Immune-mediated colitis associated with ocrelizumab: A new safety risk.

BACKGROUND: An association between certain immunomodulatory therapies (rituximab, ipilimumab, and other immune checkpoint inhibitors) and inflammatory (non-ischemic and non-infectious) colitis in oncologic and non-oncologic patient populations is well documented in the medical literature. OBJECTIVE: The purpose of this case series is to describe adverse event reports of new onset, inflammatory colitis in association with ocrelizumab in patients with multiple sclerosis submitted to U.S. Food and Drug Administration (FDA) or published in the medical literature. METHODS: The FDA Adverse Event Reporting System (FAERS) and medical literature were searched. RESULTS: A review of postmarketing cases from FAERS and published medical literature identified 38 cases consistent with inflammatory, non-ischemic, and non-infectious colitis in association with ocrelizumab. The median time-to-onset was 8 months. Cases were reported using the following diagnostic terms: Crohn's disease (13), unspecified colitis (11), microscopic colitis (5), ulcerative colitis (5), medication-induced colitis (3), and autoimmune colitis (2). CONCLUSIONS: This case series highlights ocrelizumab induced immune-mediated colitis that can be clinically severe and potentially life-threatening. Based on the findings of this review, the ocrelizumab Prescribing Information was amended to include immune-mediated colitis in the Warnings and Precautions section.

Alterations in the immune phenotype of thymectomized children and the development of atopic disorders after heart transplantation.

BACKGROUND: Atopic disorders are more common in children after heart transplant (HTx). We hypothesized that HTx at an early age and thymus excision (TE) affect development of T and B cells, especially regulatory T cells (Tregs), which help maintain tolerance. METHODS: In this single-center study including 24 patients transplanted between 2013 and 2018, we investigated lymphocyte patterns in relation to these factors using flow cytometry. Clinical data were collected from standardized questionnaires and medical charts. Patients were stratified into TE and non-TE groups as well as patients with and without post-transplant atopy development/worsening. RESULTS: 64% of TE patients experienced new or worsening asthma/eczema post-transplant compared to 20% of non-TE patients. TE patients had higher total Treg proportions (CD4+CD25+CD127lo) than non-TE patients (p = .043), but borderline significantly lower naïve Tregs (CD45RA+CD27-) (p = .057). Memory CD4+ T cells were higher in TE patients in trend (p = .084). Total Tregs did not differ between atopic/nonatopic groups, although naïve Tregs were significantly lower in atopic patients (p = .028). Memory CD4+ T cells were higher in atopic patients in trend (p = .082). IgM+IgD+ B cells were higher in nonatopic patients in trend (p = .064). CONCLUSIONS: New/worsening atopy is more common in thymectomized HTx children and is associated with alterations in T-cell profiles. Avoiding TE may prevent these alterations and reduce incidence of atopy post-HTx.

Ecological factors influencing parenting self-efficacy among working mothers with a child under 36 month old in South Korea: a cross-sectional and correlational study.

BACKGROUND: Parenting self-efficacy is an essential component for parents to successfully perform their role and is important for mother and child well-being. To support parenting self-efficacy amongst working mothers, it is necessary to understand the factors influencing parenting self-efficacy amongst this group. However, the majority of previous studies regarding factors influencing parenting self-efficacy did not focus on working mothers. Therefore, this study aimed to identify the factors influencing parenting self-efficacy of working mothers using an ecological framework. METHODS: The research design was a cross-sectional, correlational study. The participants were 298 working mothers with a child under 3 years of age, who were recruited from ten nurseries. Data were collected from August 8 to September 22, 2017 using structured questionnaires, including the Parenting Sense of Competency scale, a one-item Short Form Health Survey scale, the Maternal Role Satisfaction scale, the Parenting Stress Inventory, the Work and Parent Role Conflict scale, the Parenting Alliance Inventory, the Social Support scale, and the Childbirth and Parenting Friendly System scale. The study process of this study was approved by the Institutional Review Board. Collected data were analyzed by SPSS 23.0 Win program with descriptive statistics, t-test, one way ANOVA, Pearson correlation coefficient, and hierarchical multiple regression. RESULTS: Working mothers who were the primary caregiver had higher parenting self-efficacy compared to those who were not the primary caregiver (ß = .13, p = .022). At the individual level, the higher maternal role satisfaction, the higher parenting self-efficacy of working mothers (ß = .27, p < .001). In the micro-system level, higher parenting support by a spouse was associated with higher parenting self-efficacy of working mothers (ß = .19, p = .002). CONCLUSIONS: Educational interventions for increasing the awareness and satisfaction of maternal role and various strategies for fathers' active participation in parenting should be developed. In addition, practical interventions that reduce the burden of parenting while supporting parenting self-efficacy of working mothers who are the primary caregiver should also be considered.

