bluuebunny/crossref_metadata_2025 huggingface dataset:
Are Obese Patients Evaluated for Non-Alcoholic Fatty Liver Disease in an Endocrinology Outpatient Clinic?
Authors: Irazusta Florencia , Vidal Francisco , Pineyro Maria Mercedes , Pereda Jimena
Published: May 2021

Background: Obesity is an increasing global health problem worldwide and Uruguay mirrors these trends. It leads to various complications that include non-alcoholic fatty liver disease (NAFLD). NAFLD is one of the most common liver disorders in industrialized countries with an estimated global prevalence of 25–30%. It is one of the main causes of liver transplant, for which is considered a global public health problem. It includes simple steatosis, and nonalcoholic steatohepatitis, that can progress to cirrhosis and hepatocellular carcinoma. Several studies have shown a close relationship between NAFLD and obesity, with a reported prevalence of up to 80% in these patients. The diagnosis of NAFLD requires demonstration of hepatic steatosis by imaging and exclusion of other causes (absence of significant alcohol consumption, hepatitis infection, autoimmune hepatitis and hemochromatosis). We aimed to determine whether obese patients are evaluated for NAFLD in our endocrinology outpatient clinic. Methods: We conducted a cross-sectional study among 130 obese adults attending our clinic from December 2019 to March 2020. Results: The mean age was 53.8 years (range 19–80) and 80% were women. The mean BMI was 35.9 kg/m2 ± 5.3. Obesity class I, II and III was present in 55%, 25% and 20% of patients, respectively. Type 2 diabetes (DM2), hypertension and dyslipidemia were found in 46.2%, 61.5% and 76.2% of patients, respectively. Abdominal ultrasound was not performed in 62% of patients. Abdominal ultrasound was performed significantly more often in diabetics compared to non-diabetics (48.3% vs. 38%, p=0.046). There was no significant association between obesity class and presence of ultrasound (p=0.20), or liver steatosis (LS) (p=0.58). Seventy-eight percent showed LS (56% mild, 31% moderate and 13% severe). The majority (87.7%) had liver enzymes measured. Patients with and without LS showed similar proportion of elevated enzymes (36% and 36.4%, respectively). The most frequent raised enzyme was gamma-glutamyl transferase, present in 82.9% of patients, and in similar proportion between patients with and without LS (30.8% and 36.4%, respectively). Elevated liver enzymes were found in 22.7%, 46.6% and 80% of mild, moderate and severe LS, respectively. There was significant association between LS grade and liver enzymes elevation (p<0.01). Secondary causes of LS were evaluated in 35.9% of patients, in all cases except one by the gastroenterology service. Half of the individuals had other causes of liver disease (alcoholism (28.6%), hepatitis B virus (28.6%) and methotrexate (28.6%) and prednisone (14.2%)treatment). Conclusion: NAFLD is a scantily evaluated disorder in our obese patients. In those evaluated we found a high frequency of LS, with almost 50% having moderate or severe disease. Further research is warranted to determine its prevalence and associated complications in our population.
Fetal Growth Disorders and Influence of Maternal Adiposity
Authors: Athar Sufia , Tellisi Amna Khalifa
Published: May 2021

Introduction: Infant birth weight is recognized as the leading indicator of health among infants and affects a wide range of subsequent outcomes later in life. The incidence of neonates with high birth weight has increased in recent years. Many studies in the past have revealed that high birth weight is associated with neonatal morbidity and mortality and associated with complications in later life. These complications include shoulder dystocia, birth trauma, asphyxia, and neonatal deaths. In the later life these neonates have high risk for obesity, hypertension, diabetes mellitus and cancer. High pre-pregnancy body mass index (BMI) has been reported as a well-established risk factors for adverse pregnancy outcomes. Despite the high prevalence of maternal obesity in the gulf region, only a few studies in this regard have been published. Methods: A retrospective service evaluation was conducted at a secondary hospital to evaluate the effect of pre-pregnancy BMI on neonatal birth weight. 950 women were randomly selected from women delivered at or more than 37 weeks gestation and grouped on the basis of pregnancy BMI as group A-BMI 18.5–24.9 kg/m2, group-B- BMI 25–29.9 kg/m2 and group C-BMI >30 kg/m2. Infants were grouped according to birth weight as low birth weight(<2500 g), normal birth weight (2500–3999 g), and high birth weight >4000g and correlation was studied with maternal body mass index. Chi square test was used for statistical evaluation using Medcal online software. Results: In the study group, 34.43% women had normal body mass index, 37.21 % women were overweight and 28.36 % were obese. In group A, 6.50% and 4.64 % infants were with low and high birth weight, respectively. In group B, 4.3% and 5.73 % were with low and high birth weight, respectively. In group C, 4.51% and 20.33 % infants were with low and high birth weight, respectively. In comparison to women with normal BMI, low birth weight infants in group B (OR-0.922, 95% CI- 0.327–1.275) and group C (OR- 0.679, 95% CI-0.682–1.572) were not statistically significant. High birth weight infants in group B (OR- 1.2482, 95% CI- 0.3270 to 1.2756, p = 0.2080) and group C (OR-5.230, 95% CI-2.875–9.512, p= < 0.0001) were positively correlated with pre-pregnancy BMI. Pre-pregnancy overweight and obesity increased the risk of high birth weight (OR- 1.248 and 5.230 respectively). The results were statistically significant in obese women (p=< 0.0001). Conclusion: Women with pre-pregnancy overweight and obesity have higher likelihood of high birth weight in infants. Pre-pregnancy weight loss is the key to reduce maternal and fetal complications. Early pregnancy booking and antenatal fetal surveillance is recommended for all women with high body mass index.
Hair Cortisol, Obesity and the Immune System: Results From a 3 Year Longitudinal Study
Authors: van der Valk Eline S , van der Voorn Bibian , Iyer Anand M , Mohseni Mostafa , Leenen Pieter J M , Dik Willem A , de Rijke Yolanda B , van den Akker Erica L T , Penninx Brenda W J H , van Rossum Elisabeth F C
Published: May 2021

