Correlates of 1-Year Change in Quality of Life in Patients with Urologic Chronic Pelvic Pain Syndrome: Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

PURPOSE: We evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change. RESULTS: Physical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life. CONCLUSIONS: While several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.

Functional GI disorders: from animal models to drug development.

Despite considerable efforts by academic researchers and by the pharmaceutical industry, the development of novel pharmacological treatments for irritable bowel syndrome (IBS) and other functional gastrointestinal (GI) disorders has been slow and disappointing. The traditional approach to identifying and evaluating novel drugs for these symptom-based syndromes has relied on a fairly standard algorithm using animal models, experimental medicine models and clinical trials. In the current article, the empirical basis for this process is reviewed, focusing on the utility of the assessment of visceral hypersensitivity and GI transit, in both animals and humans, as well as the predictive validity of preclinical and clinical models of IBS for identifying successful treatments for IBS symptoms and IBS-related quality of life impairment. A review of published evidence suggests that abdominal pain, defecation-related symptoms (urgency, straining) and psychological factors all contribute to overall symptom severity and to health-related quality of life. Correlations between readouts obtained in preclinical and clinical models and respective symptoms are small, and the ability to predict drug effectiveness for specific as well as for global IBS symptoms is limited. One possible drug development algorithm is proposed which focuses on pharmacological imaging approaches in both preclinical and clinical models, with decreased emphasis on evaluating compounds in symptom-related animal models, and more rapid screening of promising candidate compounds in man.

Neural and psychological predictors of treatment response in irritable bowel syndrome patients with a 5-HT3 receptor antagonist: a pilot study.

BACKGROUND: Symptom improvement in irritable bowel syndrome (IBS) treatment trials varies widely, with only 50-70% of patients qualifying as responders. Factors predicting treatment responsiveness are not known, although we have demonstrated that symptom improvement with the 5-HT3R antagonist alosetron is correlated with reduced amygdala activity. AIM: To determine whether neural activity during rectal discomfort or psychological distress predicts symptom improvement following treatment with alosetron. METHODS: Basal psychological distress and neural activity (15O PET) during uncomfortable rectal stimulation were measured in 17 nonconstipated IBS patients who then received 3 weeks of alosetron treatment. RESULTS: Greater symptom improvement was predicted by less activity in bilateral orbitofrontal cortex (OFC) and medial temporal gyrus during pre-treatment scans. Lower levels of interpersonal sensitivity predicted greater symptom improvement and were positively related to activity in left OFC. Connectivity analysis revealed a positive relationship between activity in the left OFC and right amygdala. CONCLUSIONS: Irritable bowel disease symptom improvement with 5-HT3R antagonist alosetron is related to pre-treatment reactivity of the left OFC, which may be partially captured by subjective measures of interpersonal sensitivity. The left OFC may fail to modulate amygdala response to visceral stimulation, thereby diminishing effectiveness of treatment. Psychological factors and their neurobiological correlates are plausible predictors of IBS treatment outcome.

Resilience is decreased in irritable bowel syndrome and associated with symptoms and cortisol response.

BACKGROUND: Irritable bowel syndrome (IBS) is a stress-sensitive disorder associated with early adverse life events (EALs) and a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. Resilience is the ability to recover and adapt positively to stress but has not been well studied in IBS. The aims of this study are to compare resilience in IBS and healthy controls (HCs) and to assess its relationships with IBS symptom severity, quality of life (QOL), EALs, and HPA axis response. METHODS: Two hundred fifty-six subjects (154 IBS, 102 HCs) completed questionnaires for resilience (Connor-Davidson Resilience Scale [CD-RISC] and Brief Resilience Scale [BRS]), IBS symptoms, IBS-QOL, and EALs. Ninety-six of these subjects had serial serum adrenocorticotropic hormone (ACTH) and cortisol levels to exogenous corticotrophin-releasing hormone (CRH) and ACTH measured. The relationship between IBS status, resilience, and other variables of interest was assessed by regression analysis after adjusting for demographics and neuroticism, a predictor of resilience. KEY RESULTS: Resilience was significantly lower in IBS compared to HCs (CD-RISC: 72.16±14.97 vs 77.32±12.73, P=.003; BRS: 3.29±0.87 vs 3.93±0.69, P<.001); however, only BRS was significant after controlling for neuroticism (P=.001). Lower BRS scores were associated with greater IBS symptom severity (P=.002), poorer IBS-QOL (P<.001), and a higher number of EALs (P=.01). There was a significant interaction between BRS resilience and IBS status for ACTH-stimulated cortisol response (P=.031); more resilient IBS subjects had lower cortisol response, and more resilient HCs had higher cortisol response. CONCLUSIONS AND INFERENCES: Lower resilience is associated with IBS status, worse IBS symptom severity, lower IBS-QOL, greater EALs, and stress hyperresponsiveness.

