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

To clarify the morphological changes in renal proximal tubules at the onset of diabetic nephropathy, we observed 177 biopsy samples from patients with Non-Insulin-Dependent Diabetics (NIDDM) using light and electron microscopy. Group I had no proteinuria (p.u.), group II had p.u. < or = 0.5 g/day, group III had p.u. > 0.5 g/day, group IV had serum creatine level (Cr) > 1.5 mg/dl. Twenty age-matched normal patients and 80 patients with IgA nephropathy were used as controls. In groups I and II, the following features were significantly different from those in the controls: spherical enlargement of mitochondria (MT) in proximal tubule cells, hypertrophy of proximal tubule cells and their nuclei, and thickening of both the proximal tubule basement membrane (TBM) and the glomerular basement membrane (GBM). Among the histological changes observed in group I, the thickness of the GBM and TBM indicated that the disease would lead to diabetic nephropathy. MT enlargement was positively correlated with nuclear and cytoplasmic enlargement of the proximal tubule cells in diabetic patients (p < 0.05), but was not correlated with other morphological changes or disease prognosis. Glomerular nodular lesions, glomerular sclerotic change, and cortical tubulointerstitial fibrosis became evident in groups III and IV. From the above, we concluded that MT enlargement and thickening of the TBM are possible causes of reduced active transport in the proximal tubules, causing microalbuminuria in diabetics, and initial impairment of post-tubule transport.
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PMID:Mitochondrial enlargement and basement membrane thickening of renal proximal tubules, possible initiators of microalbuminuria in non-insulin-dependent diabetics (NIDDM). 147 27

1. Graft survival rates increased about 3-5 percentage points for patients with all primary diseases in 1989-1990. 2. Patients with different diseases had 1-year graft survival rates that varied from 73% for noninsulin-dependent diabetes (NIDDM) to 83% for IgA nephropathy (IgAN). Five-year graft survival varied from 40% for NIDDM to 66% for IgAN. 3. Our findings in Clinical Transplants 1990 that IgAN patients have a high graft survival was confirmed and 1-year graft survival improved by 5% in the last 2 years. 4. There was a 20 percentage point increase in full-time work status of patients after transplantation; 68% of patients with polycystic kidney disease (PKD) and chronic glomerulonephritis (CGN) had full-time work status after 3 years whereas patients with diabetes mellitus (DM) and atheronephrosclerosis (NS) had about 50%. 5. Good early graft function (urine output during the first 24 hours posttransplant, no dialysis within the first-week posttransplant, and no rejection episodes before discharge), predicted good 1-year graft survival for patients with different diseases but patients with NS and DM had a poorer graft survival beyond the first year posttransplant. Patients who had poor early function had 20% lower graft survival than those who had good function. However, in patients with IgAN, no urine at day 1 still resulted in graft survival comparable to those that produced urine. 6. More patients with DM were transplanted within 1 year after going into ESRD than those with other diseases. Conversely, 46% of those with NS did not get transplanted until more than 2 years after developing ESRD. 7. Only 77% of NS patients had functioning grafts at discharge compared to DM (84%), PKD (81%), IgAN (81%), and CGN (80%). 8. Black patients had a statistically significant higher incidence of anuria on the first day compared with Whites. They also had a higher incidence of dialysis and rejection during the first hospitalization. This was true for CGN, DM, PKD, and NS patients. Following excellent early function, Black CGN and DM patients had a higher incidence of rejection than White CGN and DM patients.
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PMID:Outcome of renal transplantation in different primary diseases. 182 Jan 24

A. PATIENT SURVIVAL 1. The best cadaver graft patient survival 3-years posttransplant was observed in those whose primary disease was either nephrotic syndrome (98%), renal hypoplasia (98%), renal dysplasia (98%), IgA nephropathy (96%), or medullary cystic disease (97%). The worst survival was in those with Goodpasture's syndrome (88%), hypertensive nephrosclerosis (87%), MPGN (87%), IDDM (86%), and NIDDM (85%). 2. Patient survival correlated inversely with nonimmunologic graft loss. Nonimmunologic graft loss was high in patients with hypertensive nephrosclerosis (21%), polycystic kidney disease (23%), IDDM (27%), and NIDDM (27%). 3. Females with CGN and IDDM had better patient survival than males with the same diseases. The 2-, 3-, and 5-year survivals for females with IDDM were 91%, 89%, and 87% whereas for males, they were 87%, 84%, and 81%, respectively (p = 0.01). For CGN the 2-, 3-, and 5-year survivals were 95%, 94%, and 93% for females and 93%, 91%, and 90% for males (p less than 0.01). Females with Alport's syndrome had lower patient survival rates at 1 year (86%) than males (95%, p = 0.03). B. GRAFT SURVIVAL 1. The best 3-year graft survival was in recipients whose primary pathology was IgA nephropathy with 83% for cadaver grafts and 95% for LRD grafts. This was not secondary to center effects. The worst graft survival at 3 years for cadaver kidney recipients was in those whose primary illness was NIDDM (61%), hypertensive nephrosclerosis (58%), MPGN (59%), and Goodpasture's syndrome (59%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Outcome of kidney transplantation in different diseases. 210 68

