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 encountered a patient with diabetes mellitus due to the 3243 mitochondrial tRNA mutation(DM-Mt3243), who developed insulin edema and hepatic dysfunction after starting insulin. Such a rare phenomenon was unlikely to be a fortuitous coincidence in mitochondrial diabetes, as none in 197 non-mutant NIDDM patients had same episode. Moreover, similar leg edema was noticed in another DM-Mt3243 patient, and other two DM-Mt3243 patients had leg edema which responded to coenzyme Q10. These observations suggest further a role of mitochondrial function on leg edema. The mechanism of his insulin edema may involve vasomotor changes induced by the rapidly glycemic control, because our case of insulin edema had a prominent increase of strong succinate dehydrogenase reactive vessels. Alternatively, myocardial dysfunction might have produced leg edema and hepatic dysfunction, because he had subclinical myocardial dysfunction, judged by imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid. The third explanation is that a rapid improvement of glycemic control might have induced hepatic reoxygenation and the production of reactive oxygen species in the liver that contributed to cell damage. Thus, although we cannot draw definite conclusion, our experiences here suggest that mitochondrial dysfunction is important in the etiology of insulin edema.
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PMID:Insulin edema in diabetes mellitus associated with the 3243 mitochondrial tRNA(Leu(UUR)) mutation; case reports. 859 1

Both hyperinsulinemia and free oxygen radicals have been implicated in the pathogenesis of atherosclerosis, but the relationship between insulin levels or insulin action and the oxidant/antioxidant balance has not been explored. We measured the effect of physiologic hyperinsulinemia on plasma concentrations of vitamin E, a major free radical scavenger molecule. Isoglycemic clamps (at an insulin infusion rate of 6 pmol . min-1 . kg-1) were performed in four groups of subjects: (1) 12 non-insulin-dependent diabetic (NIDDM) patients, (2) eight patients with essential hypertension, (3) 11 nondiabetic obese individuals, and (4) 12 healthy subjects. In 10 healthy volunteers, a time-control experiment was performed by replacing the insulin infusion with normal saline. Vitamin E and plasma lipid levels were determined at baseline and after 2 hours of insulin/saline infusion. Insulin sensitivity was reduced in diabetic, obese, and hypertensive groups in comparison to healthy controls, but fasting plasma vitamin E concentrations were similar in all groups. A consistent decrement in plasma vitamin E concentrations (averaging 12% of baseline, P < .0001) was observed in all subjects receiving insulin regardless of the level of insulin sensitivity, whereas no significant changes in plasma vitamin E were seen in subjects receiving saline infusion (P < .001 v insulin infusion groups). The insulin-induced decrement persisted in all study groups when plasma vitamin E concentrations were corrected for total serum cholesterol levels (-8.9% +/- 1.2% v -0.4 +/- 2.3% of saline controls, P = .0004) or serum low-density lipoprotein (LDL(-10.0% +/- 1.2% v -0.4% +/- 2.2%, P = .0002). We conclude that insulin infusion acutely depletes vitamin E in circulating lipids regardless of insulin resistance. This effect may represent a physiologic means of transferring vitamin E into cell membranes; alternatively, it might reflect a pro-oxidant action of insulin in vivo.
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PMID:Insulin decreases circulating vitamin E levels in humans. 876 59

The aim of this study was determine the effect of a 15-week individualized exercise conditioning program on glycosylated hemoglobin (HbAlc) levels on Type 2 diabetes. Thirty-nine participants were sedantary, Type 2 diabetics, on an oral hypo-glycemic drug and no specified diet regimen at study onset. Pre and post 15 weeks subjects underwent: maximal incremental exercise tests, blood analysis, body composition analysis. Twenty-one subjects were prescribed an individualized exercise program for 15 weeks. Significant differences were found in the exercise group after 15 weeks in: total body fat, trunk fat, peak oxygen consumption and MET values. Correlations existed in the exercise group between HbAlc, arm muscle area and leg lean mass. Sixty-two percent of this group showed a reduction in HbAlc values. For this group, dietary intakes of riboflavin and potassium maybe associated with HbAlc levels. Exercise in conjunction with oral drug therapy prescribed for the NIDDM individual did not directly modify HbAlc levels, but did result in favorable effects on blood lipid values, fitness levels, and body composition values.
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PMID:The effect of exercise conditioning, diet, and drug therapy on glycosylated hemoglobin levels in type 2 (NIDDM) diabetics. 877 76

