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)

We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 healthy control subjects were examined for expression of the chemokine receptors CXCR4 (naive T-cells), CCR5 and CXCR3 (Th1 associated), and CCR3 and CCR4 (Th2 associated) on CD3+ lymphocytes. Furthermore, we analyzed chemokine serum levels (monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (gamma-interferon [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]) and Th2 (interleukin [IL]-4 and -10)-associated cytokines by PBMC. The patients with newly diagnosed type 1 diabetes were followed for these parameters at 6-12 months after diagnosis. The PBMCs of patients with newly diagnosed but not with longstanding type 1 diabetes showed reduced expression of the Th1-associated chemokine receptors CCR5 (P < 0.001 vs. control subjects) and CXCR3 (P < 0.002 vs. control subjects). This reduction correlated with reduced IFN-gamma and TNF-alpha production of PBMCs after PHA stimulation and reversed 6-12 months after diagnosis to normal levels. CCR4 cells were reduced in both newly diagnosed and longstanding type 1 diabetic patients, which correlated to reduced PHA-stimulated IL-4 production. MIP-1alpha and MIP-1beta levels were considerably elevated in a subgroup of patients with newly diagnosed diabetes. We assume that Th1-associated peripheral T-cells are reduced in a narrow time window at the time of diagnosis of diabetes, possibly due to extravasation in the inflamed pancreas. Thus, chemokine receptor expression of peripheral blood lymphocytes may be a useful surrogate marker for the immune activity of type 1 diabetes (e.g., in intervention trials).
Diabetes 2002 Aug
PMID:Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes. 1214 60

Nonalcoholic steatohepatitis is now recognized as a common chronic liver disorder. Up to 16% of affected patients may progress to cirrhosis. The incidence and prevalence of this disease are noted to be increasing, in parallel with the nationwide increase in obesity and diabetes. Treatment options for these patients remain quite limited, however. Weight reduction has been advocated, but there are little data to support this practice, as most patients are unable to comply with the proper dietary modifications. We report three obese patients with biopsy-proven nonalcoholic steatohepatitis treated for 6-12 months with a weight reduction medication, orlistat, who lost between 22-42 lb, and had significant clinical and histopathological improvement on follow-up.
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PMID:Orlistat in the treatment of NASH: a case series. 1273 78

Fibrinogen is far more important as a risk factor for acute cardiovascular syndromes than generally recognized. Evidence from a recent metaanalysis (including 22 studies of 63,736 subjects and 5,717 events [1] suggests that the risk for myocardial infarction and stroke almost doubles if the fibrinogen level exceeds 3.03 g/l (measured according to Clauss) with an odds ratio of 1.99 and a 95% confidence interval of 1.85-2.13. The predictive value of fibrinogen levels equally applies to men and women, young and old, primary and secondary prevention. Repeated fibrinogen measurements are particularly helpful with emphasis on high risk patients: concentrations of the upper tertile indicate a 92% higher risk of impending acute cardiovascular syndromes, as evidenced by a metaanalysis evaluating five prospective studies with 9,639 participants and 671 events [1]. Together with other risk factors such as hypertension, hypercholesterolemia, or diabetes, the risk of fatal and nonfatal acute cardiovascular syndromes may further increase by 6-12- fold, while fibrinogen remains an independent risk factor for both cardiac and extracardiac atherothrombotic complications, as well as for iatrogenic complications like restenosis following PTCA or stenting. Fibrin(ogen) and his effector thrombin substantially determine the extent and outcome of atherothrombotic complications, because they are the molecules linking the mutually dependent events of atherogenesis, coagulation/fibrinolysis, rheology/vasotonus, and inflammation. Interventional studies on fibrinolytic and defibrinating substances, as well as GpIIb/IIIa-inhibitors for treatment of acute cardiovascular syndromes have confirmed the benefit of fibrinogen reduction and extended the experimental evidence for the relevance of fibrin(ogen) in the pathogenesis of these syndromes. Accordingly, the preventive use of fibrates leading to moderate reductions in plasma cholesterol and fibrinogen diminished significantly the rate of reinfarction. The emerging possibilities from a more than 50% fibrinogen reduction (by studies using H.E.L.P. apheresis) strengthened the therapeutic concept to free the blood from all risk factors-as effective as it can be-in order to achieve an optimal plaque regression, since changes in the blood composition strongly affect the fragility and stability of the atherosclerotic plaques.
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PMID:[Fibrinogen and atherothrombosis: vulnerable plaque or vulnerable patient?]. 1456 94

