Self-care and health outcomes of diabetes mellitus.

Studies show that self-care improves diabetes mellitus (DM) outcomes; however, previous studies have focused on self-care maintenance, and little is known about self-care management. The objective of this study is to examine the influence of DM self-care maintenance and management on number of hospitalizations and hospitalization days. A cohort design with secondary analysis of data from the Health and Retirement Study 2002-2004 was used. Data from 726 adults with DM were analyzed with logistic regression and negative binomial regression adjusting for covariates. Self-care maintenance and management were significant determinants of hospitalization outcomes. Establishing a goal for HbA1c (self-care management) and eating ≥2 snacks or desserts per day (self-care maintenance) were associated with a decrease in hospitalizations (IRR = 0.860, p = .001; IRR = 0.914, p = .043, respectively). DM self-care maintenance and management influence health outcomes but in different ways. These data provide evidence that both elements are needed in the education of patients about DM.

Biomarkers of myocardial stress and systemic inflammation in patients who engage in heart failure self-care management.

BACKGROUND: Self-care is believed to improve heart failure (HF) outcomes, but the mechanisms by which such improvement occurs remain unclear. METHODS: We completed a secondary analysis of cross-sectional data collected on adults with symptomatic HF to test our hypothesis that effective self-care is associated with less myocardial stress and systemic inflammation. Multivariate logistic regression modeling was used to determine if better HF self-care reduced the odds of having serum levels of amino-terminal pro-B-type natriuretic peptide and soluble tumor necrosis factor α receptor type 1 at or greater than the sample median. Heart failure self-care was measured using the Self-care of Heart Failure Index. RESULTS: The sample (n=168) was predominantly male (65.5%), and most (50.6%) had New York Heart Association III HF (mean left ventricular ejection fraction, 34.9% [SD, 14.0%]); mean age was 58.8 (SD, 11.5) years. Self-care management was an independent factor in the model (block χ=14.74; P=.005) after controlling for pertinent confounders (model χ=52.15; P<.001). Each 1-point increase in self-care management score (range, 15-100) was associated with a 12.7% reduction in the odds of having levels of both biomarkers at or greater than the sample median (adjusted odds ratio, 0.873; 95% confidence interval, 0.77-0.99; P=.03). CONCLUSION: Better self-care management was associated with reduced odds of myocardial stress and systemic inflammation over and above pharmacological therapy and other common confounding factors. Teaching HF patients early symptom recognition and self-care of symptoms may decrease myocardial stress and systemic inflammation.

The influence of heart failure self-care on health outcomes: hypothetical cardioprotective mechanisms.

Lapses in self-care are commonly cited as a major cause of poor outcomes in persons with heart failure (HF). Not surprisingly, self-care is assumed to be central to improving health outcomes in this patient population. Empirically, however, this assumption is not well supported, and mechanistically, relationships between self-care and outcomes in HF have not yet been described. In this review, it is proposed that effective self-care maintenance (adherence) and self-care management (symptom evaluation and management) practices are complementary to optimal medical management in delaying HF progression and improving health outcomes in this population. Potential mechanisms through which effective HF self-care practices are complementary to pharmacological therapy in improving outcomes include (a) facilitating partial blockade and partial deactivation of deleterious neurohormones, (b) limiting inflammatory processes, (c) decreasing the need for administration of detrimental pharmacological agents, and (d) minimizing myocardial hibernation. Because these mechanisms are hypothetical, research findings are required to establish their validity. Several strategic research questions are proposed.

Current concepts of neurohormonal activation in heart failure: mediators and mechanisms.

Neurohormonal activation is a commonly cited array of phenomena in the body's physiologic response to heart failure. Although various neurohormones and pharmacologic agents that moderate their pathophysiologic effects have been reviewed in the nursing literature, both the mechanisms of neurohormonal system activation and cellular and organ system effects have been described only in brief. Accordingly, this article reviews mechanisms of neurohormonal activation and describes cellular and cardiovascular effects of the (1) sympathetic nervous system, (2) renin-angiotensin-aldosterone system, (3) kallikrein-kininogen-kinin system, (4) vasopressinergic system, (5) natriuretic peptide systems, and (6) endothelin in the context of heart failure. This article implicitly details the physiologic basis for numerous current and potential future pharmacologic agents used in the management of heart failure. It is intended that this article be used as a reference for advanced clinical nursing practice, research, and education.

