Red blood cells based nanotheranostics: A smart biomimetic approach for fighting against cancer.

The technique of engineering drug delivery vehicles continues to develop, which bring enhancements in working more efficiently and minimizing side effects to make it more effective and safer. The intense capability of therapeutic agents to remain undamaged in a harsh extracellular environment is helpful to the success of drug development efforts. With this in mind, alterations of biopharmaceuticals with enhanced stability and decreased immunogenicity have been an increasingly active focus of such efforts. Red blood cells (RBCs), also known as erythrocytes have undergone extensive scrutiny as potential vehicles for drug delivery due to their remarkable attributes over the years of research. These include intrinsic biocompatibility, minimal immunogenicity, flexibility, and prolonged systemic circulation. Throughout the course of investigation, a diverse array of drug delivery platforms based on RBCs has emerged. These encompass genetically engineered RBCs, non-genetically modified RBCs, and RBC membrane-coated nanoparticles, each devised to cater to a range of biomedical objectives. Given their prevalence in the circulatory system, RBCs have gained significant attention for their potential to serve as biomimetic coatings for artificial nanocarriers. By virtue of their surface emulation capabilities and customizable core materials, nanocarriers mimicking these RBCs, hold considerable promise across a spectrum of applications, spanning drug delivery, imaging, phototherapy, immunomodulation, sensing, and detection. These multifaceted functionalities underscore the considerable therapeutic and diagnostic potential across various diseases. Our proposed review provides the synthesis of recent strides in the theranostic utilization of erythrocytes in the context of cancer. It also delves into the principal challenges and prospects intrinsic to this realm of research. The focal point of this review pertains to accentuating the significance of erythrocyte-based theranostic systems in combating cancer. Furthermore, it precisely records the latest and the most specific methodologies for tailoring the attributes of these biomimetic nanoscale formulations, attenuating various discoveries for the treatment and management of cancer.

Drug-loaded polymer-coated silver nanoparticles for lung cancer theranostics.

Lung cancer is the leading cause of death in cancer across the globe. To minimize these deaths, the replacement of traditional chemotherapy with novel strategies is significant. We have developed a nanotheranostic approach using silver nanoparticles for imaging and treatment. Silver nanoparticles (AgNPs) are fabricated by chemical reduction method. The formulation of AgNPs was confirmed by different characterization techniques like stability test, UV-Visible spectroscopy, Confocal Raman Spectroscopy, and Energy-Dispersive X-ray analysis. Further, AgNPs are coated with poly lactic-co-glycolic acid (PLGA) and then loaded with paclitaxel (Pac). Then the drug-loaded PLGA-coated AgNPs were characterized for size and zeta potential measurement by zetasizer, surface morphology study by atomic force microscopy, Fourier transform infrared spectroscopy, and release kinetics study. The imaging and anticancer properties of these nanoformulations are investigated using lung cancer cell lines. The results proved that the particles are in the nanometer range with smooth surface morphology. Moreover, the drug-loaded NPs showed a sustained release of the drug for a longer period of time. Further the formulations showed imaging property with greater anticancer efficacy. Thus, the results suggest the effective use of these nanoformulation in both lung cancer imaging and treatment using a simple and efficient approach.

Prevalence and factors associated with diagnosed diabetes mellitus among Asian Indian adults in the United States.

Higher prevalence of diabetes mellitus (DM) has been documented among South Asians living in the United States. However, combining the south Asian subgroups into one category masks the heterogeneity in the diagnosed DM, after controlling for known protective and risk factors. We assessed the association of Asian Indian ethnicity to diagnosed DM using a nationally representative sample of 1,986 Asian Indian adults in the US compared to 109,072 Non-Hispanic Whites (NHWs) using disaggregated data from the National Health Interview Survey (2012-2016) (NHIS). 2010 US census figures were used for age-sex standardization. Age-sex adjusted prevalence of DM was 8.3% in Asian Indians as compared to 5.8% in NHW. In adjusted multivariable logistic regression models, Asian Indians had higher odds ratios of reporting diagnosed DM compared to NHWs (AOR = 1.39, 95% CI: 1.12, 1.71). This association remained strong and significant even after controlling for other risk factors in the model (AOR = 1.47, 95% CI: 1.16, 1.85). Results suggest a favorable socio-economic profile of Asian Indians was not protective on diagnosed DM. In addition, they were more likely to have diagnosed DM due to higher prevalence of obesity despite healthier behaviors of smoking and exercise.