Gene expression profiles in peripheral blood mononuclear cells correlate with salience network activity in chronic visceral pain: A pilot study.

BACKGROUND: Distinct gene expression profiles in peripheral blood mononuclear cells (PBMCs) consistent with increased sympathetic nervous system activity have been described in different populations under chronic stress. Neuroinflammatory brain changes, possibly related to the migration of primed monocytes to the brain, have been implicated in the pathophysiology of chronic pain. Irritable bowel syndrome (IBS) is a stress-sensitive gastrointestinal disorder associated with altered brain-gut interactions and increased sympathetic/vagal tone and anxiety. Reports about immune alterations in IBS are conflicting. This pilot study aimed to test how PBMC gene expression inflammatory profiles are correlated with altered brain signatures in the salience system. METHODS: Sixteen IBS and 16 healthy controls (HCs) completed resting state MRI scans. Gene expression profiles in PBMCs were assessed using human transcriptome array-2. Bioinformatic analyses determined differential expression of PBMCs between IBS and HCs. Partial least squares, a multivariate analysis technique, was used to identify disease correlations between PBMC gene expression profiles and functional activity in the brain's salience network. KEY RESULTS: Regions of the salience network, including the mid cingulate cortex, and mid and superior temporal gyrus were positively correlated with several pro-inflammatory genes (interleukin 6, APOL2) in IBS, but negatively correlated with several anti-inflammatory genes (KRT8, APOA4) in HCs. CONCLUSIONS & INFERENCES: Based on rodent studies, one may speculate that chronically activated stress signaling pathways in IBS maintain a pro-inflammatory state in the periphery. Alternatively, primed monocytes may migrate to the brain during stress, inducing regional neuroinflammatory changes in salience regions involved in the modulation of visceral sensitivity.

Relationships of abdominal pain, reports to visceral and temperature pain sensitivity, conditioned pain modulation, and heart rate variability in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition with a number of pathophysiological mechanisms that appear to contribute to symptom chronicity. One of these is altered pain sensitivity. METHODS: Women between ages 18-45 were recruited the community. Of those enrolled, 56 had IBS and 36 were healthy control (HC) women. Participants completed questionnaires, kept a 4-week symptom diary and had a 12-h Holter placed to assess nighttime heart rate variability including high frequency power (HF), low frequency power (LF), and total power (TP). At mid-follicular phase approximately 80% of women completed a thermal pain sensitivity test with conditioned pain modulation and visceral pain sensitivity using a water load symptom provocation (WLSP) test. KEY RESULTS: As expected, daily abdominal pain was significantly higher in the IBS compared to HC group. There were no differences between the bowel pattern subgroups (IBS-diarrhea [IBS-D], IBS-constipation plus mixed [IBS-CM]). Thermal pain sensitivity did not differ between the IBS and the HC groups, but was significantly higher in the IBS-CM group than the IBS-D group. In the WLSP test, the IBS group experienced significantly more symptom distress than HCs and the IBS-CM group was higher than the IBS-D group. Heart rate variability indicators did not differ between the groups or IBS subgroups. Daily abdominal pain was positively correlated with LF and TP in the IBS group. CONCLUSIONS & INFERENCES: Despite similar levels of abdominal pain in IBS, the IBS-CM group demonstrated greater sensitivity to both thermal and visceral testing procedures.

Beat-to-beat blood pressure response in asymptomatic IDDM subjects.

Nine insulin-dependent diabetic (IDDM) patients (aged 25-37 yr) with no symptoms of autonomic neuropathy and 15 healthy control subjects (aged 26-39 yr) were studied at rest and during tests of Valsalva maneuver, deep breathing, cold pressor, and postural change from sitting to standing. Continuous (beat-to-beat) measures were taken of heart rate, systolic blood pressure, diastolic blood pressure, and skin conductance. The diabetic patients were differentiated from the control group by the following: less variability in diastolic blood pressure during deep breathing, failure to exhibit diastolic blood pressure decreases during recovery from a cold pressor stimulus, a flatter blood pressure response pattern when changing from sitting to standing, and a smaller standing ratio (maximum/minimum) for R-R interval. Among the patients, age was negatively correlated with systolic and diastolic standing ratios and diastolic blood pressure variability during deep breathing. By use of the tracking cuff, a method of continuously recording blood pressure noninvasively, we have been able to assess subtle blood pressure changes, thereby revealing signs of sympathetic dysfunction in a group of relatively young diabetic patients with no symptoms of neuropathy. The tracking-cuff method of recording blood pressure has potential in further research on autonomic functioning in diabetic patients.

