Smoking is not associated with autoantibody production in systemic lupus erythematosus patients, unaffected first-degree relatives, nor healthy controls.

OBJECTIVE: The objective of this paper is to examine whether smoking is associated with autoantibody production in systemic lupus erythematosus (SLE) patients, unaffected first-degree relatives (FDR) of individuals with SLE--a group at increased risk of developing SLE--or unaffected, unrelated controls. METHODS: Detailed demographic, environmental, clinical, and therapeutic information was collected by questionnaire on 1242 SLE patients, 981 FDRs, and 946 controls in the Lupus Family Registry and Repository; a blood sample was obtained. All sera were tested for multiple lupus autoantibodies by immunofluorescence and luminex bead-based assays. Generalized estimating equations, adjusting for age, gender, and ethnicity and accounting for correlation within families, were used to assess smoking status with the dichotomous outcome variables of positivity for SLE status, positivity of ANA by immunofluorescence (≥1:120), positivity for ≥1 autoantibody by the luminex assay, and positivity for each of the 11 autoantibodies. RESULTS: Current smoking was associated with being positive for ≥1 autoantibody (excluding ANA) (adjusted OR = 1.53, 95% CI 1.04-2.24) in our subjects with SLE. No association was observed in unaffected FDRs or healthy controls. Former smoking was associated with anti-Ro/SS-A60 in our unaffected FDRs. There was an increased association with anti-nRNP A seropositivity, as well as a decreased association with anti-nRNP 68 positivity, in current smokers in SLE subjects. CONCLUSIONS: No clear association between smoking status and individual autoantibodies was detected in SLE patients, unaffected FDRs, nor healthy controls within this collection. The association of smoking with SLE may therefore manifest its risk through mechanisms outside of autoantibody production, at least for the specificities tested.

Pain and depression predict self-reported fatigue/energy in lupus.

UNLABELLED: This study examined the contribution of pain and psychological distress to fatigue. METHODS: One-hundred and twenty-five adult Caucasian and Hispanic lupus patients participated in this study. Demographic data, patient- and physician-reported disease activity, as well as psychological functioning, were collected. Fatigue, pain, and vitality were measured using visual analogue scales as well as a subscale of the SF-36 questionnaire. Linear and hierarchical regression analyses were conducted. In the regression analysis, ethnicity was entered at the first step, followed by age, income and education at step 2, pain and disease activity measures at step 3, and psychological measurements at step 4. RESULTS: In the linear regression analysis, Caucasians reported more fatigue. Fatigue positively correlated with income, education, pain, patient-reported disease activity, helplessness, and depression, and negatively with internality, and the energy analysis mirrored the results of the fatigue analysis. In the first regression analysis, fatigue was the dependent variable. At step 1, Caucasians reported more fatigue. At step 2, no other demographic variables were significant. At step 3, pain and disease activity measures were significant when entered as a block; however, pain independently explained a large amount of variance. At step 4, psychological factors were significant as a block, with depression being the strongest predictor. In the second analysis, energy was the dependent variable. At step 1, Hispanics reported more energy. At step 2, demographic variables were not significant. At step 3, pain and disease activity were significant when entered as a block; however, only pain uniquely predicted energy. At step 4, psychological factors were significant as a block, with depression as the major contributor. CONCLUSIONS: Both pain and depression were found to be strong predictors of fatigue, and negatively correlated with energy. Disease activity did not appear to play a significant role in lupus fatigue. These findings support the importance of managing depression and pain in order to reduce fatigue in patients with systemic lupus erythematosus.

The Patient Reported Outcomes in Lupus (PATROL) study: role of depression in health-related quality of life in a Southern California lupus cohort.

UNLABELLED: This study examines the relationship between psychosocial factors, ethnicity, disease activity and quality of life in systemic lupus erythematosus. METHODS: One hundred and twenty-five adult Caucasian and Hispanic lupus patients were recruited from four Southern California medical centers. Linear regression analysis was performed to assess the correlation of ethnicity, socioeconomic factors (age, income), and disease activity (patient and physician reported), as well as psychological (depression, internality, helplessness) variables with quality of life (QOL) as measured by the Short Form (SF)-36. Hierarchical multiple regression analysis was then used to determine the stepwise contribution of the above determinants on the eight domains of the SF-36 questionnaire. RESULTS: Depression negatively correlated with QOL in both Caucasians (r -0.488 to -0.660) and Hispanics (r -0.456 to -0.723). Patient-reported disease activity was moderately related (r -0.456 to -0.698) to seven of the eight SF-36 domains in Hispanics, and none in Caucasians. Physician-reported disease activity, measured by SLEDAI, did not correlate with QOL among Hispanics or Caucasians. When linear and hierarchical regression was used, depression significantly correlated (p < 0.0001) with the majority of the SF-36 domains, except general health, while age had a significant effect in only one domain of the SF-36, physical functioning (p < 0.0001). CONCLUSION: Depression, and not disease activity, appears to have a major influence on quality of life in both Hispanic and Caucasian patients in this lupus cohort.