Expanding spectrum of opportunistic infections associated with dimethyl fumarate.

BACKGROUND: Only progressive multifocal leukoencephalopathy (PML) is currently described in the dimethyl fumarate (DMF) prescribing information. OBJECTIVES: To describe opportunistic infections (OIs), other than PML, reported in association with DMF. METHODS: The FDA Adverse Event Reporting System (FAERS) and medical literature were searched. RESULTS: We retrieved 34 cases of serious OIs with a causal association with DMF, including 11 central nervous system (CNS) infections and 23 extra-CNS infections. Six OIs occurred with normal circulating absolute lymphocyte counts. The median latency from DMF initiation was 13 months and was variable. CONCLUSION: DMF is associated with the development of OIs that require invasive diagnostic and/or therapeutic procedures. Patients should be monitored for OIs when treated with DMF regardless of circulating absolute lymphocyte counts.

Maternal adaptation of working mothers with infants or toddlers in South Korea: a systematic review.

BACKGROUND: The fertility rate in South Korea has been decreasing dramatically, as working women postpone or avoid childbirth due to the challenges of maintaining a career while raising a family. Working mothers with infants or toddlers have unique maternal adaptation needs, which must be understood in order to support their needs during childbearing years. Supporting successful maternal adaptation of working mothers is not only essential for each individual new working mother, but also benefits her family, her workplace, and the country. METHODS: A systematic review was conducted to describe the current state of the science on maternal adaptation of working mothers with infants or toddlers in South Korea. Eligible studies, published between 2009 and 2018, were identified by searching electronic databases. Quantitative studies related to the maternal adaptation of Korean working mothers who had a child younger than age 3 years were included. 37 articles met the inclusion criteria for narrative analysis and synthesis. RESULTS: Studies were classified into 4 major groups by maternal adaptation categories as psychological, behavioral, relational, and cognitive adaptation. The majority of studies were focused on working mothers' psychological adaptation (n = 36, 97.3%), followed by behavioral (n = 10, 27.0%), relational (n = 9, 24.3%), and cognitive (n = 3, 8.1%) adaptation. We found that maternal adaptation of working mothers was ultimately influenced by diverse variables within their communities, spousal and familial support, personal attributes, and job-related characteristics. CONCLUSIONS: These findings demonstrate the importance of understanding variable aspects of maternal adaptation of working mothers with infants or toddlers. The complexity of working mothers' needs at the individual, family, and community levels must be considered in order to develop effective intervention programs and public policy for supporting maternal adaptation in Korea.

Effects of a maternal role adjustment program for first time mothers who use postpartum care centers (Sanhujoriwon) in South Korea: a quasi-experimental study.

BACKGROUND: Many South Korean women stay in specialized postpartum care centers called Sanhujoriwon for 2 weeks after childbirth, a time which is widely recognized as a critical period for maternal role adjustment. Mothers' time within the postpartum care center offers a unique opportunity for nursing intervention to promote a successful transition to motherhood, especially for first time mothers. This study aimed to develop a maternal role adjustment program within the Sanhujoriwon based on the ecological model, and to evaluate its effects on maternal role confidence and breastfeeding success. METHODS: A non-equivalent control group pretest-posttest design was used. Data were collected from 30 participants in the experimental group and 37 in the control group at four measurement times, i.e., admission day to Sanhujoriwon, discharge day from Sanhujoriwon, 4-6 weeks postpartum, and 12 weeks postpartum. The experimental group received the maternal role adjustment program, which included family education and counseling regarding breastfeeding and infant care, and encouraged rooming-in practices during their stay in the Sanhujoriwon. The data were analyzed using the IBM SPSS statistics 25.0 program using descriptive statistics, t-test, chi-square test, ANCOVA, and GEE. RESULTS: There were significant interaction effects showing different patterns in maternal role confidence and breastfeeding success scores over the four time points. Maternal role confidence in the experimental group gradually increased over time. Maternal role confidence in the control group also increased from baseline to 4 to 6 week postpartum, but abruptly decreased at 12 week postpartum. At 12 weeks postpartum, maternal role confidence in the experimental group was significantly higher than that of the control group. In addition, breastfeeding success scores in the experimental group also gradually increased over the four time points, while those of the control group showed a gradual decline. Breastfeeding success scores were significantly higher than those of control group at both 4-6 weeks and 12 weeks postpartum. CONCLUSIONS: These results indicate that the maternal role adjustment program was effective in improving maternal role confidence and breastfeeding success among first time mothers in the postpartum care center.