Isolation, characterisation, anticancer and anti-oxidant activities of 2-methoxy mucic acid from Rhizophora apiculata: an in vitro and in silico studies.

The main objective of the present study is to isolate and characterise the novel bioactive molecule, 2-methoxy mucic acid (4) from Rhizophora apiculate Blume under the Rhizophoraceae family. In this study, the 2-methoxy mucic acid (4) was isolated for the first time from the methanolic extract of the leaves of R. apiculata. Anticancer activity of 2-methoxy mucic acid (4) was evaluated against HeLa and MDA-MB-231 cancer cell lines and they displayed promising activity with IC50 values of 22.88283 ± 0.72 µg/ml in HeLa and 2.91925 ± 0.52 µg/ml in the case of MDA-MB-231, respectively. Furthermore, the antioxidant property of 2-methoxy mucic acid (4) was found to be (IC50) 21.361 ± 0.41 µg/ml. Apart from in vitro studies, we also performed extensive in silico studies (molecular docking and molecular dynamics simulation) on four critical antiapoptotic Bcl-2 family members (Bcl-2, Bcl-w, Bcl-xL and Bcl-B) towards 2-methoxy mucic acid (4). The results revealed that this molecule showed higher binding affinity towards Bcl-B protein (ΔG = -5.8 kcal/mol) and the structural stability of this protein was significantly improved upon binding of this molecule. The present study affords vital insights into the importance of 2-methoxy mucic acid (4) from R. apiculata. Furthermore, it opens the therapeutic route for the discovery of anticancer drugs. Research HighlightsThis is a first report on a bioactive compound identified and characterised; a novel 2-methoxy mucic acid derived from methanolic crude extract from the leaves of R. apiculata from ANI.Estimated binding free energy of 2-methoxy mucic acid is found to be -5.8 kcal/mol to the anti-apoptotic Bcl-B protein.2-methoxy mucic acid showed both significant anti-cancer and anti-oxidant activity.Communicated by Ramaswamy H. Sarma.

Relationship Among Diabetes Distress, Health Literacy, Diabetes Education, Patient-Provider Communication and Diabetes Self-Care.

OBJECTIVES: Mechanisms underlying relationships among patients' health literacy, diabetes distress, diabetes education, and provider counseling for self-care of chronic conditions are unclear. This study tested these relationships using SEM with adult patients with comorbid diabetes and hypertension in rural WV. METHODS: Ninety-one participants of a 12-week self-management program reported on diabetes self-care (diet, exercise, blood glucose (BG) monitoring) and related provider counseling. RESULTS: Based on patient report, providers' recommendations included following a low-fat diet, eating fruits/ vegetables, limiting sweets, a daily low-level of exercise and/or exercise ≥20 minutes three times/week, and BG monitoring. Provider recommendations were shown to be associated with patients' self-care behaviors (r=0.22, p<0.05). Multiple factors directly influenced provider recommendations: diabetes distress, health literacy, and family history of diabetes. A positive association was also noted between prior diabetes education and provider recommendations and diabetes self-care (r=0.44, p<0.001). A negative association was noted between diabetes distress and self-care, but a positive effect on provider recommendations was found. The model demonstrated good fit [CFI=0.94, and Root Mean Square Error of Approximation (RMSEA) =0.05]. CONCLUSIONS: To enhance diabetes self-care, providers should consistently provide education on self-care behaviors as well as partner with them to address diabetes distress.

Hypoxia responsive phytonanotheranostics: A novel paradigm towards fighting cancer.

Hypoxia enhances tumor aggressiveness, thereby reducing the efficacy of anticancer therapies. Phytomedicine, which is nowadays considered as the new panacea owing to its dynamic physiological properties, is often plagued by shortcomings. Incorporating these wonder drugs in nanoparticles (phytonanomedicine) for hypoxia therapy is a new prospect in the direction of cancer management. Similarly, the concept of phytonanotheranostics for the precise tumor lesion detection and treatment monitoring in the hypoxic scenario is going on a rampant speed. In the same line, smart nanoparticles which step in for "on-demand" drug release based on internal or external stimuli are also being explored as a new tool for cancer management. However, studies regarding these smart and tailor-made nanotheranostics in the hypoxic tumor microenvironment are very limited. The present review is an attempt to collate these smart stimuli-responsive phytonanotherapeutics in one place for initiating future research in this upcoming field for better cancer treatment.