High-sensitivity C-reactive protein and erythrocyte sedimentation rate in systemic lupus erythematosus.

Levels of C-reactive protein (CRP) have been shown to rise in acute illnesses such as infections and some autoimmune diseases, but not in flares of systemic lupus erythematosus (SLE). Our goal was to investigate the high-sensitivity CRP (hsCRP) response to infection versus disease flare in patients with SLE, and to compare this with the erythrocyte sedimentation rate (ESR) response in these patients. We aimed to determine the hsCRP level that distinguishes between infection and flare in SLE, and investigated the correlation between hsCRP and organ involvement in SLE. We reviewed electronic medical records of all patients with SLE admitted to Cedars Sinai Medical Center between 28 August 2001 and 27 April 2008. Patients were divided into three groups based on the reason for hospitalization: (1) lupus flare; (2) active infection; and (3) both lupus flare and active infection. Data were collected on patient demographics, medication use, microbial culture results, organ involvement in lupus flare, ESR and CRP levels. Data were collected on 85 eligible patients, of whom 54 had a lupus flare, 22 had active infection and eight had both. While the ESR levels did not differ significantly between patients with disease flare and active infection, the hsCRP level was significantly lower in the lupus flare group than in the infection group. Most patients in the lupus flare group who had a significantly high hsCRP level had serositis. We found that at a cut-off of above 5 mg/dl, hsCRP level was correlated with infection with a specificity of 80%. At a cut-off of above 6 mg/dl, hsCRP correlated with infection with a specificity of 84%. hsCRP level was found to be significantly higher in patients with pulmonary involvement than without. hsCRP levels are significantly lower in SLE patients with disease flare than in those with active infection. Elevated hsCRP levels can be used as a predictor of active infection in SLE patients with a high specificity. We review the relationship between IL-6 and hsCRP production in lupus patients.

Depression predicts self-reported disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can significantly impact both physiological and psychological functioning. In order to examine the relationship between psychological functioning and disease activity in SLE, we administered instruments that collected sociodemographic information and measured indices of disease activity and psychosocial functioning from 125 adult Hispanic and White patients with SLE. Patients were recruited from four healthcare settings in the greater Southern California area. Both cross-sectional and longitudinal relationships between depression and disease activity were evaluated. Cross-sectional findings revealed that depression and ethnicity were independently correlated with self-reported disease activity. Longitudinally, depression alone predicted self-reported disease activity. These data suggest that depression may play a significant role in the health status of SLE patients and serve as an important target for clinical intervention.

Studies of Filipino patients with systemic lupus erythematosus: autoantibody profile of first-degree relatives.

This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1 : 40 to 1 : 160 (p < 0.001) and 1 : 320 (p = 0.003), anti-Ro/SSA (4.94% versus 0.45%, p = 0.003), and anti-dsDNA ≥ 5.0 IU/ml (4.58% versus 1.36%, p = 0.031). ANA titer ≥1 : 160, anti-dsDNA, anti-Ro/SSA and anti-chromatin had the highest predictive value for SLE diagnosis. These findings reinforce the role of genetic influence in SLE risk among Filipinos, with a significant proportion of un-affected FDRs of SLE patients testing positive for autoantibodies compared with healthy Filipino controls. A longitudinal observational study in this same cohort will determine which proportion of these un-affected FDRs will evolve into clinical SLE disease in the future.

Review: Male systemic lupus erythematosus: a review of sex disparities in this disease.

Although males with systemic lupus erythematosus (SLE) represent 4-22% of all SLE patients, it may not be appropriate that these cases should be subordinated to females with SLE in terms of most health-related issues. Over the past few decades, some distinctive features of male lupus have been observed with regard to genetic and environmental aspects of sex differences, clinical features, and outcome. In addition, recent insights into sex disparities in this disease have brought forth a few plausible and novel pathogenetic hypotheses. This review discusses these findings and sex disparities in SLE that appear to be especially noteworthy and pertinent to our understanding of male SLE.