Aradigm Corporation has developed an inhaled form of insulin using its proprietary AERx drug delivery system. The system uses liquid insulin that is converted into an aerosol containing very small particles (1-3 micro in diameter), and an electronic device suitable for either the rapid transfer of molecules of insulin into the bloodstream or localised delivery within the lung. The AERx insulin Diabetes Management System (iDMS), AERx iDMS, instructs the user on breathing technique to achieve the best results. Aradigm Corporation and Novo Nordisk have signed an agreement to jointly develop a pulmonary delivery system for insulin [AERx iDMS, NN 1998]. Under the terms of the agreement, Novo Nordisk has exclusive rights for worldwide marketing of any products resulting from the development programme. Aradigm Corporation will initially manufacture the product covered by the agreement, and in return will receive a share of the overall gross profits from Novo Nordisk's sales. Novo Nordisk will cover all development costs incurred by Aradigm Corporation while both parties will co-fund final development of the AERx device. Both companies will explore the possibilities of the AERx platform to deliver other compounds for the regulation of blood glucose levels. Additionally, the agreement gives Novo Nordisk an option to develop the technology for delivery of agents outside the diabetes area. In April 2001, Aradigm Corporation received a milestone payment from Novo Nordisk related to the completion of certain clinical and product development stages of the AERx drug delivery system. Profil, a CRO in Germany, is cooperating with Aradigm and Novo Nordisk in the development of inhaled insulin. Aradigm and Novo Nordisk initiated a pivotal phase III study with inhaled insulin formulation in September 2002. This 24-month, 300-patient trial is evaluating inhaled insulin in comparison with insulin aspart. Both medications will be given three times daily before meals in addition to basal insulin administered once or twice daily. In 2003, the US FDA adopted new GMP guidelines requiring sterile production of inhalation products and their devices. Novo Nordisk, therefore, will need to repeat phase III studies following device optimisation. These studies may begin at the end of 2004 and will include efficacy studies for 6-12 months and safety studies for up to 2 years (Lehman Brothers, Equity research, 7 August 2003). A phase IIb, 12-week clinical trial in 107 patients with type 2 diabetes was completed in the US. This trial was designed to compare the safety and efficacy of pulmonary insulin delivered via AERx iDMS, with intensified treatment with subcutaneous insulin administered at mealtimes. The results of the study positively compared pulmonary insulin with intensified subcutaneous insulin. Aradigm Corporation has a total of 85 patents pertaining to its proprietary AERx drug delivery system. Among those granted patents, 18 patents cover pulmonary insulin formulation including the method of patient breathing technique during pulmonary delivery of insulin. This patent guides patients on how to breathe in certain defined ways to achieve an effective amount and reproducibility of blood levels of insulin.
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PMID:Insulin inhalation: NN 1998. 1472 93