Multifaceted Engineered Biomimetic Nanorobots Toward Cancer Management.

The noteworthy beneficiary to date in nanotechnology is cancer management. Nanorobots are developed as the result of advancements in the nanostructure, robotics, healthcare, and computer systems. These devices at the nanoscale level are beneficial in the prevention, diagnosis, and treatment of various health conditions notably cancer. Though these structures have distinct potentialities, the usage of inorganic substances in their construction can affect their performance and can cause health issues in the body. To overcome this, naturally inspired substances are incorporated in the fabrication process of nanorobots termed biomimetic nanorobots that can overcome the immunological responses and reduce the side effects with effective functionalization. These biomimetic nanorobots can widen the opportunities in cancer imaging and therapy. Herein, an up-to-date review of biomimetic nanorobots along with their applications in cancer management is provided. Furthermore, the safety issues and future directions of biomimetic nanorobots to achieve clinical translation are also stated.

A comprehensive in silico and in vitro studies on quinizarin: a promising phytochemical derived from Rhizophora mucronata Lam.

Mangrove plants are a great source of phytomedicines, since from the beginning of human civilization and the origin of traditional medicines. In the present study, ten different mangrove leaf methanolic extracts were screened for the type of phytochemicals followed by assessing antimicrobial, anti-oxidant and anti-cancer activities. The efficient methanolic crude extract of Rhizospora mucornata was further purified and characterized for the presence of the bioactive compound. Based on UV-visible spectroscopy, FTIR, NMR and HRMS analysis, the bioactive compound was 1,4-dihydroanthraquinone; also termed as Quinizarin. This identified compound was potential in exhibiting antimicrobial, antioxidant, and cytotoxic activity. Quinizarin inhibited the growth of Bacillus cereus and Klebsiella aerogenes with minimum inhibitory concentration (MIC) of 0.78 and 1.5 mg/ml. The DPPH free radical scavenging assay revealed the maximum activity of 99.8% at the concentration of 200 µg/ml with an IC50 value of 12.67 ± 0.41 µg/ml. Cytotoxic assay against HeLa (cervical) and MDA-MB231(breast) cancer cell lines revealed IC50 values to be 4.60 ± 0.26 and 3.89 ± 0.15 µg/ml. Together the results of molecular docking and molecular dynamics simulation studies explained that Quinizarin molecule showed stronger binding affinity (-6.2 kcal/mol) and significant structural stability towards anti-apoptotic Bcl-2 protein. Thus, the study put forth the promising role of the natural molecule - Quinizarin isolated from R. mucornata in the formulation of therapeutic drugs against bacterial infections and cancer. Communicated by Ramaswamy H. Sarma.

Establishing the promising role of novel combination of triple therapeutics delivery using polymeric nanoparticles for Triple negative breast cancer therapy.

Introduction: Triple-negative breast cancer (TNBC) is a lethal tumor with an advanced degree of metastasis and poor survivability as compared to other subtypes of breast cancer. TNBC which consists of 15 % of all types of breast cancer is categorized by the absence of expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER2). This is the main reason for the failure of current hormonal receptor-based therapies against TNBCs, thus leading to poor patient outcomes. Therefore, there is a necessity to develop novel therapies targeting this devastating disease. Methods: In this study, we have targeted TNBC by simultaneous activation of apoptosis through DNA damage via cytotoxic agent such as paclitaxel (PAC), inhibition of PARP activity via PARP inhibitor, olaparib (OLA) and inhibiting the activity of FOXM1 proto-oncogenic transcription factor by using RNA interference technology (FOXM1-siRNA) in nanoformulations. Experiments conducted in this investigation include cellular uptake, cytotoxicity and apoptosis study using MDA-MB-231 cells. Results: The present study validates that co-delivery of two drugs (PAC and OLA) along with FOXM1-siRNA by cationic NPs, enhances the therapeutic outcome leading to greater cytotoxicity in TNBC cells. Conclusion: The current investigation focuses on designing a multifunctional drug delivery platform for concurrent delivery of either PAC or PARP inhibitor (olaparib) and FOXM1 siRNA in chitosan-coated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with the ability to emerge as a front runner therapeutic for TNBC therapy.