The diagnosis of diabetic nephropathy (DN) is almost always based on clinical grounds. The diagnosis is supported by a long history of diabetes, evidence of target organ damage and proteinuria preceding azotemia. The validity of this clinical approach is well established in insulin dependent diabetes mellitus but not in non-insulin dependent diabetes mellitus (NIDDM). It is thus important to determine which patients with NIDDM accompanied by non-diabetic renal disease (NDRD) should have a biopsy. However, factors clinically associated with NDRD in patients with NIDDM remain unclear. Therefore we reviewed clinical data, laboratory data and renal biopsies from 22 NIDDM patients who underwent renal biopsy between 1992 and 1998 in Wonju Christian Hospital. From this data, we identified important features that would discriminate between DN and NDRD. There were 8 women and 14 men. Age ranged from 33 to 68 (51.2 +/- 10.7) years. The duration of diabetes at biopsy ranged from 0 to 13 (4.2 +/- 4.2) years. Nephrotic syndrome was present in 13 patients. The patients with NDRD (n = 14) and DN (n = 8) had comparable 24-hour proteinuria, 24-hour albuminuria, creatinine clearance, serum creatinine, albumin, as well as incidences of neuropathy and hypertension. The significant factors that predict the NDRD included a short duration of the diabetes mellitus, the presence of dysmorphic red blood cells in urine, the absence of retinopathy and HbA1c below 9% (p < 0.05, respectively). NDRD included IgA nephropathy (n = 6), minimal change disease (n = 3), membranous nephropathy (n = 3), membranous lupus nephritis (n = 1) and acute interstitial nephritis (n = 1). Multiple logistic regression analysis revealed that the short duration of DM and the absence of retinopathy were factors significantly associated with NDRD. In summary, when there is a short duration of diabetes mellitus, or an absence of retinopathy seen in patients with NIDDM, then renal biopsy in diabetic patients aids in the detection of NDRD.
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PMID:Non-diabetic renal disease in patients with non-insulin dependent diabetes mellitus. 1048 33

The aim of this study was to examine the relationship between serum immunoglobulin A (IgA) levels and diabetic nephropathy in patients with type 2 diabetes mellitus, and to describe the role of IgA nephropathy superimposed on diabetes mellitus. A total of 127 type 2 diabetic patients were studied. Of these diabetics, 74 had no proteinuria, 35 had diabetic glomerulosclerosis confirmed by renal biopsy, 13 had superimposed IgA nephropathy, and five had superimposed non-IgA nephropathy. We also studied 93 non-diabetic patients with IgA nephropathy, 24 non-diabetic patients with non-IgA nephropathy, and 38 non-diabetic controls. Serum IgA levels were significantly higher in IgA nephropathy patients (350+/-130 mg/dl) than in non-diabetic controls (228+/-56 mg/dl) and diabetics without proteinuria (268+/-104 mg/dl). Serum IgA levels were also significantly higher in diabetics with superimposed IgA nephropathy (470+/-208 mg/dl) than in non-diabetic controls, non-IgA nephropathy patients (270+/-133 mg/dl), diabetics without proteinuria, diabetic glomerulosclerosis alone (302+/-126 mg/dl), and diabetics with superimposed non-IgA nephropathy (248+/-137 mg/dl). The prevalence of high serum IgA levels was significantly higher in diabetics with superimposed IgA nephropathy (76.9%) than in diabetic glomerulosclerosis alone (31.4%) and diabetics with superimposed non-IgA nephropathy (25.0%). In conclusion, our findings indicate that high serum IgA level is a sign of the existence of IgA nephropathy superimposed on diabetes mellitus.
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PMID:Serum IgA levels in patients with diabetic nephropathy and IgA nephropathy superimposed on diabetes mellitus. 1080 48