To evaluate whether granulocyte-colony stimulating factor (G-CSF) improves an impaired production of oxygen-derived free radicals by neutrophils from poorly controlled NIDDM patients, we studied the effect of G-CSF on myeloperoxidase (MPO) activity and chemiluminescence amplified by a Cypridina luciferin analog (CLA-DCL), which is dependent on O2 generation, and luminol (L-DCL), which is dependent on OCl(-) generation, in response to formyl-methonyl-leucyl-phenylalanine. Both CLA-DCL and L-DCL by neutrophils from the diabetic group (n = 15, HbA(1c) >10%) were significantly decreased (26 and 37%, respectively: P < 0.01) compared with the age-matched normal control group (n = 15), and L-DCL was more sensitive to this inhibition than CLA-DCL (P < 0.05). In both control and diabetic neutrophils, G-CSF significantly enhanced both CLA-DCL (175% in control and 156% in diabetic) and L-DCL (283% in control and 346% in diabetic). In diabetic neutrophils, the enhancing effect of G-CSF on L-DCL was more sensitive than on CLA-DCL (P < 0.001). There was a positive correlation between HbA(1c) and the enhancing effect of G-CSF on L-DCL in diabetic patients (P < 0.05), but not on CLA-DCL. MPO activity was also decreased in the diabetic group (63%, P < 0.05), and G-CSF improved this impaired MPO activity (184%, P < 0.01). Furthermore, there was a positive correlation between HbA(1c) and the improving effect of G-CSF on MPO activity (P < 0.05). Because bacterial infection still accounts for an important cause of morbidity and mortality in diabetic patients, these data suggest that G-CSF may be useful as a drug to prevent the aggravation of bacterial infection by improving neutrophil function, especially through H2O2-MPO-OCl(-) mechanism, in poorly controlled diabetic patients.
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PMID:Effect of granulocyte-colony stimulating factor on generation of oxygen-derived free radicals and myeloperoxidase activity in neutrophils from poorly controlled NIDDM patients. 897 Oct 93

Relationship of transcutaneous oxygen pressure (TcP(O2)) to glycemic control and diabetic complications was investigated in patients with non-insulin dependent diabetes mellitus. TcP(O2) was measured in 103 patients with non-insulin dependent diabetes mellitus. Correlation of TcP(O2) to HbA1c, fasting blood sugar (FBS), age, duration of diabetes, serum lipids, hypertension, and diabetic complications were examined. We divided the patients into three groups according to their glycemic control: good control group (HbA1c < 7.0%), fair control group (HbA1c, 7.0-8.9%) and poor control group (HbA1c > or = 9.0). We compared TcP(O2) of these three groups with 19 non-diabetic controls. In 103 patients, TcP(O2) at baseline correlated with HbA1c, FBS and age (P < 0.001, P < 0.01 and P < 0.05, respectively), but did not correlate with duration of diabetes mellitus, neuropathy, nephropathy or retinopathy. TcP(O2) of good and fair control group was not reduced comparing to the non-diabetic control (63 +/- 11, 59 +/- 10 and 64 +/- 12 mmHg, respectively). The poor control group had significantly reduced TcP(O2) (55 +/- 10 mmHg) comparing to non-diabetic control (P < 0.005) and good control group (P < 0.005). Furthermore, in an independent study, TcP(O2), arterial oxygen pressure (Pa(O2)), oxygen pressure of dorsal pedal vein (PV(O2)) and erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in eight patients with poor glycemic control were followed prospectively. Six patients with improvement of glycemic control showed a significant increase of TcP(O2) and Pa(O2) (P < 0.001 and P < 0.005, respectively). However, two patients without improvement of hyperglycemia had no change in TcP(O2) and Pa(O2). PV(O2) and 2,3-DPG levels of erythrocytes were not changed in six patients. These findings suggest that tissue oxygenation in diabetic patients was deteriorated in relation to hyperglycemia and was reversed with glycemic control. Improvement of Pa(O2) might contribute partly to the increase of TcP(O2).
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PMID:Reduced tissue oxygenation and its reversibility by glycemic control in diabetic patients. 906 68