Does mycophenolate mofetil prevent extra-renal flares in systemic lupus erythematosus? Results from an observational study of patients in a single practice treated for up to 5 years.

In this study, the clinical course and change in extra-renal manifestations of patients with SLE taking mycophenolate mofetil (MMF) were evaluated. The charts of 75 consecutively identified patients on MMF from a single practice were reviewed for demographics, dates of SLE diagnosis, initiation, indication or discontinuation of MMF and other medications. British Isles Lupus Assessment Group (BILAG) organ system data were identified for 3 months prior to MMF and then for the subsequent 5 years. BILAG scores for each organ system and an overall score were calculated for intervals of 6 months. The mean age of 75 subjects was 35.8 years with SLE mean disease duration of 99.2 months. Indications for starting MMF were renal (70.7%), musculoskeletal (10.6%), mucocutaneous (9.3%), cardiorespiratory (5.3%), haematologic (4%), vasculitic (2.7%), neurologic (1.3%) and other (18.7%). The mean duration of treatment was 3.3 years; 22 discontinuations occurred. Overall, there was a >50% improvement in composite BILAG scores for 49.3% (37/75) of patients in the first year of treatment and in 20% (15/75) of patients who were still on MMF at >or=5 years. Most flares occurred at second and third year of treatment. The general and renal systems have the most improvement and clinical remissions; the musculoskeletal, mucocutaneous and haematological systems have the most recurrences. Approximately, 50% and 20% of patients taking MMF showed improvement in overall lupus disease activity at both 1 and 5 years, respectively. When evaluating organ system subsets separately, MMF improved disease activity in the first year, but had little effect in preventing new organ-specific flares, with most flares taking place in second and third year of treatment.

The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic disease.

OBJECTIVE: The purpose of this study was to examine the safety and efficacy of anti-tumour necrosis factor (TNF) agents (etanercept, infliximab and adalimumab) in HIV-positive patients with rheumatic diseases refractory to standard therapy. METHODS: Patients were treated with anti-TNF blocker with rheumatic diseases refractory to disease modifying antirheumatic drugs who had a CD4 count of >200 mm3 and an HIV viral load of <60 000 copies/mm3 and no active concurrent infections. Changes in CD4 counts, HIV viral loads, or other adverse effects while on anti-TNF agents and clinical response were monitored for 28.1 (SD 20.9) months (range 2.5-55). RESULTS: Eight HIV-positive patients were treated with anti-TNF blockers (two patients with rheumatoid arthritis, three with psoriatic arthritis, one with undifferentiated spondyloarthritis, one with reactive arthritis and one with ankylosing spondylitis). No significant clinical adverse effect was attributed to this treatment in any patient. CD4 counts and HIV viral load levels remained stable in all patients. Three patients on etanercept therapy and two patients on infliximab had sustained clinical improvement in their rheumatic diseases. CONCLUSIONS: This retrospective series of eight patients suggests that treatment with anti-TNF-alpha therapy is a viable alternative in HIV patients without advanced disease with associated rheumatic diseases refractory to standard therapy.

The B cell in systemic lupus erythaematosus: a rational target for more effective therapy.

Current treatment options for systemic lupus erythaematosus (SLE) are diverse and poorly defined, and aggressive therapy can be associated with serious toxicity and tolerability issues. There is, therefore, a need for new and improved treatments to be studied thoroughly in well-designed controlled trials. B Cell dysfunction has emerged as a key pathophysiological component of SLE and is a prime target for the development of new agents for a wide range of lupus severity, including advanced disease. Although many current drugs appear to modify B cell function, the advent of new, targeted therapies offers the hope of improved efficacy and a better long-term tolerability profile.

Posterior reversible encephalopathy syndrome: another manifestation of CNS SLE?