Background: Long-term glucocorticoid levels measured in scalp hair (HairGC) are positively correlated to obesity in cross-sectional studies, however it is unclear whether this reflects a state of obesity or an actual maintaining or contributing factor to obesity. Objectives: To investigate whether hair cortisol (HairF) and hair cortisone (HairE) predict changes in body mass index (BMI) and waist circumference (WC) over time, and to assess whether HairGC are linked to immune parameters. Methods: We measured HairGC in 1604 participants of the Netherlands Study of Depression and Anxiety (NESDA), and correlated these to BMI, WC, and immune parameters (interleukin-6 (IL-6), high-sensitive C-reactive protein (CRP), total leukocyte, monocyte and lymphocyte counts and the neutrophil-to-lymphocyte ratio). Also, we assessed whether baseline HairGC predict changes in BMI and WC at the follow-up visit, three years later, and whether immune parameters influenced this correlation. Results: In cross-sectional analyses, HairF and HairE were positively correlated to BMI (β=2.06 and β=2.84kg/m2 respectively) and WC (β=5.36 and β= 8.54cm respectively, all p<0.001). HairF was related to IL-6 (adjusted β=0.15, p<0.05) and leukocyte count (adjusted β=0.57, p<0.01), and HairE to IL-6 (adjusted β=0.21, p<0.05). In the adjusted longitudinal analyses, baseline HairF was associated with a yearly increase in BMI (β=0.58%, p=0.009) and baseline HairE with a yearly increase in WC (β=0.84%, p=0.049). Adjusting for baseline IL-6 or leukocytes did not affect the found associations between GC and WC or BMI change. Conclusions: HairGC levels are related to BMI, WC, IL-6 and leukocytes in cross-sectional analyses. Moreover, chronically higher HairGC may be a relevant risk factor for the development of obesity in the future, although causality is yet to be proven.
Higher Peptide YY Levels Are Associated With Lower Bone Mineral Density in Low Weight Adolescent Girls With Avoidant/Restrictive Food Intake Disorder
Authors: Sella Aluma Chovel , Becker Kendra Rosamond , Slattery Meghan , Hauser Kristine , Kahn Danielle L , Kuhnle Magen , Thomas Jennifer J , Eddy Kamryn T , Misra Madhusmita , Lawson Elizabeth Austen
Published: May 2021

Background: Avoidant/Restrictive Food Intake Disorder (ARFID) is a condition characterized by lack of interest in eating or food, sensory sensitivity, and/or fear of aversive consequences of eating; as opposed to the body image disturbance and fear of weight gain that characterize anorexia nervosa (AN). While appetite regulating hormones and their associations with bone mineral density (BMD) have been well studied in AN, little is known regarding BMD and its association with appetite regulating hormones in ARFID. Peptide YY (PYY), a gut derived anorexigenic hormone, acts via the Y2 receptor to inhibit osteoblastic activity in mammals. In AN, levels of PYY are higher than in healthy controls (HC) and are negatively associated with BMD. We hypothesized that similar to AN, low-weight female adolescents with ARFID would have lower BMD and higher PYY levels than in HC and that PYY levels would be inversely associated with BMD.

Methods: We studied 24 adolescent females (10 low weight with ARFID and 14 HC). BMD variables were measured by Dual-Energy X-ray Absorptiometry. We performed cross sectional analysis to compare BMD and fasting PYY levels between low weight ARFID and HC and to determine the relationship between BMD and PYY levels.

Results: ARFID and HC were 15.1±2.9 (mean ± SEM) and 17.1±3.8 years old, respectively (p=0.178), with mean BMI Z-scores of -1.74±0.88 kg/m2 and 0.24±0.51 kg/m2, respectively (p<0.0001). Total body BMD Z-scores were significantly lower in ARFID (-1.59±1.19, n=10) compared to HC (-0.41±1.11, n=14) (p=0.022), and lumbar BMD Z-scores were numerically lower in ARFID (-1.13±1.40, n=9) vs. HC (-0.44±0.86, n=14) (p=0.212). Mean PYY levels trended higher in ARFID (104.6±39.9 pg/ml, n=8) vs. HC (71.4±24.5 pg/ml, n=9) (p=0.054). In a combined analysis of participants with ARFID and HC, PYY levels were negatively correlated with lumbar BMD and BMD Z-scores (r=-0.52, p=0.038 and r=-0.54 p=0.031, n=16). In multivariable regression analysis, PYY remained a primary determinant of lumbar BMD after adjusting for age and height (p=0.035, β= -0.36) and a borderline significant predictor of lumbar BMD Z-scores after adjusting for height (p=0.064, β=-0.5). Similar associations were noted within the ARFID group alone, with PYY being a significant predictor of lumbar BMD (p=0.031, β=-0.97) after adjusting for age and height.

