Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is commonly assumed that in patients the risks of developing nephropathy and uraemia are high in type I and low in type II diabetes mellitus. Since type II occurs mostly in elderly individuals with limited life expectancy and high cardiovascular mortality, the true risk may have been underestimated, as many patients do not survive to experience renal complications. To assess renal risk further, we evaluated all patients with type II and type I diabetes mellitus without severe secondary disease who were followed in the outpatient clinic between 1970 and 1985. The cumulative risk of proteinuria after 20 years of diabetes mellitus was 27% in type II and 28% in type I, the findings after 25 years were 57% and 46% respectively. The cumulative risk of renal failure, i.e. serum creatinine greater than 1.4 mg/dl, after 3 years of persisting proteinuria was 41% in both type II and type I, and after 5 years of proteinuria were 63% and 59% respectively. We conclude that the renal risk is similar in patients with type II and type I diabetes mellitus.
 ...
PMID:Similar risks of nephropathy in patients with type I or type II diabetes mellitus. 251 89

We have previously shown that the incubation of normal rat adipose tissue with sera from nondialyzed, nondiabetic uremic patients reduces the transport and metabolism of glucose, in the absence and presence of insulin. In this study insulin-stimulated glucose metabolism by normal rat adipocytes was used as a bioassay to identify the resistance activity, assess the effect of chemical modification on it, and the clinical states associated with its production. The resistance activity was trypsin-labile and had an apparent isoelectric point between 6 and 7, but was not retained by either protein A or concanavalin A columns. The insulin resistance activity was decreased by coincubation with the protein synthesis inhibitor, cycloheximide. Purification to greater than 200,000-fold was attained by heating (100 degrees C) uremic serum, subjecting the supernatant to Sephadex G-25 chromatography and subsequent adsorption to DEAE at pH 7.8 and elution at pH 6.5. The partially purified resistance activity was retained within dialysis tubing of 1,000-mol wt cutoff but not within 2,000-mol wt cutoff. Hemodialysis of patients over 1 wk to 18 mo reduced significantly the amount of resistance activity in their sera. The resistance activity, present in most uremic patients, was not found in the sera of individuals with normal renal function but who were either obese, fasted, elderly or had type II diabetes mellitus. Thus, a circulating small molecular weight peptide, unique to uremia, induced insulin resistance by a protein synthesis-dependent mechanism.
 ...
PMID:Characterization and partial purification of a factor from uremic human serum that induces insulin resistance. 388 60

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)
 ...
PMID:Glucose metabolism in chronic renal failure with reference to GH treatment of uremic children. 837 90

Alterations in the fibrinolytic system have been demonstrated in noninsulin-dependent diabetic patients (NIDDM) but not in insulin-dependent diabetic patients (IDDM). Since the activity of the fibrinolytic system can affect the turnover of extracellular matrix and therefore theoretically can affect the peritoneal transport, we tried to determine if there was a difference in the performance of the peritoneal equilibration test (PET) between IDDM and NIDDM patients receiving peritoneal dialysis (PD). The PET data from 11 IDDM patients (2 female, 9 male) and 13 NIDDM patients (3 female, 10 male) were reviewed. These two groups of patients were matched in gender, duration of end-stage renal disease, PD, and hypertension, blood pressure, degree of uremia, weekly KT/V, and body surface area. The IDDM patients (41.4 +/- 13.9 years) were younger than the NIDDM patients (58.8 +/- 7.1 years, p = 0.0026). There were no differences in hematocrit and serum chemistry profile including glucose and albumin between the two groups. Our data showed that there was no difference in PET performance between IDDM and NIDDM patients.
 ...
PMID:Peritoneal transport in type I (insulin-dependent) and type II (noninsulin-dependent) diabetic peritoneal dialysis patients. 853 39

We investigated serum levels of type III procollagen aminopeptide (CIII), 7S type IV collagen (CIV), and tissue inhibitor of metalloproteinase (TIMP) in 33 patients with type II diabetes mellitus (DM) without uremia (serum creatinine less than 1.5 mg/dl). The patients were divided into three groups based on measurement of the urinary albumin excretion (UAE) index obtained during two morning outpatient clinic visits: non-proteinuric patients (n = 11), UAE index less than 2.26 mg/mmol Cr; patients with microalbuminuria (n = 15), UAE index of 2.26 - 22.6 mg/mmol Cr; and patients with proteinuria (n = 7), UAE index more than 22.6 mg/mmol Cr. Serum levels of CIV and TIMP in patients with microalbuminuria and proteinuria were significantly higher than non-proteinuric patients (ANOVA, p <0.05). Serum levels of CIII in patients with proteinuria were significantly higher than those in non-proteinuric patients (p < 0.05). There was a significant positive correlation between CIV and TIMP (r = 0.502, p < 0.003), but no correlation was observed between CIII and TIMP. These results demonstrated that serum CIII and CIV increases as diabetic nephropathy progresses in terms of increasing proteinuria in type II DM patients, suggesting feasibility and usefulness of measuring serum CIV and CIII in assessing diabetic nephropathy. The increase in TIMP may be, at least in part, a possible cause for the increase in serum CIV in type II DM patients.
 ...
PMID:Serum type III, IV collagens and TIMP in patients with type II diabetes mellitus. 861 90

