Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The urinary excretions of salivary and pancreatic amylase were studied in 718 type I diabetic patients and 51 control subjects, as part of a multicenter study on diabetic nephropathy in 15 Spanish hospitals. It was found that the urinary ratio of salivary to pancreatic amylase (S/P ratio), that in normal subjects is always below 1, was elevated in 35.4% of diabetic patients, whereas microalbuminuria was present in 19.8%. The prevalence of elevated S/P ratio was also higher than that of microalbuminuria at the first years from the onset of the disease, but the prevalence of microalbuminuria was higher in patients with a long duration of the disease. alpha 1-microglobulin and microalbuminuria paralleled their prevalences during the disease, when measured in a group of patients. Overnight urine samples were obtained on three consecutive weeks from the diabetic patients, and a nested ANOVA analysis showed that the intra-individual variation of the urine parameters measured (albumin, salivary and pancreatic amylase, and beta-NAG) was very small and not statistically significant. All these findings suggest that in type I diabetes mellitus, loss of negative charges of GBM would induce preferential excretion of the anionic salivary amylase over the more cationic pancreatic amylase, and that this phenomenon is more frequent and appears earlier than microalbuminuria. The mechanisms for the increased excretion of salivary amylase and albumin into urine seem to be at least partly different. On the contrary, increase in urinary excretion of albumin and alpha 1-microglobulin in these patients are correlated, suggesting a tubular participation in the mechanisms of production of microalbuminuria.
 ...
PMID:Charge selectivity and urine amylase isoenzymes. 753 43

To clarify the clinical and pathological significance of thin glomerular basement membranes (Thin-GBM) appearing in evident diabetics, we examined the renal biopsies from 179 diabetes mellitus (DM) patients with urinary abnormalities in which the number of non insulin dependent diabetes mellitus cases was 140 cases while the remaining 39 cases had insulin dependent diabetes mellitus. In addition, 17 of these cases were found to have either segmental or diffuse Thin-GBM by electron microscopy. The clinical and morphological parameters between the diabetics with Thin-GBM (DM-Thin-GBM) and the diabetics without Thin-GBM (the controls) were significantly different regarding DM duration (DM-Thin-GBM vs control: 5.3 +/- 5.5 vs 9.8 +/- 6.5 years, p < 0.01), Ccr (67.0 +/- 25.5 ml/min vs 45.6 +/- 24.4 ml/min, p < 0.01), the incidence of hematuria (52.9% vs 24.5%, p < 0.05) and hypertension (13.3% vs 51.3%, p < 0.05). The severity of glomerular damage was mild in the DM-Thin-GBM group as compared to the control. The renal survival rate from the onset of urinary abnormalities was higher in the DM-Thin-GBM group than in the control (p < 0.01). In the case of DM-Thin-GBM, the grade of proteinuria correlated with the mean width of the thickened GBM (p < 0.01) and the spread of the thickened GBM which was more than 500 nm in width (p < 0.001). The severity of microscopic hematuria correlated with the spread of the Thin-GBM (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Thin glomerular basement membrane in diabetic patients with urinary abnormalities. 852 10

We examined type IV collagen distribution and density in human diabetic kidneys by quantitative immunogold electron microscopy. We studied normal kidney transplant donors and "slow-track" and "fast-track" insulin dependent diabetic (IDDM) patients. The "slow-track" patients had IDDM for > or = 20 years and mesangial volume fraction (VvMes/glom) of < or = 0.32. The "fast-track" patients had IDDM for < or = 20 years and VvMes/glom > or = 0.37. Renal biopsies were embedded in Lowicryl, reacted with polyclonal anti-type IV collagen (in the distribution of the classical alpha 1(IV) and alpha 2(IV) collagen chains) and monoclonal anti-alpha 4(IV) collagen chain antibody followed by gold conjugated secondary antibody. We found, by morphometric techniques, a decrease in the immunogold densities of anti-type IV collagen in the subendothelial zone of the GBM in the "fast-track" IDDM patients. There was a trend towards a decrease in mesangial matrix (MM) particle density in the "fast-track" (P = 0.07) but not in the "slow-track" patients. However, because of the marked increase in MM in the "fast-track" patients, the per glomerulus estimated quantity of these antigens in MM was increased. In contrast, the density of alpha 4(IV) collagen chain was increased in the epithelial zone of the GBM in the "fast-track" IDDM patients. It is not known whether these changes in glomerular type IV collagen represent markers of advanced diabetic lesions or whether these changes might be detected earlier in diabetic patients destined for the later development of serious lesions.
 ...
PMID:Glomerular distribution of type IV collagen in diabetes by high resolution quantitative immunochemistry. 816 29