Hospitalization and mortality of diabetes in older adults. A 3-year prospective study.

OBJECTIVE: In light of increased fatality from acute events and the increased frequency of chronic complications, life expectancy might well be shortened in older patients with diabetes. The current studies investigated factors affecting the likelihood of dying or being hospitalized in older patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 135 older patients with diabetes were followed for 3 years after predictive factors were evaluated and compared with a cohort of patients without diabetes. RESULTS: Mortality was only 3,250 per 100,000 patient-years, similar to that for patients without diabetes, but the frequency of hospitalizations was more than twice as high in patients with diabetes. Five factors predicted hospitalization and death. Of these, the geriatric depression score was the best predictor of these poor outcomes. CONCLUSIONS: Older patients with diabetes were hospitalized more often than those without diabetes, but mortality was similar. Dysphoria is a major predictor of poor outcomes in older patients with diabetes.

Increased attentional network functioning related to symptom severity measures in females with irritable bowel syndrome.

BACKGROUND: Increased attention to gastrointestinal (GI) symptoms and disease-specific contexts may play an important role in the enhanced perception of visceral stimuli frequently reported in patients with irritable bowel syndrome (IBS). In this study, we test the hypothesis that altered attentional mechanisms underlie central pain amplification in IBS. METHODS: To evaluate brain networks that support alerting, orienting, and executive attention, we employed the attention network test (ANT), a modified flanker task which measures the efficiency of functioning of core attentional networks, during functional magnetic resonance imaging in 15 IBS patients (mean age = 31 [11.96]) and 14 healthy controls (HCs; mean age = 31 [10.91]). KEY RESULTS: Patients with IBS, compared to HCs, showed shorter reaction times during the alerting and orienting conditions which were associated with greater activation of anterior midcingulate and insular cortices, and decreased activity in the right inferior frontal junction and supplementary motor cortex. Patients also showed activation in the dorsal medial prefrontal cortex and concurrent thalamic deactivation during the executive control portion of the ANT relative to HCs, but no group difference in reaction times were found. The activity in brain regions showing group differences during the ANT were associated with measures of GI-specific anxiety, pain catastrophizing, and fear of uncertainty. In IBS, activity in the anterior midcingulate during alerting correlated with duration of GI-symptoms and overall symptom severity. CONCLUSIONS & INFERENCES: Together, these results suggest that IBS patients have specific abnormalities in attentional network functioning and these deficits may underlie symptom-related anxiety, hypervigilance, and visceral hypersensitivity.

Measurement of symptoms in irritable bowel syndrome clinical trials.

Irritable bowel syndrome (IBS) is a chronic disorder with symptoms that range in intensity from mild and infrequent to severe and continuous. A variety of approaches to symptom assessment are used in IBS, although there is little literature directly comparing or validating them. Determining the presence or absence of specific symptoms is the primary focus of diagnostic evaluation and categorization. In contrast, outcome assessment usually entails assessment of symptom severity. Symptom severity scales can themselves vary on a wide range of factors, including specificity (pain, discomfort, gastrointestinal problem), scaling properties (numerical, analogue, or descriptor), range (usual, highest, lowest), time frame (now, past week), response category (intensity, unpleasantness, change, relief), and use of modifying variables (frequency, impact, location). The measurement properties of similar symptom scales have been investigated more extensively in the context of somatic pain, and these studies will be reviewed in suggesting some guidelines for IBS symptom assessment in clinical trials.

The Visceral Sensitivity Index: development and validation of a gastrointestinal symptom-specific anxiety scale.

BACKGROUND: Anxiety related to gastrointestinal sensations, symptoms or the contexts in which these may occur is thought to play a significant role in the pathophysiology as well as in the health outcomes of patients with irritable bowel syndrome. AIM: To develop a valid and reliable psychometric instrument that measures gastrointestinal symptom-specific anxiety. METHODS: External and internal expert panels as well as a patient focus group evaluated a large pool of potential item stems gathered from the psychological and gastrointestinal literature. Potential scale items were then administered to 96 patients diagnosed with irritable bowel syndrome along with a set of validating questionnaires. Final item selection was based upon rigorous empirical criteria and the psychometric properties of the final scale were examined. RESULTS: A final unidimensional 15-item scale, the Visceral Sensitivity Index, demonstrated excellent reliability as well as good content, convergent, divergent and predictive validity. CONCLUSIONS: The findings suggest that the Visceral Sensitivity Index is a reliable, valid measure of gastrointestinal symptom-specific anxiety that may be useful for clinical assessment, treatment outcome studies, and mechanistic studies of the role of symptom-related anxiety in patients with irritable bowel syndrome.