The aim of the present study was to describe the mechanism by which the combination glyburide/metformin exerts its additive hypoglycemic effects. This is a double-blind, randomized and crossover clinical trial. Patients (n = 20) were included in a run-in period of 8 weeks in which an isocaloric diet was prescribed. If they did not achieve the treatment goals (n = 15), they received glyburide, metformin or combined treatment for 10 weeks each using three possible sequences. The dosage was adjusted to reach fasting plasma glucose (FPG) < 7.7 mmol/l. Treatment periods were separated by a 6-12 week washout period. At the beginning and the end of every treatment, insulin sensitivity and insulin secretion were measured by means of a minimal model and an oral glucose tolerance test. All treatment periods were completed by 12 cases. The glycemic goal was reached in 1 case during metformin, in 5 during glyburide and in 10 during the combination. The greatest reduction in HbA1c was achieved during the combination (HbA1c 11 +/- 1.6 vs 9.8 +/- 1.9 vs 9.0 +/- 2.1% for metformin, glyburide and the combination, p < 0.001). Increased insulin secretion was the explanation for the additive effects of the combination (percentual change in acute insulin response during the minimal model = 5.8 vs 51.5 vs 88.2% for metformin, glyburide and the combination, p < 0.05). No change in insulin sensitivity resulted from the treatments. In conclusion, the additive hypoglycemic effects of the combination glyburide/metformin was caused by increased insulin secretion.
Diabetes Nutr Metab
PMID:The combination metformin/glyburide exerts its hypoglycemic effect mainly by increasing insulin secretion: a controlled, randomized, double-blind, crossover study. 1500 Apr 37

The human biological mechanisms show a predictable clinical variability in time, which has allowed a deeper reevaluation of present-day medical practices, regarding the circadian rhythm (CR) and the mechanisms that produce the supported variations in all biological levels. We have made a study aiming to relate the CR and onset of the neurological clinic situation due to the encephalic vascular lesion, correlating with modifying risk factors. Fifty three patients were studied, 50,94% female (n=27) and 49,50% male (n=26), at average age 66.4 years old. Four intervals of six hours each (0-6; 6-12; 12-18; 18-24) were used to analyze the frequency of the ictus and the incidence in each interval. We found an incidence of 6(11.32%) patients in the 0-6 hs interval; 21 (39.62%) patients in the 6-12 hs interval; 10(18.86%) patients in the 12-18 hs interval; 16 (30.18%) patients in the 18-24 interval. A correlative study with the risk factors has shown that arterial hypertension [(81.25%)] and smoking habit [ (56.25)] were predominant during the 18-24 hs interval, while sedentary [11(52.38%)] stress [11(52.38%)] diabetes [(47.61%)] hyperlipidemia [8 (38.09%)] and alcoholism [8 (38.09%] were predominant during the 6-12 hs interval; and cardiac diseases in the 12-18hs interval.
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PMID:[Circadian rhythm and encephalic vascular disease: a correlative study with risk factors]. 1523 33

The aim of this study was to determine whether home telehealth, when integrated with the health facility's electronic medical record system, reduces healthcare costs and improves quality-of-life outcomes relative to usual home healthcare services for elderly high resource users with complex co-morbidities. Study patients were identified through the medical center's database. Intervention patients received home telehealth units that used standard phone lines to communicate with the hospital. FDA-approved peripheral devices monitored vital signs and valid questionnaires were used to evaluate quality-of-life outcomes. Out-of-range data triggered electronic alerts to nurse case managers. (No live video or audio was incorporated in either direction.) Templated progress notes facilitated seamless data entry into the patient's electronic medical record. Participants (n = 104) with complex heart failure, chronic lung disease, and/or diabetes mellitus were randomly assigned to an intervention or control group for 6-12 months. Parametric and nonparametric analyses were performed to compare outcomes for (1) subjective and objective quality-of-life measures, (2) health resource use, and (3) costs. In contrast to the control group, scores for home telehealth subjects showed a statistically significant decrease at 6 months for bed-days-of-care (p < 0.0001), urgent clinic/emergency room visits (p = 0.023), and A1C levels (p < 0.0001); at 12 months for cognitive status (p < 0.028); and at 3 months for patient satisfaction (p < 0.001). Functional levels and patient-rated health status did not show a significant difference for either group. Integrating home telehealth with the healthcare institution's electronic database significantly reduces resource use and improves cognitive status, treatment compliance, and stability of chronic disease for homebound elderly with common complex co-morbidities.
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PMID:Home telehealth reduces healthcare costs. 1531 47

