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Singapore managed the COVID-19 pandemic in the past three years and gleaned valuable lessons on patient management when the public healthcare system was inundated with COVID-19 patients. There were several initiatives, which included setting up of community treatment facilities to help hospitals manage in-patient loads that did not require acute monitoring, leveraging telemedicine, and developing heuristics to sort patients based on their clinical disposition to various care pathways and to effectively manage patients of different medical needs. These initiatives were implemented in the second year of the epidemic in 2021 and did not include the dormitory-based migrant workers and migrant workers in the construction, maritime and production sectors who were under the care of the Assurance, Care and Engagement Group (ACE) in the Ministry of Manpower that had its own set of treatment management measures. The different care pathways ensured that patients received appropriate levels of care and allowed healthcare facilities to focus on more acute cases. In 2022 alone, 23,159 patients were discharged from community treatment facilities against the background of 1.9 million COVID-19 patients. These initiatives would not be possible without the oversight of an advisory board comprising senior leadership from the healthcare clusters and the Ministry of Health to align clinical governance with medical policies, and prompt and immense support from medical specialist panels. The strong public-private partnership forged in the process was instrumental in the successful operation of community facilities and implementation of patient care protocols, coupled with harnessing information technology and leveraging on emerging data to refine care protocols.

Introduction: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically., Methods: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups., Results: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups (P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life., Conclusions: RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients., Competing Interests: None

Background: The popular statistics-based Genome-wide association studies (GWAS) have provided deep insights into the field of complex disorder genetics. However, its clinical applicability to predict disease/trait outcomes remains unclear as statistical models are not designed to make predictions. This study employs statistics-free machine-learning (ML)-optimized polygenic risk score (PRS) to complement existing GWAS and bring the prediction of disease/trait outcomes closer to clinical application. Rheumatoid Arthritis (RA) was selected as a model disease to demonstrate the robustness of ML in disease prediction as RA is a prevalent chronic inflammatory joint disease with high mortality rates, affecting adults at the economic prime. Early identification of at-risk individuals may facilitate measures to mitigate the effects of the disease., Methods: This study employs a robust ML feature selection algorithm to identify single nucleotide polymorphisms (SNPs) that can predict RA from a set of training data comprising RA patients and population control samples. Thereafter, selected SNPs were evaluated for their predictive performances across 3 independent, unseen test datasets. The selected SNPs were subsequently used to generate PRS which was also evaluated for its predictive capacity as a sole feature., Results: Through robust ML feature selection, 9 SNPs were found to be the minimum number of features for excellent predictive performance (AUC > 0.9) in 3 independent, unseen test datasets. PRS based on these 9 SNPs was significantly associated with (P < 1 × 10 -16 ) and predictive (AUC > 0.9) of RA in the 3 unseen datasets. A RA ML-PRS calculator of these 9 SNPs was developed ( https://xistance.shinyapps.io/prs-ra/ ) to facilitate individualized clinical applicability. The majority of the predictive SNPs are protective, reside in non-coding regions, and are either predicted to be potentially functional SNPs (pfSNPs) or in high linkage disequilibrium (r2 > 0.8) with un-interrogated pfSNPs., Conclusions: These findings highlight the promise of this ML strategy to identify useful genetic features that can robustly predict disease and amenable to translation for clinical application., (© 2023. The Author(s).)