Allergies and autoimmune disorders in children after heart transplantation.

Pediatric heart transplantation requires lifelong immune suppression and may require thymectomy, both of which alter T-cell repertoires. We hypothesized that atopic and autoimmune diseases are more common in pediatric heart transplant patients than the general population, and that transplantation in early childhood increases the risk of development or worsening of atopic or autoimmune disease. A cross-sectional single-center study including 21 heart transplant patients aged ≤18 years was conducted. Data collected included age at transplant, induction, thymectomy, and development and severity of atopic or autoimmune disease. A majority (67%) reported having any atopic disease post-transplant, all of whom reported onset or worsening post-transplantation. Thymectomized patients were significantly more likely to have asthma (P = 0.018) and report asthma worsening post-transplant (P = 0.045). Patients with worsening of asthma post-transplant were transplanted at a significantly younger age (P = 0.040). ABO incompatible and ABO compatible recipients presented similarly. Anemia was common (38%) but not always clearly of autoimmune origin. Atopic diseases are common in children following heart transplantation: Compared to the general population, there is a higher prevalence of eczema (43% vs 11%) and asthma (33% vs 9%). Both thymectomy and younger age at transplant are associated with atopic disorders, possibly due to altered T-cell repertoires.

Peripheral IV Insulin Infusion Infiltration Presenting as "Insulin Resistance".

OBJECTIVES: We present the case of a 66-year-old woman who developed hypoglycemia following the prolonged infiltration of a high dose continuous peripheral IV insulin infusion. STUDY SELECTION: Case report. DATA SOURCES AND EXTRACTION: PubMed was searched for relevant literature on exogenous hyperinsulinemic hypoglycemia. DATA SYNTHESIS: The patient was postlung transplantation and was receiving high doses of glucocorticoids. Despite increasing the peripheral IV insulin rate, hyperglycemia persisted. We discovered that the IV insulin infusion line infiltrated, resulting in a large subcutaneous insulin depot, estimated to be 450 units of regular insulin. She subsequently experienced prolonged hypoglycemia that was managed with concentrated dextrose containing fluids. In our literature search, there were no similar case reports. The literature on insulin overdose, usually from suicide attempts, can help guide the management of iatrogenic hyperinsulinemic hypoglycemia. Important management considerations include anticipated duration of hypoglycemia, supplemental glucose, fluid management, and electrolyte monitoring. CONCLUSION: Peripheral IV insulin infusion infiltration should be considered when patients do not respond to increasing rates of insulin infusion.

Diabetes and Bone Marrow Adiposity.

PURPOSE OF REVIEW: This study aims to describe bone marrow fat changes in diabetes and to discuss the potential role of marrow fat in skeletal fragility. RECENT FINDINGS: Advances in non-invasive imaging have facilitated marrow fat research in humans. In contrast to animal studies which clearly demonstrate higher levels of marrow fat in diabetes, human studies have shown smaller and less certain differences. Marrow fat has been reported to correlate with A1c, and there may be a distinct marrow lipid saturation profile in diabetes. Greater marrow fat is associated with impaired skeletal health. Marrow fat may be a mediator of skeletal fragility in diabetes. Circulating lipids, growth hormone alterations, visceral adiposity, and hypoleptinemia have been associated with greater marrow fat and may represent potential mechanisms for the putative effects of diabetes on marrow fat, although other factors likely contribute. Additional research is needed to further define the role of marrow fat in diabetic skeletal fragility and to determine whether marrow fat is a therapeutic target.

