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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin action in vivo and insulin binding to monocytes in vitro were correlated in patients with myotonic dystrophy (MyD) and compared with healthy controls. Confirming our previous studies and those of others, the present results show that the glucose infusion rate (DR), an estimate of in vivo insulin sensitivity, was significantly diminished in MyD. At the same per cent of ideal body weight DR in MyD patients was considerably less than controls suggesting that obesity could not solely account for decreased insulin sensitivity in MyD. The relative capacity (RC), and relative affinity (ED50) of the insulin receptor in monocytes was significantly less in patients. The relative affinity (ED50) was improved by changing environmental insulin levels while receptor numbers (RC) were not. Insulin sensitivity and RC showed a trend toward a positive correlation although this did not reach statistical significance. Our data suggest that the alteration of the insulin receptor in MyD is different from obesity and from other disorders of the motor unit such as amyotrophic lateral sclerosis, where insulin sensitivity and RC are reduced but ED50 is unchanged. Thus, in MyD the receptor may be one of the loci where the resistance occurs.
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PMID:Environmental influence on altered receptor function in a genetic disease: insulin and glucose affect insulin receptors in myotonic dystrophy. 264 9

We describe the anesthetic management of an obese myotonic patient who underwent bilio-pancreatic diversion for severe obesity. A female, 35 years old (weight 137 kg, height 160 cm, excess body weight 120%) suffered from myotonic dystrophy and obesity, complicated by a mild heart failure and restrictive disease. Induction of anesthesia and tracheal intubation were performed after propofol (1 mg/kg). Anesthesia was maintained with isoflurane and fentanyl muscular blockade by vecuronium bromide. Perioperatively extensive hemodynamic monitoring has been performed. The patient was discharged successfully the 12th day postoperatively. One year later she had lost 50 kgs of body weight; oxygen blood tension and pulmonary function tests were greatly improved.
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PMID:Anesthetic management of a patient combining myotonic dystrophy and obesity. 925 74

Metabolic-endocrine dysfunctions, including hyperinsulinemia, hypertriglyceridemia, increased fat mass, and dysregulation of the hypothalamic-pituitary-adrenal axis, are common in myotonic dystrophy (MD). We hypothesized that increased production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) may be important underlying mechanisms. We studied the diurnal rhythmicity of cytokines and cortisol, ACTH, and dehydroepiandrosterone in 18 men with adult onset MD and 18 controls. Morning levels of androstenedione, 17-hydroxyprogesterone, testosterone, and insulin were also determined. Genetic analyses were performed, including calculation of allele sizes. Median circulating 24-h levels of IL-6 (P < 0.001), TNF-alpha (P = 0.05), ACTH (P < 0.05), and cortisol (P < 0.05) were all significantly increased in MD, whereas dehydroepiandrosterone levels were decreased (P < 0.001). The diurnal rhythms of these cytokines/ hormones were disturbed in patients. Morning testosterone levels were decreased and insulin levels increased (P < 0.01 for both). Patients with high body fat mass had significantly increased insulin levels and decreased morning levels of cortisol, ACTH, and testosterone. IL-6 and TNF-alpha levels are increased and adrenocortical hormone regulation is disturbed in MD. Adiposity may contribute to these disturbances, which may be of importance for decreased adrenal androgen hormone production and metabolic, muscular, and neuropsychiatric dysfunction in MD.
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PMID:Abnormal cytokine and adrenocortical hormone regulation in myotonic dystrophy. 1099 4

