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 investigate the influence of diabetes mellitus on higher cognitive functions electrophysiologically, we studied auditory P300 event-related potentials (P300) in 40 NIDDM patients, taking into account wave I-V latencies (I-V) in auditory brainstem evoked potentials, clinical parameters and head MRI findings. Compared with 20 controls, diabetics had significantly longer P300 and I-V latencies. P300 latencies in diabetics correlated with neither I-V, HbA1, blood glucose levels, nor disease duration. Of the 13 diabetics investigated neuroradiologically, four had lacunar infarcts with prolonged electrophysiological values. The remaining nine had normal MRI scans, but their physiological parameters were still significantly longer than those of controls. These findings suggest that NIDDM can independently alter higher cognitive and the central auditory pathway functions. Our data also suggest that these alterations occur regardless of the recent metabolic derangement and disease duration. Cerebrovascular ischemia, if present, also appears to contribute in part to cognitive alterations.
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PMID:Changes in auditory P300 event-related potentials and brainstem evoked potentials in diabetes mellitus. 884 38

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

Sulfonylurea (SU) derivatives exert their hypoglycemic effect by blockade of adenosine-5'-triphosphate-sensitive potassium (KATP) channels in the beta-cell of the pancreas. Interestingly, KATP channels also occur in the cardiovascular system, where they are thought to play an important role in cardioprotective mechanisms against ischemia. We have recently shown that the classical second generation SU-derivative glibenclamide is able to block vascular KATP channels in man, whereas the newly developed second generation derivative glimepiride was devoid of this property. The aim of this study was to determine whether the first generation SU derivative tolbutamide has KATP channel blocking properties in humans. In a group of 12 healthy male non-smoking volunteers, we investigated whether therapeutic concentrations of tolbutamide were able to inhibit the forearm vasodilation in response to the infusion of the KATP channel opening drug diazoxide into the brachial artery. Changes in forearm blood flow were recorded by venous occlusion mercury-in-silastic strain-gauge plethysmography. Diazoxide alone increased the forearm blood flow ratio dose-dependently by ultimately 691 +/- 198%. A second diazoxide infusion in the presence of tolbutamide revealed a comparable vasodilator response with a percentage increase in forearm blood flow ratio of ultimately 542 +/- 111%. This response did not differ from the vasodilator response to diazoxide alone. The present study shows that therapeutic concentrations of tolbutamide are not able to attenuate the vasodilation caused by the KATP channel opener diazoxide in man. When compared with published data on second generation SU derivatives, tolbutamide shows an intermediate position between glibenclamide (with significant blockade of vascular KATP channels) versus glimepiride (with no blockade at all). It remains to be determined whether these acute effects of SU derivatives on pharmacological opening of forearm vascular KATP channels can be extrapolated to the chronic effects of these drugs on ischemia-mediated opening of myocardial KATP channels during treatment of NIDDM patients.
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PMID:Effects of tolbutamide on vascular ATP-sensitive potassium channels in humans. Comparison with literature data on glibenclamide and glimepiride. 891 89

Subopitmal glycemic control in hospitalized patients with type 2 (non-insulin-dependent) diabetes mellitus can have adverse consequences, including increased neurologic ischemia, delayed wound healing and an increased infection rate. Poor glycemic control can also affect the outcome of the primary illness. If possible, hospitalized diabetic patients should continue their previous antihyperglycemic treatment regimen. Decreased physical activity and the stress of illness often lead to hyperglycemia in hospitalized patients with type 2 diabetes. When indicated, insulin is given either as a supplement to usual therapy or as a temporary substitute. The overall benefit of the traditional sliding-scale insulin regimen has been questioned. Insulin supplementation given according to an algorithm may be a logical alternative. Any antihyperglycemic regimen should be administered and monitored in a manner coincident with the intake of food or other sources of calories. Factors that can alter glycemic control acutely, including specific medical conditions and medications, should be identified and anticipated.
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PMID:Management of hospitalized patients with type 2 diabetes mellitus. 951 54

