Continuous Glucose Monitor: Reclaiming Type 2 Diabetes Self-efficacy and Mitigating Disparities.

Context: The rise in continuous glucose monitor (CGM) use has been characterized by widening disparities between the least and most socially marginalized. Given access barriers, there is limited CGM patient experience information that is inclusive of those with type 2 diabetes mellitus from socially marginalized backgrounds. Objective: To understand the CGM usage experience in the primary care setting across a US Medicaid population with type 2 diabetes at federally qualified health centers. Methods: This qualitative study used semi-structured phone interviews with 28 English- or Spanish-speaking participants prescribed the CGM who were enrolled in a US Medicaid program that subsidized CGMs. Audio recordings of interviews were transcribed and analyzed by reflective thematic analysis. Results: Twenty-eight participants (75% female, median age 56 years with interquartile-range 48-60 years) were interviewed. Participants were from different racial/ethnic backgrounds: 21% non-Hispanic White, 57% Hispanic, and 18% non-Hispanic Black. Participants primarily spoke English (68%) or Spanish (32%), and 53% reported 9 or fewer years of formal education. We identified 6 major themes: initial expectations and overcoming initiation barriers, convenience and ease promote daily use, increased knowledge leads to improved self-management, collaboration with provider and clinical team, improved self-reported outcomes, and barriers and burdens are generally tolerated. Conclusion: CGM use was experienced as easy to understand and viewed as a tool for diabetes self-efficacy. Expanded CGM access for socially marginalized patients with type 2 diabetes can enhance diabetes self-management to help mitigate diabetes outcome disparities.

Power Dynamics Perpetuate DEI Inaction: A Qualitative Study of Community Health Clinic Teams.

PURPOSE: Despite increased clinician awareness of systemic racism, lack of substantial action toward antiracism exists within health care. Clinical staff perspectives, particularly those of racial-ethnic minorities/persons of color (POC) who disproportionately occupy support staff roles with less power on the team, can yield insights into barriers to progress and can inform future efforts to advance diversity, equity, and inclusion (DEI, also referred to as EDI) within health care settings. This qualitative study explored the perspectives of staff members on race and role power dynamics within community health clinic teams. METHODS: We conducted semistructured 45-minute interviews with staff members working in community health clinics in a large urban health care system from May to July 2021. We implemented purposeful recruitment to oversample POC and support staff and to achieve equal representation from the 13 community health clinics in the system. Interviews were audio recorded, transcribed, and analyzed over 6 months using a critical-ideological paradigm. Themes reflecting experiences related to race and role power dynamics were identified. RESULTS: Our cohort had 60 participants: 42 (70%) were support staff (medical assistants, front desk clerks, care navigators, nurses) and 18 (30%) were clinicians and clinic leaders. The large majority of participants were aged 26 to 40 years (60%), were female (83%), and were POC (68%). Five themes emerged: (1) POC face hidden challenges, (2) racial discrimination persists, (3) power dynamics perpetuate inaction, (4) interpersonal actions foster safety and equity, and (5) system-level change is needed for cultural shift. CONCLUSIONS: Understanding the race and role power dynamics within care teams, including experiences of staff members with less power, is critical to advancing DEI in health care.

Real-world Accuracy of CGM in Inpatient Critical and Noncritical Care Settings at a Safety-Net Hospital.

OBJECTIVE: We sought to determine real-world accuracy of inpatient continuous glucose monitoring (CGM) at multiple levels of acuity in a large safety-net hospital. RESEARCH DESIGN AND METHODS: We analyzed records from hospitalized patients on Dexcom G6 CGM, including clinical, point of care (POC), and laboratory (Lab) glucose, and CGM data. POC/Lab values were matched to the closest timed CGM value. Encounters were divided into not critically ill (NCI) versus critically ill (CI). CGM accuracy was evaluated. RESULTS: Paired readings (2,744 POC-CGM; 3,705 Lab-CGM) were analyzed for 233 patients with 239 encounters (83 NCI, 156 CI). POC-CGM aggregated and average mean absolute relative differences (MARD) were 15.1% and 17.1%. Lab-CGM aggregated and average MARDs were 11.4% and 12.2%. Accuracy for POC-CGM and Lab-CGM was 96.5% and 99.1% in Clarke Error Grid zones A/B. CONCLUSIONS: Real-world accuracy of inpatient CGM is acceptable for NCI and CI patients. Further exploration of conditions associated with lower CGM accuracy in real-world settings is warranted.