Insulin sensitivity, food intake, and cravings with premenstrual syndrome: a pilot study.

OBJECTIVE: The objective of this pilot study was to evaluate possible differences in insulin sensitivity, food intake, and cravings between the follicular and luteal phases of the menstrual cycle in women with premenstrual syndrome (PMS). METHODS: Subjects were screened for PMS using the Penn Daily Symptom Rating (DSR) scale. Each subject had two overnight admissions (once in each cycle phase) to the Hospital of the University of Pennsylvania. They performed 3-day diet histories prior to each hospitalization. After admission, subjects received dinner and a snack, then were fasted until morning, when they underwent a frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity was determined by Minimal Model analysis. Blinded analysis of diet histories and inpatient food intake was performed by a registered dietitian. RESULTS: There was no difference found in insulin sensitivity between cycle phases (n = 7). There were also no differences in proportions of macronutrients or total kilocalories by cycle phase, despite a marked difference in food cravings between cycle phase, with increased food cravings noted in the luteal phase (p = 0.002). Total DSR symptom scores decreased from a mean of 186 (+/-29.0) in the luteal phase to 16.6 (+/-14.2) in the follicular phase. Women in this study consumed relatively high proportions of carbohydrates (55%-64%) in both cycle phases measured. CONCLUSIONS: These findings reinforce the suggestion that although the symptom complaints of PMS are primarily confined to the luteal phase, the neuroendocrine background for this disorder may be consistent across menstrual cycle phases.

Methods of measuring insulin sensitivity.

Insulin resistance is a component of several health disorders, most notably impaired glucose tolerance and type 2 diabetes mellitus. Insulin-resistant individuals have an impaired biological response to the usual action of insulin; that is, they have reduced insulin sensitivity. Various methods are used to assess insulin sensitivity both in individuals and in study populations. Validity, reproducibility, cost, and degree of subject burden are important factors for both clinicians and researchers to consider when weighing the merits of a particular method. This article describes several in vivo methods used to assess insulin sensitivity and presents the advantages and disadvantages of each.

Menstrual cycle effects on insulin sensitivity in women with type 1 diabetes: a pilot study.

BACKGROUND: Many women complain of difficulty maintaining euglycemia during the luteal phase of the menstrual cycle. This pilot study's objective was to evaluate possible differences in insulin sensitivity between follicular and luteal phases in women with type 1 diabetes. METHODS: Women using insulin infusion pumps (n = 5, mean age 29.2 +/- 10.9 years, mean body mass index 24 +/- 1.8 kg/m(2)) underwent frequently sampled intravenous glucose tolerance tests during each cycle phase. Insulin sensitivity and glucose effectiveness were determined by Minimal Model analysis. RESULTS: Non-insulin-mediated glucose disposal increased during the luteal phase (0.009 +/- 0.004 min(1)) versus the follicular phase (0.005 +/- 0.003 min(1)) (P < 0.05). Although no significant differences were found in mean insulin sensitivity between follicular (0.76 +/- 0.27 x 10(4)/min(1) /microU/mL) and luteal phase (0.58 +/- 0.26 x 10(4)/min(1) /microU/ mL), three of the five subjects had a decline in insulin sensitivity. CONCLUSIONS: Elevated blood glucose during the luteal phase may increase insulin-independent glucose disposal. Some individuals appear more responsive to menstrual cycle effects on insulin sensitivity. Women should be encouraged to use available self-monitoring technology to identify possible cyclical variations in blood glucose that might require clinician review and insulin dosage adjustments.

Hypoglycemia activates arousal-related neurons and increases wake time in adult rats.

