Hyperglycemia at the time of acute ischemic stroke has been linked to worse outcome in both human and animal studies.
To describe the prevalence and severity of hyperglycemia on hospital admission ...among acute ischemic stroke patients, to examine the independent relationship of admission hyperglycemia to all-cause mortality, and to document the inpatient management of hyperglycemia.
Patients hospitalized with acute ischemic stroke at one hospital from July 1993 to June 1998 (n = 656) were identified. Demographic data, diagnoses, and blood glucose (BG) values were retrieved from the electronic medical record system. Admission stroke severity, fingerstick BG results, and new diabetes diagnoses were obtained by chart review. Hyperglycemia was defined as admitting random serum BG > or = 130 mg/dL. Hazard ratios (HR) for 30-day, 1-year, and 6-year mortality were calculated using multivariable Cox regression models.
Hyperglycemia at admission to hospital was present in 40% of patients with acute stroke. Patients with hyperglycemia were more often women and more likely to have prior diagnoses of diabetes and heart failure. Almost all of these patients remained hyperglycemic during their hospital stay (mean BG = 206 mg/dL), and 43% received no inpatient hypoglycemic drugs. Hyperglycemic patients had longer hospital stay (7 vs 6 days, p = 0.015) and higher inpatient hospital charges ($6,611 vs $5,262, p < 0.001). Hyperglycemia independently increased the risk for death at 30 days (HR 1.87, p < or = 0.01), 1 year (HR 1.75, p < or = 0.01), and 6 years after stroke (HR 1.41, p </= 0.01).
Admitting hyperglycemia was common among patients with acute ischemic stroke and was associated with increased short- and long-term mortality and with increased inpatient charges. Inpatient blood glucose management was suboptimal in this hospital. A trial of intensive treatment of hyperglycemia should be considered.
Although factors such as age, blood pressure, and its responsiveness to changes in sodium balance and extracellular fluid volume status (salt sensitivity) are associated with an increased risk of ...end-organ disease and cardiovascular events in hypertensive subjects, no such relationship with mortality has been demonstrated for salt sensitivity in normotensive subjects. We conducted long-term follow-up of 430 normal and 278 hypertensive subjects in whom assessment of salt sensitivity of blood pressure was performed as long as 27 years ago. We ascertained the status of 596 subjects (85% of the total population), 123 (21%) of whom had died. The following initial measurements were significantly (P <0.002) associated with subjects who had died compared with subjects known to be aliveage at study, pulse pressure, systolic, diastolic, and mean arterial pressures, hypertension, salt sensitivity, baseline renin levels, and body mass index (but not body weight). A stepwise logistic regression found the following independent predictors of death (odds ratio, 95% CI)age at initial study (1.08, 1.06 to 1.10), baseline blood pressure (1.03, 1.01 to 1.04), sodium sensitivity (1.73, 1.02 to 2.94), and male gender (1.91, 1.15 to 3.17). When survival curves were examined, normotensive salt-sensitive subjects aged >25 years when initially studied were found to have a cumulative mortality similar to that of hypertensive subjects, whereas salt-resistant normotensive subjects had increased survival (P <0.001). These observations provide unique evidence of a relationship between salt sensitivity and mortality that is independent of elevated blood pressure.
Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both.
To analyze the relationship between admission glucose level and clinical ...outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure.
There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio OR = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased (p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA.
In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.
Background. Gambling and gaming disorders have been included as “disorders due to addictive behaviors” in the International Classification of Diseases (ICD-11). Other problematic behaviors may be ...considered as “other specified disorders due to addictive behaviors (6C5Y).” Methods. Narrative review, experts' opinions. Results. We suggest the following meta-level criteria for considering potential addictive behaviors as fulfilling the category of “other specified disorders due to addictive behaviors”: 1. Clinical relevance: Empirical evidence from multiple scientific studies demonstrates that the specific potential addictive behavior is clinically relevant and individuals experience negative consequences and functional impairments in daily life due to the problematic and potentially addictive behavior. 2. Theoretical embedding: Current theories and theoretical models belonging to the field of research on addictive behaviors describe and explain most appropriately the candidate phenomenon of a potential addictive behavior. 3. Empirical evidence: Data based on self-reports, clinical interviews, surveys, behavioral experiments, and, if available, biological investigations (neural, physiological, genetic) suggest that psychological (and neurobiological) mechanisms involved in other addictive behaviors are also valid for the candidate phenomenon. Varying degrees of support for problematic forms of pornography use, buying and shopping, and use of social networks are available. These conditions may fit the category of “other specified disorders due to addictive behaviors”. Conclusion. It is important not to over-pathologize everyday-life behavior while concurrently not trivializing conditions that are of clinical importance and that deserve public health considerations. The proposed meta-level-criteria may help guide both research efforts and clinical practice.
