Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In summary, little progress has been made in the past several years with respect to the treatment of the baby with BPD. The conduct of convincing clinical research seems to be a casualty of budget cuts and a rush to learn the tools of molecular biology. To date, there are no clinical trials that have convincingly demonstrated that long-term diuretic, bronchodilator, vasodilator, or antioxidant therapy is effective in the treatment of chronic BPD. Short-term corticosteroid therapy hastens extubation, but long-term outcome is unaffected and serious questions remain about its safety. Multicenter clinical trials should be carefully designed and implemented to address the values of these therapies. In the design of these trials, care should be taken to stratify treatment groups for known risk factors for BPD. What are the future directions for the treatment of BPD? It is hoped that new BPD treatment strategies will be based on an improved understanding of mechanisms of lung repair and inflammation. Enzyme, gene, cytokine, antioxidant, and antiprotease therapies are being developed in animal models of lung injury. In addition, the use of lung transplantation has begun to be explored for severe cases of BPD. It is also possible, as has occurred in many chronic idiopathic diseases, that nonspecific treatment may prove beneficial. Perhaps it is only a matter of time before intravenous immunoglobulin, cyclosporine, methotrexate, or "biological response modifiers" will be administered to infants with severe BPD. For example, there is anecdotal evidence that recombinant human growth hormone may improve respiratory muscle function in adults with chronic obstructive pulmonary diseases. In the absence of convincing clinical trials, the clinician should reserve existing therapies for the ventilator-dependent infant or infants whose high oxygen requirement is prohibiting discharge or resulting in complex home care or frequent rehospitalizations. It should be emphasized that continuous oxygen therapy combined with avoidance of environmental inhalant and infectious hazards have the strongest rationale and widest margin of safety for treatment of the infant with BPD. Ironically, oxygen therapy is frequently underutilized and discontinued too rapidly. Early discontinuation of oxygen therapy with alveolar hypoxia results in feeding difficulty, slow growth, nutrient malabsorption, bronchoconstriction, and pulmonary hypertension. Oxygen therapy, although more cumbersome and certainly less glamorous than other pharmacologic agents, remains the essential element of BPD care.
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PMID:Current therapy of bronchopulmonary dysplasia. 152 72

Obesity is a frequent cause of insulin resistance and poses a major risk for diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. We tested the hypothesis that dietary lipid deprivation may selectively deplete intramyocellular lipids, thereby reversing insulin resistance. Whole-body insulin sensitivity (by the insulin clamp technique), intramyocellular lipids (by quantitative histochemistry on quadriceps muscle biopsies), muscle insulin action (as the expression of Glut4 glucose transporters), and postprandial lipemia were measured in 20 morbidly obese patients (BMI = 49 +/- 8 [mean +/- SD] kg x m(-2)) and 7 nonobese control subjects. Patients were restudied 6 months later after biliopancreatic diversion (BPD; n = 8), an operation that induces predominant lipid malabsorption, or hypocaloric diet (n = 9). At 6 months, BPD had caused the loss of 33 +/- 10 kg through lipid malabsorption (documented by a flat postprandial triglyceride profile). Despite an attained BMI still in the obese range (39 +/- 8 kg x m(-2)), insulin resistance (23 +/- 3 micromol/min per kg of fat-free mass; P < 0.001 vs. 53 +/- 13 of control subjects) was fully reversed (52 +/- 11 micromol/min per kg of fat-free mass; NS versus control subjects). In parallel with this change, intramyocellular-but not perivascular or interfibrillar-lipid accumulation decreased (1.63 +/- 1.06 to 0.22 +/- 0.44 score units; P < 0.01; NS vs. 0.07 +/- 0.19 of control subjects), Glut4 expression was restored, and circulating leptin concentrations were normalized. In the diet group, a weight loss of 14 +/- 12 kg was accompanied by very modest changes in insulin sensitivity and intramyocellular lipid contents. We conclude that lipid deprivation selectively depletes intramyocellular lipid stores and induces a normal metabolic state (in terms of insulin-mediated whole-body glucose disposal, intracellular insulin signaling, and circulating leptin levels) despite a persistent excess of total body fat mass.
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PMID:Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. 1175 34

Severe obesity is associated with multiple comorbidities and is refractory to dietary management with or without behavioral or drug therapies. There are a number of surgical procedures for the treatment of morbid obesity, including purely gastric restrictive, a combination of malabsorption and gastric restriction or primary malabsorption. The purely gastric restrictive procedures, including vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding, do not provide adequate weight loss. African-American patients do especially poorly after the banding procedure with the loss of only 11% of excess weight in one study. Gastric bypass (GBP) is associated with the loss of 66% of excess weight at 1 to 2 years after surgery, 60% at 5 years and 50% at 10 years. For unknown reasons, African-American patients lose significantly less weight than Caucasians after GBP. There is a risk of micronutrient deficiencies after GBP, including iron deficiency anemia in menstruating women, vitamin B12, and calcium deficiencies. Prophylactic supplementation of these nutrients is necessary. Recurrent vomiting after bariatric surgery may be associated with a severe polyneuropathy and must be aggressively treated with endoscopic dilatation before this complication is allowed to develop. The malabsorptive procedures include the partial biliopancreatic bypass (BPD) and BPD with duodenal switch (BPD/DS). The BPD appears to cause severe protein-calorie malnutrition in American patients; the BPD/DS may be associated with less malnutrition. Weight loss failure after GBP does not respond to tightening a dilated gastrojejunal stoma or reducing the size of the gastric pouch. These patients may require conversion to a malabsorptive distal GBP, similar to the BPD. However, because of the risk of severe protein-calorie malnutrition and calcium deficiency BPD should be reserved for patients with severe obesity comorbidity. The risk of death following bariatric surgery is between 1% and 2% in most series but is significantly higher in patients with respiratory insufficiency of obesity. In most patients, surgically induced weight loss will correct hypertension, type II diabetes mellitus, sleep apnea, obesity hypoventilation syndrome, gastroesophageal reflux, venous stasis disease, urinary incontinence, female sexual hormone dysfunction, pseudotumor cerebri, degenerative joint disease pains, as well as improved self-image and employability.
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PMID:Bariatric surgery for severe obesity. 1185 Dec 1