Dysfunction of the hypothalamic-pituitary-adrenal axis might contribute to metabolic disturbances frequently encountered in myotonic dystrophy. We hypothesized that abnormal adrenocortical sensitivity to ACTH and/or glucocorticoid metabolism could be important in myotonic dystrophy. We assessed diurnal rhythmicity of saliva cortisol, adrenocortical reactivity by a low-dose (1 microg) Synacthen test, and glucocorticoid metabolism in blood and urine in 42 myotonic dystrophy patients (22 males) and 50 controls (27 males). CTG triplet repeat expansions were quantified by Southern blot. Diurnal rhythmicity of saliva cortisol was flattened in both men and women with myotonic dystrophy, with significantly increased afternoon/evening levels (P < 0.013). The cortisol response to ACTH was associated with increased (CTG)(n) expansions in myotonic dystrophy men and women (P < 0.01). Male myotonic dystrophy patients also had increased activation of cortisol from cortisone by 11beta-hydroxysteroid dehydrogenase type 1. Both men and women with myotonic dystrophy had an increased 5alpha/5beta-reductase ratio (P < 0.05 and P < 0.01, respectively). Cortisol metabolites were related to the genetic defect in myotonic dystrophy men (P < 0.05), whereas ratios reflecting 11beta-hydroxysteroid dehydrogenase type 1 activity in myotonic dystrophy women were positively associated with obesity (P < 0.05). Increased 11beta-hydroxysteroid dehydrogenase type 1 activity and adrenocortical reactivity to ACTH are related to the genetic defect in myotonic dystrophy men, whereas abnormal glucocorticoid metabolism is associated with alterations in body composition in female myotonic dystrophy patients. These disturbances may explain altered circulating cortisol levels and contribute to features of the metabolic syndrome in myotonic dystrophy.
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PMID:Glucocorticoid metabolism and adrenocortical reactivity to ACTH in myotonic dystrophy. 1154 62

In obese humans and rodents there is increased expression of the key glucocorticoid (GC) regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), in adipose tissue. This increased expression appears to be of pathogenic importance because transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue exhibit a full metabolic syndrome with visceral obesity, dyslipidemia, insulin-resistant diabetes, and hypertension. In this model, while systemic plasma GC levels are unaltered, GC delivery to the liver via the portal vein is increased. 11beta-HSD1 is most highly expressed in liver where inhibition or deficiency of its activity improves glucose and lipid homeostasis. To determine the potential contribution of elevated intrahepatic GCs alone toward development of insulin-resistant syndromes we generated transgenic mice expressing increased 11beta-HSD1 activity selectively in the liver under transcriptional control of hepatic regulatory sequences derived from the human apoE gene (apoE-HSD1). Transgenic lines with 2- and 5-fold-elevated 11beta-HSD1 activity exhibited mild insulin resistance without altered fat depot mass. ApoE-HSD1 transgenic mice exhibited fatty liver and dyslipidemia with increased hepatic lipid synthesis/flux associated with elevated hepatic LXRalpha and PPARalpha mRNA levels as well as impaired hepatic lipid clearance. Further, apoE-HSD1 transgenic mice have a marked, transgene-dose-associated hypertension paralleled by incrementally increased liver angiotensinogen expression. These data suggest that elevated hepatic expression of 11beta-HSD1 may relate to the pathogenesis of specific fatty liver, insulin-resistant, and hypertensive syndromes without obesity in humans as may occur in, for example, myotonic dystrophy, and possibly, the metabolically obese, normal-weight individual.
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PMID:Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. 1511 95

Obese, insulin-resistant patients have been shown to have metabolic inflexibility. The goal of this study was to examine the effect of insulin administration on energy metabolism in lean, type 1 diabetic (DM1) patients. Eleven DM1 patients without vascular complications and 11 healthy controls (C) were examined. We performed a 2-step hyperinsulinemic euglycemic clamp (240 minutes; period 1: 1 mU. kg(-1). min(-1) and period 2: 10 mU. kg(-1). min(-1)) combined with indirect calorimetry during basal period B (B, -45 to 0 minutes), period 1, and period 2 of the clamp. The metabolic clearance rates of glucose (MCR) were lower in DM1 compared with C in period 1 (12.54 +/- 3.38 v 17.41 +/- 6.18 mL. kg(-1). min(-1); P <.02), as well as in period 2 (21.63 +/- 6.47 v 26.61 +/- 4.45 mL. kg(-1). min(-1); P <.05). Basal respiratory quotient (RQ) was lower in DM1 compared with C (0.72 +/- 0.04 v 0.75 +/- 0.04; P <.03). Insulin administration was accompanied by an increase in RQ in both groups, which was lower in DM1 compared with C (period 1: +0.09 +/- 0.04 v +0.11 +/- 0.07; P <.001; period 2: +0.13 +/- 0.04 v +0.16 +/- 0.04; P <.001). Glucose oxidation did not differ between the groups in period B; however, it was lower in DM1 compared with C in periods 1 (1.17 +/- 0.67 v 3.28 +/- 1.11 mg. kg(-1). min(-1); P <.003); and 2 (2.10 +/- 0.64 v 3.28 +/- 0.93 mg. kg(-1). min(-1); P <.009). Lipid oxidation was higher in DM1 in all periods compared with C; period B (3.28 +/- 0.77 v 1.16 +/- 0.55 mg. kg(-1). min(-1); P <.001), period 1 (1.10 +/- 0.41 v 0.67 +/- 0.54 mg. kg(-1). min(-1); P <.05), and period 2 (0.99 +/- 0.29 v 0.52 +/- 0.58 mg. kg(-1). min(-1); P <.01). The groups did not differ in protein oxidation. In conclusion, DM1 patients with secondary insulin resistance (IR) are characterized by metabolic inflexibility manifesting itself by smaller increases in RQ and glucose oxidation after insulin administration during the euglycemic clamp.
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PMID:Inflexibility of energy substrate oxidation in type 1 diabetic patients. 1513 73