Several lines of evidence support peripheral nerve ischemia as a contributing factor in the etiology of human diabetic neuropathy. We questioned whether diabetic subjects with relatively normal nerve function in the baseline state would be more likely than healthy control subjects to show either improvement of ulnar nerve function with acute intraarterial infusion of nitroprusside (vasodilation) or be more sensitive than control subjects to worsening of nerve function with acute intraarterial infusion of norepinephrine (vasoconstriction). We measured forearm blood flow (FABF) using venous occlusion plethysmography and assessed ulnar nerve function at baseline and during two intrabrachial artery infusions. Six nondiabetic control subjects (mean age, 56 years) and 11 subjects with type 2 diabetes (mean age, 58 years) in good general health participated. Only three type 2 diabetic subjects had peripheral sensory neuropathy, which was mild. Among control subjects, there was no significant change in sensory distal latency, motor distal latency, motor proximal latency, or sensory or motor conduction velocity during norepinephrine infusion. In contrast, among type 2 diabetic subjects, there was a significant increase in sensory (baseline vnorepinephrine, 2.73+/-0.10 v 2.94+/-0.10 milliseconds [MS], P< or =.01) and motor distal latencies (baseline v norepinephrine, 2.90+/-0.06 v 3.18+/-0.1 ms, P< or =.001) and motor proximal latency (baseline v norepinephrine, 7.15+/-0.18 v 7.60+/-0.23 ms, P<.01) and a decrease in sensory conduction velocity (baseline v norepinephrine, 52.1+/-2.0 v 47.7+/-1.6 m/s, P<.01) during norepinephrine infusion. There were no consistent changes in nerve function during nitroprusside infusion in either group. In summary, we found that subjects with type 2 diabetes, but not control subjects, demonstrate a decrement in nerve function with vasoconstriction during intraarterial infusion of norepinephrine, but no consistent change during nitroprusside-induced vasodilation. These findings suggest there may be enhanced sensitivity of nerve function to ischemia in type 2 diabetic subjects with mild or absent clinical neuropathy.
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PMID:Acute effects of adrenergic-mediated ischemia on nerve conduction in subjects with type 2 diabetes. 1020 44

We examined the mechanisms responsible for myocardial ischemia-reperfusion (MI-R) injury in a well-characterized animal model of type II diabetes mellitus. Diabetic (db/db) mice and their littermate nondiabetic controls were subjected to 30 min of left anterior descending coronary artery occlusion and 2 h of reperfusion. Diabetic and nondiabetic mice experienced similar-sized areas at risk per left ventricle: 50.4 +/- 2.0 and 53.4 +/- 4.1%, respectively. However, myocardial necrosis (percentage of area at risk) was significantly greater (P < 0.001) in diabetic than in nondiabetic animals: 56.3 +/- 2.8 and 27.2 +/- 3.1%, respectively. Histological examination revealed significantly (P < 0.05) more neutrophils (PMNs) in the diabetic than in the nondiabetic hearts. Coronary endothelial expression of P-selectin was determined using radiolabeled monoclonal antibodies (MAbs). MI-R elicited a more intense (P < 0.05) upregulation of P-selectin in the ischemic zone of diabetic than of nondiabetic myocardium: 0.310 +/- 0.034 and 0. 161 +/- 0.042 microgram MAb/g tissue. Immunoneutralization of P-selectin (RB40.34) reduced PMN accumulation in the diabetic myocardium but failed to reduce the extent of myocardial necrosis. Conversely, administration of an MAb directed against CD18 (GAME46) reduced PMN infiltration and attenuated the infarct size in the diabetic hearts. These results suggest that the diabetic heart is more susceptible to ischemia-reperfusion injury than normal myocardium. Furthermore, the mechanism of this injury may not be critically dependent on P-selectin in diabetic hearts.
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PMID:Reperfusion injury is not affected by blockade of P-selectin in the diabetic mouse heart. 1044 4

Tumor necrosis factor-alpha (TNF-alpha) level, tissue-typed plasminogen activator(t-PA) activity and PA inhibitor (PAI) activity were determined in three groups: (1) 25 NIDDM patients with silent myocardial ischemia (SMI) or silent cerebral ischemia (SCI); (2) 18NIDDM patients without SMI or SCI; (3) 20 age-matched normal controls. Diagnosis of SMI or SCI was based on the finding of ischemic evidence by SPECT of myocardiotomograph or cerebrotomograph. All patients ECG and blood pressure were normal, and they had no history of clinical symptoms and signs of MI or CI. The result showed that the TNF-alpha level and PAI activity in the ischemia group were the highest and the t-PA activity in the ischemia group was the lowest, as compared with those in the other two groups respectively. It suggests that in NIDDM patients who have high TNF-alpha, high PAI activity, low t-PA, and even no symptoms and signs of MI or CI, anticoagulant therapy might be useful to prevent the progression of diabetic macroangiopathies.
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PMID:[Changes of serum TNF-alpha level, t-PA activivty and PAI activity in patients with silent myocardial ischemia or silent cerebral ischemia]. 1068 70

