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)

We measured class-specific antibodies to the mycobacterial hsp70 protein in 67 patients with diabetes mellitus (27 type 1 and 40 type 2) with or without vascular complications. Using ELISA, the levels of IgG and IgM antibodies in the sera of diabetic patients did not significantly differ either from those of healthy control subjects or between both types of diabetes, regardless of gender, disease duration, HbA1 level, or type of vascular complication. In patients with type 2 diabetes, the mean serum IgA levels were significantly higher than those in their matched controls [274(71) mg/dl vs 208(88) mg/dl; P < 0.01]. In this group of patients, the IgA antibody titer was significantly correlated to the serum IgA level (r = 0.334; P < 0.01). Serological autoimmunity (IgG or IgM type) to hsp70 protein is common in both the normal and the diabetic population. The increased IgA levels and anti-hsp70 IgA titers in the sera of diabetics suggest a possible role of IgA in the pathogenesis of the vascular complications of diabetes mellitus.
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PMID:Increased serum levels of IgA antibodies to hsp70 protein in patients with diabetes mellitus: their relationship with vascular complications. 863 83

The present study was undertaken in order to determine the possible alterations in whole saliva and the periodontal status in patients with diabetes mellitus (DM), and was conducted on 17 patients with DM and 17 systemically and periodontally healthy subjects. When the subjects were evaluated clinically, significantly increased probing depths were noticed in the DM group when compared with the healthy subjects. In whole saliva samples, sodium, potassium, total protein, amylase, thiocyanate, and secretory IgA levels were determined in both groups. Difference between the two groups regarding the mean salivary potassium levels were found to be statistically significant since the mean salivary potassium levels in the DM and the control groups were 2.470 +/- 9.04 mmol/L and 14.30 +/- 8.88 mmol/L, respectively. The mean salivary total protein, amylase and secretory IgA levels in the DM group were 2.41 +/- 1.0 mg/mL, 124.2 +/- 79.7 U/mL and 6.86 +/- 3.50 mg/L, all being significantly higher than the control group. However, no significant differences could be shown for the salivary sodium and thiocyanate levels. Nor was there any difference between non-insulin dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). The findings of the present study suggest that, besides the clinical examinations, the determination of the possible alterations in the composition of whole saliva might also be helpful in understanding the increased severity of periodontal disease in diabetic patients.
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PMID:The alterations of whole saliva constituents in patients with diabetes mellitus. 876 45

Chlamydia trachomatis oculogenital infection is a common disease in western societies. Despite the fact that diabetes is accompanied by increased risk for infections, no data on chlamydial infections in the non-insulin-dependent diabetic (NIDDM) patient exist. In our study Chlamydia antibodies were determined using an immunoperoxidase reaction in NIDDM patients (n = 79) and in a local nondiabetic control population (n = 125) which was randomly invited to a medical control visit without any preselection criteria. In total, 46% of diabetics and 55% of controls were IgG-Chlamydia antibody positive (ns). Using IgA-Chlamydia antibodies to define 'seroactive' chlamydial infection, 22% of NIDDM patients and 14% of controls were positive. Thus seroactive chlamydial infection of all patients with proven contact to Chlamydia (IgG-Chlamydia antibody positive) was 47% in diabetics versus 25% in controls, respectively (P < 0.05). Forming subgroups, significance was reached in females (52% vs. 32%, P < 0.05) only, but a similar trend was observed in males (36% vs. 21%, ns). Seroactivity was neither correlated with HbA1c nor with nephelometrically determined total serum immunoglobulins (IgG, IgA). Additionally we observed significantly elevated total IgM and IgA-levels in NIDDM patients whereas IgG-levels were comparable in both groups. In conclusion, seroactive chlamydial infections in subjects with proven contact to Chlamydia are more frequent in NIDDM patients than in nondiabetic controls. Additionally, higher IgM and IgA serum levels might indicate a higher susceptibility to active surface infections in NIDDM.
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PMID:Increased prevalence of IgA-Chlamydia antibodies in NIDDM patients. 880 87

