Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test whether insulin is a regulatory factor of myocardial MB creatine kinase content, we investigated the correlation between the ability of insulin secretion and the MB fraction of cumulative CK released in patients with acute myocardial infarction. We analyzed 18 patients who underwent successful direct angioplasty within 10 hours of the onset of their first myocardial infarction. Exclusion criteria were age more than 75 years, heart failure, severe obesity, multivessel disease, and history of diabetes mellitus. Cumulative activity of serum MB CK divided by that of total CK was defined as MB%, which was considered to represent myocardial MB CK content. Two weeks or more after the onset of myocardial infarction, 75 gm oral glucose tolerance test with serial determination of plasma glucose and serum insulin (0, 0.5, 1, 2, 3 hours) was done. Urinary and plasma catecholamines and echocardiographic left ventricular (LV) mass were measured. MB% significantly correlated with insulinogenic index (r = 0.564, p = 0.019), insulin area (r = 0.594, p = 0.012), insulin area/glucose area (r = 0.630, p = 0.007), and urinary adrenaline (r = -0.542, p = 0.025) and tended to correlate with plasma adrenaline (r = -0.431, p = 0.084). Age, body mass index, infarct size, glucose metabolism, and LV mass were not significant univariate predictors of MB%. Multivariate analysis showed that the ability of insulin secretion contributed to MB% more than catecholamines did and that insulin area/glucose area was the strongest independent predictor of MB% (t = 3.01, p = 0.015). Thus MB fraction of cumulative CK released, indicative of Myocardial MB CK distribution, strongly related to the ability of insulin secretion in subjects without overt insulin resistance. Regulation by insulin of myocardial MB CK is suggested.
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PMID:MB fraction of cumulative creatine kinase correlates with insulin secretion in patients with acute myocardial infarction: insulin as a possible determinant of myocardial MB creatine kinase. 855 15

This study examined the profile and management of acute myocardial infarction in patients hospitalized in the coronary care unit of Henry Ford Hospital to determine risk factors or treatments that best explained a decline in in-hospital mortality rates. During the 1980s and early 1990s, many therapeutic advances occurred in management of acute infarction. Overall and in-hospital mortality were observed also to decline, but little is known about the relation of newer treatments to clinical outcome. The study population consisted of 1798 patients with a confirmed diagnosis of myocardial infarction. Of these, 982 consecutive patients were hospitalized in the coronary care unit of Henry Ford Hospital from January 1981 through December 1984 and compared with the 816 consecutive patients hospitalized from January 1990 through October 1992. Data on baseline demographics, initial clinical features, in-hospital management, and in-hospital outcome were compared for the two groups. Logistic regression was used to define independent predictors of the improved outcome of the two groups. Demographic features of the earlier group were similar to those of the later cohort, with the exception of a greater incidence of diabetes and hypertension and a lesser incidence of angina and prior heart failure. The occurrence of non-Q wave infarction increased from 27% in the earlier to 39% in the later group, whereas the magnitude of peak creatine kinase elevation in serum was higher in the later group. Medical management differed significantly, with increased use of aspirin, thrombolytics, heparin, warfarin, nitrates, and beta-blockers and decreased use of antiarrhythmic agents, digoxin, and vasopressors in the later group. Coronary revascularization was performed during hospitalization in 6.4% of the earlier group of patients and 31.6% of the later group. In-hospital mortality was 14.7% in the earlier group and 7.4% in the later group. Multivariate logistic regression analysis showed that the difference in mortality between the two groups was best accounted for by increased use of beta-blockers, angioplasty, and thrombolytics, decreased incidence of cardiogenic shock and asystole, and decreased use of lidocaine. In conclusion, the presentation and in-hospital management of patients with acute myocardial infarction has changed from the early 1980s to the early 1990s. The improved hospital mortality rate may be associated with both the expanded use of effective therapies and a more favorable in-hospital course, although these are not mutually exclusive.
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PMID:Decline in the rate of hospital mortality from acute myocardial infarction: impact of changing management strategies. 857 16