Conclusion: Female adolescents with low-weight ARFID have lower BMD and a trend toward higher levels of PYY compared with HC. Increased PYY levels may contribute to the lower BMD observed in ARFID. These findings are an initial step in understanding the neuroendocrine dysregulation in low weight adolescents with ARFID, which may predict bone outcomes in this condition.
Longitudinal Weight Gain and Lifestyle Factors in Women With and Without Polycystic Ovary Syndrome
Authors: Awoke Mamaru Ayenew , Earnest Arul , Joham Anju Elizabeth , Hodge Allison M , Brown Wendy J , Teede Helena Jane , Moran Lisa J
Published: May 2021

Background: While women with polycystic ovary syndrome (PCOS) have a higher prevalence of overweight/obesity and increased weight gain than women without PCOS, the association of lifestyle behaviours with weight change is not known. Methods: We used data from the 1973–78 cohort of the Australian Longitudinal Study on Women’s Health for longitudinal analysis over 19 years (N=14127 at survey 1). Linear mixed-effects models were used to examine weight change and its association with diet, physical activity and sitting time, adjusted for sociodemographic, psychological factors and health care utilisation. Results: Women with PCOS gained more weight annually (0.27 kg/year, 95% CI 0.14, 0.40; P<0.001) and over 19 years (15.3 kg 95% CI 10.9, 19.7 Vs. 10.8 kg 95% CI 5.5, 16.2) than women without PCOS. There was a three-way interaction between energy intake (0.31 kg, 95% CI 0.004, 0.61; P=0.047), glycaemic index (0.44 kg, 95% CI 0.13, 0.74; P=0.005), sitting time (0.55 kg 95% CI 0.002, 1.10; P=0.049), physical activity (-0.37 kg, 95% CI -0.69, -0.05; P=0.022) and PCOS and time. While women with PCOS had higher weight gain than those without PCOS overall, this difference was greater for women with PCOS with higher energy intake, glycaemic index and longer sitting time and those not meeting PA guidelines. Conclusions: Women with PCOS had a higher rate of weight gain than those without PCOS with those with unhealthy lifestyle behaviours having the greatest weight gain. Women with PCOS may be biologically predisposed to weight gain when experiencing adverse lifestyle factors. This reinforces the contribution of lifestyle factors to weight change and the importance of early lifestyle intervention in PCOS.
Misperception of Weight Is Greater in Healthy Asian Indian Urban Men Than Women
Authors: Lathia Tejal , Chakravarti Sujata
Published: May 2021

Background: Recognizing being overweight is one step towards implementing weight-management behaviors and appropriate interventions Objective: This observational study was designed to study whether the self-perceived body mass index (BMI) status matched the calculated BMI status. Weight loss measures undertaken by overweight or obese participants in real life were also investigated Methods: Healthy men (M) and women (W) (18–65 years old) attending a health check-up at Fortis Hiranandani Hospital, Navi Mumbai, India from 1 August 2019 to 30 November 2019 were systematically included. Information on participants’ perception about their weight, intention of weight management and actual weight-management behavior were collected through simple structured questionnaire. Anthropometric measurements were obtained from all participants to compute their current BMI. Results: Overall, 148 (68%) of 218 (M=158; W=60; median [range] age: 36 [21–44] years) participants were overweight/obese (BMI>25 kg/m2). Majority of the participants were graduate and above (93%). A significant association was seen between increasing age and overweight/obesity (p=0.006). Although similar number of M and W were overweight/obese (70% vs 63%), fewer M perceived themselves to be overweight/obese than W (58% vs 77%, p=0.049). Both M and W attributed their overweight/obese status to lack of exercise (44% vs 46%) and poor dietary habits (38% vs 28%). Additionally, W also attributed their overweight/obese status to hormonal imbalance (hypothyroidism, polycystic ovarian syndrome, post pregnancy, menopause; 28%). Most common (>20% incidence) reasons stated to lose weight were to be healthier and disease-free (82 [55%], M=51; W=31) and look better (36 [24%], M=13; W=23). Majority of the participants attempted to lose weight by exercise (60 [73%], M=43; W=25) and dietary interventions (55 [67%], M=29, W=26). The most common (>40%) exercise regimen used to lose weight was cardio/aerobic activity (31 [52%], M=19; W=12) followed by morning walks (29 [48%], M=20; W=9). Most common dietary intervention practiced was healthy eating based on general knowledge (34 [62%], M=17, W=17) and guidance from family and friends (10 [18%], M=6; W=4); only 1 woman consulted professional dietician. Conclusion: Discrepancy exists between self-perceived and actual calculated BMI status, especially so in men. Though women better perceived weight, they were less likely to participate in scientifically proven methods or professional guidance to lose weight.
Neurobiology of Avoidant/Restrictive Food Intake Disorder in Youth With Overweight/Obesity Versus Healthy Weight
Authors: Liya Kerem , Van De Water Avery L , Kuhnle Megan C , Harshman Stephanie , Hauser Kristine , Eddy Kamryn T , Becker Kendra R , Misra Madhusmita , Micali Nadia , Thomas Jennifer J , Holsen Laura , Lawson Elizabeth A
Published: May 2021

Objective: Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistence of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight.

Method: Youth with full/subthreshold ARFID (11 with healthy weight [HW], 12 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation and hunger.

Results: Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW subjects with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect=18.39, SE=11.27, 95% CI [-45.09, -3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB.