Objective: To develop a hypothesis-free model that best predicts response to MTX drug in RA patients utilizing biologically meaningful genetic feature selection of potentially functional single nucleotide polymorphisms (pfSNPs) through robust machine learning (ML) feature selection methods., Methods: MTX-treated RA patients with known response were divided in a 4:1 ratio into training and test sets. From the patients' exomes, potential features for classifier prediction were identified from pfSNPs and non-genetic factors through ML using recursive feature elimination with cross-validation incorporating the random forest classifier. Feature selection was repeated on random subsets of the training cohort, and consensus features were assembled into the final feature set. This feature set was evaluated for predictive potential using six ML classifiers, first by cross-validation within the training set, and finally by analysing its performance with the unseen test set., Results: The final feature set contains 56 pfSNPs and five non-genetic factors. The majority of these pfSNPs are located in pathways related to RA pathogenesis or MTX action and are predicted to modulate gene expression. When used for training in six ML classifiers, performance was good in both the training set (area under the curve: 0.855-0.916; sensitivity: 0.715-0.892; and specificity: 0.733-0.862) and the unseen test set (area under the curve: 0.751-0.826; sensitivity: 0.581-0.839; and specificity: 0.641-0.923)., Conclusion: Sensitive and specific predictors of MTX response in RA patients were identified in this study through a novel strategy combining biologically meaningful and machine learning feature selection and training. These predictors may facilitate better treatment decision-making in RA management., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Major challenges in large scale genetic association studies include not only the identification of causative single nucleotide polymorphisms (SNPs), but also accounting for SNP-SNP interactions. This study thus proposes a novel feature engineering approach integrating potentially functional coding haplotypes (pfcHap) with machine-learning (ML) feature selection to identify biologically meaningful, possibly causative genetic factors, that take into consideration potential SNP-SNP interactions within the pfcHap, to best predict for methotrexate (MTX) response in rheumatoid arthritis (RA) patients., Methods: Exome sequencing from 349 RA patients were analysed, of which they were split into training and unseen test set. Inferred pfcHaps were combined with 30 non-genetic features to undergo ML recursive feature elimination with cross-validation using the training set. Predictive capacity and robustness of the selected features were assessed using six popular machine learning models through a train set cross-validation and evaluated in an unseen test set., Findings: Significantly, 100 features (95 pfcHaps, 5 non-genetic factors) were identified to have good predictive performance (AUC: 0.776-0.828; Sensitivity: 0.656-0.813; Specificity: 0.684-0.868) across all six ML models in an unseen test dataset for the prediction of MTX response in RA patients., Interpretation: Majority of the predictive pfcHap SNPs were predicted to be potentially functional and some of the genes in which the pfcHap resides in were identified to be associated with previously reported MTX/RA pathways., Funding: Singapore Ministry of Health's National Medical Research Council (NMRC) [NMRC/CBRG/0095/2015; CG12Aug17; CGAug16M012; NMRC/CG/017/2013]; National Cancer Center Research Fund and block funding Duke-NUS Medical School.; Singapore Ministry of Education Academic Research Fund Tier 2 grant MOE2019-T2-1-138., Competing Interests: Declaration of Competing Interest CGL, KPL, CCK, SSC, AJWL, and LJL declare that they have a pending Coversheet IP application., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: We evaluated the impact of type 2 diabetes mellitus (T2DM) on RA treatment and outcomes in a longitudinal RA cohort., Methods: We analysed data collected in the period 2001-2013 involving 583 RA patients, including demographics, diabetes diagnosis, clinical features, treatment, ACR functional class, HAQ, and quality-of-life measurement using the Short-Form 36., Results: Seventy-seven (13.2%) of the RA patients had T2DM. DAS28 was not different in patients with T2DM at 5 years post-RA diagnosis. Fewer T2DM patients received MTX than those without T2DM (51% vs 80%, P < 0.001). Using univariate analysis, T2DM patients were more likely to experience poorer outcomes in terms of ACR functional status ( P = 0.009), joint surgery ( P = 0.007), knee arthroplasty ( P < 0.001) and hospital admissions ( P = 0.006). Multivariate regression analyses showed more knee arthroplasty ( P = 0.047) in patients with T2DM., Conclusion: Fewer patients with T2DM received MTX compared with those without T2DM. Patients with RA and T2DM were at higher risk of knee arthroplasty than RA patients without T2DM., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: This study aims to uncover variants of large effect size and allele frequency below 5% by sequencing all extant genes associated with rheumatoid arthritis (RA) in a homogeneous patient cohort., Patients and Methods: This retrospective study was conducted between January 2001 and December 2017. We selected Chinese RA patients positive for anti-citrullinated peptide antibody (ACPA). All the 128 known candidate genes identified through genome-wide association studies were sequenced in 48 RA patients (15 males, 33 females; mean age 53.32±8.98 years; range, 32 to 75 years) and 45 controls (11 males, 34 females; mean age 32.18±9.54; range, 21 to 57 years). The exonic regions of these genes were sequenced. The resultant data were analyzed for association using single variant association and pathway-based association enrichment tests. The genetic burden due to low-frequency variants was assessed with the C-alpha test. The candidate variants that showed significant association were validated in a larger cohort of 500 RA cases (71 males, 429 females; mean age 48.6±12.2 years; range, 24 to 92 years) and 500 controls (66 males, 434 females; mean age 32.3±10.1 years; range, 21 to 73 years)., Results: Thirty-nine variants in 21 genes were identified using single variant association analysis and C-alpha test, with stepwise filtering. Among these, the missense variant in interleukin-6 signal transducer (IL-6ST) 5:55260065 (p.Cys47Phe) was significantly associated with RA in Chinese patients in Singapore., Conclusion: Our results suggest that a mutation in IL-6ST (5:55260065) confers risk of RA in Chinese patients in Singapore., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2021, Turkish League Against Rheumatism.)