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B(1) deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.
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PMID:Neurodegenerative disorders associated with diabetes mellitus. 1517 61

We report a case of a 35-year-old woman with myotonic dystrophy and severe obesity of BMI 43.3 who showed persistent apnea at emergence after ovarian resection. The patient received an iv induction with minimum dose of propofol and vecuronium 3 mg. Anesthesia was maintained with propofol, 50% nitrous oxide and 50% oxygen mixture and epidural anesthesia. Additional vecuronium 0.5 mg was administered twice. Surgery was performed uneventfully within 130 minutes and iv propofol was discontinued. The patient awoke promptly after termination of nitrous oxide but no spontaneous breathing appeared with end-tidal CO2 of 60 mmHg. Because she could obey the order to breathe, the endotracheal tube was removed 40 minutes after discontinuation of propofol. Spontaneous breathing at the rate of 17 x min(-1) started soon after extubation. We assume that this apnea was caused by breath holding. Whether this breath holding is specific to myotonic dystrophy or not, anesthesia for patients with this disease requires careful attention for perioperative respiratory management.
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PMID:[Persistent apnea in an obese patient with myotonic dystrophy]. 1596 86

Aberrant accumulation of lipids in the liver ("fatty liver" or hepatic steatosis) represents a hallmark of the metabolic syndrome and is tightly associated with obesity, type II diabetes, starvation, or glucocorticoid (GC) therapy. While fatty liver has been connected with numerous abnormalities of liver function, the molecular mechanisms of fatty liver development remain largely enigmatic. Here we show that liver-specific disruption of glucocorticoid receptor (GR) action improves the steatotic phenotype in fatty liver mouse models and leads to the induction of transcriptional repressor hairy enhancer of split 1 (Hes1) gene expression. The GR directly interferes with Hes1 promoter activity, triggering the recruitment of histone deacetylase (HDAC) activities to the Hes1 gene. Genetic restoration of hepatic Hes1 levels in steatotic animals normalizes hepatic triglyceride (TG) levels. As glucocorticoid action is increased during starvation, myotonic dystrophy, and Cushing's syndrome, the inhibition of Hes1 through the GR might explain the fatty liver phenotype in these subjects.
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PMID:The glucocorticoid receptor controls hepatic dyslipidemia through Hes1. 1876 22

Roux-en-Y gastric bypass surgery (RYGB) reverses type 2 diabetes (DM2) in approximately 83% of patients with morbid or severe obesity. This procedure has been performed in small numbers of severely obese patients with type 1 diabetes (DM1), but the impact on glycemic control and insulin requirement in this population has not been widely described. We report three patients with DM1 and severe obesity that underwent RYGB. Weight, glycemic control, and insulin requirements before and one year after the procedure were compared. Significant weight loss was achieved by all three patients but insulin requirements decreased in only 2 patients. In contrast, glycemic control (A1C) remained suboptimal in all three patients up to one year after the surgery. These findings suggest that RYGB leads to important weight loss and positively affects insulin sensitivity. However, reaching optimal glycemic control in patients with DM1 diabetes remains challenging due to persisting insulin deficiency.
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PMID:Outcomes of Roux-en-Y gastric bypass surgery for severely obese patients with type 1 diabetes: a case series report. 2143 96


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