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)

The effect of sample pre-treatment as a source of variability of apolipoprotein (apo) AI, AII and B assays was demonstrated with lipid dissociating agents. The average mean percentage change ranged from -58 to +133% compared with untreated samples. The apolipoprotein method selected was validated by comparing their concentrations with their corresponding lipoprotein lipid or protein in normal controls and Type 2 (non-insulin-dependent) diabetic patients. The coefficient of variation was maintained below 3.5% for apo AI, AII, B and HDL2-apo AI. The apolipoprotein concentrations of fasting plasma lipoproteins were determined in a cross-sectional study of non-obese (body-mass index less than or equal to 30) patients with Type 2 diabetes mellitus. Compared with normal subjects matched for sex, age, body-mass index, exercise, alcohol consumption and smoking. Type 2 patients at diagnosis showed reduced apo AI and HDL2-apo AI concentrations, lowered apo AI:B ratio and increased concentrations of apo B. Type 2 patients treated by diet alone (for 6-72 months) and diet plus glibenclamide (2.5-15 mg/day for 6-48 months) exhibited similar abnormalities of plasma apolipoprotein concentration to Type 2 patients at diagnosis. However, in Type 2 patients treated with insulin (25-65 U/day for 8-144 months) concentrations of apo AI and HDL2-apo AI, and the apo AI:B ratio were normal. Apo B concentrations were generally lower compared with all groups of non-insulin treated patients. These abnormalities of apolipoprotein metabolism, which are associated with premature coronary disease, are still evident in patients treated by diet and diet plus glibenclamide, but are not seen in Type 2 patients treated with insulin.
 ...
PMID:Apolipoprotein assays: methodological considerations and studies in non-insulin-dependent diabetes treated by diet, glibenclamide and insulin. 250 Jun 99

Factors to be checked concerning local and systemic condition were studied statistically in order to clarify the methodology for clinical management of diabetic retinopathy. NIDDM (n = 1517) and IDDM (n = 30) persons participating in baseline and follow-up examinations were included. The vitreous fluorophotometric values were selected for local check factors. Glycosylated hemoglobin was selected for systemic check factors. To determine the retinopathy status at both the baseline and follow-up examinations, all fundus photographs were graded in a masked fashion, using the author's classification scheme (1983) which specified six levels of retinopathy for each excepted from the interrupted proliferative retinopathy. Level 0: no retinopathy, Level 1: microaneurysms only (AI), Level 2: microaneurysms and retinal hemorrhages (AII), Level 3: preproliferative retinopathy (soft exudates, increased capillary occlusion and intraretinal microvascular abnormalities) (BI), Level 4: neovascularization elsewhere (BII), Level 5: neovascularization of the disc (BIII), Level 6: vitreous hemorrhages or proliferative tissue (BIV, V). A positive correlation between the progression of retinopathy and glycosylated hemoglobin or vitreous fluorophotometric values were observed. The coefficient of correlation was 0.67 between posterior vitreous fluorophotometric values and levels (scores) of retinopathy. The coefficient of correlation was 0.41 between glycosylated hemoglobin and levels of retinopathy. These data suggest that these two factors can predict the progression of diabetic retinopathy.
 ...
PMID:[Clinical management of diabetic retinopathy]. 261 Jan 68

Plasma lipoproteins and apoproteins were compared among Chinese and American controls and non-insulin-dependent diabetic (NIDDM) subjects in the same laboratory. Apoprotein AI concentrations in Chinese subjects, both NIDDM subjects and controls (men, 147 and 158 mg/dl, respectively), were significantly higher than those in American subjects (men, 104 and 124 mg/dl, respectively). Apoprotein AII concentrations, however, were comparable between Chinese and American subjects. Chinese NIDDM subjects had lower high-density lipoprotein cholesterol (HDLC), higher low-density lipoprotein cholesterol (LDLC), and higher apoprotein B levels than Chinese controls. Chinese subjects with NIDDM had HDLC and LDLC levels similar to those of American controls but trends of higher HDLC and lower LDLC compared with American subjects with NIDDM. These differences may in part explain the relatively higher incidence of atherosclerotic vascular disease in Americans.
 ...
PMID:Comparison of plasma lipoproteins and apoproteins in Chinese and American non-insulin-dependent diabetic subjects and controls. 374 15