Urinary excretion rate and total clearances of albumin, IgG, IgA and alpha 1-microglobulin, together with selectivity index and proteinuria, were determined by computerized nephelometry in 187 IDDM and NIDDM diabetic out-patients and in 39 healthy subjects in order to perform a prompt clinical assessment of diabetic nephropathy. Significant correlations between nephelometric and RIA procedures were demonstrated for the urinary excretion of albumin (p < 0.001) and total IgG (p < 0.001) in diabetic patients and healthy subjects. Nephelometry allowed us to classify diabetic patients in different stages of nephropathy: non nephropathic, normoalbuminuric with hyperfiltration, with incipient (microalbuminuric) and overt nephropathy (macroalbuminuric). Thirty consecutive subjects were analyzed within 1 h from the beginning of the procedure. A normal tubular function was demonstrated in non nephropathic, hyperfiltering and in 34% of microalbuminuric diabetic patients. On the contrary, in 66% of microalbuminuric and in 93% of macroalbuminuric patients alpha 1-microglobulin urinary levels were found above the upper normal limit. Urinary excretion of IgA was significantly increased only in macroalbuminuric diabetic patients (p < 0.001); this marker might therefore characterise the stage of overt nephropathy. Computerized nephelometry can be considered as a prompt, reproducible and high sensitive approach in the clinical evaluation of proteinuria and tubular function in diabetic renal disease.
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PMID:Nephelometry in the clinical assessment of glomerular proteinuria and tubular function in diabetic nephropathy. 934 86

Approximately 30% of patients with type 1 and type 2 diabetes develop diabetic nephropathy. Apart from metabolic control, genetic predisposition plays an important role in its genesis. Analysis of intermediate phenotypic markers showed that the activity of Na/Li- and Na+/H(+)-countertransport is increased in patients with diabetic nephropathy. The renin-angiotensin system is of crucial importance as a system for therapeutic intervention and as genetic marker for susceptibility to renal disease. Consequently, the analysis of molecular genetic markers has focused on a polymorphism in the gene for the angiotensin II converting enzyme (ACE). However, the analysis of the I/D-polymorphism with respect to development of diabetic nephropathy in type 1 and type 2 diabetes has yielded conflicting results, at least in type 1 diabetes. These discrepant results may be due to differences in definition, sample size and ethnic background of the patients. In IgA glomerulonephritis it has been shown that the DD genotype (which is correlated with higher serum and tissue ACE activity compared to II genotype) is associated with a more rapid deterioration of renal function. The same adverse effect of the DD genotype could also be demonstrated in patients with diabetic nephropathy. Two studies examined the response to treatment according to the different genotypes, with contradictory results. A Japanese study showed a more pronounced reduction in proteinuria under ACE inhibitor treatment in patients with DD genotype, whereas a Danish study showed that patients with the DD genotype exhibited a steeper decline in renal function despite ACE inhibitor treatment. The data available for other candidate genes are fragmentary and negative throughout.
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PMID:Genetic determinants of diabetic renal disease and their impact on therapeutic interventions. 940 16

Several tribes of North American Indians are known to have poor glucose control and are at a high risk of developing type 2 diabetes. Similarly some tribes also exhibit RA at a high frequency. We have recently determined that a subset of Caucasian patients with RA mount an immune response to IgG modified with advanced glycation endproducts (AGE). The AGE modifications on IgG in vivo include N(epsilon)-(carboxymethyl) lysine, imidazolone and pentosidine. The presence of IgG-AGE and the antibody response to the IgG-AGE in the Ojibwe tribe of First Nations native Indians where both NIDDM and RA are prevalent was investigated. AGE modified IgG and albumin were determined using a modified nitroblue tetrazolium assay. Rheumatoid factors (RFs) and IgM and IgA anti-IgG-AGE were detected by ELISA. Of the 108 individuals tested, 21 had RA only, 3 had both RA and type 2 diabetes, 30 had type 2 diabetes only and 51 had no diagnosed disease. AGE modified IgG was significantly elevated in the RA group compared to the diabetic group. IgM and IgA RFs were detected in 83% and 50% of the RA patients, compared to 31-37% and 7-10% of the diabetics or normal individuals. IgM anti-IgG-AGE was detected in 54% of the RA patients, in contrast to 7-14% in the diabetics or normal individuals. IgA anti-IgG-AGE was detected in 42% of the RA patients and only 7 to 8% of the NIDDM or normal individuals. The IgM or IgA anti-IgG-AGE antibodies likely contribute to the accumulation of IgG-AGE, possibly through blocked clearance through AGE receptors. A trend towards more severe disease was seen in those Ojibwe RA patients with circulating anti-AGE antibodies. Non-enzymatic glycation may be an important pathogenic link in the RA seen in North American Indians.
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PMID:Advanced glycation endproducts (AGE) on IgG, a target for circulating antibodies in North American Indians with rheumatoid arthritis (RA). 984 95