Although a variety of factors have been shown to influence vascular compliance in humans, few studies have been large enough to adequately assess the effects of age, race, gender, blood pressure ...(BP), and estrogen therapy.
As part of a long-term follow-up study, 272 subjects, 50% women, 26% African American, 71% currently hypertensive, ranging in age from 33 to 80 years were studied with noninvasive measures of vascular compliance by pulse wave analysis.
A significant age-related decrease in large and small vessel compliance and increase in vascular resistance and impedance was seen in all hypertensive subjects and in normotensive women. The slope of the relationship was significantly steeper for women than for men. No effect of estrogen or race could be observed. In hypertensive subjects, pulse pressure exerted an effect similar to that of age.
Studies of vascular compliance must consider a variety of demographic and physiologic factors including age, gender, and BP. Race and estrogen administration do not appear to contribute to the variables independent of the factors identified.
Objective: To compare antibody responses to inhaled human insulin vs. sc human insulin and to determine whether insulin antibody binding is associated with adverse clinical consequences.
Research ...Design and Methods: Insulin antibody data from initial phase II/III trials were analyzed comparing the efficacy and safety of inhaled insulin with various agents, including sc insulin. Additionally, data from a 24-month extension of the phase III studies were examined. Data were pooled into the following three groups based on insulin treatment status at baseline: patients with type 1 diabetes, and patients with type 2 diabetes using insulin and not using insulin at baseline. Ig class analysis was also performed on randomly selected sera from type 1 patients at the end of the initial trials.
Results: In the initial trials, greater insulin antibody binding was observed in patients receiving inhaled insulin vs. sc insulin. The greatest antibody responses to inhaled insulin were observed in patients with type 1 diabetes nonparametric comparison of medians at the end of the study, 22.0% binding (unadjusted 95% confidence interval: 19.5, 24.5), and the lowest responses were observed in non-insulin-using patients with type 2 diabetes in which there was no difference in median values at the end of the study. There were no correlations between antibody binding and glycemic control (measured using glycosylated hemoglobin), insulin dose requirements, hypoglycemic events, or pulmonary function (measured by changes in forced expiratory volume in 1 sec and diffusion capacity of carbon monoxide). Antibody responses were IgG in type. Differences in antibody levels observed in patients with type 1 vs. type 2 diabetes were maintained over the 24-month extension trials. Peak antibody levels across all groups were generally observed after 6–12 months of insulin therapy. Inhaled insulin therapy was not associated with a greater incidence of allergy or other hypersensitivity reactions.
Conclusion: Inhaled insulin was observed to produce a larger antibody response than sc insulin. Insulin antibody binding has not been associated with adverse clinical consequences in trials to date.
Two-dimensional echocardiography performed during dobutamine infusion has been proposed as a potentially useful method for detecting coronary artery disease. However, the safety and diagnostic value ...of dobutamine stress echocardiography has not been established.
In this study, echocardiograms were recorded during step-wise infusion of dobutamine to a maximum dose of 30 micrograms/kg/min in 103 patients who also underwent quantitative coronary angiography. The echocardiograms were digitally stored and displayed in a format that allowed simultaneous analysis of rest and stress images. Development of a new abnormality in regional function was used as an early end point for the dobutamine infusion. No patient had a symptomatic arrhythmia or complications from stress-induced ischemia. Significant coronary artery disease (greater than or equal to 50% diameter stenosis) was present in 35 of 55 patients who had normal echocardiograms at rest. The sensitivity and specificity of dobutamine-induced wall motion abnormalities for coronary artery disease was 89% (31 of 35) and 85% (17 of 20), respectively. The sensitivity was 81% (17 of 21) in those with one-vessel disease and 100% (14 of 14) in those with multivessel or left main disease. Forty-one of 48 patients with abnormal echocardiograms at baseline had localized rest wall motion abnormalities. Fifteen had coronary artery disease confined to regions that had abnormal rest wall motion, and 26 had disease remote from these regions. Thirteen of 15 patients (87%) without remote disease did not develop remote stress-induced abnormalities, and 21 of 26 (81%) who had remote disease developed corresponding abnormalities.