Disturbances in lipid metabolism and in blood fibrinolytic system may play a role in pathogenesis of vascular complications of diabetes mellitus. The aim of the study was to evaluate fibrinolytic parameters (antigen of tissue plasminogen activator-tPA, its inhibitor-PAI, tPA/PAI complexes measured by enzyme immunoassays, euglobulin clot lysis time-ECLT), cholesterol, triglycerides, lipoprotein (a) and apolipoproteins (AI, AII, B) in diabetic patients with and without diabetic nephropathy. The studies were performed in 25 patients with type II diabetes mellitus (age range 42-69), 31 patients with diabetic nephropathy (age range 46-76) and healthy volunteers (age range 31-66). There were no significant differences among the groups studies in tPA:Ag, tPA/PAI complexes, total PAI:Ag and free PAI. ECLT was slightly prolonged in patients with diabetic nephropathy when compared to controls. Cholesterol and triglycerides were significantly elevated in patient with diabetic nephropathy and without nephropathy when compared to healthy volunteers. Triglicerides levels were higher in patients with diabetic nephropathy when compared to subjects without it. Apolipoprotein AI and AII were significantly lower, whereas lipoprotein (a) and apolipoprotein B were significantly higher in patient with diabetic nephropathy when compared to healthy volunteers and diabetic subjects without nephropathy. Lipid metabolism disturbances and impairment in fibrinolysis might contribute to the progression of atherosclerosis and nephropathy in diabetic patients.
 ...
PMID:[Lipid metabolism and fibrinolysis in diabetic nephropathy in the course of diabetes type II]. 883 26

Isolated hypoaldosteronism is found in 75% diabetics where the disease has persisted for 10 or more years. Sporadically it is found in congenital autonomous neuropathy, in acute glomerulonephritis, in gouty kidney, tubulointerstitial nephritis, after transplantation of the kidney, on mytomycin etc. During dynamic testing of the response of plasma renin activity and aldosterone to the administration of furosemide and a vertical position in diabetics a significantly reduced response was recorded as compared with non-diabetic hypertonic subjects. In 18.3% no response was observed (decompensated form of IHH). Diabetic hypertonics behaved like control hypertonics on long-term beta-blocker treatment. In the decompensated form of IHH after administration of drugs interfering with the activity of SNS-RAAS activity (ACEI, spirolactone etc.) a hyperkalaemic crisis may develop which threatens the patient with acidosis, dehydration, myoplegia, muscular spasms, however, in particular with fatal disorders of the cardiac rhythm. A similar effect may be exerted also by blockers of prostaglandin synthetase (non-steroid antirheumatics) and other drugs. The cause of IHH in diabetics is the coincidence of several pathogenic factors: 1. hypersecretion of ANF with hyperosmolar hyperglycaemic hypervolaemia and hyperfiltration already at the onset of DN, 2. early development of autonomous neuropathy of the sympathetic nerve, 3. reduced renin and prostaglandin formation already in the early stages of DN, 4. reduced extrarenal isorenin formation, 5. reduced conversion of prorenin into active renin, 6. reduced reactivity of the zona glomerulosa to AII, hyperkalaemia and ACTH for its functional reconstruction as a result of periodic activation of contraregulative hormones by fluctuations of the blood sugar level in diabetic patients, 7. reduced response of the distal renal tubule to aldosterone because of tubulointerstitial changes. IHH is thus another serious but rarely diagnosed late complication of diabetes which depends only partly on the stage of DN. It must be, however, diagnosed and respected with regard to the selection of drugs for the treatment of arterial hypertension and the syndrome of insulin resistance and the 5H syndrome resp., i.e. the association of hyperinsulinism which compensates insulin resistance with hyperglycaemia (NIDDM), hypertension, hyperlipoproteinaemia and hirsutism in women (so-called Stein-Leventhal syndrome).
 ...
PMID:[Diabetic nephropathy and isolated hyporeninemic hypoaldosteronism]. 892 9