This study included 25 patients receiving hemodialysis (HD) but in whom diabetes mellitus was not the primary disease (HD-non DM group), 25 patients receiving hemodialysis with diabetes mellitus as the primary disease (HD-DM group), and 50 patients with diabetes mellitus who had not yet been treated with hemodialysis (DM group). The following markers of myocardial injury were measured in these patients: troponin T (TnT), creatine kinase (CK), myoglobin (Mb), and myosin light chain-1 (MLC-1). No significant correlation was found between myocardial TnT and Cr in any study group. The Mb and MLC-1 values in patients receiving HD were markedly higher than normal regardless of the primary disease involvement, while myocardial TnT was found to be only slightly abnormal. These results suggest that myocardial TnT may be a more useful marker of myocardial injury in HD patients than the markers in current use. In the present investigation, myocardial TnT was the only marker that was higher in the HD-DM group than in the HD-non DM group. This suggests the possibility that the HD-DM group included more patients with arteriosclerotic lesions, such as myocardial injury.
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PMID:A comparative study of myocardial troponin T levels in patients undergoing hemodialysis. 858

A 64-year-old female with McArdle's disease and non-insulin-dependent diabetes mellitus (NIDDM) is reported. She had none of the characteristic symptoms of McArdle's disease such as muscle cramps but her serum creatine kinase level was elevated. Muscle biopsy with negative muscle phosphorylase staining showed McArdle's disease. Modified forearm ischemic exercise test was done at two conditions; fasting and two hours after a meal. When fasting, the level of lactic acid did not elevate after exercise. After a meal, however, the serum lactic acid level rose with the elevation of plasma glucose and IRI. Thus, we suggested that high plasma glucose and insulin due to NIDDM may induce blood-borne glucose uptake with exercise.
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PMID:McArdle's disease with non-insulin-dependent diabetes mellitus: the beneficial effects of hyperglycemia and hyperinsulinemia for exercise intolerance. 879 56

Insulin resistance is a predictor of the development of noninsulin-dependent diabetes mellitus (NIDDM) in humans. It is unclear whether insulin resistance is a primary defect leading to NIDDM or the result of hyperinsulinemia and hyperglycemia. To determine if insulin resistance is the result of extrinsic factors such as hyperinsulinemia primary skeletal muscle cell cultures were established from muscle biopsies from Pima Indians with differing in vivo insulin sensitivities. These cell cultures expressed a variety of muscle-specific phenotypes including the proteins alpha-actinin and myosin, muscle-specific creatine kinase activity, and RNA encoding GLUT4, MYF5, MYOD1, and MYOGENIN. Labeled glucose was used to measure the insulin-stimulated conversion of glucose to glycogen in these cultures. The in vivo rates of insulin-stimulated glycogen production (insulin resistance) were correlated with in vitro measures of glycogen production (P = 0.007, r = 0.58). This defect in insulin action is stable in a uniform culture environment and is retained over time. The retention of insulin resistance in myoblast derived cell cultures is consistent with the expression of an underlying biochemical defect in insulin resistant skeletal muscle.
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PMID:Human primary myoblast cell cultures from non-diabetic insulin resistant subjects retain defects in insulin action. 894 52

We report the clinical, pathological, and genetic findings of 23 patients in 8 families with hereditary motor and sensory neuropathy (proximal dominant form) (HMSN-P) in Okinawa, Japan. The clinical features were unique with respect to autosomal dominant inheritance, Kennedy-Alter-Sung syndrome-like proximal dominant neurogenic atrophy, obvious sensory involvement, painful muscle cramp, fasciculations, areflexia, and high incidences of elevated creatine kinase levels, hyperlipidemia, and diabetes mellitus. Electrophysiological and pathological studies revealed typical motor and sensory axonal neuropathy, and decreased numbers of anterior born and dorsal ganglion cells, which suggested the presence of neuronopathy in HMSN-P. Genetic linkage studies showed a lod score of 4.04 (two-point analysis) in DNA marker D3S1284. Haplotype analysis showed that the gene locus of the disease was mapped to 3p14.1-q13 bracketed by D3S1285 and D3S1281. In this region, the patients' chromosomes showed an obvious increase in the allele frequency of five markers. One allele in D3S1591 was identical in all patients but had a low frequency in the control population. This finding suggested the presence of linkage disequilibrium and a common origin of this allele in all patients with HMSN-P. The HMSN-P described here is a new clinical entity characterized by unique clinical manifestations and a new gene locus.
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PMID:A new type of hereditary motor and sensory neuropathy linked to chromosome 3. 918 38