Diabetic cardiopathy represents a cardiac disorder with involvement of myocardial, interstitial, coronary, and neural structures. One of the main manifestations refers to coronary microangiopathy, which has not yet been clearly identified. Coronary hemodynamics, including the determination of coronary flow reserve, were therefore analyzed in normal subjects and in nine patients with NIDDM and clinically suspected coronary heart disease but normal coronary arteriogram. Coronary flow reserve was determined as the quotient of baseline and minimal coronary resistance after dipyridamole (0.5 mg/kg i.v.). Coronary blood flow was measured quantitatively by the argon method. Systolic left ventricular function was analyzed by ventriculography and diastolic function by M-mode and Doppler echocardiography. Twelve healthy normotensive subjects served as the control group (CON). In the diabetic patients, maximal coronary flow was significantly reduced (172 +/- 50 vs. 395 +/- 103 ml/min x 100 g; P < 0.001), and minimal coronary resistance was increased (0.60 +/- 0.19 vs. 0.24 +/- 0.06 mmHg x min x 100 g/ml; P < 0.001). Coronary reserve in the diabetic subjects was markedly reduced (1.84 +/- 0.39 vs. 4.23 +/- 0.52; P < 0.001). No difference existed with respect to myocardial oxygen consumption (12.4 +/- 2.3 vs. 11.8 +/- 2.8 ml O2/100 g x min; NS). Global systolic function was normal in all patients (ejection fraction: NIDDM 72 +/- 13 vs. CON 77 +/- 12%, NS; CI: NIDDM 3.2 +/- 0.8 vs. CON 3.3 +/- 1.2 l/min x m2, NS). Diastolic function was impaired in diabetic patients with an increase in relaxation time index (97 +/- 23 vs. 45 +/- 18 ms; P < 0.01) and an impaired diastolic inflow pattern, indicated by the ratio between early and late transmitral flow (0.75 +/- 0.14 vs. 1.66 +/- 0.13; P < 0.05). We conclude that the markedly reduced coronary flow reserve in diabetic patients may play a key role in the induction and perpetuation of coronary insufficiency in myocardial ischemia, in diastolic and systolic dysfunction, and in the initiation of diabetic cardiopathy.
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PMID:Impaired coronary flow reserve in NIDDM: a possible role for diabetic cardiopathy in humans. 928 13

1. The specific role of physical activity in the treatment of type 2 diabetes is still subject to discussion. A randomized prospective study was performed, investigating both the influence of physical training on metabolic control and the feasibility of physical training in the elderly. 2. A total of 58 patients (mean age: 62 +/- 5 years; range: 55-75 years) with type 2 diabetes were randomized to either a physical training or a control programme. The training programme consisted of three sessions a week, aiming at 60-80% of the maximal oxygen uptake (VO2max). The 12 week supervised period was followed by a 14 week non-supervised one. The control group followed an educational programme. VO2max was assessed during exercise on a cycle ergometer. Glycosylated haemoglobin (HbA1c) was used as a measure for glucose control, and an insulin tolerance test was performed to test insulin sensitivity. Multivariate analysis of variance, with repeated measures design, was used to test differences between groups. 3. Fifty-one patients completed the study. VO2max was higher in the training group than in the control group both after 6 weeks (P < or = 0.01 between groups) and after 26 weeks [training group: 1796 +/- 419 ml/min (prestudy), 1880 +/- 458 ml/min (6 weeks), 1786 +/- 591 ml/min (26 weeks); control group: 1859 +/- 455 ml/min (prestudy), 1742 +/- 467 ml/min (6 weeks), 1629 +/- 504 ml/min (26 weeks)]. Blood glucose control and insulin sensitivity did not change during the study. Levels of total triacylglycerols, very-low-density lipoprotein-triacylglycerols and apolipoprotein B were significantly lower after 6 weeks (P < or = 0.01, P < or = 0.05, P < or = 0.05 between groups respectively), and so was the level of total cholesterol after 12 weeks of training (P < or = 0.05 between groups). 4. Physical training in obese type 2 diabetic patients over 55 years of age does not change glycaemic control or insulin sensitivity in the short-term. Regular physical activity may lower triacylglycerol and cholesterol levels in this group of patients. 5. Finally, physical training in motivated elderly type 2 diabetic patients without major cardiovascular or musculoskeletal disorders is feasible, but only under supervision.
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PMID:Effects of physical training on metabolic control in elderly type 2 diabetes mellitus patients. 930 27

