNA-induced increase in MAP in either group. The LNA-induced increase in MAP was greater in nephrectomized rats compared with that in intact rats. These data indicate that (1) neither changes in the synthesis of NO nor changes in the actions of AngII, alone, are responsible for the hyperfiltration observed in streptozotocin-induced diabetes; (2) a combined alteration in these two systems may account for diabetes-induced hyperfiltration; (3) the LNA-induced decrease in GFR in control but not in diabetic rats is an AngII-mediated event; and (4) AngII is not involved in the LNA-induced increase in MAP in either control or diabetic rats but other renal factors cannot be ruled out in this response.
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PMID:Role of nitric oxide and angiotensin II in diabetes mellitus-induced glomerular hyperfiltration. 880 16

It has been considered unlikely that patients with insulin-dependent diabetes and diabetic nephropathy with nephrotic range proteinuria can substantially reduce proteinuria and continue for many years without further loss of renal function. We present a patient who had the diagnosis of insulin-dependent diabetes made at age 15, had his first of 6 laser treatments for proliferative and hemorrhagic retinopathy at age 27 and was found to have nephrotic range proteinuria and edema with hypertension at age 29, when results of a renal biopsy were typical of diabetic nephropathy. Ten years later, with the last 5.5 years on ACE inhibitors, proteinuria has been < 0.65 g/24 h for 2 years and recently 0.22 g, serum creatinine is unchanged at 90 to 102 mu mol/l, DTPA GFR is 104 ml/min and retinopathy has remained stable without laser therapy for 7 years. Blood pressure on clinic visits has averaged 126/74 for the last 8 years. This duration of stable renal function and the major decrease in proteinuria after being in the neprotic range is very rare in reports, if not unique.
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PMID:Stable renal function in insulin-dependent diabetes mellitus 10 years after nephrotic range proteinuria. 890 67

Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria, a relentless decline in GFR, raised arterial blood pressure, and increased relative mortality for cardiovascular diseases. Diabetic nephropathy is a leading cause of end-stage renal failure. The pathogenesis of diabetic nephropathy is multifactorial, with contributions from metabolic abnormalities, hemodynamic alterations, and various growth factors and genetic factors. Epidemiologic and family studies have demonstrated that only a subset of the patients develop this complication that family clustering of nephropathy is present, and that ethnicity plays an important role in the risk of developing this kidney disease. Short stature and low birth weight are both associated with increased risk of developing diabetic nephropathy, supporting the hypothesis that genetic predisposition or factors operating in utero, in early childhood, or both contribute to the development of diabetic nephropathy. Studies elucidating phenotypic markers such as parenteral hypertension and systemic blood pressure elevation have yielded conflicting results. The contribution from elevated blood pressure only plays a minor role in the majority of the patients developing diabetic nephropathy. The majority of the studies have demonstrated increased sodium/lithium countertransport activity in insulin-dependent diabetes mellitus patients with nephropathy, whereas studies of this phenotypic marker in parents of patients with and without nephropathy have yielded conflicting results. Recently, studies of genetic markers involved in the regulation of blood pressure and levels of cardiovascular risk factors have been conducted. Several studies have demonstrated that the deletion polymorphism in the angiotensin-I-converting enzyme acts as a risk factor for cardiovascular disease in diabetic patients. However, a meta-analysis does not support the suggestion that this factor plays any role for the initiation of diabetic nephropathy. Similar negative results have been obtained in relation to polymorphisms of the genes encoding for angiotensinogen and the angiotensin II Type 1 receptor. However, studies in diabetic and non-diabetic glomerulopathies have clearly demonstrated a deleterious effect of the deletion polymorphism in the angiotensin-converting enzyme on the progression of kidney function.
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PMID:Genetics of diabetic nephropathy. 898 28


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