Energy expenditure and substrate utilization in adults with cystic fibrosis and diabetes mellitus.
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BACKGROUND: The onset of cystic fibrosis-related diabetes mellitus (CFDM) is often associated with a decline in clinical and nutritional status. OBJECTIVE: The purpose of this study was to characterize energy expenditure (EE) and substrate utilization during rest, exercise, and recovery from exercise in patients with CF diagnosed with diabetes mellitus. DESIGN: EE, substrate utilization, minute ventilation, tidal volume, and respiratory rate were calculated by indirect calorimetry durng rest; a 30-min, low-to-medium-intensity exercise bout on a treadmill; and a 45-min postexercise recovery period (in reclining position) in 10 CF, 7 CFDM, and 10 control subjects between 18 and 45 y of age. RESULTS: In all 3 periods, minute ventilation was higher in the CF and CFDM groups than in the control subjects (P < 0.01). During rest and exercise, the CF and CFDM groups maintained EE values at the high end of the normal range of the control subjects. However, during recovery, EE was higher in the CF and CFDM groups than in the control group (P < 0.01). CONCLUSIONS: EE may be higher than usual for the patients with CF and CFDM during periods of recovery from mild exercise or activity because of increased work of breathing consistent with higher ventilatory requirements. This information may be useful for patients receiving nutritional counseling who may choose to exercise regularly, but are concerned about possible weight loss. (+info)
Effect of troglitazone on plasma lipid metabolism and lipoprotein lipase.
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AIMS: To clarify how troglitazone, an insulin-sensitizing agent, affects lipid metabolism and postheparin plasma lipoprotein lipase (LPL). METHODS: Fifteen patients (3 male, 12 female) (the average age 62+/-7 years; the mean body mass index (BMI) 25+/-3 kg/m2 ) were recruited for this study. The serum lipids and postheparin plasma lipoprotein lipase (LPL) mass before and 4 weeks after oral administration of troglitazone (200 mg day-1 ) were measured. A mouse preadipocyte cell line, 3T3-L1, was incubated with troglitazone and LPL enzyme protein mass in the culture media was measured by an enzyme linked immunosorbent assay. A reverse transcription polymerase chain reaction (RT-PCR) using primers specific for the carboxyl terminal 135 amino acid of mouse LPL cDNA was used to evaluate the effect of troglitazone on expression of LPL and Northern blot analysis carried out to determine expression of LPL. RESULTS: The average levels before treatment of fasting serum total cholesterol, triglycerides, high density lipoprotein cholesterol, plasma glucose and glycohaemoglobin A1c were 5.6+/-0.9, 1.8+/-1.0, 1.5+/-0.5, 8.1+/-1.7 mmol l-1 and 7.8+/-1.6% respectively. Four weeks after treatment, those levels were 5.4+/-0.9, 1.2+/-0.3 (P=0.004), 1.6+/-0.5 (P=0.02) mmol l-1, 7.7+/-2.3 mmol l-1 and 7. 3+/-0.6% (P=0.01), respectively. The postheparin plasma LPL mass increased from 226+/-39 to 257+/-68 ng ml-1 (P=0.03) during that period. The LPL mass in the media of 3T3 L1 cells cultured in the presence of 10, 20 or 30 microm of this compound increased in a dose dependent manner. RT-PCR revealed that the area of the bands of the RT-PCR products on 1.5% agarose gel analyzed with NIH image from the cell extracts cultured in the presence of 10 microm troglitazone was significantly larger (P=0.0069) than that in the absence of this compound. Northern blot analysis revealed that in the cultured 3T3-L1 cells, the expression of LPL was enhanced in the presence of 10 microm troglitazone. CONCLUSIONS: Troglitazone improves plasma triglyceride-rich lipoproteins metabolism by enhancing the expression of LPL in adipocytes. (+info)
Intravenous insulin infusion in diabetic emergencies.
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Continuous intravenous insulin and dextrose infusions were used in managing various diabetic emergencies. Standard and constant rates of insulin and dextrose infusion resulted in satisfactory control of blood glucose concentrations during labour, after major surgery, and in patients recovering from ketoacidosis (average insulin infusion rates 1, 2, and 3 U/h respectively). Higher infusion rates were used to correct or prevent ketoacidosis in pregnant diabetic women who had received steroids and sympathomimetic agents. The infusion method is simple, reliable, and flexible, and may help to simplify management of diverse types of diabetic emergencies. (+info)
Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.
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BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population. (+info)
Rising tide of cardiovascular disease in American Indians. The Strong Heart Study.