The effect of the 5-HT3 receptor antagonist, alosetron, on brain responses to visceral stimulation in irritable bowel syndrome patients.

AIM: To conduct a placebo-controlled functional brain imaging study to assess the effect of the 5-hydroxytryptamine-3 receptor antagonist, alosetron, on irritable bowel syndrome symptoms, regional brain activation by rectosigmoid distension and associated perceptual and emotional responses. METHODS: Fifty-two non-constipated irritable bowel syndrome patients (28 female) were enrolled in a randomized, placebo-controlled trial with alosetron (1-4 mg b.d.). Thirty-seven patients completed both brain scans following randomization. Rectosigmoid stimulation was performed with a computer-controlled barostat. Changes in regional cerebral blood flow were assessed using H215O positron emission tomography. Stimulus ratings and changes in gastrointestinal symptoms were assessed using verbal descriptor scales. RESULTS: Alosetron, but not placebo, treatment was associated with a decrease in symptom ratings, and reductions in emotional stimulus ratings. Compared to baseline, alosetron treatment was associated with reduced regional cerebral blood flow in bilateral frontotemporal and various limbic structures, including the amygdala. Compared to placebo, decreases in activity of the amygdala, ventral striatum, hypothalamus and infragenual cingulate gyrus were significantly greater after alosetron. CONCLUSIONS: In non-constipated irritable bowel syndrome patients, 3 weeks of treatment with a 5-hydroxytryptamine-3 receptor antagonist decreases brain activity in response to unanticipated, anticipated and delivered aversive rectal stimuli in structures of the emotional motor system, and this is associated with a decrease in gastrointestinal symptoms.

Depression, anxiety, and the gastrointestinal system.

Functional disorders of the digestive system, such as irritable bowel syndrome, are often associated with affective disorders, such as depression, anxiety, panic, and posttraumatic stress disorder (PTSD). Some of these associations are observed not only in clinical populations, but also in population-based samples, suggesting a relationship with pathophysiologic mechanisms underlying both gastrointestinal (GI) dysfunction and certain affective disorders. Sustained and acute life-threatening stressors play an important role in the onset and modulation of GI symptoms as well as in the development of affective disorders and PTSD. A neurobiological model is proposed that attempts to explain the development of visceral hypersensitivity, the neuroendocrine and autonomic dysfunction characteristic of functional GI disorders, as well as the overlap with affective disorders.

Effects of age on complications in adult onset diabetes.

The prevalence of diabetes is greatest among older persons, yet few studies have specifically addressed the impact of age on diabetic complications. The present study examines the prevalence of four diabetic complications: retinopathy, peripheral neuropathy, autonomic neuropathy, and hypertension, as well as depression, in older male patients with noninsulin-dependent diabetes. Participants ranged in age from 53 to 80 years. Multiple risk factors, including age, duration of illness, type of treatment, metabolic control, and obesity were evaluated as predictors of these complications using logistic regression. Results suggest a significant increase in the prevalence of retinopathy with aging, independent of the effects of metabolic control, duration of illness, and other risk variables. Age was also related to prevalence of peripheral neuropathy symptoms, hypertension, and impotence. Current metabolic control was significantly associated with retinopathy, peripheral neuropathy, and hypertension prevalence. Time since diagnosis was only independently related to impotence and hypertension. These findings suggest that the increase in many diabetic complications in older persons cannot be wholly accounted for by simple disease status variables, and may result from an interaction of diabetes variables and general age-related changes.

Acute autonomic responses to postural change, Valsalva maneuver, and paced breathing in older type II diabetic men.

PURPOSE: To examine the effects of advanced age and diabetes on the response to standard tests of cardiovascular reflexes. DESIGN: Group comparison. SETTING: Psychophysiology laboratory, Department of Veterans Affairs Medical Center. PATIENTS: Sixteen elderly male (67-81 years old) non-insulin dependent diabetic subjects without hypertension and nine elderly male (63-77 years old) controls. MAIN OUTCOME MEASURES: Continuous (beat-by-beat) measures of heart rate, systolic blood pressure, diastolic blood pressure, and skin conductance were studied during tests of Valsalva maneuver, deep breathing, and postural change from sitting to standing. RESULTS: In comparison with elderly controls, the diabetic patients showed altered cardiovascular responses in measures of heart rate variability during Valsalva and standing. None of the subjects evidenced frank postural hypotension, but there was a greater fall in diastolic blood pressure immediately after standing for the diabetic patients compared with the controls. There was also a significant relationship between this response and decreased heart rate variability during Valsalva. CONCLUSIONS: Older type II diabetic patients compared with healthy controls had mild cardiovascular abnormalities. These results parallel those of studies comparing younger diabetics and controls.