Conclusions: Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation.
No Differences in Metabolic Parameters Between Roux-en-Y Gastric Bypass and Sleeve Gastrectomy, Regardless of Achieved Weight Loss
Authors: Holanda Narriane Chaves Pereira , Lacerda Mariana Braga , de Holanda Limeira Caio Chaves , Borges Heloisa Calegari , Sales Marilia Moreira , de Oliveira Viana Gabrielly , Cavalcante Arthur Gomes , Nobrega Medeiros Igor Rosembergh , Carvalho Nara Nóbrega Crispim , Bandeira Francisco Farias
Published: May 2021

Background: Roux-en-y (RYGB) is considered a procedure with more malabsorptive impact than sleeve Gastrectomy (SG), so the risk of chronic complications seems greater. Aim: To describe the metabolic profile and weight regain of patients who underwent bariatric surgery, according to each procedure. Method: A retrospective cohort with patients who underwent bariatric surgery (2003–2018). The sample was divided into SG group and RYGB group. Comparisons were made to analyze the relationship between the procedure itself and metabolic improvements, weight loss and weight regain. Results: We included 117 eligible participants (91.5 % female, 51.2% RYGB surgery), mean follow-up was 4.4± 3.3 years. Mean age was 41.8±6.8 years, without significant difference between the groups. Before the surgery, the groups were similar according metabolic profile (fasting glucose, Hba1c, total cholesterol, LDLc, triglycerides and HOMA IR), except by non-HDLc (RYGB 108.8±26.3 vs SG 127.2±33.2 mg/dl, p=0,002) and 25OHD (RYGB 28.9±4,7 vs SG 34.3±9,5 ng/ml, p=0.044). The RYGB group had greater weight than the SG group (mean 114.1±13.5 kg vs 122.7±20.5 Kg, p<0.0001) and almost 23.3% of the participants had T2DM and 36.2% of them had systemic arterial hypertension, without significant difference between the groups. The RYGB group had a greater postoperative time than the SG group (mean 5.0±4.0 vs 3.6± 2.9 years, respectively). After the surgery, although weight loss was greater in the RYGB group than the SG group (mean 39%±10.2 vs 34.1%±9.8, p<0.0001, respectively), both groups were similar regarding BMI, body fat percentage (BFP) and abdominal circumference. Also, there were no differences in the metabolic profile (fasting glucose, Hba1c, HOMA IR, leptin, triglycerides and HDLc), according to the type of surgery, except in the total cholesterol and LDLc levels (RYGB 167.9±28.2 vs SG 187.9±35.1 and RYGB 92.6±25.6 vs SG 109.5±30.8). Nearly the whole sample (95%) has reached > 20% weight loss. Despite that, 37.6% of the patients have regained > 20% of weight loss, with no relation regarding the type of surgery. Only 7% of the patients remained with some degree of glucose intolerance, with no difference between the groups. Conclusion: We found similar benefits among metabolic markers and weight regain after SG, compared to RYGB.
Obesity, Body Fat Distribution, and Circulating Glutamate Concentrations, A BI-Directional Mendelian Randomization Study
Authors: Maltais-Payette Ina , Bourgault Jérôme , Arsenault Benoît , Tchernof Andre
Published: May 2021

Background: Various observational studies have reported that circulating levels of the amino acid glutamate was significantly associated with central fat accumulation in men and women. This is the case in the Framingham Heart Study Generation 3 for waist circumference, in the TwinsUK cohort for trunk fat and in a cohort of 1449 Japanese for visceral adipose tissue area measured by computed tomography. However, whether the association between abdominal adiposity and circulating glutamate is causal, as well as the direction of this association, is unknown. Here, we aimed to determine whether obesity and abdominal obesity were causally associated with circulating glutamate levels. Methods: We used a two-sample bi-directional inverse-variance weighted Mendelian randomization study design (IVW-MR). We derived summary statistics for our exposures and outcomes from published genome-wide association studies from the GIANT consortium (n = 681 275) and blood metabolites (n = 7 804). We identified independent genetic variants (r2 < 0.1) associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI, p < 5x10-8) as well as circulating glutamate (p < 5x10-5). Results: We found no causal association between circulating glutamate levels and BMI (beta = 0.082, SE = 0.0413, p = 0.0471) or WHRadjBMI (beta = -0.00106, SE = 0.0401, p = 0.979). However, there was a positive effect of BMI (beta = 0.0608, SE = 0.0150, p = 5.19x10-5) and WHRadjBMI (beta = 0.0701, SE = 0.0198, p = 3.98x10-4) on circulating glutamate level. Conclusion: This Mendelian randomization analysis suggests that obesity and abdominal obesity are causally related to elevated circulating glutamate levels. Glutamate levels are not causally related to adiposity. Whether the downregulation of branched-chain amino acid catabolism in adipose tissue reported in obesity underlies this association should be explored.
Profile of Intestinal Microbiota and Anxiety Level in Overweight Children and Adolescents
Authors: Bandeira Farias Maria Paula Costa , Carvalho Bruno , Neto Adauto
Published: May 2021

Justification: Obesity is considered a worldwide epidemic, with a significant increase in its prevalence in the last 30 years in both children and adolescents. Anxiety disorders can be considered both a cause and a consequence of obesity. The intestinal microbiota has been identified as a participant in the inflammatory process of both obesity and depression / anxiety disorders. Objective: Describe and compare the intestinal microbiota profile of overweight/obese children/teenagers with and without signs of anxiety. METHODOLOGICAL PROCEDURES: descriptive, observational, cross-sectional study with an analytical character (comparison of groups), carried out during the months of January to October of the year 2019. 30 overweight/obesity children/teenagers (BMI greater than P85 – WHO 2007), between seven and 17 years old, convenience sampling. None of the participants had taken antibiotics during the past eight weeks of participation on the study or had chronic or endocrine disease that was not being adequately treated. The participants were divided into two groups: the first group consists of children/adolescents with excess weight without signs of anxiety (n 16) and the second group consists of children/adolescents with excess weight with signs of anxiety (n 14), assessed by a Screen for Child Anxiety Related Emotional Disorders (SCARED) screening questionnaire. Results: The group with signs of anxiety showing higher HOMA IR compared to the group without signs of anxiety with values ​​of 5.05 ± 2.08 and 3.47 ± 1.6 (p = 0.041), respectively. There was a statistically significant difference for beta diversity of the intestinal microbiota profile using the CHAO method (p = 0.025) and the Jackknife method (p = 0.01) between the groups with signs of anxiety and without signs of anxiety. Conclusion: difference was found between the intestinal microbiota diversity of obese children / adolescents with signs of anxiety in relation to the intestinal microbiota diversity of obese children / adolescents without signs of anxiety. This finding suggests a possible involvement of the imbalance of the intestinal microbiota with anxiety disorders and depression in children/adolescents with weight excess.
Renal Outcomes One Year After Metabolic Bariatric Surgery: A Clinical Audit
Authors: Wee Zongwen , Tham Kwang Wei , Tan Hong Chang , Ganguly Sonali , Lim Chin Hong , Chan Weng Hoong , Hock Eng Alvin Kim , Hui Tan Jeremy Tian , Wee Lim Eugene Kee , Lin Ho Emily Tse , Kovalik Jean-Paul , Lee Phong Ching
Published: May 2021