A WIC-Based Behavior Change Intervention for Postpartum Women With Overweight and Obesity: A Pilot Feasibility Randomized Trial.

Background. Postpartum weight retention is a risk factor for obesity and is particularly important among Hispanic women who have an increased rate of obesity. Given its broad reach, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program provides an ideal setting to implement community-based interventions for low-income postpartum women. Purpose. To examine the feasibility, acceptability, and preliminary efficacy of a multicomponent intervention delivered by staff within the WIC program designed to promote behavior changes in urban, postpartum women with overweight/obesity. Method. This was a 12-week pilot trial randomizing participants to a health behavior change (Intervention) or control (Observation) group. The Intervention included monthly visits with trained WIC staff providing patient-centered behavior change counseling, with multiple touchpoints between visits promoting self-monitoring and offering health behavior change support. Results. Participants (n = 41), who were mainly Hispanic (n = 37, 90%) and Spanish-speaking (n = 33, 81%), were randomized to the Intervention (n = 19) or Observation (n = 22) group. In the Intervention group, 79% (n = 15) of eligible participants were retained for the study duration. All Intervention participants endorsed that they would participate again. Regarding physical activity, participant readiness to change and self-efficacy improved for Intervention participants. About one-quarter of women in the Intervention group (27%, n = 4) had a 5% weight loss compared with one woman (5%) in the Observation group; this difference was not statistically significant (p = .10). Conclusions. This pilot demonstrated the feasibility and acceptability of delivering a low-intensity behavior change intervention within the WIC setting for postpartum women with overweight/obesity. Findings support the role of WIC in addressing postpartum obesity.

Effect of CGM Access Expansion on Uptake Among Patients on Medicaid With Diabetes.

OBJECTIVE: Current studies on continuous glucose monitor (CGM) uptake are revealing for significant barriers and inequities for CGM use among patients from socially underprivileged communities. This study explores the effect of full subsidies regardless of diabetes type on CGM uptake and HbA1c outcomes in a U.S. adult patient population on Medicaid. RESEARCH DESIGN AND METHODS: This retrospective cohort study examined 3,036 adults with diabetes enrolled in a U.S. Medicaid program that fully subsidized CGM. CGM uptake and adherence were assessed by CGM prescription and dispense data, including more than one fill and adherence by medication possession ratio (MPR). Multivariate logistic regression evaluated predictors of CGM uptake. Pre- and post-CGM use HbA1c were compared. RESULTS: CGM were very well received by both individuals with type 1 diabetes and individuals with type 2 diabetes with similar high fill adherence levels (mean MPR 0.78 vs. 0.72; P = 0.06). No significant difference in CGM uptake outcomes were noted among major racial/ethnic groups. CGM use was associated with improved HbA1c among those with type 2 diabetes (-1.2% [13.1 mmol/mol]; P < 0.001) that was comparable between major racial/ethnic groups and those with higher fill adherence achieved greater HbA1c reduction (-1.4% [15.3 mmol/mol]; P < 0.001) compared with those with lower adherence (-1.0% [10.9 mmol/mol]; P < 0.001). CONCLUSIONS: CGM uptake disparities can largely be overcome by eliminating CGM cost barriers. CGM use was associated with improved HbA1c across all major racial/ethnic groups, highlighting broad CGM appeal, utilization, and effectiveness across an underprivileged patient population.

Anti-Glutathione S Transferase T1 Antibodies After Renal Transplant and Their Impact on Graft Outcome.