Hypoglycemia resulting from excess of exogenous or endogenous insulin elicits central nervous system activation that contributes to counterregulatory hormone secretion. In adult humans without diabetes, hypoglycemia occurring during sleep usually produces cortical activation with awakening. However, in adult humans with type 1 diabetes, hypoglycemic arousal appears blunted or absent. We hypothesized that insulin injection sufficient to produce hypoglycemia would induce awakening in adult male rats. Polysomnographic studies were carried out to characterize the effect of insulin injection on measures of sleep and waking during a circadian time of increased sleep. Compared to a baseline day, insulin treatment more than doubled the time spent awake, from 18.4+/-2.6% after saline injection to 48.0+/-5.5% after insulin. Insulin injection also reduced rapid eye movement sleep (REMS) from 27.3+/-1.8% to 5.6+/-1.3%. The percent of time in non-REM sleep (NREMS) sleep was not different between saline and insulin days, however, NREMS after insulin was fragmented, with increased number and decreased duration of episodes. These electrophysiological data indicate that insulin-induced hypoglycemia is an arousing stimulus in rats, as in nondiabetic adult humans. We also studied the effect of insulin on activation of selected arousal-related neurons using immunohistochemical detection of Fos. Fos-immunoreactivity increased in orexin (OX) neurons after insulin, from 8.7+/-4.9% after saline injection to 37+/-9% after insulin. Basal forebrain cholinergic nuclei also showed increased Fos-immunoreactivity after insulin. These correlated behavioral and histological data provide targets for future studies of the neural pathways underlying hypoglycemic arousal.

From bedside to bench and back again: research issues in animal models of human disease.

To improve outcomes for patients with many serious clinical problems, multifactorial research approaches by nurse scientists, including the use of animal models, are necessary. Animal models serve as analogies for clinical problems seen in humans and must meet certain criteria, including validity and reliability, to be useful in moving research efforts forward. This article describes research considerations in the development of rodent models. As the standard of diabetes care evolves to emphasize intensive insulin therapy, rates of severe hypoglycemia are increasing among patients with type 1 and type 2 diabetes mellitus. A consequence of this change in clinical practice is an increase in rates of two hypoglycemia-related diabetes complications: hypoglycemia-associated autonomic failure (HAAF) and resulting hypoglycemia unawareness. Work on an animal model of HAAF is in an early developmental stage, with several labs reporting different approaches to model this complication of type 1 diabetes mellitus. This emerging model serves as an example illustrating how evaluation of validity and reliability is critically important at each stage of developing and testing animal models to support inquiry into human disease.

Cortical Fluoro-Jade staining and blunted adrenomedullary response to hypoglycemia after noncoma hypoglycemia in rats.

Intensive insulin therapy in patients with type 1 diabetes mellitus reduces long-term complications; however, intensive therapy is also associated with a three-fold increase in hypoglycemic episodes. The present study in conscious rats characterizes the physiologic and neuropathologic consequences of a single episode of moderate hypoglycemia. In this model, intravenous insulin is used to reduce plasma glucose to 30 to 35 mg/dL for 75 mins. This single hypoglycemic insult acutely induces hypoglycemia-associated autonomic failure (HAAF), with epinephrine responses to hypoglycemia reduced more than 36% from control. Neuropathology after this insult includes the appearance of dying cells, assessed with the marker Fluoro-jade B (FJ). After hypoglycemic insult, FJ+ cells were consistently seen in subdivisions of the medial prefrontal cortex, the orbital cortex, and the piriform cortex. There was a significant correlation between depth of hypoglycemia and number of FJ+ cells, suggesting that there is a critical threshold below which vulnerable cells begin to die. These data suggest that there is a population of cells that are vulnerable to moderate levels of hypoglycemia commonly experienced by patients with insulin-treated diabetes. These cells, which may be neurons, are primarily found in cortical regions implicated in visceral perception and autonomic control, raising the possibility that their loss contributes to clinically reported deficits in autonomic and perceptual responses to hypoglycemia.

Development of posttraumatic hyperthermia after traumatic brain injury in rats is associated with increased periventricular inflammation.