Risk Factors for Bleeding in Hospitalized Patients with Elevated INR: No Vitamin K Therapy Received Versus Vitamin K Received.

BACKGROUND: Supratherapeutic international normalized ratio (INR) in patients on warfarin is a common side effect. Updated guidelines recommend against using vitamin K to correct INRs 4.5 to 10 in the absence of bleeding. The impact of compliance with updated guidelines during hospitalization has not been fully explored. METHODS: A retrospective, observational study was performed utilizing electronic medical records. The goal was to evaluate management of supratherapeutic INR values for medicine inpatients and identify differences in clinical outcomes among inpatients treated and not treated with vitamin K. Records from adult inpatients with at least one INR value between 4.5 and 9 were reviewed. A total of 51 records were evaluated. Thirty-four patients did not receive vitamin K compared to 17 who did. Bleeding events, readmissions rates, length of stay, and familiarity with new guidelines were studied. RESULTS: Mean age of patients was 73 years, and 71% were female. No statistically significant differences were observed in bleeding events between patients who received vitamin K and those who did not: 2/17 (12%) and 1/34 (3%), respectively (P = .30). No differences in 30-day readmission rates (24% vs 18%; P = .71) or in length of stay (7 vs 4 days; P = .11) were found. All pharmacists (13 of 13) were familiar with CHEST 2012 guidelines on the management of supratherapeutic INR compared to 10 of 21 (48%) hospitalists (P = .001). CONCLUSIONS: With the national focus on reduction of health care costs, health systems are looking at innovative ways to reduce readmission rates and length of stay. This study, which evaluated the use of vitamin K administration, showed no statistical difference between bleeding events, readmission rates, and length of stay in patients who received vitamin K. Education on the updates of guidelines may be beneficial, as many providers were not familiar with the changes in recommendations.

Review of oral cholecystographic agents for the management of hyperthyroidism.

OBJECTIVE: Although the use of oral cholecystographic agents (OCAs) had declined due to limited availability, there is literature to suggest it is an effective medication for thyrotoxicosis in appropriate clinical situations. METHODS: The authors performed a PubMed search and systematically reviewed all the English written case reports, original studies and reviews from 1953 to 2012. Additional information was supplemented from available online pharmacologic databases. RESULTS: The off-label use of OCAs was reviewed for the management of neonatal and adult Graves' disease, subacute thyroiditis, amiodarone-induced thyroiditis (AIT), exogenous hyperthyroidism, toxic multinodular goiter (TMNG), thyrotropinoma, thyrotoxicosis during pregnancy, rapid pre-operative control of hyperthyroidism, and thyroid storm. Adverse effects were also reviewed. CONCLUSION: OCAs generally are effective agents in treating thyrotoxicosis in the etiologies reviewed. OCAs are clinically relevant in patients who require rapid control, such as in the pre-operative state or patient who cannot tolerate a thyrotoxicosis state. OCA may also be beneficial in situations where other anti-thyroidal medication would be hazardous or ineffective, such as thionamide allergy or exogenous thyrotoxicosis. Given concern for long-term relapse, OCAs should be considered a short-term bridge to definitive therapy. OCAs are limited in TMNG and should be second line after glucocorticoids in AIT II. OCAs do not preclude the use of radioactive iodine, which can be performed one week after OCA therapy.

A rare and unique case: aortic valve replacement in a young adult with a stenotic unicommissural unicuspid aortic valve.

Unicuspid aortic valve (UAV) is a rare congenital cardiac anomaly. There are two forms of UAV, including unicuspid acommissural and unicuspid unicommissural. Definitive management for UAV is surgical intervention, but due to the rarity of UAV, the long-term surgical outcomes as well as overall prognosis are not known. Here, we present the case of a 19-year-old patient who was found to have a UAV prenatally and underwent a mechanical aortic valve replacement through an upper hemi-sternotomy due to elevated aortic stenosis gradients and presence of symptoms.

Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6 mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1 N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P < .01) and femoral neck BMD decreased (mean -3.3%, P < .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (ß-diversity) postoperatively had greater increases in P1NP level (ρ = 0.48, P = .02) and greater bone loss at the femoral neck (ρ = -0.43, P = .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ = 0.56, P < .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ = 0.43, P = .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ = -0.43, P = .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, is a highly effective treatment for obesity because it produces dramatic weight loss and improves obesity-related medical conditions. However, it also results in abnormalities in bone metabolism. It is important to understand how LSG affects the skeleton, so that bone loss after surgery might be prevented. We studied adult men and women before and 6 mo after LSG, and we explored the relationship between the altered gut bacteria and bone metabolism changes. We found that: Those with greater shifts in their gut bacterial composition had more bone loss.Butyrate, a metabolite produced by gut bacteria from fermentation of dietary fiber, was associated with less bone breakdown and higher IGF-1 level (a bone-building hormone). We conclude that changes in the gut bacteria may contribute to the negative skeletal impact of LSG and reduced butyrate production by the gut bacteria leading to lower IGF-1 levels is a possible mechanism.

Current progress of cerebral organoids for modeling Alzheimer's disease origins and mechanisms.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease that has emerged as a leading risk factor for dementia associated with increasing age. Two-dimensional (2D) cell culture and animal models, which have been used to analyze AD pathology and search for effective treatments for decades, have significantly contributed to our understanding of the mechanism of AD. Despite their successes, 2D and animal models can only capture a fraction of AD mechanisms due to their inability to recapitulate human brain-specific tissue structure, function, and cellular diversity. Recently, the emergence of three-dimensional (3D) cerebral organoids using tissue engineering and induced pluripotent stem cell technology has paved the way to develop models that resemble features of human brain tissue more accurately in comparison to prior models. In this review, we focus on summarizing key research strategies for engineering in vitro 3D human brain-specific models, major discoveries from using AD cerebral organoids, and its future perspectives.

Bone Marrow Adiposity Alterations in Type 2 Diabetes Are Sex-Specific and Associated with Serum Lipid Levels.

Type 2 diabetes (T2D) has negative effects on skeletal health. A proposed mechanism of diabetic bone disease connects hyperlipidemia to increased bone marrow adiposity and decreased bone quality. Previous research on Type 1 diabetes reported positive associations between serum lipid levels and marrow adiposity, but no data exist for T2D. In addition, marrow adiposity is sex-dependent in healthy populations, but sex has not been addressed adequately in previous reports of marrow adiposity in T2D. The purpose of this study was to quantify associations of marrow adiposity and composition with T2D status, serum lipid levels, and sex. T2D patients and normoglycemic controls (n = 39/37) were included. Single-voxel magnetic resonance spectroscopy (MRS) was performed at the spine and tibia. Quantitative MRS outcomes of marrow adiposity and composition were calculated. Linear regression models were used to compare MRS outcomes among groups and to evaluate associations of MRS outcomes with serum lipid levels. All analyses were performed on sex-stratified subgroups. Total, unsaturated, and saturated fat content at the spine were lower in T2D participants compared to controls in age-adjusted models; these differences were significant in men but not in women. In our study cohort, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were lower in T2D participants compared to controls. Adjustment for LDL, HDL, and statin use attenuated the association of T2D status with unsaturated fat but not saturated fat in men. Further analysis confirmed significant associations between serum lipid levels and MRS outcomes. Specifically, we found a positive association between LDL cholesterol and total marrow fat in the male T2D group and a negative association between HDL and total marrow fat in the female T2D group. In conclusion, our results suggest that marrow adiposity and composition are associated with lipid levels as well as T2D status, and these relationships are sex-specific. © 2023 American Society for Bone and Mineral Research (ASBMR).

Intestinal Calcium Absorption Decreases After Laparoscopic Sleeve Gastrectomy Despite Optimization of Vitamin D Status.