Echocardiography combined with dobutamine infusion is a safe and accurate method for detecting coronary artery disease and for predicting the extent of disease in those who have localized rest wall motion abnormalities.
Insulin lispro Lys (B28), Pro (B29) human insulin is a rapidly absorbed analog that has diminished tendency to self-associate. In four open-label, 1-year-long international randomized trials, we ...contrasted the immunogenicity of insulin lispro versus regular human insulin (RHI) in patients previously treated with insulin who had IDDM or NIDDM. Using a self-blank subtraction assay, we assessed sera for the presence of insulin-specific antibodies (ISA), insulin lispro-specific antibodies (LSA), and cross-reactive antibodies (CRA). Basal insulin needs were provided either with human ultralente (UL) or NPH insulins. After 2 to 4 weeks of therapy with RHI plus UL or RHI plus NPH, 50% of patients were randomly assigned to begin insulin lispro or continue on RHI. At baseline, few pretreated patients had LSA (0-4%) and approximately 10% had ISA, whereas 41-45% of patients with IDDM and 23-27% of patients with NIDDM had CRA (IDDM vs. NIDDM, P < 0.001). Within studies, no significant differences were noted over time in ISA, LSA, or CRA attributable to the type of short-acting insulin. When data were pooled, inconsistent changes were noted in ISA and LSA (LSA were greater in NIDDM vs. IDDM at baseline, P = 0.001, and ISA were greater in IDDM vs. NIDDM at 6 months, P = 0.007). Significant levels of CRA were more common in IDDM at all times (P < 0.001, P = 0.022, and P = 0.002 at baseline, 6 months, and 12 months, respectively). For patients receiving insulin lispro, no significant changes occurred in antibody status among IDDM and NIDDM patients throughout the study (became positive, remained positive, became negative, or remained negative). IDDM patients were more likely to develop or maintain CRA levels (P = 0.008 vs. NIDDM), whereas antibody levels were comparable among positive individuals. No evidence was noted that insulin lispro differs in immunogenicity from RHI in previously treated IDDM and NIDDM patients.
OBJECTIVE
To characterize the long-term impact of four hormone therapy regimens on insulin and glucose concentrations measured during a standard oral glucose tolerance test.
RESEARCH DESIGN AND ...METHODS
The Postmenopausal Estrogen/Progestin Intervention Study was a 3-year placebo-controlled randomized trial to assess effects of four hormone regimens on cardiovascular risk factors. This efficacy analysis describes glucose and insulin concentrations from 788 adherent women at baseline and at 1 and 3 years' postrandomization
RESULTS
When compared with women taking placebo, those taking conjugated equine estrogen (CEE) at 0.625 mg/day with or without a progestational agent had mean fasting insulin levels that were 16.1% lower, mean fasting glucose levels 2.2 mg/dl lower, and mean 2-h glucose levels 6.4 mg/dl higher (each nominal P < 0.05). No significant differences were apparent between women taking CEE only versus the three progestin regimens: medroxyprogesterone acetate (MPA) at 2.5 mg daily (continuous MPA), MPA at 10 mg on days 1–12 (cyclical MPA), and micronized progesterone (MP) (cyclical) at 200 mg on days 1–12. The impact of hormone therapy on insulin and glucose depended on baseline levels of fasting insulin and 1-h glucose (P < 0.05). However, the treatment effects on carbohydrate metabolism appeared to be consistent across participant subgroups formed by lifestyle, clinical, and demographic characteristics.
CONCLUSIONS
Oral hormone therapy involving 0.625 mg/day of CEE may modestly decrease fasting levels of insulin and glucose. Postchallenge glucose concentrations are increased, however, which may indicate delayed glucose clearance.
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