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. Existing feature selection methods perform inconsistently across datasets, occasionally even resulting in poorer clustering accuracy than without feature selection. Moreover, existing methods ignore information contained in gene-gene correlations. Here, we introduce DUBStepR (Determining the Underlying Basis using Stepwise Regression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. Additionally, DUBStepR was the only method to robustly deconvolve T and NK heterogeneity by identifying disease-associated common and rare cell types and subtypes in PBMCs from rheumatoid arthritis patients. DUBStepR is scalable to over a million cells, and can be straightforwardly applied to other data types such as single-cell ATAC-seq. We propose DUBStepR as a general-purpose feature selection solution for accurately clustering single-cell data., (© 2021. The Author(s).)

Objective: Disease activity indices for rheumatoid arthritis (RA) are important in clinical practice and research. Although they are closely correlated, they are not in good agreement. We derived formulae to convert values from one of the four 28-joint count indices (disease activity score using erythrocyte sedimentation rate [DAS28-ESR], disease activity score using C-reactive protein [DAS28-CRP], clinical disease activity index [CDAI], and simple disease activity index [SDAI]) to any of the others., Methods: We obtained data from 175 patients from our RA registry with concurrent CRP and ESR and established the nature of relationships between the indices using these data. Subsequently, we developed empiric conversion formulae. Furthermore, we developed new cutoff values for classifying disease activity to minimize the disparity among indices, using an iterative method., Results: The relationships between DAS28-ESR and DAS28-CRP and between SDAI and CDAI were approximately linear; the others were quadratic. Quadratic equations approximated the relationship between DAS, SDAI, and CDAI, whereas natural logarithms function approximated the relationship between DAS28-ESR and DAS28-CRP. Patients are frequently categorized into inconsistent disease activity states with any two indices, with the disparity ranging from 9.7% to 40.6%. The new cutoff values were developed to minimize the discrepant activity state categorization, reducing the disparity range to 6.3%-32.6%., Conclusion: We derived empiric formulae that connect DAS28-ESR, DAS28-CRP, SDAI, and CDAI. Moreover, we developed new cutoff values to minimize the discrepant activity state categorization with different indices.

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies., (© 2017 British Society for Immunology.)

Background: The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore., Methods: Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis., Results: Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512)., Conclusion: The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

Our objective was to investigate the serum levels of interferon-inducible protein-10 (IP-10) in systemic lupus erythematosus (SLE) and their correlation with disease activity and organ manifestations. Serum IP-10 levels were assessed in 464 SLE patients and 50 healthy donors. Disease activity was assessed by the revised SLE Activity Measure, and the concomitant active organ manifestations, anti-ds DNA antibody titres, complement levels and erythrocyte sedimentation rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP-10 in SLE patients and controls was determined by in vitro cultures stimulated with mitogen or lipopolysaccharide. Elevated serum IP-10 levels were observed in SLE patients, which were significantly higher in the presence of active haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced spontaneous IP-10 production in vitro. Serial IP-10 levels correlated with longitudinal change in SLE activity, even at low levels where anti-dsDNA antibody and complement levels remain unchanged. These data demonstrate that IP-10 levels are increased in SLE and serum IP-10 may represent a more sensitive marker for monitoring disease activity than standard serological tests.