The Ramipril Efficacy in Nephropathy (REIN) study found that angiotensin-converting enzyme (ACE) inhibitors effectively decreased proteinuria, glomerular filtration rate (GFR) decline (DeltaGFR), and incidence of end-stage renal disease (ESRD) in patients with proteinuric chronic nephropathies. In this study, we prospectively investigated the main clinical determinants of progression and response to treatment in the 352 patients enrolled into the REIN study. Mean DeltaGFR (0.56 +/- 0.05 [SEM] versus 0.21 +/- 0.05 mL/min/1.73 m(2)/mo; P = 0.0001) and incidence of ESRD (30% and 10%; P = 0.0001) were more than twice that in patients with proteinuria of 2 g/24 h or greater of protein compared with those with protein less than 2 g/24 h (relative risk [RR], 4.07; 95% confidence interval [CI], 2.20 to 7.52), as well as in patients with hypertension compared with normotension (mean DeltaGFR, 0.48 +/- 0. 05 versus 0.22 +/- 0.05 mL/min/1.73 m(2)/mon; P = 0.0006; ESRD, 25% versus 10%; P = 0.004; RR, 3.18; 95% CI, 1.38 to 7.32). Hypertension at study entry (P = 0.038), greater mean blood pressure on follow-up (P = 0.002), and urinary protein excretion rate (P = 0.0001) were independent predictors of faster DeltaGFR. DeltaGFR was approximately twofold faster in patients with type 2 diabetes than in those with primary glomerular disease (P = 0.002; including immunoglobulin A [IgA] nephropathy, P = 0.009); nephrosclerosis (P = 0.03), adult polycystic kidney disease (APKD), or chronic interstitial nephritis (P = 0.006). Diabetes at study entry (P = 0. 02) and greater mean blood pressure (P = 0.0001) and urinary protein excretion rate (P = 0.0001) on follow-up were independent predictors of faster DeltaGFR. After correction for baseline covariates, diabetes was also associated with an increased risk for progression to ESRD (RR, 2.39; 95% CI, 1.01 to 5.68; P < 0.05). At multivariate analyses, ramipril significantly decreased DeltaGFR (regression coefficient,-0.23 +/- 0.11 [SEM]; P = 0.036) and ESRD (RR, 2.08; 95% CI, 1.21 to 3.57; P = 0.008) in patients with baseline proteinuria of 2 g/24 h or greater of protein, and the renoprotective effect increased for increasing levels of proteinuria. Ramipril decreased DeltaGFR to a similar extent in normotensive and hypertensive patients (-0.14 +/- 0.11 versus -0.14 +/- 0.09) and significantly limited ESRD in hypertensive patients (RR, 2.03; 95% CI, 1.26 to 3. 26; P = 0.004). DeltaGFR was decreased by 42% in primary glomerular disease (P = 0.017), by 35% in IgA nephropathy, and by 37% in nephrosclerosis, but was not improved in type 2 diabetes, APKD, or interstitial nephritis. At multivariate analyses, ramipril significantly slowed DeltaGFR (-0.24 +/-0.08; P = 0.004) and progression to ESRD (RR, 2.32; 95% CI, 1.36 to 3.96; P = 0.002) in patients without diabetes, but not in patients with diabetes, who tended to have a faster DeltaGFR (+0.62 +/- 0.44) on ramipril therapy. In summary, patients with proteinuria of 2 g/24 h or greater of protein, preexisting hypertension, or type 2 diabetes were faster progressors. Greater blood pressure and degree of proteinuria were the strongest determinants of faster GFR decline. The renoprotective effect of ramipril was similar in patients with normotension and hypertension. Hypertensive patients and those with proteinuria of 2 g/24 h or greater of protein, primary glomerular disease, or nephrosclerosis gained the most from ACE inhibitor treatment. During the study period, those with proteinuria less than 2 g/24 h of protein, type 2 diabetes, or polycystic kidney disease did not benefit by treatment to an appreciable extent.
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PMID:Chronic proteinuric nephropathies: outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury. 1084 31

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.
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PMID:Proteinuria: clinical signficance and basis for therapy. 1176 58