OBJECTIVES: Anti-glutathione S transferase T1 (GSTT1) antibodies, a type of non-HLA antibody, have been associated with chronic hepatic graft rejection. Despite the presence of this enzyme in the kidney, there are not enough studies on the development of anti-GSTT1 antibodies and their impact on renal grafts. Our objective was to evaluate the presence of anti-GSTT1 antibodies after renal transplant and their impact on graft outcomes. MATERIALS AND METHODS: We conducted an ambispective cohort study. We performed real-time polymerase chain reaction to screen for GSTT1 alleles in 293 recipients and their donors. In null GSTT1 (GSTT1*0) genotype recipients of GSTT1-positive donors, the presence of anti-GSTT1 antibodies was evaluated using indirect immunofluorescence and Luminex assays, and their effects on graft function were evaluated. The median follow-up period was 54.3 months. RESULTS: Of the 293 patients studied, 42 recipients (14.4%) with GSTT1-positive donors did not have the GSTT1 allele (GSTT1-positive donor/GSTT1*0 recipient). Using Luminex assay, we detected antibodies in 16 patients (38.1%), 12 of which were already present at the time of transplant. Of these cases, 37.5% with antibodies had undergone a previous renal transplant. Using indirect immunofluorescence, we found that only 12 patients tested positive, 4 at the time of transplant. Antibody presence did not effect graft glomerular filtration rates or graft loss at 1 year, at 2 years, or end of follow-up. CONCLUSIONS: The presence of anti-GSTT1 antibodies is frequent in renal transplant GSTT1*0 recipients of GSTT1-positive donors but has no effects on graft outcome.

Perspectives of Latinx Individuals Who Were Unvaccinated And Hospitalized for COVID-19: A Qualitative Study.

Importance: Latinx individuals in the United States have lower COVID-19 vaccination rates and higher rates of COVID-19 infections, hospitalizations, and deaths than non-Latinx White individuals. Little is known about the perspectives of Latinx adults who had not received the COVID-19 vaccination and were hospitalized for COVID-19. Objective: To describe the perspectives of Latinx individuals who were unvaccinated and subsequently hospitalized for COVID-19. Design, Setting, and Participants: This qualitative study was conducted using semistructured phone interviews with 25 Latinx adults who were unvaccinated and survived a COVID-19 hospitalization in a public safety net hospital in Colorado from February to November 2021. Interviews were audio recorded, and transcripts were analyzed using thematic analysis. Main Outcomes and Measures: Themes and subthemes of perspectives on vaccination. Results: Among 25 adults (14 [56.0%] women, 11 [44.0%] men; mean [SD] age, 51 [15] years) who participated, all participants self-identified as Latino, Latina, or Latinx or Hispanic. There were 11 individuals who relied on emergency Medicaid (hospital coverage for Denver residents who are undocumented), while 10 individuals (40.0%) were essential workers and 13 individuals (52.0%) were unemployed. In interviews, 3 themes (with subthemes) were identified: factors associated with vaccination after hospitalization (subthemes: fear of death, avoiding hospitalization and reinfection, convinced COVID-19 is real, and responded to pressure from others), concerns about the COVID-19 vaccine (subthemes: experimental status and short timeline for production, contents of vaccine unknown or concerning, vaccine considered ineffective, worrisome immediate and long-term adverse effects, mixed and conflicting information, and government aimed to control or mark population through vaccination), and opportunities to improve vaccine uptake (subthemes; sharing personal experiences through social media, testimonials about minimal vaccine adverse effects, connecting with friends and family about the hospitalization experience, making the vaccine more accessible, and connecting with trusted sources of information). Conclusions and Relevance: This study found that Latinx individuals who were unvaccinated and subsequently hospitalized for COVID-19 were motivated to engage in advocacy to encourage vaccination in their communities. These findings suggest that supporting patient advocacy after hospital discharge and continued efforts to create low-barrier, patient-informed public health strategies may be associated with increased vaccine uptake in Latinx communities.

Eradicating Racism: An Endocrine Society Policy Perspective.

The Endocrine Society recognizes racism as a root cause of the health disparities that affect racial/ethnic minority communities in the United States and throughout the world. In this policy perspective, we review the sources and impact of racism on endocrine health disparities and propose interventions aimed at promoting an equitable, diverse, and just healthcare system. Racism in the healthcare system perpetuates health disparities through unequal access and quality of health services, inadequate representation of health professionals from racial/ethnic minority groups, and the propagation of the erroneous belief that socially constructed racial/ethnic groups constitute genetically and biologically distinct populations. Unequal care, particularly for common endocrine diseases such as diabetes, obesity, osteoporosis, and thyroid disease, results in high morbidity and mortality for individuals from racial/ethnic minority groups, leading to a high socioeconomic burden on minority communities and all members of our society. As health professionals, researchers, educators, and leaders, we have a responsibility to take action to eradicate racism from the healthcare system. Achieving this goal would result in high-quality health care services that are accessible to all, diverse workforces that are representative of the communities we serve, inclusive and equitable workplaces and educational settings that foster collaborative teamwork, and research systems that ensure that scientific advancements benefit all members of our society. The Endocrine Society will continue to prioritize and invest resources in a multifaceted approach to eradicate racism, focused on educating and engaging current and future health professionals, teachers, researchers, policy makers, and leaders.