Smart nanotheranostic hydrogels for on-demand cancer management.

Theranostics is a revolution in cancer therapy. Hydrogels have many implications as a drug delivery vehicle and theranostics hydrogels could be a model nanotherapeutic for simultaneous cancer diagnosis and treatment.

The effect of rurality on the risk of primary amputation is amplified by race.

OBJECTIVE: Primary amputation (ie, without attempted revascularization) is a devastating complication of peripheral artery disease. Racial disparities in primary amputation have been described; however, rural disparities have not been well investigated. The purpose of this study was to examine the impact of rurality on risk of primary amputation and to explore the effect of race on this relationship. METHODS: The national Vascular Quality Initiative amputation data set was used for analyses (N = 6795). The outcome of interest was primary amputation. Independent variables were race/ethnicity (non-Latinx whites vs nonwhites) and rural residence. Multivariable logistic regression examined impact of rurality and race/ethnicity on primary amputation after adjustment for relevant covariates and included an interaction for race/ethnicity by rural status. RESULTS: Primary amputation occurred in 49% of patients overall (n = 3332), in 47% of rural vs 49% of urban patients (P = .322), and in 46% of whites vs 53% of nonwhites (P < .001). On multivariable analysis, nonwhites had a 21% higher odds of undergoing primary amputation overall (adjusted odds ratio [AOR], 1.21; 95% confidence interval [CI], 1.05-1.39). On subgroup analysis, rural nonwhites had two times higher odds of undergoing primary amputation than rural whites (AOR, 2.06; 95% CI, 1.53-2.78) and a 52% higher odds of undergoing primary amputation than urban nonwhites (AOR, 1.52; 95% CI, 1.19-1.94). In the urban setting, nonwhites had a 21% higher odds of undergoing primary amputation than urban whites (AOR, 1.21; 95% CI, 1.05-1.39). CONCLUSIONS: In these analyses, rurality was associated with greater odds for primary amputation in nonwhite patients but not in white patients. The effect of race on primary amputation was significant in both urban and rural settings; however, the effect was significantly stronger in rural settings. These findings suggest that race/ethnicity has a compounding effect on rural health disparities and that strategies to improve health of rural communities need to consider the particular needs of nonwhite residents to reduce disparities.

Mediating Role of Acculturation and Lifestyle Behaviors on Cardiometabolic Risk Among a National Sample of U.S. Asian Indians.

Asian Indians are the third largest and fastest growing Asian subgroup in the U.S. and have high risks for diabetes and cardiovascular disease. This study explored the mediating role of lifestyle behaviors on the relationship between acculturation and cardiometabolic risk factors among Asian Indians using the Diabetes in Indian Americans national study. The cross-sectional study sample comprised 1038 randomly selected adult Asian Indians in seven U.S. sites. Acculturation was assessed using the Acculturation Scale for Southeast Asians. Diet and lifestyle behaviors were measured using the Health-Promoting Lifestyle Profile II subscales. Path analyses with bootstrap methods were conducted. Dietary behavior significantly mediated the relationship between acculturation and HbA1C (ß = 0.004, p = 0.047), and physical activity mediated the relationship between acculturation and HDL (ß = 0.08, p = 0.011). Other mediation models were not significant (p > 0.05). Mediating factors besides lifestyle behaviors should be explored in future studies.

Geographic variation in amputation rates among patients with diabetes and/or peripheral arterial disease in the rural state of West Virginia identifies areas for improved care.