Decreased HDL cholesterol levels are associated with an increased risk of coronary artery disease (CAD) in non insulin dependent diabetes mellitus (NIDDM). The aim of this study was to compare HDL subparticles with apo A-I (LpAI) and those with apo A-I and apo A-II (LpAI/AII) in subjects with and without NIDDM and to study the relationship between HDL subparticles and CAD in NIDDM. Lipids, apo A-I and HDL subparticles were measured in 240 subjects with NIDDM and in 248 age and gender matched controls. Subjects with NIDDM had higher triglyceride levels (2.5 +/- 1.8 vs. 1.4 +/- 0.8 mmol/1, P < 0.001), lower HDL cholesterol (0.9 +/- 0.3 vs. 1.2 +/- 0.3 mmol/l, P < 0.001), apo A-I (124.7 +/- 22.4 vs. 139.8 +/- 24.1 mg/dl, P < 0.001) and LpAI/AII (82.4 +/- 18.2 vs. 94.9 +/- 16.7 mg/dl, P < 0.001) in comparison to controls. LpAI levels were similar in both groups. Diabetic subjects with CAD (n = 109) had higher triglycerides (2.7 +/- 1.9 vs. 2.3 +/- 1.8 mmol/l, P = 0.02) and lower HDL cholesterol (0.8 +/- 0.2 vs. 1.0 +/- 0.3 mmol/l, P <0.001), apo A-I (115.5 +/- 20.1 vs. 132.3 +/- 21.4 mg/dl, P < 0.001), LpAI (40.2 +/- 9.1 vs. 44.4 +/- 12.4 mg/dl, P = 0.06), and LpAI/AII levels (75.4 +/- 18.0 vs. 88.3 +/- 16.2 mg/dl, P < 0.001) in comparison to diabetic subjects without CAD (n = 131). In a multivariate analysis, apo A-I was found to be the best predictor of CAD in subjects with NIDDM. In conclusion, reduced HDL cholesterol levels found in NIDDM are, principally, due to reduced concentrations of apo A-I and apo A-II-containing particles (LpAI/AII). While LpAI and LpAI/AII levels were lower in NIDDM subjects with CAD, plasma apo A-I is the best predictor of CAD in NIDDM.
 ...
PMID:HDL subparticles and coronary artery disease in NIDDM. 912 2

The main pharmacodynamic difference between angiotensin-converting enzyme-inhibitors (ACE-i) and angiotensin-II-receptor antagonists (AII-r) is that ACE-i increase levels of bradykinin, which, in addition to vasodilation, may cause a decrease in insulin resistance. Hypertensive patients with diabetes type II suffering from side effects from ACE-i are frequently changed over to AII-r. The objectives of this study were (1) to study whether this procedure reduces metabolic control, (2) to study effects on blood pressure and forearm blood flow (FLOW), and (3) to study possible associations between the variables hemoglobin A (1c) (HbA(1c)) and FLOW. A self-controlled sequential comparison is required to address such questions. Sixteen patients were treated with 10 mg enalapril or equipotent doses of other ACE-i for 6 months and subsequently with the AII-r losartan at 50 mg daily for 6 more months. Patients were examined at the outpatient clinic every 4 to 8 weeks during the trial. FLOW was measured by iridium strain gauge venous occlusion plethysmography. Mean arterial pressure (MAP) increased by 4 +/- 5 mm Hg (P <.05) after 6 months of losartan treatment as compared with the point of withdrawal of ACE-i. FLOW decreased by 5.4 +/- 5.0 mL/100 mL tissue/min (P <.001), and HbA (1c) increased by 0.6 +/- 0.8 mmol/L (P <.05). Other metabolic variables, including cholesterol, high-density lipoprotein cholesterol, and triglycerides, were not significantly influenced by the change in therapy. Multiple regression analysis revealed that after adjustment for difference in HbA (1c), the correlation between FLOW and MAP was unchanged, and after adjustment for difference in FLOW, the correlation between HbA (1c) and MAP was no longer significant. Replacement of ACE-i by AII-r in hypertensive patients with type II diabetes mellitus induced a significant increase in HbA (1c) and MAP and a decrease in FLOW. The associations of HbA (1c) and FLOW with MAP were at least partly independent of each other, suggesting that mechanisms other than the bradykinin system (eg, the angiotensin (2) -receptor system) are involved. Our study design did not control for placebo and time effects, and so the data are of a preliminary nature.
 ...
PMID:Replacement of angiotensin-converting enzyme inhibitors by angiotensin-II-receptor antagonists in hypertensive patients with type II diabetes mellitus: metabolic and hemodynamic consequences. 1042 54

Hypertension and proteinuria are risk factors for renal disease progression. There is clear evidence that pharmacological blockade of the RAS with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) reduces proteinuria and slows down the progression of renal disease in diabetic and non diabetic nephropathies, a beneficial effect not related to blood pressure control. However, not all patients respond similarly to these treatments. Some patients exhibit a significant beneficial response while others do not. The absence of response may be explained by the incomplete blockade of the RAS obtained with ACEI, which are unable to block completely the formation of AII, some generation of AII is produced via other non ACE pathways. In the search of new alternatives that could improve the antiproteinuric and nephroprotective effects of RAS blockers, the association of ACEI and ARB might prove to be useful. ARB produces a complete blockade of the RAS and stimulates the vasodilating and non-proliferative actions of AII via the AT-2 receptor. Furthermore, ACE inhibitors but not ARB; inhibit the metabolism of kinins, which increases the level of bradykinin, a potent vasodilator. Recently, several authors have shown a more marked antiproteinuric effect of the dual blockade of the RAS versus ACEI or ARB alone in spite of a similar effect on blood pressure. A recent study also has demonstrated that this more marked antiproteinuric effect is associated with a less progression of renal disease in primary, non diabetic nephropathies. Furthermore, at least two studies have shown that, treatment with ARB postpones end-stage renal disease and reduces the rate of decline in renal function in patients with type 2 diabetes and nephropathy, but until now, there is not any clear evidence of a superior beneficial effect of dual blockade versus maximal recommended dose of ARB regarding renal progression in type 2 diabetic nephropathy, which is the most frequent cause of end stage renal disease. Long-term clinical trials are needed and encouraged to further establish the significant role of dual blockade in renal protection particularly in diabetic nephropathy.
 ...
PMID:The reno-protective effect of the dual blockade of the renin angiotensin system (RAS). 1585 85