Introduction: Obesity increases the risk of incident chronic kidney disease (CKD), being one of the strongest risk factors for new-onset CKD even in the metabolically normal obese. Weight loss has been shown to reduce renal hyperfiltration and proteinuria. Metabolic Bariatric Surgery (MBS) remains an effective treatment for obesity and its metabolic related complications. However, literature on its impact on long term renal function remains limited.

Methods: This was an observational retrospective study in a tertiary centre in Singapore. MBS cases performed at the centre between 2008 and 2019 were included. The primary outcome measure was estimated Glomerular Filtration Rate (eGFR), calculated using the CKD Epidemiology Collaboration equation, and albuminuria (defined as urine Albumin-Creatinine Ratio (uACR) >3.5 mg/mmol) at baseline and at one-year post surgery.

Results: 557 patients were included. Baseline parameters are as follows: mean age 41.7 ±10.1 years; female 65.4%; ethnic composition: Chinese (35.2%), Malay (33.0%), Indian (26.9%); BMI 42.5 ±7.9 kg/m²; glycaemic status: Diabetes Mellitus (34.5%), Pre-diabetes (13.5%), Non-diabetic (52.1%); Hypertensive status: Hypertension (55.2%), Pre-Hypertension (1.9%), Normotensive (42.9%). Median eGFR was 110.9 (92.4 - 121.5) mL/min/1.73 m² and median uACR was 1.00 (0.40 - 3.55) mg/mmol. At one-year post surgery, patients achieved statistically significant reductions in mean BMI (-11.3 ±4.2 kg/m2), systolic BP (-3.24 ±19.3 mmHg), diastolic BP (-5.23 ±13.8 mmHg), fasting glucose (-1.95 ±2.89 mmol/L) and improvement in HDL (0.29 ±0.26 mmol/L). In addition, statistically significant reductions in the proportion of patients on anti-hypertensive (48.8% to 14.4%), anti-diabetic (34.1% to 12.7%) and lipid-lowering medications (37.8% to 20.4%) were seen. In particular, ACE-inhibitor and/or angiotensin receptor blocker (32.9% to 9.2%, p< 0.001) usage was reduced. At one-year post surgery, median eGFR increased by 1.66 mL/min/1.73 m² (p<0.001). Further stratification by glycemic status showed significant increases in GFR in patients without diabetes or pre-diabetes. There was a decrease in median uACR (0.30 mg/mmol, p=0.001) at one-year post surgery; this remained statistically significant in patients with diabetes and pre-diabetes. 12.9% of patients had improvements in CKD staging. The proportion of patients with albuminuria decreased from 24.8% at baseline to 1.89% one-year post surgery (p<0.001).

Conclusions: Metabolic bariatric surgery had a positive impact on renal function as shown by the improvement in eGFR in the non-diabetic group, and the reduction in albuminuria in the diabetes and pre-diabetes group at one-year post surgery. More adequately powered, longer-term data is required to investigate the durability of this impact.
Serum Levels of Lipocalin Are Lower in Adolescents With X-Linked Hypophosphatemia
Authors: Simpson Christine A , Santoro Anna Maria , Carpenter Thomas O , Insogna Karl Leonard
Published: May 2021