To explore the possible role of a reduced physical fitness for the diminished insulin sensitivity in first-degree relatives of NIDDM patients, 21 relatives and 22 matched control subjects were examined employing a hyperinsulinaemic (insulin infusion rate 0.6 mU/kg/min) euglycaemic clamp combined with the isotope dilution technique (3-3H-glucose), the forearm technique and indirect calorimetry. During hyperinsulinaemia glucose disposal (Rd) was significantly diminished in the relatives (p < 0.01). Maximal oxygen uptake (VO2 max) was 15% lower in the relatives than in the controls (p = 0.03). There was a highly significant correlation between Rd and VO2 max in both groups. In multiple linear regression analyses with Rd as the dependent variable VO2 max significantly determined the level of Rd (p < 0.01), whereas forearm blood flow and anthropometric data did not. We concluded that the insulin resistance in healthyfirst degree relatives of patients with NIDDM is associated with a diminished physical work capacity. Whether this finding is ascribable to environmental or genetic factors remains to be determined.
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PMID:[Insulin resistance among relatives of patients with NIDDM. Significance of physical fitness and muscle metabolism]. 946 52

Persons with type II diabetes mellitus (DM), even without cardiovascular complications have a decreased maximal oxygen consumption (VO2 max) and submaximal oxygen consumption (VO2) during graded exercise compared with healthy controls. We evaluated the hypothesis that change in the rate of VO2 in response to the onset of constant-load exercise (measured by VO2-uptake kinetics) was slowed in persons with type II DM. Ten premenopausal women with uncomplicated type II DM, 10 overweight, nondiabetic women, and 10 lean, nondiabetic women had a VO2 max test. On two separate occasions, subjects performed 7-min bouts of constant-load bicycle exercise at workloads below and above the lactate threshold to enable measurements of VO2 kinetics and heart rate kinetics (measuring rate of heart rate rise). VO2 max was reduced in subjects with type II DM compared with both lean and overweight controls (P < 0.05). Subjects with type II DM had slower VO2 and heart rate kinetics than did controls at constant workloads below the lactate threshold. The data suggest a notable abnormality in the cardiopulmonary response at the onset of exercise in people with type II DM. The findings may reflect impaired cardiac responses to exercise, although an additional defect in skeletal muscle oxygen diffusion or mitochondrial oxygen utilization is also possible.
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PMID:Abnormal oxygen uptake kinetic responses in women with type II diabetes mellitus. 965 91

The relationship between magnesium levels and oxygen uptake in patients with non-insulin dependent diabetes mellitus (NIDDM) without apparent visceral dysfunction was studied. Magnesium levels in plasma, erythrocytes and urine as well as oxygen uptake parameters were determined in NIDDM patients and controls. Oxygen uptake parameters were measured with an exercise ergometer and expired gas analysis according to Wasserman et al. Low oxygen uptake in NIDDM patients was correlated significantly with plasma and erythrocyte magnesium levels, but not with urinary magnesium excretion. In NIDDM patients, higher correlation coefficients were seen between oxygen uptake parameters at peak in men and at the anaerobic threshold in women and plasma or erythrocyte magnesium levels. These results confirm previous results indicating that plasma and erythrocyte magnesium levels in NIDDM patient are decreased, and further demonstrate that the decreased magnesium levels are positively correlated with oxygen uptake. Although the mechanism remains to be established, it is possible that the magnesium deficiency in NIDDM patients due to environmental or genetic factors may result in low oxygen uptake and decreased work capacity.
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PMID:Plasma and erythrocyte magnesium levels are correlated with oxygen uptake in patients with non-insulin dependent diabetes mellitus. 970 Apr 83


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