Objective: To assess the reliability, validity and sensitivity to change of a Chinese version of the 36-item Short-Form Health Survey (SF-36) in Chinese-speaking patients with rheumatoid arthritis (RA) in Singapore., Methods: The psychometric properties of the Chinese Hong Kong standard version of the SF-36 were assessed in 401 RA patients. The construct validity of the Chinese SF-36 was assessed by comparison with the American College of Rheumatology (ACR) functional status, a validated Chinese Health Assessment Questionnaire (C-HAQ) and markers of RA activity and severity., Results: The overall Cronbach's coefficient alpha was 0.921, reflecting excellent internal consistency. The instrument showed reasonable test-retest reliability except in the social functioning (SF) subscale. There was a significant ceiling effect in the role physical (RP), SF and role emotional (RE) subscales and a floor effect in the RP and RE subscales. Physical function (PF) and SF were strongly correlated with C-HAQ and patient's assessment of RA activity [Pearson's correlation coefficient (r) ranging from -0.41 to -0.53] and moderately correlated with ACR functional status (r = -0.35 and -0.3, respectively). Weak correlations were also found between the Chinese SF-36 and markers of RA activity, deformed joint count and radiographic damage. PF and SF were the subscales most responsive to change in quality of life (QOL)., Conclusion: The Chinese SF-36 showed reasonable reliability, criterion validity and responsiveness with limitations in certain subscales. Overall, the physical domains and PF in particular may be the most ideal psychometric measures of QOL in RA.

Objectives: Systemic lupus erythematosus (SLE), a chronic illness with an unpredictable and variable course, profoundly affects the quality of life (QOL). General health questionnaires are used to assess QOL in SLE, but a disease-specific instrument could offer enhanced responsiveness and content validity. We detail the steps we took to develop and validate a new SLE-specific QOL instrument, SLEQOL., Methods: Rheumatology professionals nominated items that they felt were important determinants of QOL of SLE patients. One hundred SLE patients were asked to assess the importance and frequency of occurrence of these items and to suggest those that had not been listed. Item reduction was performed using Rasch model and factor analyses to create a new questionnaire in English. This final questionnaire was administered to a cohort of 275 patients to study its psychometric properties., Results: Fifty-one items covering a wide range of QOL concerns were identified. The patients' responses led to the elimination of 11. The new questionnaire of 40 items was found to have Cronbach's alpha of 0.95 and to consist of eight domains covering physical, mental and social QOL issues. It has good test-retest reliability, poor to fair cross-sectional correlation with the SF-36, with poor correlation with lupus activity or damage indices. The SLEQOL was more responsive to change than the SF-36., Conclusions: We have developed a new 40-item SLEQOL in English and showed that it is valid for use in SLE patients in Singapore. It offers better content validity and responsiveness to change than the SF-36.

Objectives: To study serum levels of transforming growth factor beta-1 (TGFbeta1) and the expression of TGFbeta1 in in vitro peripheral blood mononuclear cell (PBMC) cultures in oriental ankylosing spondylitis (AS) patients, and to determine their association with codon 10 and 25 TGFB1 gene polymorphisms., Methods: Serum levels of TGFbeta1 were measured by enzyme-linked immunosorbent assay (ELISA). The ability of PBMCs to synthesize TGFbeta1 and other cytokines was assessed by in vitro cultures stimulated with mitogen. Genomic DNA was extracted from PBMCs of AS patients (n=72) or unrelated healthy controls (n=96). The codon 10 and 25 polymorphisms in the TGFB1 gene were analysed using standard polymerase chain reaction-based methods., Results: AS patients had significantly higher serum TGFbeta1 levels than controls (P<0.001). There was no difference in the distribution of codon 10 and 25 TGFB1 genotypes between AS patients and controls. Incubation of AS and control PBMC with phytohaemagglutinin (PHA) led to upregulation of TGFbeta1, interleukin-10, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) assessed by ELISA. Importantly, PHA-induced TGFbeta1 production was significantly enhanced in AS patients compared with normal controls whereas the production of the pro-inflammatory cytokines TNFalpha and IFNgamma was reduced., Conclusions: Our results show that AS patients express significantly higher levels of serum TGFbeta1 independent of the codon 10 and 25 genotype. Activation of AS PBMCs led to enhanced TGFbeta1 production accompanied by reduction of TNFalpha and IFNgamma while the converse was observed in normal controls.