Individuals with X-linked hypophosphatemia (XLH) are at greater risk for being overweight or obese. It has generally been assumed that the primary reason for this is impaired mobility due to accelerated osteoarthritis, abnormal biomechanics of ambulation, pseudofractures and enthesopathy. These known complications limit the ability of patients with XLH to engage in regular aerobic exercise. Whether there are underlying metabolic abnormalities that also put patients with XLH at greater risk for excessive weight gain is largely unknown. A recent French study1 confirmed that patients with XLH, especially adolescents, have a predilection to obesity. Evidence suggests that elevated circulating levels of fibroblast growth factor 23 (FGF23) are associated with an increase in fat mass and dyslipidemia in elderly normal individuals. Whether the elevated levels of FGF23 in XLH play a direct pathogenic role in the risk for excessive weight gain in XLH is unclear. Lipocalin (LCN2) has recently received considerable attention as a factor regulating energy consumption and specifically is postulated to be anorexigenic and improve insulin sensitivity. We therefore measured circulating levels of LCN2, leptin and insulin in 32 patients with XLH, ages 2–60 y.o., all of whom were being treated with burosumab and 40 Cntrl subjects, matched for age, sex, and BMI or weight/height z-score for children and adolescents. Serum was obtained from excess sample from clinical 25-hydroxy vitamin D testing in our laboratory. All patients were de-identified for the study. In 7 adults with XLH 20–60 y.o. (mean age 35) and 11 Cntrls (mean age 41), mean values for BMI, LCN2, leptin and insulin levels in the two group were as follows, (XLH vs. Cntrl); BMI: 36 vs. 34 kg/m2, LCN2: 83 vs. 108 ng/mL, leptin: 26 vs. 39 ng/mL, insulin: 19 vs. 20 µIU/mL. The pediatric patients were separated into two groups: 2–10 and 11–18 y.o.. In the 2–10 y.o. group the mean values were (XLH vs. Cntrl); age: 5.5 y.o. vs. 5.8 y.o., weight/height Z-score: 0.8 vs. 1.1, LCN2: 47 vs. 60, leptin: 2.2. vs. 6.7, and insulin: 8.4 vs. 13. In the 11–18 group, mean values were (XLH vs. Cntrl); age: 14 y.o. vs. 14 y.o., weight/height Z-score: 1.0 vs. 1.2, LCN2: 65 vs. 105, leptin: 24 vs.19, and insulin: 17 vs. 48. In all age groups LCN2 was lower in the patients with XLH than Cntrls and this difference reached significance in the adolescents with XLH (p=0.04). No other parameters were significantly different among the groups. Since all patients with XLH were treated with burosumab it is unlikely that a direct effect of excess FGF23 production explains this finding. We conclude that reduced expression of lipocalin in adolescents with XLH may contribute to their risk for obesity.1Lecoq et.al. Obesity and Impaired Glucose Metabolism in Adult Patients with X-Linked Hypophosphatemia, J, Endo. Soc. 2020 https://doi.org/10.1210/jendso/bvaa046.1355
Timing of Onset of Adverse Events With Setmelanotide, an MC4R Agonist, in Patients With Severe Obesity Due to LEPR or POMC Deficiency
Authors: Clément Karine , van den Akker Erica L T , Gordon Gregory , Yuan Guojun , Kühnen Peter
Published: May 2021

Introduction: Setmelanotide is a melanocortin 4 receptor agonist indicated for chronic weight management in patients with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. This analysis aimed to assess the timing of the onset of adverse events (AEs) of special interest in patients with POMC/PCSK1 or LEPR deficiency obesity treated with setmelanotide. Methods: The timing of AE onset with setmelanotide was evaluated in a pooled set of patients with POMC/PCSK1 or LEPR deficiency who received setmelanotide in Phase 2 (RM-493-011 [NCT02507492]) or Phase 3 (RM-493-012 [NCT02896192] and RM-493-015 [NCT03287960]) clinical trials. Patients in the Phase 2 investigator-initiated trial (Charité Universitätsmedizin Berlin) received open-label setmelanotide for 12 to 13 weeks followed by an extension study for eligible patients. The Phase 3 trials included a 12-week open-label phase, an 8-week placebo-controlled phase, and a subsequent 32-week open-label phase, for a total treatment length of at least 1 year. AEs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). AEs of special interest were defined as those related to treatment-emergent AEs (TEAEs) commonly occurring with setmelanotide (hyperpigmentation disorders, disturbances in sexual arousal, nausea, vomiting, injection site reactions [ISRs]). Results: As of November 10, 2020, 35 patients (15 POMC, 2 PCSK1, 18 LEPR) were enrolled and included across the 3 trials; 2 patients in the Phase 2 trial were ongoing treatment as of the cutoff. Daily setmelanotide dose ranged from 0.25 to 3.0 mg. All patients experienced ≥1 TEAE, the most common being skin hyperpigmentation (85.7%), injection site erythema (68.6%), nausea (57.1%), and headache (51.4%). For AEs of special interest, hyperpigmentation disorders occurred in 85.7% of patients (30/35), disturbances in sexual arousal in 17.1% (6/35), nausea in 57.1% (20/35), vomiting in 28.6% (10/35), and ISRs in 88.6% (31/35). The onset of most hyperpigmentation disorder (34/53 events; 64.2%) and disturbances in sexual arousal

(6/11 events; 54.6%) AEs were during Month 1 after starting setmelanotide. Onset of nausea and vomiting were most frequent during Month 1 of treatment (nausea: 12/34 events [35.3%]; vomiting: 6/19 events [31.6%]). ISRs occurred throughout the trial, with 41.6% (91/219 events) having an onset within Month 1 of treatment. Eighteen serious AEs occurred, none were interpreted as related to the study drug. Conclusions: In patients with POMC/PCSK1 or LEPR deficiency obesity who received setmelanotide treatment, the onset of AEs of special interest in any month was generally highest during Month 1 of treatment, with fewer events occurring during subsequent months. Apart from hyperpigmentation, all AEs occurred intermittently.
Weight Loss Mobile Apps: Do They Address COVID-19 and Diabetes
Authors: Wu Gloria , Nguyen Brian , Lau Chap-Kay Kendra , Siu Vincent
Published: May 2021