A variety of neuropsychiatric findings may complicate systemic lupus erythematosus (SLE) and pose diagnostic and therapeutic dilemmas. We describe the clinical and radiographic features of posterior reversible encephalopathy syndrome (PRES) and distinguish PRES from other conditions seen in SLE. Patient charts and magnetic resonance imaging (MRI) findings of four patients with SLE on immunosuppressive therapy with acute or subacute neurologic changes initially suggesting cerebritis or stroke were reviewed. The English language literature was reviewed using the Medline databases from 1996-2006 for other reports of PRES with SLE. Literature review yielded 26 other SLE cases reported with PRES. SLE patients with PRES were more commonly on immunosuppressive drugs, had episodes of relative hypertension, and had renal involvement. Characteristic findings are seen on MRI, which differentiate PRES from other CNS complications of SLE. Clinical and radiographic resolution of abnormalities within 1-4 weeks is typically seen. PRES has been increasingly recognized. Reversible changes are found on brain MRI accompanied by sometimes dramatic signs and symptoms. The therapeutic implications for separating PRES from stroke or cerebritis are important. We propose that PRES should be considered in the differential diagnosis in SLE patients with new-onset neurologic signs and symptoms.

The lowest surviving birth weight reported in a systemic lupus erythematosus patient: a review of the literature.

The success rates for pregnancies in women with systemic lupus erythematosus (SLE) have improved over the years: however, pregnancy for women with active, serious, organ-threatening lupus continues to be a challenge. Preeclampsia and HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome may complicate pregnancy especially in the setting of advanced maternal age, underlying SLE and chronic renal disease. We report the pregnancy course and outcome for a 35-year old woman with active lupus nephritis at the time of conception who developed severe preeclampsia and HELLP syndrome. The infant was delivered at 26-5/7 weeks gestation, which, associated with intrauterine growth retardation, led to a birth weight of only 470 g. We have reviewed the relevant literature for similar cases of prematurity, very low birth weight, and preeclampsia in the setting of underlying lupus in Medline between 1986 and 2006. This report represents the lowest birth weight pregnancy survival in a lupus patient and the first case of a survival in the second trimester with preeclampsia and HELLP syndrome.

Morning granulocytopenia in a case of Graves' disease.

A 65-year-old woman with Graves' disease presented marked diurnal changes in white blood cell (WBC) and granulocyte counts. Granulocyte count was low and sometimes decreased to 0.2-0.3 x 10(9)/l in the early morning and increased in the afternoon irrespective of her thyroid status. She did not develop sore throat or fever during the investigation period. The present study indicates that these unusual diurnal changes in WBC and granulocyte counts should be considered in the differential diagnosis of agranulocytosis in Graves' disease patients treated with an antithyroid drug.

Differences in dietary habits, serum fatty acid compositions and other coronary risk characteristics between freshmen and fourth-year male university students.

Westernization of lifestyles among Japanese, in particular among young generations, is a matter of concern for future increase in coronary heart disease. We surveyed a total of 349 male university students to examine changes in lifestyles and coronary risk factors in campus life. We compared dietary habits and serum fatty acid compositions as well as other coronary risk characteristics between freshmen (n=171) and fourth-year (senior) students (n=178). Serum fatty acid compositions and dietary intakes of selected foods as well as serum lipids, blood pressures and physical characteristics were examined at the 1996 and 1997 annual health examinations.Compared to freshmen, senior students had a lower frequency of fish, vegetable, milk and egg intake, and a higher frequency of oil and fat intake. The proportions of serum saturated and monounsaturated fatty acids were significantly higher among senior students than among freshmen, whereas the proportion of serum polyunsaturated fatty acids was significantly lower among senior students than among freshmen. Senior students also had higher systolic and diastolic blood pressures, percent body fat, smoking rate and alcohol usage than freshmen. Mean body weight and mean body mass index were not different between the two groups.Senior students generally showed Westernized dietary habits and higher coronary risk profiles than freshmen as indicated by the change of serum fatty acid compositions. Modification of these dietary habits and lifestyles may be important for the prevention of future CHD among Japanese young adults.

Serum IgE response to orally ingested antigen: a novel IgE response model with allergen-specific T-cell receptor transgenic mice.

BACKGROUND: The mechanism by which orally ingested allergens elicit an IgE response remains unclear because there are few animal models available for investigation of this response. OBJECTIVE: We tried to develop a murine model suitable for investigation of the IgE response to orally ingested allergens, which would allow us to identify T cells that could promote IgE production. METHODS: Ovalbumin (OVA)-specific T-cell receptor transgenic mice were fed a diet containing OVA, and both the serum antibody response and cytokine production by splenocytes were examined. RESULTS: Oral administration of OVA to transgenic mice led to an increase in the levels of both antigen-specific IgE and total IgE in the sera. Subsequent intravenous challenge of OVA-fed transgenic mice with OVA resulted in anaphylactic shock. Analysis of cytokine production by splenocytes revealed that high IL-4-producing T cells appeared in the spleen 1 week after the start of feeding the OVA diet. T cells from these mice were found to promote IgE secretion by BALB/c B cells in vitro. This helper activity and the levels of IL-4 secretion were diminished after long-term feeding. These findings suggest the possibility that the orally ingested antigen elicited a response by a subpopulation of T cells that produce high levels of T(H2)-type cytokines and that promote IgE secretion, and these same T cells were tolerized by the orally ingested antigen. CONCLUSION: This experimental model with transgenic mice may be a useful tool for further studies of the cellular and molecular mechanisms of the T-cell and IgE responses to orally ingested antigens.