The etiology of painful diabetic neuropathy is poorly understood, but may result from neuronal hyperexcitability secondary to alterations of Ca2+ signaling in sensory neurons. The naturally occurring amino acid taurine functions as an osmolyte, antioxidant, Ca2+ modulator, inhibitory neurotransmitter, and analgesic such that its depletion in diabetes may predispose one to neuronal hyperexcitability and pain. This study reports the effects of taurine replacement on hyperalgesia and sensory neuron Ca2+ homeostasis in streptozotocin-diabetic (STZ-D) rats. Nondiabetic and STZ-D rats were treated with a 2% taurine-supplemented diet for 6-12 wk. Thermal hyperalgesia and mechanical allodynia were determined by measuring hindpaw withdrawal latency to radiant heat and the withdrawal threshold to the von Frey anesthesiometer. Intracellular Ca2+ signaling was explored in neurons from L4-L6 dorsal root ganglia (DRG), using fura 2 fluorescence. Taurine replacement of diabetic rats attenuated deficits of nerve conduction and prevented reductions of mechanical and thermal withdrawal threshold and latency, respectively. In small DRG sensory neurons from diabetic rats, recovery of intracellular Ca2+ concentration ([Ca2+]i) in response to KCl was slowed and 73% corrected by taurine. The amplitudes of caffeine and ATP-induced [Ca2+]i transients were decreased by 47 and 27% (P < 0.05), respectively, in diabetic rat DRG sensory neurons and corrected by 74 and 93% (P < 0.05), respectively, by taurine replacement. These data indicate that taurine is important in the regulation of neuronal Ca2+ signaling and that taurine deficiency may predispose one to nerve hyperexcitability and pain, complicating diabetes.
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PMID:Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats. 1558

Historically, addiction treatments have been delivered and evaluated under an acute-care format. Fixed amounts or durations of treatment have been provided and their effects evaluated 6-12 months after completion of care. The explicit expectation of treatment has been enduring reductions in substance use, improved personal health and social function, generally referred to as 'recovery'. In contrast, treatments for chronic illnesses such as diabetes, hypertension and asthma have been provided for indeterminate periods and their effects evaluated during the course of those treatments. Here the expectations are for most of the same results, but only during the course of continuing care and monitoring. The many similarities between addiction and mainstream chronic illnesses stand in contrast to the differences in the ways addiction is conceptualized, treated and evaluated. This paper builds upon established methods of during-treatment evaluation developed for the treatment of other chronic illnesses and suggests a parallel evaluation system for out-patient, continuing-care forms of addiction treatment. The suggested system retains traditional patient-level, behavioral outcome measures of recovery, but suggests that these outcomes should be collected and reported immediately and regularly by clinicians at the beginning of addiction treatment sessions, as a way of evaluating recovery progress and making decisions about continuing care. We refer to this paradigm as 'concurrent recovery monitoring' and discuss its potential for producing more timely, efficient, clinically relevant and accountable evaluations.
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PMID:Reconsidering the evaluation of addiction treatment: from retrospective follow-up to concurrent recovery monitoring. 1578 59

Diabetes disease management programs (DDMP) are proliferating, but their overall impact in improving quality of care using Health Employer Data and Information Set (HEDIS) quality metrics has not been well studied. Furthermore, DDMPs are usually ongoing, but the incremental benefits of continuing the program beyond the initial patient educational intervention have not been rigorously tested. This study evaluates the impact of length of DDMP participation on diabetes-related HEDIS 2002 quality indicators across 20 health plans. Results are stratified by duration of DDMP participation into three levels, "full participants" (6-12 months duration), "partial participants" (<6 months duration) and "non-participants" (0 months duration). The overall national compliance rate across all six combined HEDIS quality measures was 65.6% among full-participants (FP), 58.4% among partial-participants (PP) and 57.0% among non-participants (NP). This study demonstrates that participants in a comprehensive DDMP fair better than non-participants and that those with sustained participation (>6 months) benefit the most.
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PMID:A cohort study of the impact of a national disease management program on HEDIS diabetes outcomes. 1581 57


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