Background: Over 70 million Americans are obese and 99 million are overweight. There are over 3.7 billion ehealth mobile app downloads per year. Weight loss apps offer information on exercise and nutrition as well as weight tracking. Obesity is a risk factor for COVID-19 infection, along with diabetes and hypertension. In addition, obesity plays a role in the increased mortality of COVID patients. In March of 2020, the U.S. government, through the Small Business Administration and through the Small Business Innovation Research program, as well as through Facebook and Google, offered individuals and companies money for public education and/or solutions for the COVID-19 epidemic. Thus, are software app developers adding information about COVID-19 for their audience? Specifically, do weight loss apps mention obesity being a risk factor for DM, Hypertension, and COVID-19? Weight loss apps target a young demographic, and for public health purposes, COVID-19 information needs to reach this demographic since obesity can be a risk factor for COVID-19 infection. Purpose: Do weight loss apps provide information about DM, HTN, and COVID-19 during this pandemic era? Methods: Evaluation of the 10 most popular apps in the Apple (iOS) and Google (Android) stores via the search term “weight loss.” Apps were ranked by downloads/star rating respectively for Android and iOS apps. Apple does not provide information about the number of downloads. App inclusion criteria: 1) Free 2) iOS: star ratings greater than 4 (greater than 10K ratings); Android: greater than or equal to 1 Million downloads; App features: DM, HTN, Race, Gender, COVID-19, BMI, Heart Disease, Calorie Count, and Fitness. Results: DM: 0/20, HTN: 0/20, BMI: 19/20, while Race is 0/20; Gender 19/20; COVID-19: 0/20; Calorie Count 11/20; Fitness 13/20. Conclusion: 1) Weight Loss apps have not ventured in the public education realm of risk factors and comorbidities of COVID-19 despite the pandemic in 2020. 2) As physicians, we should continue to educate our patients with weight issues and other risk factors in the era of a worldwide pandemic.
Weight Loss With a Novel Peptide YY Analogue for Obesity: A Randomised, Placebo-Controlled Phase I Trial
Authors: Tan Tricia , Minnion James , Eu Khoo Bernard Chong , Ball Laura-Jayne , Malviya Reshma , Day Emily , Fiorentino Francesca , Brindley Charlie , Bush Jim , Bloom Stephen R
Published: May 2021

Background: Obesity and its co-morbidities remain a prime driver of global morbidity and mortality. Current therapies for obesity are limited in efficacy and durability, have serious adverse effects or are not scalable to the numbers required to treat this widespread disease. Gut hormones such as peptide YY (PYY) have emerged as candidate therapies for obesity which activate natural satiety pathways, reduce food intake and therefore body weight. We report the results from a Phase I trial of a PYY analogue, Y14, in overweight volunteers. Methods: In a first time in human Phase I randomized placebo-controlled trial, an extended-release formulation of Y14 with zinc chloride for subcutaneous injection, utilizing various Zn:peptide molar ratios, was tested. Part A of the trial was a partially blinded single ascending dose study. Part B was double-blinded and tested multiple ascending doses given at 7–14 day intervals over the course of 28 days with up to 5 doses given per subject. The primary outcome was the safety and tolerability of extended-release Y14; the secondary outcome was to assess its pharmacokinetics. Exploratory outcomes included the assessment of food consumption, body weight and glucose tolerance in response to 75g oral glucose load after multiple doses of Y14. [ClinicalTrials.gov NCT03673111]. Findings: Between Apr 11, 2017, and Dec 24, 2018 44 participants were enrolled into Part A of the trial and 24 into Part B and were included in the full analysis and safety datasets. The multiple doses of Y14 given in Part B led to significant mean placebo-subtracted reductions in body weight of 2.76 to 3.59 kg at 31 days after the first dose, in association with profound reductions in food intake and no evidence of tachyphylaxis. No significant changes in glucose tolerance were detected. The most common adverse events were nausea, vomiting and injection site reactions. No serious adverse events occurred. The pharmacokinetic characteristics of extended-release Y14 were compatible with administration every 7–14 days. Interpretation: Our results support the continued development of Y14 as a novel treatment for obesity. Funding: UK Medical Research Council Developmental Pathway Funding Scheme.
Metabolic Improvements After Gastric Sleeve Surgery in a Patient With Familial Partial Lipodystrophy
Authors: Niaz Azra , Sophia Ali
Published: May 2021

Familial Partial Lipodystrophy (FPLD) is a rare genetic disorder characterized by loss of subcutaneous adipose tissue mainly from peripheral areas but preservation, or increase, of fat in the face, neck, and trunk. This abnormal fat redistribution leads to a characteristic phenotype and severe metabolic derangements that are difficult to manage. FPLD often present with severe insulin resistance causing type 2 diabetes mellitus (DM2), acanthosis nigricans, hypertriglyceridemia (HTG), and non-alcoholic steatohepatitis (NASH). We present a case of FPLD with severe HTG and HTG induced pancreatitis requiring plasmapheresis, with dramatic metabolic improvements after gastric sleeve surgery. Case presentation: Our patient is a 40-year-old Caucasian male who was diagnosed with DM2 and HTG at age 18 when he presented with pancreatitis. He reported eruptive xanthomas with triglyceride (TG) >3000 mg/dl on the initial presentation. He has central obesity with disproportionately thin extremities and NASH. He has a strong family history of HTG and premature coronary artery disease. He was in a leptin trial; however, he was not included in an extended arm due to deterioration of his metabolic profile, specifically NASH. Despite aggressive therapy with dietary changes, fenofibrate, statin, omega-3, and niacin, he had multiple episodes of pancreatitis with TG levels >5000 mg/dl on many occasions. As a result, he was started on biweekly plasmapheresis that was later changed to weekly. His insulin requirement increased to 450 units daily on U-500. A decision was made for him to proceed with bariatric surgery with his history of insulin-resistant DM2 and morbid obesity. He lost 54 lbs in one year with sleeve gastrectomy and his insulin requirement decreased to 120 units daily. Above all, he had only a single incomplete session of plasmapheresis since his bariatric surgery. He has not required plasmapheresis for over a year so far and his TG levels are consistently <500 mg/dl while only on rosuvastatin 40 mg, with the most recent TG level of 182 mg/dl. Discussion: Bariatric surgery has shown tremendous results in terms of reversal of diabetes and other metabolic derangements. These metabolic benefits are attributed mainly to weight loss in restrictive surgeries and proposed increased GLP-1 levels with Roux-en-Y Gastric Bypass Surgery (RYGB). There are a few case reports of FPLD patients with positive outcomes in terms of metabolic profile with RYGB. In our patient, bariatric surgery was decided due to his DM2 and morbid obesity. He had an unexpected dramatic improvement in the metabolic control of his lipodystrophy. To our knowledge, this is the first case of a FPLD patient with severe HTG requiring plasmapheresis with striking metabolic improvements after sleeve gastrectomy. Gastric sleeve surgery may be an important adjunct or alternative treatment option to the current standard of therapy in patients with FPLD.
Novel Heterozygous LMNA Variants Causing Familial Partial Lipodystrophy, Dunnigan Variety
Authors: Wadhwa Akhilesh , Vasandani Chandna , Garg Abhimanyu
Published: May 2021