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BACKGROUND: Although cardiovascular disease (CVD) used to be rare among American Indians, Indian Health Service data suggest that CVD mortality rates vary greatly among American Indian communities and appear to be increasing. The Strong Heart Study was initiated to investigate CVD and its risk factors in American Indians in 13 communities in Arizona, Oklahoma, and South/North Dakota. METHODS AND RESULTS: A total of 4549 participants (1846 men and 2703 women 45 to 74 years old) who were seen at the baseline (1989 to 1991) examination were subjected to surveillance (average 4.2 years, 1991 to 1995), and 88% of those remaining alive underwent a second examination (1993 to 1995). The medical records of all participants were exhaustively reviewed to ascertain nonfatal cardiovascular events that occurred since the baseline examination or to definitively determine cause of death. CVD morbidity and mortality rates were higher in men than in women and were similar in the 3 geographic areas. Coronary heart disease (CHD) incidence rates among American Indian men and women were almost 2-fold higher than those in the Atherosclerosis Risk in Communities Study. Significant independent predictors of CVD in women were diabetes, age, obesity (inverse), LDL cholesterol, albuminuria, triglycerides, and hypertension. In men, diabetes, age, LDL cholesterol, albuminuria, and hypertension were independent predictors of CVD. CONCLUSIONS: At present, CHD rates in American Indians exceed rates in other US populations and may more often be fatal. Unlike other ethnic groups, American Indians appear to have an increasing incidence of CHD, possibly related to the high prevalence of diabetes. In the general US population, the rising prevalence of obesity and diabetes may reverse the decline in CVD death rates. Therefore, aggressive programs to control diabetes and its risk factors are needed. (+info)
Association of the alpha-fibrinogen Thr312Ala polymorphism with poststroke mortality in subjects with atrial fibrillation.
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BACKGROUND: The alpha-fibrinogen Thr312Ala polymorphism occurs in close proximity to several sites important for factor XIIIa-dependent cross-linking, which raises the possibility that it affects fibrin clot stability. METHODS AND RESULTS: We determined the association of this polymorphism with ischemic stroke, stroke subtype, and poststroke mortality. There was no significant difference in the genotype distributions of patients with acute ischemic stroke (n=519) and healthy control subjects (n=423), nor was there any association of this polymorphism with stroke subtype. In a Cox regression model, a significant interaction between Thr312Ala and atrial fibrillation was identified in relation to poststroke mortality (P=0.002). In subjects in sinus rhythm (n=418), there was no difference according to genotype in the proportion of subjects who survived (approximately 60% in each group), whereas in subjects with atrial fibrillation (n=101), there was decreased survival in those possessing the A allele (TT=42.1%, TA=18%, AA=0%). CONCLUSIONS: The Thr312Ala polymorphism may give rise to an increased susceptibility for embolization of intra-atrial clot, and these findings could have important implications for identifying subjects most at risk of developing thromboembolic complications. (+info)
Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia.
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To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the absence of Cdk4 but have a delayed S phase on re-entry into the cell cycle. Moreover, mice devoid of Cdk4 are viable, but small in size and infertile. These mice also develop insulin-deficient diabetes due to a reduction in beta-islet pancreatic cells. In contrast, mice expressing a mutant Cdk4 that cannot bind the cell-cycle inhibitor P16INK4a display pancreatic hyperplasia due to abnormal proliferation of beta-islet cells. These results establish Cdk4 as an essential regulator of specific cell types. (+info)
Quality of care of patients with diabetes: collation of data from multi-practice audits of diabetes in primary care.
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BACKGROUND: GPs are now playing a greater role in the care of patients with diabetes. The challenges described in the Saint Vincent Joint Task Force Report include achievement of a reduction in long-term complications by collecting key clinical information and systematically organizing care of patients with diabetes. The number of practices conducting audit and the number of primary care audit groups conducting multi-practice audits of diabetes have increased since the introduction of audit in 1991. OBJECTIVES: We aimed to determine the feasibility of collating data from multi-practice audits of diabetes in primary care and to describe the pattern of care for diabetes patients in primary care. METHODS: A confidential postal questionnaire was sent to all medical audit advisory groups that had completed a multi-practice audit of diabetic care. The main outcome measures studied were prevalence and treatment of known diabetes and annual compliance with key process measures. RESULTS: Data could be collated for 17 of the 25 audit groups that supplied data representing information from 495 practices with 38 288 diabetic patients. Seven audit groups supplied data from a population denominator comprising 1475512 patients giving a prevalence of 1.46% (range 1.1-1.7%), 50.7% (range 32.5-69.0%) were managed by general practice only, 19.1% (7.6-39.7%) by hospital care only and 30.2% (11.0-49.5%) by shared care. Annual mean compliance for process measures showed wide variations: glycated haemoglobin or fructosamine checked for 72.5% (range 25.3-89.3%), fundi checked for 67.5% (57.8-86.6%), urine checked for 65.8% (27.5-80.0%), blood pressure checked for 87.6% (76.9-96.5%), smoking checked for 71.45 (21.9-86.0%), feet checked for 67.7% (40.0-90.8%) and BMI checked for 52.5% (26.4-68.2%). CONCLUSION: This study shows the feasibility of collating audit data and the potential of this approach for describing patterns of care and highlighting general and local deficiencies. Information about levels of performance in large numbers of patients can be used to set standards or norms against which individual practitioners can compare their own activity. Comparison of the health needs of local populations with national data could be used to inform commissioning services. However, audits should employ uniform evidence-based criteria so as to facilitate collation and allow comparison. (+info)