Effects of long-term interferon-alpha treatment on glucose tolerance in patients with chronic hepatitis C.

BACKGROUND/AIMS: Interferon-a has been reported to acutely induce insulin resistance and glucose intolerance. The effects of long-term treatment with interferon-a on glucose metabolism remain unclear. METHODS: Thirty-two Japanese patients with chronic hepatitis C were given interferon-a (6x10(6)U/day) daily for 2 weeks and thereafter 3 times weekly up to 6 months. The patients received a 75-g oral glucose tolerance test before the treatment. Fifteen patients also had an intravenous glucose tolerance test for an assessment of insulin sensitivity with Bergman's minimal model. These tests were repeated 3 months after the treatment. RESULTS: Insulin sensitivity was not affected by the treatment (5.7+/-3.8 vs 5.2+/-3.8 10(-4) x min(-1) x mU(-1) x l , not significant) and a statistically significant but minimum decrease in area under the curve of plasma glucose (1012+/-332 vs 928+/-282 mmol x l(-1) x min, p<0.01) in a 75-g oral glucose tolerance test was noted. Acute insulin response to intravenous glucose tolerance tests (214+/-275 vs 294+/-334 mU x l(-1) x min, p<0.05) increased slightly. CONCLUSION: Contrary to the known acute metabolic effects, interferon-a therapy for 3 months in patients with chronic hepatitis C did not have deleterious effects on insulin sensitivity and glucose tolerance.

Pharmacological treatments for GH-induced insulin resistance.

Troglitazone (T) and d-chiroinositol (DCI) have been reported to improve insulin resistance associated with obesity and NIDDM. We tested whether these compounds counteract the insulin antagonistic effects of recombinant human GH. Male Wistar rats were allocated to 4 different treatment groups, rhGH (n=8), rhGH+T (n=7), rhGH+DCI (n=8) and control (saline, n=8). rhGH (2 IU/100 g/day) was injected sc twice daily for 2 days. T and DCI were given (20 mg/day) po for 5 days preceding and 2 days along with rhGH. Euglycemic hyperinsulinemic clamp studies were done to assess the hepatic glucose output (HGO) and glucose disappearance rate (GDR). Fasting plasma glucose, insulin, serum FFA and basal HGO were similar in all 4 treatment groups. During the hyperinsulinemic clamp which raised plasma insulin levels to 7.2 +/- 0.4 ng/ml, HGO was suppressed in the control and rhGH+T treated rats but not in the rats treated with rhGH and rhGH+DCI. GDR decreased in the rats which received rhGH (18.1 +/- 5.8 vs 30.3 +/- 5.2 mg/kg/min) compared to the control rats. The rats given either T (24.7 +/- 2.7) or DCI (31.4 +/- 2.7) along with rhGH showed comparable GDR to the control rats. These results indicated that rhGH induced hepatic and peripheral insulin resistance. Troglitazone counteracted the insulin-antagonistic action of rhGH both in the liver and the peripheral tissues. DCI was effective in offsetting peripheral insulin resistance but without any effect on hepatic insulin resistance associated with rhGH treatment.

Effects of troglitazone on hepatic and peripheral insulin resistance induced by growth hormone excess in rats.