Normalbuminuric patients who have long-standing IDDM have a wide range of renal structure, from within normal limits to advanced lesions that overlap those of patients who have high levels of MA and border on those seen in patients who have overt DN. Patients who have low-level MA have reduced glomerular structure similar to that of patients who have NA. Low GFR, hypertension, or both can occur in patients who have NA or low-level MA and are associated with more advanced lesions. Patients who have MA and AER greater than 45 mg/24 hr have more advanced lesions than do patients with NA or low-level MA, but similar lesions are present in these patients whether AER is greater than or less than 100 mg/24 hr. Increasing AER in NA and MA patients who have long-standing IDDM is associated with GBM and mesangial expansion. A structural basis for MA cannot currently be deduced from studies of glomerular epithelial cell fine structure, capillary wall charge site analysis, or immunohistochemical studies of renal ECM composition. Hemodynamic adaptations to mesangial expansion and reduced filtration surface and, perhaps, hydraulic conductivity may accelerate glomerular damage, as expressed by increasing AER. Microalbuminuria derives its clinical utility in IDDM, as it identifies a population of patients at statistically increased risk of progression to overt DN by acting as a marker of already well-established DN lesions. Although MA is currently the best of the widely used indicators of DN risk, it is not precise. Therapies that reduce MA may ultimately slow or prevent progression toward ESRD, but this finding requires confirmation by demonstrating that a given treatment strategy can preserve GFR.
 ...
PMID:Glomerular changes in normo- and microalbuminuric patients with long-standing insulin-dependent diabetes mellitus. 892 36

A 5-year randomized, double blind, placebo-controlled study was carried out to determine the effect of the angiotensin-converting enzyme (ACE) inhibitor enalapril (E) on the progress of renal function and histology in subjects with type 1 diabetes and microalbuminuria. Seventy three type 1 diabetic patients with BP <140/90 and with persistent albuminuria (AER 20-200 microg/min) and normal renal function were randomly assigned to receive E (n=37) or placebo (n=36). A percutaneous renal biopsy was successfully performed in 69 patients and repeated in 59 patients after 5 years. The mean glomerular volume (MGV), mesangial volume (Vv mes) and glomerular basement membrane thickness (GBMT) were measured histomorphometrically. Before treatment, both groups had similar clinical characteristics, blood pressure, HbA(1c), albumin excretion rate (AER), glomerular filtration rate (GFR), serum creatinine and renal structural damage. Blood pressure was well controlled in both groups. In the patients treated with E, albuminuria decreased significantly (P<0.05) and only 8.1% (3/37) of subjects progressed to clinical albuminuria (AER >300 mg/24 h) compared with 30.5% (11/36) in the placebo group. The E treatment resulted in absolute risk reduction of 22.4 percentage points for the development of clinical albuminuria over a 5-year period (P<0.01). After 5 years of treatment, GBM thickness showed a consistent, though statistically insignificant, increase in the placebo group, whereas it remained stable in the E group. A significant increase in MGV and Vv mes was also observed in the placebo group on completion of the study. The present study indicates that long term therapy with E may decrease or delay the progression of structural glomerular damage in microalbuminuric diabetic subjects without marked hypertension (BP <140/90).
 ...
PMID:Effect of 5-year enalapril therapy on progression of microalbuminuria and glomerular structural changes in type 1 diabetic subjects. 1270 22

Directed immunotherapy at the programmed cell death-1 receptor has demonstrated efficacy in non-small-cell lung cancer, metastatic melanoma, and various other malignancies. Immune checkpoint inhibitors are innovative therapies producing some impressive clinical responses with a more manageable adverse effect profile when compared to traditional chemotherapy. The more common adverse effects associated with these agents include fatigue, rash, myalgia, pyrexia, and cough, but less common yet serious adverse effects have included immune-mediated colitis, pneumonitis, hepatitis, type 1 diabetes, and encephalitis. Here we present a case of a female patient with glioblastoma multiforme, who was treated with the programmed cell death-1 receptor inhibitor nivolumab and subsequently developed aplastic anemia.
 ...
PMID:Nivolumab-induced aplastic anemia: A case report and literature review. 2882 74