According to extensive autopsy studies, non-diabetic renal disease seems to be rare in diabetes mellitus, but recent publications suggest a significant prevalence of non-diabetic renal disease in non-insulin-dependent diabetic (NIDDM) patients, especially in the absence of retinopathy. The purpose of this study was to evaluate the prevalence of non-diabetic renal disease in NIDDM patients in renal biopsies from clinical practice, in patients suspected of having non-diabetic renal disease. In addition we systematically reviewed the literature. Biopsies were evaluated at the University Department of Pathology, Aarhus, Denmark, but had been collected at several departments of nephrology. In total 33 consecutive biopsies were available from 1988-1995 (mean age of patients: 62 years (range 39-75) (mean known diabetes duration 8 years (range 1-25); the main clinical reason for a biopsy was proteinuria. Renal function changes ranged from slight elevation of serum creatinine to uraemia. In addition 9 original papers, including our own material 580 patients were examined. On the basis of careful morphological evaluation according to international criteria, no patient exhibited an unequivocal sign of non-diabetic glomerular disease. Two patients had strongly but not completely convincing evidence of glomerulonephritis. One patient had some evidence of glomerulonephritis. These 3 patients also exhibited diabetic lesions. One patient with end-stage renal disease showed evidence of interstitial nephropathy without glomerular lesions. Thus, in 4 patients evidence of non-diabetic lesions was found. In the remaining 29 patients typical diffuse (n = 9) or nodular (n = 20) diabetic lesions were found. Twenty patients showed evidence of diabetic retinopathy. One of the patients with evidence of non-diabetic renal disease had simplex retinopathy. In the literature a considerable bias exists towards including patients with non-diabetic renal disease. In non-biased materials with proteinuria the prevalence of non-diabetic renal disease is very similar to our series. In microalbuminuric patients non-diabetic renal disease seems to be very rare. It can be concluded that in our material non-diabetic renal disease is uncommon in NIDDM patients, even if a clinician has suggested renal disease of other origin. A considerable bias towards including non-diabetic renal disease in NIDDM patients exists in the literature. The indication for biopsy should be evaluated carefully, and biopsy should by no means be routinely performed in NIDDM patients with proteinuria.
 ...
PMID:How often is NIDDM complicated with non-diabetic renal disease? An analysis of renal biopsies and the literature. 896 Aug 56

To investigate the association between insulin resistance and diabetic nephropathy, peripheral insulin sensitivity indices (M/I values) were evaluated via euglycemic-hyperinsulinemic clamp in 45 non-obese, non-insulin-dependent diabetic (NIDDM) subjects. The patients were divided into four groups: 18 with normoalbuminuria (urinary albumin excretion rate [AER] < 30 mg/24 h, stage I), 10 with microalbuminuria (30 < or = AER < or = 300 mg/24 h, stage II), seven with overt proteinuria (AER > 300 mg/24 h, stage III), and 10 with uremia (serum creatinine levels > 2.0 mg/dL, stage IV). There were no significant differences in age, body mass index (BMI), fasting plasma glucose, or hemoglobin A1c (HbA1c) among the four groups. No significant difference in M/I values was seen between stage I and stage II (6.30 +/- 0.73 and 5.95 +/- 0.85 mg/kg/(min per microU/mL) x 100, respectively). M/I values in the stage I and stage II groups were strongly correlated with BMI (r = -.790, P = .0001 and r = -.785, P = .007, respectively). M/I values in the stage III group (4.53 +/- 0.51) were lower than in the stage I group, although not significantly so. M/I values in the stage IV group (3.16 +/- 0.37) were significantly lower than in the stage I group (P = .025). In multiple regression analysis with a model in which age, sex, BMI, HbA1c, and creatinine clearance (Ccr) were included as independent variables, BMI and Ccr were demonstrated to be significant and independent contributors to insulin sensitivity indices as the dependent variable (beta = -0.716 and beta = 0.272, respectively, R2 = .564, P < .0001). In conclusion, the present cross-sectional study demonstrated in non-obese NIDDM patients with nephropathy that microalbuminuria did not affect peripheral insulin resistance, but uremia did, as in nondiabetic patients, and that the peripheral insulin resistance was significantly contributed to by the degree of obesity and uremia.
 ...
PMID:Insulin resistance in non-obese, non-insulin-dependent diabetic patients with diabetic nephropathy. 928 89