Objective: To examine the relationship between ethnicity and major organ involvement at and after diagnosis in community-based cohorts of Caucasian and Chinese systemic lupus erythematosus (SLE) patients resident in Rochester, Minnesota, and Singapore, respectively., Methods: Clinical manifestations at and after diagnosis were compared in Caucasian and Chinese SLE patients. The association between ethnicity and disease manifestations at and after diagnosis was determined using logistic regression and Cox proportional hazards models, respectively, adjusting for the influence of demographic, socioeconomic, disease-related, and therapy-related factors., Results: At diagnosis, Caucasian SLE patients were 3 times more likely than Chinese SLE patients to have serositis (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.01-9.71), nearly 7 times more likely to have a hematologic disorder (OR 6.95, 95% CI 2.20-21.97), and far less likely to have a malar rash (OR 0.19, 95% CI 0.07-0.54) or positive antinuclear antibodies (OR 0.11, 95% CI 0.03-0.52). Ethnicity was not associated with the prevalence of proteinuria or central nervous system (CSN) and other major organ involvement at diagnosis. After diagnosis, there was a trend toward less development of proteinuria and other major organ involvement in Caucasians (relative risk [RR] 0.47, 95% CI 0.19-1.15, and RR 0.22, 95% CI 0.05-1.04, respectively)., Conclusion: Chinese SLE patients are far less likely to have serositis or a hematologic disorder at diagnosis and may be more likely to develop proteinuria or CNS or other major organ involvement over the course of the disease, compared with Caucasian SLE patients. This may contribute to the increased mortality seen in Chinese SLE patients.

A retrospective chart review was carried out on 344 patients with systemic sclerosis (SSc) followed prospectively for the occurrence of pulmonary hypertension (PHT). Seventeen patients (4.9%) were found to have PHT. Eight patients had isolated PHT, while in nine PHT was associated with restrictive lung disease (RLD). The subset with RLD developed PHT earlier, but had longer survival than patients with isolated PHT. Patients with limited scleroderma tend to develop isolated PHT, while in those with diffuse disease PHT is associated with RLD. Irrespective of disease type, PHT in SSc has an extremely poor prognosis with a median survival of 12 months following diagnosis.

Effects of fructose feeding in moderate amounts on lipid metabolism of obese versus lean, and diabetic versus nondiabetic Zucker rats, were studied. Forty pairs of male lean and obese animals were assigned to two dietary groups, fructose and glucose. For each diet, one-half of lean and obese animals were injected with streptozotocin intraperitoneally (i.p.) to induce diabetes, and the other half were injected with buffer i.p. as a nondiabetic control group. After 9 wk of feeding, animals were fasted overnight, decapitated and exsanguinated. Organs were removed and weighed. Blood glucose, insulin, lactic acid, triglycerides, cholesterol, total liver lipids and urinary glucose were determined. Hyperphagia was observed in obese, non-diabetic and lean-diabetic animals. Streptozotocin injection drastically reduced insulin levels, and produced an impairment of growth, hyperglycemia, glucosuria, polydipsia and polyuria. Fructose feeding increased organ weights in kidney, liver and retroperitoneal adipose tissue, regardless of diabetic state. However, lactic acid levels were lower in fructose-fed groups than glucose-fed groups. In obese rats serum triglyceride levels were also lower in fructose-fed groups than in glucose-fed groups. Serum cholesterol was not affected by fructose feeding. The results indicated that fructose feeding did not produce hyperlipemia and lactic acidosis in the blood circulation in Zucker rats. However, fructose feeding did not improve glucose intolerance in diabetic animals, rather fructose feeding produced hyperinsulinemia in nondiabetic, obese animals.