Diabetic glomerulosclerosis is the most frequent cause of renal disease in patients with type II diabetes mellitus (DM), sometimes accompanied by vascular lesions. However, other glomerular pathologies are important in these patients. The aim of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) in selected patients with type II DM, and to identify clinical markers that may predict its presence in this population. We reviewed 20 renal biopsies performed on twenty patients with type II DM. Nine of them showed diabetic nephropathy (DN) (45%), whereas eleven showed NDN (55%): 1 IgA nephropathy, 3 vasculitis and 7 membranous nephropathy. We found no differences between the two groups with regard to sex, duration of DM, insulin therapy, glycosylated haemoglobin, proteinuria, presence of nephrotic syndrome, hypertension, serum IgA level or renal size. The NDN group had haematuria in 63.6%, whereas the patients with NDN had it in 44.4% (NS). Body mass index was higher in NDN patients (30 +/- 6.7 vs 22 +/- 2.9; p < 0.01), The same was true for creatinine clearance (82.2 +/- 51.4 ml/m vs 40.4 +/- 19.6 ml/m; p < 0.05). The age at the moment of diagnosis was higher in ND patients (67 +/- 11.2 vs 54.3 +/- 4.6; p < 0.05). The 3 patients who had diabetic retinopathy were found to have DN on renal biopsy (diagnostic specificity = 100%), although 66.7% of the patients with diabetic glomerulopathy had no retinopathy. We conclude that patients with type II DM with renal findings suggesting non-diabetic renal disease frequently it have NDN, and a renal biopsy must be performed. The presence of retinopathy has a predictive value of 100% in predicting DN, therefore its existence may make this diagnostic procedure unneccesary.
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PMID:[Renal histological lesions in patients with type II diabetes mellitus]. 1208 17

Two pathological patterns of acute poststaphylococcal glomerulonephritis are well defined and include (1) an acute proliferative and exudative glomerulonephritis closely resembling classical acute poststreptococcal glomerulonephritis in patients with Staphylococcus aureus infection and (2) a membranoproliferative glomerulonephritis in patients with Staphylococcus epidermidis infection secondary to ventriculovascular shunts. In this study, we report a novel immunopathologic phenotype of immunoglobulin (Ig) A-dominant acute poststaphylococcal glomerulonephritis occurring in patients with underlying diabetic nephropathy. Five patients with type 2 diabetes presented with acute renal failure occurring after culture-positive staphylococcal infection. Renal biopsy disclosed an atypical pattern of acute endocapillary proliferative and exudative glomerulonephritis with intense deposits of IgA as the sole or dominant immunoglobulin, mimicking IgA nephropathy. The deposits were predominantly mesangial in distribution with few subepithelial humps. All five cases occurred superimposed on well-established diabetic nephropathy. Outcome was poor with irreversible renal failure in four of five (80%) cases. The possible pathophysiological basis of this atypical form of acute poststaphylococcal glomerulonephritis in diabetic patients is explored. Proper recognition of this entity is needed to avoid an erroneous diagnosis of IgA nephropathy, with corresponding therapeutic and prognostic implications.
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PMID:IgA-dominant acute poststaphylococcal glomerulonephritis complicating diabetic nephropathy. 1469 5

The insulin resistance syndrome (syndrome X, metabolic syndrome) has become the major health problem of our times. Associated obesity, dyslipidemia, atherosclerosis, hypertension, and type 2 diabetes conspire to shorten life spans, while hyperandrogenism with polycystic ovarian syndrome affect the quality of life and fertility of increasing numbers of women. Whereas a growing number of single genetic diseases affecting satiety or energy metabolism have been found to produce the clinical phenotype, strong familial occurrences, especially in racially prone groups such as those from the Indian subcontinent, or individuals of African, Hispanic, and American Indian descents, together with emerging genetic findings, are revealing the polygenetic nature of the syndrome. However, the strong lifestyle factors of excessive carbohydrate and fat consumption and lack of exercise are important keys to the phenotypic expression of the syndrome. The natural history includes small for gestational age birth weight, excessive weight gains during childhood, premature pubarche, an allergic diathesis, acanthosis nigricans, striae compounded by gynecomastia, hypertriglyceridemia, hepatic steatosis, premature atherosclerosis, hypertension, polycystic ovarian syndrome, and focal glomerulonephritis appearing increasingly through adolescence into adulthood. Type 2 diabetes, which develops because of an inherent and/or an acquired failure of an insulin compensatory response, is increasingly seen from early puberty onward, as is atheromatous disease leading to coronary heart disease and stroke. A predisposition to certain cancers and Alzheimer's disease is also now recognized. The looming tragedy from growing numbers of individuals affected by obesity/insulin resistance syndrome requires urgent public health approaches directed at their early identification and intervention during childhood. Such measures include educating the public on the topic, limiting the consumption of sucrose-containing drinks and foods with high carbohydrate and fat contents, and promoting exercise programs in our nation's homes and schools.
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PMID:Insulin resistance syndrome in children. 1518 Oct 20


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