Posttraumatic hyperthermia (PTH) is a noninfectious elevation in body temperature that negatively influences outcome after traumatic brain injury (TBI). We sought to (1) characterize a clinically relevant model and (2) investigate potential cellular mechanisms of PTH. In study I, body temperature patterns were analyzed for 1 week in male rats after severe lateral fluid percussion (FP) brain injury (n=75) or sham injury (n=17). After injury, 27% of surviving animals experienced PTH, while 69% experienced acute hypothermia with a slow return to baseline. A profound blunting or loss of circadian rhythmicity (CR) that persisted up to 5 days after injury was experienced by 75% of brain-injured animals. At 2 and 7 days after injury, patterns of cell loss and inflammation were assessed in selected brain thermoregulatory and circadian centers. Significant cell loss was not observed, but PTH was associated with inflammatory changes in the hypothalamic paraventricular nucleus (PVN) by one week after injury. In brain-injured animals with altered CR, reactive astrocytes were bilaterally localized in the suprachiasmatic nucleus (SCN) and the PVN. Occasional IL-1beta+/ED-1+ macrophages/microglia were observed in the PVN and SCN exclusively in brain-injured animals developing PTH. In animals with PTH there was a significant positive correlation (r=0.788, P<0.01) between the degree of postinjury hyperthermia and the total number of cells positive for inflammatory markers within selected thermoregulatory and circadian nuclei. In study II, a separate group of animals underwent the same injury and temperature monitoring paradigm as in study I, but had additional physiologic data obtained, including vital signs, arterial blood gases, white blood cell counts, and C-reactive protein levels. All parameters remained within normal ranges after injury. These data suggest that PTH and the alteration in CR of temperature may be due, in part, to acute reactive astrocytosis and inflammation in hypothalamic centers responsible for both thermoregulation and CR.

Obesity-prone rats have preexisting defects in their counterregulatory response to insulin-induced hypoglycemia.

Rats that develop diet-induced obesity (DIO) on a 31% fat [high-energy (HE)] diet have defective sensing and responding to altered glucose levels compared with diet-resistant (DR) rats. Thus we postulated that they would also have defective counterregulatory responses (CRR) to insulin-induced hypoglycemia (IIH). Chow-fed selectively bred DIO and DR rats underwent three sequential 60-min bouts of IIH separated by 48 h. Glucose levels fell comparably, but DIO rats had 22-29% lower plasma epinephrine (Epi) levels during the first two bouts than DR rats. By the third trial, despite comparable Epi levels, DIO rats had lower 30-min glucose levels and rebounded less than DR rats 85 min after intravenous glucose. Although DIO rats gained more carcass and fat weight after 4 wk on an HE diet than DR rats, they were unaffected by prior IIH. Compared with controls, DR rats with prior IIH and HE diet had higher arcuate nucleus neuropeptide Y (50%) and proopiomelanocortin (POMC; 37%) mRNA and an inverse correlation (r = 0.85; P = 0.004) between POMC expression and body weight gain on the HE diet. These data suggest that DIO rats have a preexisting defect in their CRR to IIH but that IIH does not affect the expression of their hypothalamic neuropeptides or weight gain as it does in DR rats.

A single episode of central glucoprivation reduces the adrenomedullary response to subsequent hypoglycemia in rats.

Hypoglycemia-associated autonomic failure (HAAF) is a complication of recurrent hypoglycemia in patients with diabetes. The present experiments were performed to study the contribution of brain glucose-sensitive structures to HAAF. In conscious rats, brain glucoprivation was elicited by injection of 2 deoxy-D-glucose (2-DG) into the third cerebral ventricle (intracerebroventricular, ICV), while controls received saline ICV. Two days after ICV injection, hormone responses to systemic hypoglycemic challenge were measured. The epinephrine response 60 min after insulin injection was reduced by 46% in rats treated with prior ICV 2-DG, relative to saline-treated controls (SAL: 10,050+/-970 pg/ml; 2-DG: 5590+/-880 pg/ml). Thus, the adrenomedullary response to sustained hypoglycemia is attenuated after prior brain glucoprivation induced by intracerebroventricular injection of 2-DG. These data support the hypothesis that the brain contributes to the loss of responsiveness to repeated hypoglycemia that may ultimately result in HAAF.

Hyperthermia following traumatic brain injury: a critical evaluation.

Hyperthermia, frequently seen in patients following traumatic brain injury (TBI), may be due to posttraumatic cerebral inflammation, direct hypothalamic damage, or secondary infection resulting in fever. Regardless of the underlying cause, hyperthermia increases metabolic expenditure, glutamate release, and neutrophil activity to levels higher than those occurring in the normothermic brain-injured patient. This synergism may further compromise the injured brain, enhancing the vulnerability to secondary pathogenic events, thereby exacerbating neuronal damage. Although rigorous control of normal body temperature is the current standard of care for the brain-injured patient, patient management strategies currently available are often suboptimal and may be contraindicated. This article represents a compendium of published work regarding the state of knowledge of the relationship between hyperthermia and TBI, as well as a critical examination of current management strategies.