Effects of bovine prostate powder on zinc, glucose, and insulin metabolism in old patients with non-insulin-dependent diabetes mellitus.

Since rabbit prostate extract strongly stimulated intestinal zinc absorption and improved the diabetic condition of streptozotocin-induced diabetic rats, we examined the effects of 200 mg bovine prostate powder supplemented with 20 mg zinc (Pro-Z) on the clinical manifestations of older male patients with type II diabetes. Twenty-two male patients who received Pro-Z capsules two to four times per day for 3 months showed reduced mean fasting blood glucose levels from 202 to 169 mg/dL, hemoglobin A1C-(HbA1C) concentrations from 12.2% to 9.5%, and mean values for the 3-hour area response above the fasting glucose concentration (TAFGC) from 141 to 102 mg glucose/dL/h. In eighteen patients who received placebo, mean values for fasting blood glucose decreased from 167 to 165 mg/dL and HbA1C from 10.4% to 10.2%, and for TAFGC increased from 121 to 126 mg glucose/dL/h. No detrimental changes occurred in the liver and kidney function of patients receiving either Pro-Z or placebo. However, blood cholesterol and low-density lipoprotein in patients receiving Pro-Z decreased slightly, whereas values in the placebo group tended to increase. The mean fasting plasma insulin decreased 15.5 to 13.8 microU/mL in subjects given Pro-Z, while the zinc concentration increased from 1.21 to 1.39 microg/mL. In contrast, the mean value for plasma insulin in the placebo group changed from 14.4 to 15.4 microU/mL (worsened), and for zinc, from 1.24 to 1.30 microg/ml. Interestingly, fasting urinary glucose concentrations in subjects given Pro-Z decreased from 1,249 to 378 mg/dL, whereas in those given placebo the values changed from 877 to 778 mg/dL. Since plasma zinc concentrations in both the placebo and the Pro-Z group were normal, these results suggest that biochemical constituents in the prostate including zinc may be involved in controlling glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

History of physical and sexual abuse in women with chronic pelvic pain.

The history of physical and sexual abuse in childhood and adulthood was assessed in 31 women with chronic pelvic pain, 142 women with chronic pain in other locations, and 32 controls. Thirty-nine percent of patients with chronic pelvic pain had been physically abused in childhood. This percentage was significantly greater than that observed in other chronic-pain patients (18.4%) or controls (9.4%), though the prevalence of childhood sexual abuse did not differ among the groups (19.4, 16.3, and 12.5%, respectively). Abuse in adulthood was less common and was not significantly more likely to have occurred in patients with chronic pelvic pain than in other chronic-pain patients or controls. These data suggest that pelvic pain is unlikely to be specifically and psychodynamically related to sexual abuse but that the pernicious nature of abuse, whether physical or sexual, may promote the chronicity of painful conditions.

Gender differences in regional brain response to visceral pressure in IBS patients.

In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed.

Mental and physical stress as moderators of the postural response in insulin-dependent diabetic patients.

Two simple stressors, mental arithmetic and isometric handgrip, were studied as moderators of the physiological response to standing in insulin-dependent diabetic patients and in healthy controls. Continuous (beat-to-beat) measures were taken of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and skin conductance (SC) during postural change under baseline and stressor conditions. Diabetic patients without symptoms of neuropathy and healthy controls showed generally similar responses to postural change and to the stressor conditions. SBP and DBP were more responsive to the mental and physical stressors than were HR or SC, especially after standing. Two diabetic patients with postural hypotension showed significant increases in overall BP levels and less of a fall in BP during postural change under the stressor conditions, despite minimal HR or SC responses. Results indicate that these strategies are effective in increasing BP during postural change in both diabetic and nondiabetic individuals and may be useful in the management of orthostatic hypotension.

Physiological and metabolic responses to brief stress in non-insulin dependent diabetic and control subjects.

Eight non-insulin dependent diabetic subjects and eight controls were studied during physical and psychological stress. Physiological measures of heart rate, finger pulse amplitude and blood pressure, as well as metabolic measures of blood glucose, insulin, catecholamines and glucagon were sampled during the experiment. Results indicate substantial physiological arousal during the tasks for both groups, but no changes in blood glucose. Despite signs of mild autonomic neuropathy, the diabetic subjects showed responses similar to the controls on the stress tasks. Overall, this study suggests that diabetic instability does not necessarily follow from physiological activity and stress hormone elevations.