A Mixed Method Examination of Sleep Patterns and Barriers to Sleep in Hispanic Women.

Research on Hispanic sleep (1) remains far behind research on non-Hispanic White sleep, and (2) seldom focuses solely on Hispanic women. A convergent parallel mixed-methods study design was used to examine (1) sleep quantity, quality, and habits; (2) the association of sleep and health; and (3) perceived barriers to healthy sleep in middle-aged Hispanic women living in [a large Midwest city]. A total of 78 Hispanic women were surveyed, and 27 of these Hispanic women participated in focus groups. Participants had: poor sleep quantity, quality, and sleep hygiene. In focus groups, participants identified three barriers to healthy sleep: poor sleep hygiene, responsibilities and related stress, and additional mental health concerns. While poor sleep quantity and quality have serious health consequences for Hispanic women, sleep disorders in Hispanic women have been understudied. This study underscores barriers to healthy sleep and the associations between sleep and health in Hispanic women.

How Well Do U.S. Hispanics Adhere to the Dietary Guidelines for Americans? Results from the Hispanic Community Health Study/Study of Latinos.

Purpose: To examine alignment between 2010 Dietary Guidelines for Americans (DGA) and dietary choices of individuals in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) between 2008 and 2011. Methods: Data are from 15,633 adults 18-74 years from the population-based cohort in HCHS/SOL. The Healthy Eating Index (HEI) 2010 was used to measure diet quality. Means and standard errors (SEs) for the HEI total and each of the 12 component scores were calculated overall and by Hispanic/Latino heritage, sex, age group, and measures of acculturation. Linear regression was used to examine correlates of the HEI 2010 total score. All analyses accounted for complex survey design. Results: The overall HEI mean of 63.8 (SE: 0.4) varied across groups from a high (healthier diet) of 71 (SE: 0.9) among Mexicans to a low of 56 (SE: 0.1) among Puerto Ricans. The proportion with a maximum score for the HEI components varied across heritage groups; >25% of adults adhered to recommendations for total proteins, and seafood and plant proteins, whole fruits, and greens and beans, with the exception of Cubans and Puerto Ricans, who had lower adherence scores for the latter two. The components with the lowest adherence were sodium (<2%) and fatty acids (overall 7.4%) among all heritage groups. Characteristics associated with better adherence included sociodemographic variables, Spanish language preference, weight status, medical conditions, and lifestyle behaviors. Conclusions: Individuals with Mexican, Dominican, and Central American heritage had better overall dietary quality compared to other groups. However, all can improve their eating habits to align more with the DGAs by reducing sodium consumption and improving fatty acid ratios.

Associations Among Dietary Fat Oxidation Responses to Overfeeding and Weight Gain in Obesity-Prone and Resistant Adults.

OBJECTIVE: This study tested the hypothesis that 3 days of overfeeding (OF) decreases dietary fat oxidation and predicts longitudinal weight change in adults classified as obesity prone (OP) and obesity resistant (OR) based on self-identification and personal and family weight history. Changes in diurnal profiles of plasma metabolites and hormones were measured to probe mechanisms. METHODS: Adults identified as OP (n = 22; BMI: 23.9  ±  2.4 kg/m2 ) and OR (n = 30; BMI: 20.5  ±  2.2 kg/m2 ) completed 3 days of eucaloric (EU) feeding and 3 days of OF. On day 3, the 24-hour total and dietary fat oxidation was measured using room calorimetry and an oral 14 C tracer. Plasma glucose, insulin, triglycerides, and nonesterified fatty acid (NEFA) concentrations were frequently sampled over 24 hours. Body composition was measured annually for 4.0  ±  1.4 years in a subsample (n = 19 OP and 23 OR). RESULTS: Dietary fat oxidation over 24 hours was not altered by OF versus EU (P = 0.54). Weight gain in OP correlated with lower nocturnal NEFA concentrations during OF (r  = -0.60; P = 0.006) and impaired fuel selection over 24 hours (metabolic inflexibility, wake respiratory quotient-sleep respiratory quotient) (r = -0.48; P  = 0.04). CONCLUSIONS: Short-term OF did not alter dietary fat oxidation. Lower nocturnal NEFA availability and metabolic inflexibility to overfeeding may be factors contributing to weight gain.

Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study.

C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value <2.5E-7. Three loci have no (HACL1, OLFML2B) or only limited (PLA2G6) previous associations with CRP levels. Six loci had different top hits in race/ethnicity-specific versus overall analyses. Fine-mapping refined the signal in six loci, particularly in HNF1A. Conditional analyses provided evidence for secondary signals in LEPR, IL1RN and HNF1A, and for multiple independent signals in CRP and APOE. We identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals at several loci and found evidence for multiple independent signals at several well-known loci. This study demonstrates the benefit of conducting inclusive genetic association studies in large multiethnic populations.

Effect of the National Diabetes Prevention Program on Weight Loss for English- and Spanish-Speaking Latinos.

PURPOSE: To study the effect of the National Diabetes Prevention Program (NDPP) on weight loss in Latinos. DESIGN: No-control, cohort study comparing Latino and non-Hispanic white (NHW) participants. SETTING: A health-care system. PARTICIPANTS: Five hundred sixty-seven Latino and 175 NHW patients who enrolled in the NDPP. A total of 45.2% of Latinos selected the Spanish-language NDPP. INTERVENTION: The NDPP is a nationwide translation of a clinical trial and seeks to prevent diabetes through weight loss in a yearlong group program. MEASURES: Independent variables included ethnicity, class language, and number of sessions attended. Main outcomes were initial attendance, number of sessions attended, and weight loss. ANALYSIS: Multivariate logistic regression and analysis of covariance were used to determine differences in NDPP outcomes by ethnicity, language, and number of sessions attended. RESULTS: Mean attendance was 8.60 of 22 sessions. Each session was associated with 0.30% (±0.02; P < .001) body weight loss. Latinos were half as likely to attend as NHWs, odds ratio 0.52 ( P < .001). Latino attendees came to 2.67 ± 0.63 ( P < .001) fewer sessions than NHWs. There were no weight loss differences by ethnicity after controlling for attendance. Outcomes did not differ among Latinos in the English- and Spanish-language NDPP. CONCLUSION: Latinos appeared to benefit less from the NDPP compared to NHWs, likely due to lower attendance rates. Further efforts are needed to support their participation.

The ratio of pericardial to subcutaneous adipose tissues is associated with insulin resistance.

OBJECTIVE: To examine the association between pericardial adipose tissue (PAT) and the ratio of PAT to subcutaneous adipose tissue (SAT) with insulin resistance in adults with and without type 1 diabetes (T1D). METHODS: Data for this report came from a substudy of the Coronary Artery Calcification in Type 1 Diabetes cohort (n = 83; 38 with T1D, 45 without T1D). Insulin resistance was measured by hyperinsulinemic-euglycemic clamp. Abdominal computed tomography (CT) was used to measure visceral adipose tissue (VAT) and SAT. PAT was measured from CT scans of the heart. RESULTS: PAT and the ratio of PAT to SAT was higher in males compared to females. After adjustment for demographics, diabetes, blood pressure and lipid factors, BMI, VAT, and log PAT/SAT ratio, log PAT was positively associated with the glucose infusion rate (GIR) in females only (ß = 3.36 ± 1.96, P = 0.097, P for sex interaction = 0.055). Conversely, the log PAT/SAT ratio was significantly associated with decreased GIR in both males and females (ß = -2.08 ± 1.03, P = 0.047, P for sex interaction = 0.768). CONCLUSIONS: A significant association between the PAT/SAT ratio and insulin resistance was found, independent of BMI, VAT, and PAT. These results highlight the importance of considering fat distribution independent of volume.

Estradiol-mediated improvements in adipose tissue insulin sensitivity are related to the balance of adipose tissue estrogen receptor α and ß in postmenopausal women.