It is well known that short-term growth hormone (GH) administration in humans and animals induces insulin resistance and glucose intolerance. The purpose of the present study was to clarify whether troglitazone, a new insulin-sensitizing drug of the thiazolidinedione class, counteracts the insulin antagonistic effects of recombinant human (rh) GH on glucose metabolism in rats. Male Wistar rats weighing 184 to 226 g were treated either with rhGH (n = 8) or rhGH plus troglitazone (n = 8). rhGH (20 IU/kg body weight/d) was given by subcutaneous injection twice daily for 2 days. Troglitazone was given at 100 mg/kg/d orally for 5 days before and 2 days during rhGH. Saline was injected to the control rats (n = 7). Euglycemic clamp studies with an insulin infusion rate of 8 mU/kg/min were performed in these rats after an overnight fast. Hepatic glucose output (HGO), glucose infusion rate (GIR), and glucose disappearance rate (GDR) were measured. Fasting levels of plasma glucose (6.6 +/- 0.1, 6.1 +/- 0.3, 6.5 +/- 0.2 mmol/L), insulin (187.5 +/- 24.1, 206.4 +/- 24.1, 182.3 +/- 31.0 pmol/L), and serum free fatty acid (FFA) (1.58 +/- 0.18, 1.43 +/- 0.16, 1.61 +/- 0.25 mEq/L) were comparable among rats treated with rhGH, rhGH plus troglitazone, and controls, respectively. Basal HGO was also comparable among the three treatment groups. HGO was suppressed significantly during the hyperinsulinemic glucose clamp in control rats, but not in rhGH rats. When troglitazone was coadministered with rhGH, suppressibility of HGO during the glucose clamp was comparable to that of controls. GIR (13.5 +/- 4.5 v 24.1 +/- 4.1 mg/kg/min) and GDR (18.1 +/- 5.8 v 30.3 +/- 5.2 mg/kg/min) were decreased by rhGH treatment compared with control values. They returned to normal levels in rats treated with both rhGH and troglitazone (GIR, 22.4 +/- 5.9; GDR, 24.7 +/- 7.1). From these results, it is evident that rhGH treatment impaired insulin's ability to suppress HGO and stimulate peripheral glucose utilization. Troglitazone could block the insulin antagonistic effects of GH on hepatic glucose output and peripheral glucose utilization.

Effects of troglitazone on dexamethasone-induced insulin resistance in rats.

Troglitazone, a thiazolidinedione derivative, has been shown to counteract insulin resistance in obesity and non-insulin-dependent diabetes mellitus (NIDDM). To test its effects on dexamethasone-induced insulin resistance, we measured hepatic glucose production (HGP) and the insulin-stimulated glucose disposal rate (Rd) by a euglycemic-hyperinsulinemic glucose clamp technique coupled with 3-3H-glucose infusion in male Wistar rats treated with low-dose dexamethasone ([LoDex] 0.05 mg/kg/d, n = 7), high-dose dexamethasone ([HiDex] 0.1 mg/kg/d, n = 7), or dexamethasone plus troglitazone (LoDex + T, n = 8; HiDex + T, n = 6). Dexamethasone was injected subcutaneously for 4 days. Troglitazone was administered orally at 20 mg/d for 3 days before and for 4 days along with the dexamethasone treatment. The glucose clamp study was performed after an overnight fast in chronically catheterized conscious rats with a continuous insulin infusion of 57.4 pmol/kg/min. Basal HGP was comparable among the control (45.8 +/- 2.1 micromol/kg/min, n = 7), LoDex (47.9 +/- 4.7 micromol/kg/min), LoDex + T (46.0 +/- 2.6 micromol/kg/min), and HiDex + T (54.7 +/- 3.4 micromol/kg/min) groups. It increased about twofold in the HiDex group (80.1 +/- 5.2 micromol/kg/min, P < .05 v control). Under hyperinsulinemia, HGP was suppressed to a similar level in the control (11.3 +/- 8.8 micromol/kg/min), LoDex (10.2 +/- 8.4 micromol/kg/min), and LoDex + T (7.8 +/- 7.9 micromol/kg/min) groups. The suppressive effect of insulin on steady-state HGP during the clamp was impaired in HiDex (63.7 +/- 9.7 micromol/kg/min, P < .05) and HiDex + T (64.0 +/- 6.5 micromol/kg/min, P < .05). Rd decreased 27% in LoDex (81.5 +/- 5.8 micromol/kg/min, P < .05) and 36% in HiDex (71.3 +/- 9.4 micromol/kg/min, P < .05) compared with the controls (111.4 +/- 7.4 micromol/kg/min). Troglitazone prevented the decrease in Rd in LoDex + T (102.6 +/- 5.7 micromol/kg/min), but not in HiDex + T (67.0 +/- 6.4 micromol/kg/min). These results indicate that the development of peripheral insulin resistance was prevented by troglitazone in LoDex rats. Troglitazone may be a useful drug to treat steroid-induced diabetes.