OBJECTIVE: Amputation is a devastating but preventable complication of diabetes and peripheral arterial disease (PAD). Multiple studies have focused on disparities in amputation rates based on race and socioeconomic status, but few focus on amputation trends in rural populations. The objective of this study was to identify the prevalence of major and minor amputation among patients admitted with diabetes and/or PAD in a rural, Appalachian state, and to identify geographic areas with higher than expected major and minor amputations using advanced spatial analysis while controlling for comorbidities and rurality. METHODS: Patient hospital admissions of West Virginia residents with diagnoses of diabetes and/or PAD and with or without an amputation procedure were identified from the West Virginia Health Care Authority State Inpatient Database from 2011 to 2016 using relevant International Classification of Diseases, 9th edition and 10the edition codes. Bayesian spatial hierarchical modeling was conducted to identify areas of high risk, while controlling for important confounders for amputation. RESULTS: Overall, there were 5557 amputations among 459,452 hospital admissions with diabetes and/or PAD from 2011 to 2016. The majority of the amputations were minor (61.7%; n = 3430), with a prevalence of 7.5 per 1000 and 40.4% (n = 2248) were major, with a prevalence of 4.9 per 1000. Geographic analysis found significant variation in risk for both major and minor amputation across the state, even after adjusting for the prevalence of risk factors. Analyses indicated an increased risk of amputation in the central and northeastern regions of West Virginia at the county level, although zip code-level patterns of amputation varied, with high-risk areas identified primarily in the northeastern and south central regions of the state. CONCLUSIONS: There is significant geographic variation in risk of amputation across West Virginia, even after adjusting for disease-related risk factors, suggesting priority areas for further investigation. The level of granularity obtained using advanced spatial analyses rather than traditional methods demonstrate the value of this approach, particularly when risk estimates are used to inform policy or public health intervention.

The mesenchymal stem cell secretome: A new paradigm towards cell-free therapeutic mode in regenerative medicine.

Mesenchymal Stem Cells (MSCs) have been shown to be a promising candidate for cell-based therapy. The therapeutic potential of MSCs, towards tissue repair and wound healing is essentially based on their paracrine effects. Numerous pre-clinical and clinical studies of MSCs have yielded encouraging results. Further, these cells have been shown to be relatively safe for clinical applications. MSCs harvested from numerous anatomical locations including the bone marrow, adipose tissue, Wharton's jelly of the umbilical cord etc., display similar immunophenotypic profiles. However, there is a large body of evidence showing that MSCs secrete a variety of biologically active molecules such as growth factors, chemokines, and cytokines. Despite the similarity in their immunophenotype, the secretome of MSCs appears to vary significantly, depending on the age of the host and niches where the cells reside. Thus, by implication, proteomics-based profiling suggests that the therapeutic potential of the different MSC populations must also be different. Analysis of the secretome points to its influence on varied biological processes such as angiogenesis, neurogenesis, tissue repair, immunomodulation, wound healing, anti-fibrotic and anti-tumour for tissue maintenance and regeneration. Though MSC based therapy has been shown to be relatively safe, from a clinical standpoint, the use of cell-free infusions can altogether circumvent the administration of viable cells for therapy. Understanding the secretome of in vitro cultured MSC populations, by the analysis of the corresponding conditioned medium, will enable us to evaluate its utility as a new therapeutic option. This review will focus on the accumulating evidence that points to the therapeutic potential of the conditioned medium, both from pre-clinical and clinical studies. Finally, this review will emphasize the importance of profiling the conditioned medium for assessing its potential for cell-free therapy therapy.

Cardiovascular Disease & Cancer Risk Among South Asians: Impact of Sociocultural Influences on Lifestyle and Behavior.

A comprehensive literature review revealed cultural beliefs, societal obligations, and gender roles within the South Asian community to be indirect contributors to the health of South Asian immigrants (SAIs). Health professionals need to increase their work with SAI communities to change less beneficial cultural elements such as misconceptions about health and exercise, and lack of communication when using alternative medicines. Community engaged efforts and continuing medical education are both needed to improve the health of the South Asian immigrant population in a culturally appropriate manner.

Red Meat Consumption (Heme Iron Intake) and Risk for Diabetes and Comorbidities?

PURPOSE OF REVIEW: To examine the role of red meat consumption, especially heme iron intake, and risk for diabetes and its comorbidities. RECENT FINDINGS: Studies consistently show that consumption of red meat has been contributory to a multitude of chronic conditions such as diabetes, CVD, and malignancies. There are various emerging reasons that strengthen this link-from the basic constituents of red meat like the heme iron component, the metabolic reactions that take place after consumption, and finally to the methods used to cook it. The causative links show that even occasional use raises the risk of T2DM. Prior studies show how nitrites and nitrates in red meat can lead to increased insulin resistance, dysregulated blood glucose levels, and elevated oxidative stress all leading to chronic diseases. With the rise in these preventable chronic diseases, we examine how disease-causing links can be eliminated with appropriate lifestyle choices.