It has previously been shown that Wortmannin, a phosphatidylinositol 3-kinase inhibitor, inhibits glucose transport activated by insulin but not by ischemia, suggesting the importance of an activating mechanism that bypasses the insulin signal. To evaluate the relevance of this insulin-independent pathway in insulin-resistant subjects, the ability of ischemia to stimulate glucose uptake was investigated in 9 patients with type 2 diabetes and in 9 healthy control subjects (fasting glucose level 9.4 +/- 0.8 vs. 5.1 +/- 0.1 mmol/l, P < 0.001, in type 2 diabetic patients and control subjects, respectively; fasting insulin level insulin 8.1 +/- 2.6 vs. 4.5 +/-0.7 mU/l, P < 0.05, respectively) matched for sex, age, and BMI. Arterial plasma and interstitial concentrations of glucose and lactate (measured by subcutaneous and muscle microdialysis) were recorded in the forearm before, during, and after ischemia induced locally for 20 min. During ischemia, the muscle interstitial glucose concentration decreased significantly from 7.7 +/- 0.6 to 5.4 +/- 0.4 mmol/l (P < 0.01) and from 4.4 +/- 0.3 to 3.6 +/- 0.3 mmol/l (P < 0.05) in type 2 diabetic patients and control subjects, respectively. The arterial-interstitial (A-I) glucose concentration difference was 1.7 +/- 0.6 and 0.7 +/- 0.3 mmol/ at basal, and it increased significantly to 3.5 +/- 0.7 (P < 0.01) and 1.4 +/-0.3 mmol/l (P < 0.05) during ischemia in each group, respectively. Interstitial lactate increased significantly during ischemia from 0.8 +/- 0.1 to 1.1 +/- 0.1 mmol/l (P < 0.05) and from 0.5 +/- 0.1 to 0.9 +/- 0.2 mmol/l (P < 0.05), respectively. The A-I glucose concentration difference was abolished immediately postischemia and regained after approximately 15 min, whereas high interstitial lactate levels remained elevated throughout the study. Subcutaneous interstitial glucose concentrations remained unchanged during ischemia and postischemia in both groups, whereas the interstitial lactate concentration in adipose tissue increased during ischemia from 1.4 +/- 0.2 to 2.0 +/- 0.2 mmol/l (P < 0.05) and from 1.1 +/- 0.1 to 1.8 +/- 0.3 mmol/l (P < 0.05) in type 2 diabetic patients and control subjects, respectively. Plasma glucose and lactate levels were unchanged in both groups during the study period. The results show that in muscle, but not in adipose tissue, glucose uptake is efficiently activated by ischemia in insulin-resistant type 2 diabetic subjects, suggesting the activation of a putative alternative pathway to the insulin signal in muscle cells.
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PMID:Muscle glucose uptake is effectively activated by ischemia in type 2 diabetic subjects. 1090 76

Diabetic patients have a higher prevalence of hypertension, dyslipidemia and obesity. However, diabetes is by itself a major independent risk factor for cardiovascular disease. About two-thirds of total mortality are due to diabetic macroangiopathy. It is characterised by accelerated atherosclerosis, with more severe, more extensive and more diffuse lesions, as compared with nondiabetic patients. Patients with diabetes present more frequently acute pulmonary oedema despite similar infarct sizes than do nondiabetic patients. They are more frequently at risk for ventricular dysfunction, for ventricular aneurysm and for congestive heart failure. At the time of diagnosis of type 2 diabetes, more than 50% of patients have pre-existing coronary heart disease, probably related to painless ischemia, caused by an autonomic denervation of the heart in diabetic patients. International recommendations suggest that all diabetic patients should be evaluated at least annually for the development or progression of risk factors that would prompt cardiac testing. The standard bicycle exercise test should be chosen in an asymptomatic patient with only one other risk factor and with a normal resting ECG. For all other diabetic patients, stress echocardiography or stress myocardial perfusion imaging should be preferably chosen.
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PMID:[Cardiac complications of type 2 diabetes]. 1092 96

This study determined whether sulfonylurea derivatives affect cardiac function prior to and after a mild ischemic incident (stunning). This was investigated using an isolated, erythrocyte-perfused, working rat heart model. In total, 11 groups were studied: five increasing (clinically relevant) concentrations of the classical glibenclamide (range 0.005-4 micromol l(-1)), five increasing concentrations of the newly developed glimepiride (range 0.005-0.8 micromol l(-1)), and one control group. Pre-ischemically, glibenclamide and glimepiride reduced coronary blood flow concentration dependently to 55.2+/-4.5% and 58.5+/-5.5%, respectively (P<0.001). Twenty minutes after a 12-min ischemic incident, these reductions of flow were even more pronounced (to 38.3+/-6.7% and 45.8+/-5.8%, P<0.001). This shows that both sulfonylureas reduce coronary blood flow at concentrations slightly higher than therapeutic ones. In the control group, the ischemic incident significantly lowered cardiac function by 22.2+/-2.9%. In the therapeutic range, glimepiride, but not glibenclamide, significantly reduced this ischemia-induced cardiac functional loss to 4.9+/-1.2% (P<0.01). Therefore, we suggest that both sulfonylureas and in particular glimepiride can be used safely in patients with type 2 diabetes mellitus, as long as the coronary vascular system is not compromised. Because of the obvious vasocontrictor response to sulfonylurea derivatives, these drugs must be used with caution in patients with a reduced coronary reserve.
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PMID:Effects of sulfonylurea derivatives on ischemia-induced loss of function in the isolated rat heart. 1134 34


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