The insulin resistance of skeletal muscle in glucose-tolerant obese individuals is associated with reduced activity of oxidative enzymes and a disproportionate increase in activity of glycolytic enzymes. Because non-insulin-dependent diabetes mellitus (NIDDM) is a disorder characterized by even more severe insulin resistance of skeletal muscle and because many individuals with NIDDM are obese, the present study was undertaken to examine whether decreased oxidative and increased glycolytic enzyme activities are also present in NIDDM. Percutaneous biopsy of vatus lateralis muscle was obtained in eight lean (L) and eight obese (O) nondiabetic subjects and in eight obese NIDDM subjects and was assayed for marker enzymes of the glycolytic [phosphofructokinase, glyceraldehyde phosphate dehydrogenase, hexokinase (HK)] and oxidative pathways [citrate synthase (CS), cytochrome-c oxidase], as well as for a glycogenolytic enzyme (glycogen phosphorylase) and a marker of anaerobic ATP resynthesis (creatine kinase). Insulin sensitivity was measured by using the euglycemic clamp technique. Activity for glycolytic enzymes (phosphofructokinase, glyceraldehye phosphate dehydrogenase, HK) was highest in subjects with subjects with NIDDM, following the order of NIDDM > O > L, whereas maximum velocity for oxidative enzymes (CS, cytochrome-c oxidase) was lowest in subjects with NIDDM. The ratio between glycolytic and oxidative enzyme activities within skeletal muscle correlated negatively with insulin sensitivity. The HK/CS ratio had the strongest correlation (r = -0.60, P < 0.01) with insulin sensitivity. In summary, an imbalance between glycolytic and oxidative enzyme capacities is present in NIDDM subjects and is more severe than in obese or lean glucose-tolerant subjects. The altered ratio between glycolytic and oxidative enzyme activities found in skeletal muscle of individuals with NIDDM suggests that a dysregulation between mitochondrial oxidative capacity and capacity for glycolysis is an important component of the expression of insulin resistance.
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PMID:Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in NIDDM. 921 60

We analyzed mitochondrial DNA (mtDNA) from 7 patients in four families with adult onset limb-girdle type mitochondrial myopathy to clarify their genetic background. The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers. Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients. Southern blotting and direct sequence analyses showed an A-to-G homoplasmic transition at np8291 and intergenic COII/tRNA (Lys) 9bp deletion in all patients. This substitution was detected in only 2 of 600 control individuals including healthy subjects and patients with other neuromuscular disorders; these 2 individuals had diabetes mellitus and myotonic dystrophy, respectively. Consequently, the mtDNA transition at np8291 was a rare polymorphism. However, the 7 patients we studied had identical clinical, pathological, biochemical, and genetic features. Therefore, limb-girdle type mitochondrial myopathy with this rare polymorphism may form a subgroup of adult onset mitochondrial myopathy.
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PMID:Adult onset limb-girdle type mitochondrial myopathy with a mitochondrial DNA np8291 A-to-G substitution. 1031 90