Sociodemographic Correlates of Tobacco Consumption in Rural Gujarat, India.

Background. The purpose of this study was to examine occupation-, education-, and gender-specific patterns of tobacco use and knowledge of its health effects among 23,953 rural Asian Indians ≥18 years in Gujarat. Methodology. A statewide, community-based, cross-sectional survey was conducted in 26 districts of Gujarat (December 2010-May 2015), using face-to-face interviews by trained community health workers called SEVAKS. Results. Mean age was 39.8 ± 15.2 years. Eighteen percent of respondents used tobacco in various forms. Tobacco consumption was significantly higher among males (32%), 18-34 years' age group (35%), those who were self-employed (72%), and those with elementary education (40%). The prevalence was 11 times higher among males than females (95% CI = 9.78, 13.13). Adjusted ORs for tobacco use showed strong gradient by age and educational level; consumption was lower among the illiterates and higher for older participants (≥55 years). Tobacco consumption also varied by occupation; that is, those who were self-employed and employed for wages were more likely to use tobacco than those who were unemployed. Knowledge of health effects of tobacco lowered the odds of consumption by 30-40%. Conclusions. Effective educational programs should be tailored by gender, to improve knowledge of health risks and dispel myths on perceived benefits of tobacco.

Reversal of multidrug resistance in vitro by co-delivery of MDR1 targeting siRNA and doxorubicin using a novel cationic poly(lactide-co-glycolide) nanoformulation.

Over expression of drug efflux transporters such as P-glycoprotein (P-gp) cumulatively leading to multidrug resistance (MDR) embodies a major hindrance for successful cancer therapy. A paradigm nanomedicinal approach involving an anticancer drug and modulators of drug resistance within one multifunctional nanocarrier-based delivery system represent an ideal modality for the treatment of MDR. In this regards, we have developed a cationic polymeric nanoparticulate system loaded with MDR1-siRNA and doxorubicin. Results indicated augmented synergistic effect of combinational nanoformulation in overcoming MDR in MCF-7/ADR cells. Therefore, the above regime could be a promising co-delivery system for effective therapy of drug resistant breast cancer.

Racial disparities in hepatitis B infection in Ohio: screening and immunization are critical for early clinical management.

OBJECTIVE: Chronic hepatitis B virus (HBV) infection and liver cancer mortality represent a neglected health disparity among Asian Americans. The purposes of this study were to compare the prevalence of hepatitis B among a diverse group of 1311 Ohioans in Franklin County, OH (85% Asians, 7.5% African Americans, and 6.5% whites) and to improve access to care for high-risk Asian adults through advocacy and policy changes. RESEARCH DESIGN AND METHODS: The Asian subgroups comprised of Chinese, Filipino, Asian Indian, Pakistani, Vietnamese, Korean, Laotian, Indonesian, Japanese, Cambodian, Thai, and Malaysian nationalities. The HBV screening was completed at health fairs, restaurants, churches, and temples from 2006 to 2011. RESULTS: The prevalence of HBV infection (9.5% vs 5%) and family history of liver cancer was significantly higher among Asians than other racial ethnic groups (P = 0.001). Cambodian, Vietnamese, and Chinese participants were disproportionately infected with the virus compared with other Asian subgroups (P < 0.001). Advocacy and policy changes for resources allowed vaccine-eligible Asians included as "high risk" group to receive free vaccinations at the health department. However, although vouchers were provided to vaccine-eligible Asian adults, compliance in getting vaccinated was very low (11%). Common barriers for compliance were lack of time and knowledge of completing the 3 shot series, low English proficiency, and fear of adverse effects. CONCLUSIONS: Outreach education may use community liaisons to improve screenings, education, and vaccination/treatment. A hepatitis free clinic was established in 2009 to provide culturally and linguistically appropriate treatment for low-income Asian Americans in Franklin County, OH.

Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART).

BACKGROUND: HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. METHODS: Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined. RESULTS: African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW's. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge. CONCLUSIONS: Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response.