Aim of the investigation was to study safety of therapy with metformin and its effect on clinical, hemodynamic, functional and neurohumoral status in patients with chronic heart failure and type 2 diabetes mellitus DM). Eighty one patients with light and moderate NYHA functional class (FC) II-III CHF, left ventricular ejection fraction < 45%, and DM were examined. As a result of randomization 2 groups were formed: with active (n=41) and usual (n=40) treatment. In active group with achievement of target levels of glycemia 24 (59%) patients were on oral hypoglicemic drags, 17 (41) patients received. All patients were on basal therapy of CHF. Initially efficacy and safety of metformin was investigated in a cohort of active treatment (jn metformin n=29, control n=12), including patients who were prescribed metformin not for the whole period. In addition in active group analysis was carried out among patients, who continually were treated with metformin for 12 months (n=30) in comparison with patients never treated with metformin (n=8). Total duration of the period of treatment and supervision was 12 months. Control examination was conducted before randomization, after 6 months of treatment, at the end of the study and included assessment of clunico-functional status of patients, renal function (GFR), neurohumoral profile (MNUP, NA, AII). The state of carbohydrate metabolism was assessed with the help of determination of HBA1C level and test with nutritional load given as of common breakfast -- 2-3 in the course of which fasting and postprandial level (in 2 hours after breakfast) of glucose (GLC), and fasting insulin and C-peptide. Overall safety of metformin was confirmed -- throughout whole period of follow up with different variants of comparative analysis no cases of lactic acidosis were revealed. Practical lack of positive influence of metformin on glycemia at its initially not high level was accompanied with improvement of FC CHF, parameters of central hemodynamics, augmentation of functional capacities of patients, improvement of quality of life, lowering of number of decompensations of CHF and diminishment of degree of activation of SAS. It can be suggested that this dynamics is conditioned by the presence of cardioprotective properties in metformin what allows to recommend its application in patients with CHF and type 2 DM.
 ...
PMID:[Efficacy and safety of the use of metformin in patients with chronic heart failure and type 2 diabetes mellitus. results of the study "rational effective mulicomponent therapy in the battle against diabetes mellitus in patients with chronic heart failure"]. 1842 58

Inflammasomes activate caspase-1 for processing and secretion of the cytokines interleukin-1beta (IL-1beta) and IL-18. Cryopyrin/NALP3/NLRP3 is an essential component of inflammasomes triggered by microbial ligands, danger-associated molecular patterns (DAMPs), and crystals. Inappropriate Cryopyrin activity has been incriminated in the pathogenesis of gouty arthritis, Alzheimer's, and silicosis. Therefore, inhibitors of the Nalp3 inflammasome offer considerable therapeutic promise. In this study, we show that the type 2 diabetes drug glyburide prevented activation of the Cryopyrin inflammasome. Glyburide's cyclohexylurea group, which binds to adenosine triphosphatase (ATP)-sensitive K(+) (K(ATP)) channels for insulin secretion, is dispensable for inflammasome inhibition. Macrophages lacking K(ATP) subunits or ATP-binding cassette transporters also activate the Cryopyrin inflammasome normally. Glyburide analogues inhibit ATP- but not hypothermia-induced IL-1beta secretion from human monocytes expressing familial cold-associated autoinflammatory syndrome-associated Cryopyrin mutations, thus suggesting that inhibition occurs upstream of Cryopyrin. Concurrent with the role of Cryopyrin in endotoxemia, glyburide significantly delays lipopolysaccharide-induced lethality in mice. Therefore, glyburide is the first identified compound to prevent Cryopyrin activation and microbial ligand-, DAMP-, and crystal-induced IL-1beta secretion.
 ...
PMID:Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. 1980 29


1 2 3 Next >>