Myotonic dystrophy (MyD) is a multisystem autosomal dominant disorder associated with progressive muscle wasting and weakness. The striking metabolic abnormality in MyD is insulin resistance. The mechanism by which target tissues are insensitive to insulin action remains uncertain. In a recent study, plasma soluble tumor necrosis factor receptor (sTNFR)2 levels were found to be associated with muscle tissue mass and insulin resistance. Given these associations, we speculated that disorders of the muscle cell membrane could lead simultaneously to insulin insensitivity and sTNFR2 leakage in MyD. To test this hypothesis, we measured the levels of circulating sTNFR1 and sTNFR2 and insulin resistance in MyD patients. We studied 22 MyD patients and 24 age-, BMI-, and fat mass-matched control subjects. Both MyD men and women showed higher plasma insulin levels in the presence of comparable glucose concentrations than did control subjects. sTNFR2, but not sTNFR1, levels were approximately 1.5-fold higher in MyD patients. In parallel with these findings, the fasting insulin resistance index (FIRI) was also higher in MyD patients. In fact, in the whole population, fasting insulin and FIRI strongly correlated with sTNFR2 in both men (r = 0.77 and r = 0.81, P<0.0001, respectively) and women (r = 0.67 and r = 0.64, P = 0.001, respectively). sTNFR2 levels were also associated with the insulin sensitivity index (S(I)), calculated from an oral glucose tolerance test (OGTT) according to the method by Cederholm and Wibell (r = -0.43, P = 0.006). We constructed a multiple linear regression to predict FIRI, with BMI, waist-to-hip ratio, and sTNFR2 as independent variables. In this model, both BMI (P = 0.0014) and sTNFR2 (P = 0.0048) levels contributed independently to 46% of the variance of FIRI. In another model, in which FIRI was substituted for S(I) from the OGTT, both BMI (P = 0.0001) and sTNFR2 (P = 0.04) levels contributed independently to 48% of the variance of S(I) from the OGTT. Plasma cholesterol and triglyceride concentrations were significantly increased in MyD patients. sTNFR1 and sTNFR2 levels were found to be strongly associated with plasma cholesterol, LDL cholesterol, and triglycerides. sTNFR1 and sTNFR2 also correlated with serum creatine kinase activity in MyD patients (r = 0.57, P = 0.006; r = 0.75, P<0.0001, respectively). In conclusion, here we describe, for the first time to our knowledge, a relationship between insulin action and plasma sTNFR2 concentration in MyD patients. We have also found increased concentrations of plasma triglycerides and cholesterol levels in parallel with sTNFR1 and sTNFR2 concentrations in MyD patients. We speculate that the latter associations are dependent on, and secondary to, increased tumor necrosis factor (TNF)-alpha action. Whether TNF action is implicated in the pathogenesis of MyD or is a simple marker of disease activity awaits further studies.
Diabetes 1999 May
PMID:Tumor necrosis factor system activity is associated with insulin resistance and dyslipidemia in myotonic dystrophy. 1033 17

A 30-year-old female complained of lancinating pain in the bilateral thighs for 10 days. The patient had a 22-year history of insulin-dependent diabetes mellitus. Physical examination revealed swelling of the bilateral lower extremities. There was exquisite tenderness on palpation over the medial thighs, with marked increase in pain on hip and knee flexion. Muscle strength of quadriceps, hamstrings, and hip adductor was decreased due to muscle pain. Pedal pulses were palpable bilaterally. Roentogenograms of the left femur revealed calcification of the left femoral arterial wall. Venogram revealed no obstruction with normal drainage. Complete blood cell count showed left shift of the neutrophils, markedly accelerated erythrocyte sedimentation rate, prolonged prothorombin time of 9 sec (normal 11.7 sec), C-reactive protein of 7.3 mg/dl and serum creatine kinase level of 175 IU/L. FBS was 225 mg/dl and Hb A 1 c was 16.4%. An MR imaging of the thighs revealed high signal intensities in the bilateral adductor muscles on T 2-weighted images. The symptoms resolved spontaneously over a three week period. From the course of the illness and MR imaging, the patient was diagnosed having diabetic muscle infarction (DMI), a rare complication of diabetes mellitus. To our knowledge, this is the first reported case of DMI in Japan. Diabetic microangiopathy and hypercoagulability are thought to be responsible for inducing DMI. Because the diagnosis can be made from the characteristic clinical and the typical MR imaging findings, muscle biopsy is not always necessary to obtain the diagnosis of DMI.
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PMID:[Bilateral diabetic infarction of the thigh adductor muscles in a diabetic female patient-- A case report and review of the literature]. 1039 Oct 74


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