Coeliac disease has been reported to occur in 2-5 per cent of insulin-dependent diabetic patients (IDDM). Suitable non-invasive screening tests would allow identification of these patients. The aim of this study was to determine the value of the red cell distribution width (RDW) in detecting unrecognised coeliac disease in insulin-dependent diabetic patients (IDDM). All patients (n = 208) attending the Diabetic out-patient clinics at 2 adjacent centres who had a full blood picture and RDW carried out in the past 18 months were included. IDDM patients with an elevated RDW were identified and their charts were reviewed to determine if they had symptoms or laboratory abnormalities compatible with coeliac disease. They were invited to attend for serological screening. Ninety-five of 208 patients had an elevated RDW of whom 66 had non-insulin dependent diabetes mellitus and 29 had IDDM. Two of the 29 IDDM patients had died in the interim period. Six of the remaining 27 IDDM patients had previously been tested for serological markers associated with coeliac disease, of whom 1 had a positive antigliadin antibody titre (IgA-AGA 199 EU) and normal duodenal biopsy. Eighteen of the remaining 21 patients with IDDM consented to serological testing of whom only 1 had a positive titre of antiendomysial antibody (IgA-EMA) and villous atrophy. Although the RDW is known from previous studies to be a sensitive predictor for coeliac disease, this study has demonstrated its poor specificity in predicting IDDM patients who may have coeliac disease. The RDW is not recommended as a screening test for coeliac disease in patients with IDDM.
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PMID:Application of red cell distribution width to screening for coeliac disease in insulin-dependent diabetes mellitus. 1054 Jul 81

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

We investigated the hypothesis that modified lipoproteins trigger an immune response leading to the production of autoantibodies and subsequently to the formation of atherogenic immune complexes (IC). We recruited 20 type 2 diabetic patients with macrovascular disease, 14 nondiabetic patients with coronary artery disease (CAD), and 34 healthy control subjects matched for age, sex, and race. Serum antibodies to oxidized and glycated LDL did not differ significantly among the 3 groups. Serum IC contained variable, but not statistically different, amounts of IgG, IgM, and IgA. In contrast, the content of cholesterol in IC isolated from diabetic patients was significantly higher than that in IC isolated from control subjects, and the content of apolipoprotein (apo)-B was significantly higher than that in IC isolated from control subjects and patients with CAD. Cholesteryl ester accumulation in human monocyte-derived macrophages incubated with IC, a measure of the atherogenic potential of IC, was significantly higher in macrophages incubated with red blood cell-adsorbed IC isolated from diabetic patients compared with IC isolated from control subjects (P < 0.03) or from patients with CAD (P < 0.04) and was strongly correlated with the content of apoB (r = 0.68, P < 0.001) and cholesterol (r = 0.61, P < 0.001) in IC. LDL from diabetic patients was more susceptible to oxidation in vitro, was significantly smaller, and contained significantly less alpha-tocopherol than LDL isolated from subjects in the other groups. In addition, the n-3 polyunsaturated fatty acid content of phospholipids and cholesteryl esters in LDL isolated from diabetic patients was significantly increased (P < 0.05) compared with that from patients with CAD or from control subjects. We postulate that LDL size, susceptibility to oxidation, and lipid fatty acid composition may play a critical role in the production of antibodies to oxidized LDL and consequently in the formation of LDL-containing IC in patients with type 2 diabetes.
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PMID:Anti-modified LDL antibodies, LDL-containing immune complexes, and susceptibility of LDL to in vitro oxidation in patients with type 2 diabetes. 1086 57

One of the most important tasks of clinical and experimental nephrology is to identify the risk factors of progression of renal failure. A major renal risk factor which has not been sufficiently acknowledged despite increasing evidence is cigarette smoking. Diabetologists were the first to recognize the adverse effects of smoking on the kidney: both in type 1 and in type 2 diabetes smoking (i) increases the risk of development of nephropathy and (ii) nearly doubles the rate of progression to end-stage renal failure. Until recently it was not known whether smoking also increases the risk to progress to end-stage renal failure in patients with primary renal disease. A retrospective multicenter European case-control study showed that smoking is an independent risk factor for end-stage renal failure in patients with inflammatory and noninflammatory renal disease, i.e. IgA glomerulonephritis and polycystic kidney disease. The pathogenesis of the smoking-related renal damage is largely unknown. The intermittent increase in blood pressure during smoking seems to play a major role in causing renal damage, but further potential pathomechanisms are presumably also operative. Smoking as a renal risk factor is of great interest to diabetologists as well as nephrologists, but unfortunately so far this information has had little impact on patient management. The present article reviews the current knowledge about the renal risks of smoking and discusses the potential mechanisms of smoking-mediated renal injury.
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PMID:Smoking--a renal risk factor. 1097 Nov 49


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