We recently demonstrated that short-term estradiol (E2) treatment improved insulin-mediated suppression of lipolysis in postmenopausal women, but to a greater extent in those who were late compared to early postmenopausal. In this follow-up study we tested whether subcutaneous adipose tissue (SAT) expression of estrogen receptors (ER) α and ß differs between early and late postmenopausal women. We further tested whether the balance of ERα to ERß in SAT determined the effect of E2 on SAT insulin sensitivity. The present study included 35 women who were ≤6 years past menopause (EPM; n = 16) or ≥10 years past menopause (LPM; n = 19). Fasted SAT samples were taken following 1-week transdermal E2 treatment or placebo (PL) in a random cross-over design. Samples were analyzed for nuclear/cytosolic protein content and mRNA expression using Western blot and qPCR, respectively. While ESR1 increased slightly (~1.4-fold) following E2 treatment in both groups, ERα and ERß protein expression did not differ between groups at baseline or in response to E2. However, the balance of ERα/ERß protein in the SAT nuclear fraction increased 10% in EPM compared to a 25% decrease in LPM women (group x treatment interaction, p<0.05). A greater proportion of ERα/ERß protein in the nuclear fraction of SAT at baseline (placebo day) was associated with greater reduction in SAT insulin resistance (i.e., better suppression of lipolysis, EC50) in response to E2 (r = -0.431, p<0.05). In conclusion, there do not appear to be differences in the proportion of adipose tissue ERα/ERß protein in late, compared to early, postmenopausal women. However, the balance of ERα/ERß may be important for E2-mediated improvement in adipose tissue insulin sensitivity. TRIAL REGISTRATION: Clinical Trials#: NCT01605071.

Time since menopause and skeletal muscle estrogen receptors, PGC-1α, and AMPK.

OBJECTIVE: Short-term administration of estradiol (E2) improves insulin-stimulated glucose disposal rate in early postmenopausal (EPM) women compared with a reduction in late postmenopausal (LPM) women. The underlying mechanisms by which E2 action on glucose disposal rate reversed from beneficial early to harmful late in menopause is unknown, but might include adverse changes in estrogen receptors (ERs) or other biomarkers of cellular energy metabolism with age or duration of estrogen deficiency. METHODS: We retrospectively analyzed skeletal muscle samples from 27 postmenopausal women who were 6 years or less past menopause (EPM; n = 13) or at least 10 years past menopause (LPM; n = 14). Fasted skeletal muscle (vastus lateralis) samples were collected after 1 week administration of transdermal E2 or placebo, in random cross-over design. RESULTS: Compared with EPM, LPM had reduced skeletal muscle ERα and ERß nuclear protein. Short-term E2 treatment did not change nuclear ERα or ERß, but decreased cytosolic ERα, so the proportion of ERα in the nucleus compared with the cytosol tended to increase. There was a group-by-treatment interaction (P < 0.05) for nuclear proliferator-activated receptor γ co-activator 1-α and phosphorylated adenosine monophosphate-activated protein kinase, such that E2 increased these proteins in EPM, but decreased these proteins in LPM. CONCLUSIONS: These preliminary studies of skeletal muscle from early and late postmenopausal women treated with E2 suggest there may be declines in skeletal muscle ER and changes in the E2-mediated regulation of cellular energy homeostasis with increasing time since menopause.

Region-specific effects of oestradiol on adipose-derived stem cell differentiation in post-menopausal women.

The goal of this study was to determine the effect of acute transdermal 17ß-oestradiol (E2 ) on the adipogenic potential of subcutaneous adipose-derived stem cells (ASC) in post-menopausal women. Post-menopausal women (n = 11; mean age 57 ± 4.5 years) were treated for 2 weeks, in a randomized, cross-over design, with transdermal E2 (0.15 mg) or placebo patches. Biopsies of abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) were obtained after each treatment and mature adipocytes were analysed for cell size and ASC for their capacity for proliferation (growth rate), differentiation (triglyceride accumulation) and susceptibility to tumour necrosis factor alpha-induced apoptosis. Gene expression of oestrogen receptors α and ß (ESR1 and ESR2), perilipin 1 and hormone-sensitive lipase (HSL), was also assessed. In FEM SAT, but not AB SAT, 2 weeks of E2 significantly (P = 0.03) increased ASC differentiation and whole SAT HSL mRNA expression (P = 0.03) compared to placebo. These changes were not associated with mRNA expression of oestrogen receptors α and ß, but HSL expression was significantly increased in FEM SAT with transdermal E2 treatment. Adipose-derived stem cells proliferation and apoptosis did not change in either SAT depot after E2 compared with placebo. Short-term E2 appeared to increase the adipogenic potential of FEM, but not AB, SAT in post-menopausal women with possible implications for metabolic disease. Future studies are needed to determine longer term impact of E2 on regional SAT accumulation in the context of positive energy imbalance.