ResearchPad - rare-causes-and-conditions-of-obesity:-prader-willi-syndrome-lipodystrophy Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-596 A Rare Presentation of Early Onset Wernicke Encephalopathy Following Sleeve Gastrectomy]]> Background: Wernicke encephalopathy (WE) has been reported after malabsorptive bariatric surgeries but is an uncommon complication of sleeve gastrectomy. Since 2011, the number of patients receiving a sleeve gastrectomy has tripled, with almost 60% of patients undergoing bariatric surgery receiving a sleeve gastrectomy in 2017 (1). We present a case of WE in a young woman as a rare and early complication of sleeve gastrectomy.

Clinical Case: A 32-year old female with a past medical history significant for hypertension, pseudotumor cerebri, and morbid obesity status post sleeve gastrectomy two months prior presented to the emergency department with complaints of blurry vision and lower extremity numbness. Physical examination showed sluggish light reflex and decreased extraocular movements. Given history of pseudotumor cerebri, patient underwent a therapeutic lumbar puncture with removal of 13 ml of CSF. Opening pressure was 20 cm of water and patient experienced no relief of her symptoms. Ophthalmology consult did not offer an explanation for the blurry vision. MRI-brain with and without contrast showed findings highly suggestive of WE. It showed faint linear symmetric hyperintensities along the bilateral mesial thalamus, dorsal midbrain and periaqueductal gray matter, which were determined to be acute in nature in comparison with a MRI performed three weeks prior. Upon further investigation, thiamine level was low at 43.6 nmol/L [66.5 – 200] confirming the diagnosis of WE. Thiamine supplementation was started immediately and patient reported improvement of her vision the next day with return to baseline in 3 days.

Conclusion: There have been a handful of cases of WE reported in literature as a complication of sleeve gastrectomy. Zheng, L also reported a case of WE 7 weeks after sleeve gastrectomy (2). Although sleeve gastrectomy does not directly affect the primary absorptive pathway of thiamine in the gastrointestinal tract, it is imperative to consider WE in patients presenting with suspicious neurologic symptoms after a recent sleeve gastrectomy. WE was suspected in our case due to typical MRI findings and neurological presentation after bariatric surgery, which was later confirmed by low serum thiamine level. Early detection and thiamine supplementation resulted in complete reversal of symptoms in our patient. WE is a rare but severe and preventable consequence of bariatric surgery that warrants attention given its rapid onset and detrimental course.

Reference: (1) Estimate of Bariatric Surgery Numbers, 2011-2017. (2018, June 26). Retrieved from (2) Zheng, L. (2016).

Wernicke Encephalopathy and Sleeve Gastrectomy. American Journal of Therapeutics, 23(6).

<![CDATA[SUN-610 Acquired Generalized Lipodystrophy: A Rare Side Effect of PD1-Inhibitor Therapy]]> Background:Program cell death-1 (PD1) inhibitors, such as nivolumab and pembrolizumab, have shown efficacy as adjuvant treatment for cancers, including melanoma, and their frequency of use is increasing. A potential, but rare, side effect of PD1-inhibitors is acquired generalized lipodystrophy (AGL), an immune-related adverse event characterized by loss of subcutaneous adipose tissue (SAT) and insulin resistance-associated complications. AGL can result in irreversible endocrinopathies, including diabetes. Clinical Case: A 60-year-old overweight female (BMI 29.2), with no related metabolic complications or medical history of autoimmune disorders, was treated with nivolumab (240mg IV q2 weeks) for 1 year for metastatic melanoma on her right arm (staged T4bN2a) that underwent wide local resection. She completed therapy with no complications or lab abnormalities.One-month post-treatment, she noticed rapid weight loss and facial atrophy. Within 3 months, she had a 58% weight loss withsignificant loss of SAT; insulin resistance and diabetes(impaired fasting glucose 201; A1c 9.2%);hepatic steatosis diagnosed by liver biopsy; hypertriglyceridemia (5,309 mg/dL,); and undetectable leptin levels. She also developed prominent forearm muscles and leg veins. GAD antibody was negative. The loss of SAT and rapid weight loss, physical exam findings, onset of diabetes, steatosis and hypertriglyceridemia—all closely following therapy with nivolumab—led to a diagnosis of nivolumab-associated AGL. In addition to treatment for hypertriglyceridemia, the patient was placed on multiple oral and parenteral antihyperglycemic medications, including metformin, SGLT2i, GLP-1, and DPP4, but all were discontinued due to side effects. Ultimately, her A1c increased to 12.4% and she was placed on basal/bolus therapy. Discussion: AGL is associated with an increased risk of lymphoma. Metreleptin, a recombinant analogue of human leptin, is approved for treatment of metabolic complications of AGL. Some instances of lymphoma in AGL have occurred while the patient was receiving metreleptin, but data is inconclusive as to whether development of lymphoma is a side effect of metreleptin.(Brown RJ, Chan JL, Jaffe ES, et al, 2016) We believe treatment with metreleptin would have benefited our patient, but she declined due to potential side effects, including lymphoma. Nine months after nivolomuab therapy, her melanoma is in remission but she still has lipodystrophic characteristics with insulin resistant diabetes. She is being treated with pioglitazone and multiple daily insulin injections but has not achieved euglycemia despite a total daily insulin dose of 2 u/kg. Of note, injecting insulin and use of a continuous glucose monitor have been a challenge given the lack of SAT. Although AGL resulting from PD1-inhibitor therapy is rare, it is a condition for which this patient will need life-long treatment.