Protein alteration resulting from a nonenzymatic reaction between ambient glucose and primary amino groups on proteins to form glycated residues called Amadori products is termed the Maillard reaction. By dehydration and fragmentation reactions, Amadori products are transformed to stable covalent adducts called advanced glycosylation end products (AGEs). In diabetes, accelerated synthesis and tissue deposition of AGEs is proposed as a contributing mechanism in the pathogenesis of clinical complications. Uremia in diabetes is associated with both a high serum level of AGEs and accelerated macro- and microvasculopathy. Diabetic uremic patients accumulate advanced glycosylated end products in "toxic" amounts that are not decreased to normal by hemodialysis or peritoneal dialysis but fall sharply to within the normal range within 8 h of restoration of half-normal glomerular filtration by renal transplantation. It follows that the higher mortality of hemodialysis-treated diabetic patients compared with those given a renal transplant may relate, in part, to persistent AGE toxicity. Pharmacologic prevention of AGE formation is an attractive means of preempting diabetic microvascular complications because it bypasses the necessity of having to attain euglycemia, an often unattainable goal. Pimagidine (aminoguanidine) interferes with nonenzymatic glycosylation and reduces measured AGE levels leading to its investigation as a potential treatment. The mechanism by which pimagidine prevents renal, eye, nerve, and other microvascular complications in animal models of diabetes is under investigation. Separate multicenter clinical trials of pimagidine in type 1 and type 2 diabetes, where proteinuria is attributable to diabetic nephropathy, are in progress. The effect of treatment on the amount of proteinuria, progression of renal insufficiency, and the course of retinopathy will be monitored.
 ...
PMID:Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications. 1009 2

Recent studies using a combination of isotope and balance techniques have shown that, in the postabsorptive state, the human kidney contributes substantially to overall glucose production and consumption. The kidney may contribute as much as the liver to gluconeogenesis and play an important role in the counterregulation of hypoglycemia. Furthermore, increased renal glucose production may contribute to fasting hyperglycemia found in type I and type II diabetes mellitus. Finally, loss of renal tissue as a consumer of glucose could explain the insulin resistance of uremia. We hypothesize that the human kidney may play a more important role in human carbohydrate metabolism than previously appreciated.
 ...
PMID:Important role of the kidney in human carbohydrate metabolism. 1041 40

To compare end-stage progression of nephropathy in type 1 and type 2 diabetic patients and non-diabetic subjects, we prospectively studied 92 patients with advanced uraemia not yet on dialysis (mean age 57.2 +/- 15.0 years), with a serum creatinine level above 200 mumol/L. The study included monthly serum creatinine (SC) measurements and quarterly outpatient follow-up (mean 10.8 +/- 7.1 months, range 1-21). Sixty subjects (65.2%) were diabetic (28 type 1 and 32 type 2). At inclusion, 95.6% of patients had anti-hypertensive medications. Drug category, dosage and combination were similar for both groups. Blood pressure (< or = 130/85 mmHg) and glucose level targets (fasting < or = 7.5 mmol/L and postprandial < or = 10 mmol/L) were obtained in all patients. Initial SC was not significantly different between diabetic and non-diabetic patients (426.5 +/- 189.4 mumol/L vs. 405.1 +/- 201.9 mumol/L). SC increased significantly faster in diabetic than non-diabetic patients (respectively 3.9 +/- 6.1% and 1.5 +/- 4.6% monthly, p < 0.05), with no difference between type 1 and type 2 diabetes. One-third (33.7%) of all patients started dialysis during follow-up (40% diabetic and 22% non-diabetic). Their weight, body mass index, age, sex ratio, treatment and aetiology were similar. During follow-up, the patients (29.4%) who sustained a major vascular event differed only in age (62.1 years vs. 55.2 years; p < 0.001). In this study, diabetic renal disease worsened significantly faster than other nephropathies, in spite of proper normalisation of blood pressure and glucose level. Therefore, it is essential to diagnose and manage Type 2 diabetes early to avoid encumbering dialysis centres with older patients.
 ...
PMID:The outcome of advanced chronic nephropathy in type 1 and type 2 diabetic and non-diabetic patients: a prospective study. 1044 25


1 2 3 4 Next >>