Familial partial lipodystrophy (FPLD) is a rare, mostly autosomal dominant disorder characterized by selective loss of subcutaneous fat from the extremities. Patients with FPLD are predisposed to insulin resistance, dyslipidemia, diabetes mellitus, cardiac abnormalities (coronary heart disease [CHD], cardiomyopathy and conduction system disorders) and hepatic steatosis. FPLD2 (the Dunnigan variety) is the most common subtype which is caused by heterozygous variants in the lamin A/C (LMNA) gene. Over 50 LMNA causal variants have been reported in patients with FPLD2, with p.R482W and p.R482Q comprising ~75% of the families. We report 5 novel LMNA variants (c.722T>C, p.L241P; c.848A>G, p.N283S; c.1396A>G, p.N466D; c.1543A>G, p.K515E; c.1744C>A, p.R582S) in 5 families, where a female proband presented to us with moderately-severe FPLD, from among a total cohort of 264 FPLD2 families, with 259 families harboring other known pathogenic LMNA variants. The p.L241P variant was found in a 62-year-old female with a body mass index (BMI) of 28 kg/m2. She had hypertriglyceridemia. She is adopted and has two offsprings, who have not yet been examined and genotyped. The p.N283S variant was found in two males and two females from the same family (Age 40–74 y; BMI 18–45 kg/m2). Of these, only the 74-year-old female proband had clinical lipodystrophy, diabetes and hypertriglyceridemia. The other three subjects did not have lipodystrophy. Thus, this variant did not segregate with the phenotype of lipodystrophy in this family likely due to low penetrance or reduced clinical expressivity. The p.N466D variant was found in a 53-year-old female (BMI 26 kg/m2) who had diabetes and hypertriglyceridemia. The p.K515E variant was found in 4 females and 1 male who belonged to the same family (Age 29–62 y; BMI 19–26 kg/m2). All of them had lipodystrophy and hypertriglyceridemia and three of them had diabetes. The p.R582S variant was found in 3 males and one female who belonged to the same family (Age 19–76 y; BMI 16–30 kg/m2). All of them had lipodystrophy but only two of them had diabetes and hypertriglyceridemia. Eight of them had hypertension, three had CHD, one of them had acute pancreatitis and another one had a stroke. None of these patients had cardiomyopathy, cardiac conduction system defects or myopathy. In conclusion, we report genotype-phenotype relationship of 5 novel LMNA variants in patients presenting with FPLD2, with variable prevalence of diabetes, hypertriglyceridemia hypertension and CAD. None of these variants are associated with cardiomyopathy or myopathy or progeroid features. Our report adds to the allelic and clinical heterogeneity associated with LMNA variants.
Obesity Is Associated With Higher odds of Hepatorenal syndrome in Patients Admitted With Alcoholic Hepatitis: Analysis of the National Inpatient Sample (2016–2017)
Authors: Asotibe Jennifer Chiagoziem , Shaka Hafeez , Achebe Ikechukwu , Pudasaini Garima , Akuna Emmanuel , Rashad Essam , Busari Olukayode A , Palomera Emmanuel Tejeda
Published: May 2021

Introduction: Obesity is a significant independent risk factor for the development of liver disease. There is some available data suggesting worse outcomes of alcoholic hepatitis (AH) in obese patients however, national sample data supporting these findings are scarce. The aim of our study was to study the severity of AH in patients with concurrent obesity thus we analyzed data from the national inpatient sample.

Methods: We queried the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for hospitalization of adult patients with alcoholic hepatitis as a principal diagnosis with and without Obesity (BMI = 30 and above) as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality while the secondary outcomes were severe sepsis with shock, hospital length of stay (LOS), NSTEMI, hepatorenal syndrome (HRS) and bleeding esophageal varices (BEV) development. STATA software was used for analysis. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders.

Results: There were over 71 million discharges in the combined 2016 and 2017 NIS database. Out of 32,584 adult AH hospitalizations, 3,720 (11.4%) had a concomitant diagnosis of obesity. There were no differences between mean age, sex and race in both groups of patients. Patients with AH and concurrent obesity had no significant difference in inpatient mortality (aOR= 0.74, P = 0.272, CI = 0.438 -1.261) however, they were found to have higher odds of developing HRS (aOR = 1.54, P= 0.020, CI= 1.069 -2.209) and lower odds of developing BEV(aOR 0.22, P= 0.008, CI= 0.070 -0.670). Patients with AH and concurrent obesity were also found to have similar odds of developing NSTEMI (aOR = 2.29, P= 0.180, CI= 0.680 - 7.762), severe sepsis with shock (aOR = 0.97%, P= 0.945, CI= 0.486 -1.954) and a 0.5 day mean increase in LOS (P =0.045, CI = 0.011 - 0.987) when compared to those without obesity.

Conclusion: In conclusion, patients with obesity admitted with AH have higher odds of developing HRS, lower odds of developing BEV and no statistically significant difference in mortality, development of NSTEMI and severe sepsis with septic shock. It is important to identify these patients at higher risk and provide better surveillance to prevent the development of HRS.