CONTEXT: Laparoscopic sleeve gastrectomy (LSG), now the most commonly performed bariatric operation, is a highly effective treatment for obesity. While Roux-en-Y gastric bypass is known to impair intestinal fractional calcium absorption (FCA) and negatively affect bone metabolism, LSG's effects on calcium homeostasis and bone health have not been well characterized. OBJECTIVE: We determined the effect of LSG on FCA, while maintaining robust 25-hydroxyvitamin D (25OHD) levels and recommended calcium intake. DESIGN, SETTING, PARTICIPANTS: Prospective pre-post observational cohort study of 35 women and men with severe obesity undergoing LSG. MAIN OUTCOMES: FCA was measured preoperatively and 6 months postoperatively with a gold-standard dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and bone mineral density (BMD) by dual-energy X-ray absorptiometry and quantitative computed tomography. RESULTS: Mean ± SD FCA decreased from 31.4 ± 15.4% preoperatively to 16.1 ± 12.3% postoperatively (P < 0.01), while median (interquartile range) 25OHD levels were 39 (32-46) ng/mL and 36 (30-46) ng/mL, respectively. Concurrently, median 1,25-dihydroxyvitamin D level increased from 60 (50-82) pg/mL to 86 (72-107) pg/mL (P < 0.01), without significant changes in parathyroid hormone or 24-hour urinary calcium levels. Bone turnover marker levels increased substantially, and areal BMD decreased at the proximal femur. Those with lower postoperative FCA had greater areal BMD loss at the total hip (ρ = 0.45, P < 0.01). CONCLUSIONS: FCA decreases after LSG, with a concurrent rise in bone turnover marker levels and decline in BMD, despite robust 25OHD levels and with recommended calcium intake. Decline in FCA could contribute to negative skeletal effects following LSG.

Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT.

Bone marrow adiposity in diabetes and clinical interventions.

PURPOSE OF REVIEW: This study aims to review bone marrow adipose tissue (BMAT) changes in people with diabetes, contributing factors, and interventions. RECENT FINDINGS: In type 1 diabetes (T1D), BMAT levels are similar to healthy controls, although few studies have been performed. In type 2 diabetes (T2D), both BMAT content and composition appear altered, and recent bone histomorphometry data suggests increased BMAT is both through adipocyte hyperplasia and hypertrophy. Position emission tomography scanning suggests BMAT is a major source of basal glucose uptake. BMAT is responsive to metabolic interventions. SUMMARY: BMAT is a unique fat depot that is influenced by metabolic factors and proposed to negatively affect the skeleton. BMAT alterations are more consistently seen in T2D compared to T1D. Interventions such as thiazolidinedione treatment may increase BMAT, whereas metformin treatment, weight loss, and exercise may decrease BMAT. Further understanding of the role of BMAT will provide insight into the pathogenesis of diabetic bone disease and could lead to targeted preventive and therapeutic strategies.

Bone marrow adipose tissue composition and glycemic improvements after gastric bypass surgery.

Fracture risk is increased in type 2 diabetes, which may in part be due to altered bone marrow adiposity. Cross sectional studies have reported that people with type 2 diabetes have lower unsaturated BMAT lipid levels than people without diabetes, although there are limited data on longitudinal changes. We hypothesized that Roux-en-Y gastric bypass (RYGB), which dramatically improves glycemic status, would have differential effects on BMAT composition, with increases in the unsaturated lipid index in people with diabetes. Given reports that axial BMAT is responsive to metabolic stimuli while appendicular BMAT is stable, we hypothesized that BMAT changes would occur at the spine but not the tibia. We enrolled 30 obese women, stratified by diabetes status, and used magnetic resonance spectroscopy to measure BMAT at the spine in all participants, and the tibia in a subset (n = 19). At baseline, BMAT parameters were similar between those with and without diabetes, except tibial marrow fat content was lower in women with diabetes (97.4 % ± 1.0 % versus 98.2 % ± 0.4 %, p = 0.04). Six months after surgery, both groups experienced similar weight loss of 27 kg ± 7 kg. At the spine, there was a significant interaction between diabetes status and changes in both marrow fat content and the unsaturated lipid index (p = 0.02, p < 0.01 for differences, respectively). Women with diabetes had a trend towards a decline in marrow fat content (-4.3 % ± 8.2 %, p = 0.09) and increase in the unsaturated lipid index (+1.1 % ± 1.5 %, p = 0.02). In contrast, BMAT parameters did not significantly change in women without diabetes. In all women, changes in the unsaturated lipid index inversely correlated with hemoglobin A1c changes (r = -0.47, p = 0.02). At the tibia, there was little BMAT change by diabetes status. Our results suggest that vertebral BMAT composition is responsive to changes in glycemic control after RYGB.