The aim of this study was to investigate the sterol regulatory element-binding protein 1c (SREBP1c) mRNA muscle expression in morbid obese subjects before and after massive lipid malabsorption due to bariatric surgery (bilio-pancreatic diversion, BPD). We studied 11 obese subjects (BMI 49+/-2 kg/m2) before and 24 months after BPD. Skeletal muscle SREBP1c mRNA expression was determined using RT-competitive PCR. Intramyocytic triglycerides were quantified by HPLC. Insulin sensitivity (M/I) was assessed by euglycemic-hyperinsulinemic clamp. Energy expenditure and respiratory quotient (RQ) were measured over 24 h in a calorimetric chamber. Total cardiovascular risk dropped from 2 before to -2.5 after BPD (P<0.0001). The M/I value was normalized after surgery (0.036+/-0.0148 to 0.095+/-0.0147 micromol kgFFM(-1) min(-1) pmoles(-1) P<0.001). SREBP-1c mRNA levels were decreased (from 4.12+/-2.43 to 2.69+/-1.83% of cyclophilin mRNA, P=0.02) after BPD. In a multiple regression analysis, M/I values (P<0.0001) as well as the intramyocytic triglyceride levels (P=0.039) were the most powerful independent variables for predicting cardiovascular risk. Our results show that the reduction of cardiovascular risk after bariatric massive weight loss is strongly related to the reversion of insulin resistance and to the lowering of intramyocytic triglyceride depots. These two parameters are associated with a significant reduction in SREBP-1c mRNA expression in skeletal muscle, suggesting that this transcription factor might be involved in the accumulation of triglycerides in muscle cells of morbidly obese subjects.
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PMID:Intramyocitic lipid accumulation and SREBP-1c expression are related to insulin resistance and cardiovascular risk in morbid obesity. 1295 94

The mechanisms underlying the body weight and fat loss after the biliopancreatic diversion with duodenal switch (BPD/DS) remain to be fully delineated. The aim of this study was to examine the contributions of the two main components of BPD/DS, namely sleeve gastrectomy (SG) and duodenal switch (DS), on energy balance changes in rats rendered obese with a high-fat (HF) diet. Three different bariatric procedures (BPD/DS, SG, and DS) and three sham surgeries were performed in male Wistar rats. Sham-operated animals fed HF were either fed ad libitum (Sham HF) or pair weighed (Sham HF PW) by food restriction to the BPD/DS rats. A group of sham-operated rats was kept on standard chow and served as normal diet control (Sham Chow). All three bariatric surgeries resulted in a transient reduction in food intake. SG per se induced a delay in body weight gain. BPD/DS and DS led to a noticeable gut malabsorption and a reduction in body weight and fat gains along with significant elevations in plasma levels of glucagon-like peptide-1(7-36) and peptide YY. BPD/DS and DS elevated energy expenditure above that of Sham HF PW during the dark phase. However, they reduced the volume, oxidative metabolism, and expression of thermogenic genes in interscapular brown adipose tissue. Altogether the results of this study suggest that the DS component of the BPD/DS, which led to a reduction in digestible energy intake while sustaining energy expenditure, plays a key role in the improvement in the metabolic profile led by BPD/DS in rats fed a HF diet.
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PMID:Metabolic changes induced by the biliopancreatic diversion in diet-induced obesity in male rats: the contributions of sleeve gastrectomy and duodenal switch. 2564 12

Intestinal nutrients stimulate insulin secretion more potently than intravenous (IV) glucose administration under similar plasma glucose levels (incretin effect). According to the anti-incretin theory, intestinal nutrients should also cause a reduction of insulin sensitivity and/or secretion (anti-incretin effect) to defend against hyperinsulinemia-hypoglycemia. An exaggerated anti-incretin effect could contribute to insulin resistance/type 2 diabetes, whereas reduction of anti-incretin signals might explain diabetes improvement after bariatric surgery. In this study, we tested some of the predictions made by the anti-incretin theory. Eight healthy volunteers and eight severely obese subjects with insulin resistance were studied. Insulin secretion, insulin sensitivity, Ra, and disposition index were measured after oral glucose tolerance test and isoglycemic IV glucose injection (IGIV). Obese subjects were studied before and after intestinal bypass surgery (biliopancreatic diversion [BPD]). The d-xylose test and lactulose-to-rhamnose ratio were used to test for possible malabsorption of glucose after surgery. Monte Carlo mathematical simulations were used to test whether insulin secretion induced by oral glucose could cause hypoglycemia when coupled with the levels of insulin sensitivity measured during IGIV. Despite isoglycemic conditions, insulin sensitivity was lower during oral than during IV glucose administration. This difference was amplified in obese subjects and reduced to normal after BPD. No evidence of glucose malabsorption was found. Mathematical simulations showed that hypoglycemia would occur if insulin sensitivity were not reduced by oral glucose stimulation. This study demonstrates an anti-incretin effect of intestinal glucose stimulation, which downregulates insulin sensitivity. The findings support a new model for how foodborne factors can induce insulin-resistance and provide a possible explanation for the improvement of insulin resistance/diabetes after gastrointestinal bypass surgery.
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PMID:Downregulation of Insulin Sensitivity After Oral Glucose Administration: Evidence for the Anti-Incretin Effect. 2885 12