<![CDATA[SUN-593 Variants in Known Monogenic Causal Genes of Hypertriglyceridemia Are Not Major Contributors for Hypertriglyceridemia in Lipodystrophy Due to a LMNA Mutation]]> Background: Lipodystrophy is a heterogeneous disorder of adiposity, and one common lipid manifestation is hypertriglyceridemia (HTG). The LMNA gene, which encodes for nuclear envelope proteins, is a known causal gene for heritable lipodystrophy. At present, underlying mechanisms for each clinical manifestation of lipodystrophy due to a LMNA mutation are unknown.

Hypothesis: A likely explanation for HTG in lipodystrophy is the paucity of adipose tissue where excess triglycerides (TGs) are normally stored, thus it may not be due to a specific defect in lipoprotein metabolism. Consequently, rare variants in HTG-associated genes would not be expected to be major contributors for HTG in lipodystrophy with LMNA mutations.

Method: A proband and her father with a clinical diagnosis of lipodystrophy were recruited into an IRB-approved study investigating molecular etiologies of dyslipidemia at the University of Pennsylvania. Next-generation sequencing (NGS) with the LipidSeq panel, targeting causal genes for lipodystrophy, and monogenic HTG was performed, and confirmed by Sanger sequencing. Also, unweighted TG-polygenic scores by summing the number of TG-raising alleles from 14 single nucleotide polymorphisms (SNPs) associated with TG levels were assessed.

Results: The proband and her father were diagnosed with lipodystrophy of two different subtypes, generalized in the daughter and partial in the father. The proband reported a gradual loss of subcutaneous fat starting around age 10. A highest reported TG in the proband was19,000 mg/dL with eruptive xanthomas, whereas TG in the father was never >500 mg/dL. Their BMI’s and DEXA body fat% were 12.9 kg/m2 and 7% in the proband, and 25.7 kg/m2 and 25% in the father, corresponding to their fat storage capacities.

The molecular analyses revealed only a lipodystrophy causal mutation in LMNA, c.29C>T, T10I with no other significant findings in18 other lipodystrophy-related genes. No deletion or duplication was identified by a targeted array CGH of LMNA.

As predicted, no rare monogenic variants in HTG-causal genes (LPL, GPIHBP1, APOA5, APOC2, LMF1, GPD1) were identified in either subject. However, TG-polygenic scores were 17/28 (95th %ile) in the proband, and 13/28 (50th %ile) in the father, the same trend as the level of HTG levels seen in them. Apolipoprotein E genotypes were non-contributory, (3/3) in the proband, and (3/4) in the father.


Our findings support that the pathophysiology of HTG in lipodystrophy is likely to be due to lack of TG-storage space (adipose tissues), and is unlikely due to a defect in lipoprotein metabolism seen in patients with rare monogenic HTG-variants. Although the HTG-polygenic score was higher in the proband, and the accumulative effects of the at-risk alleles may be contributor to the HTG phenotype, it is unlikely to be the leading cause of severe HTG seen in the proband.

<![CDATA[SUN-608 Juvenile Toxicity Study of Livoletide: A Peptide Analogue of Unacylated Ghrelin for the Treatment of Hyperphagia in Prader-Willi Syndrome]]> Background: Prader-Willi syndrome (PWS) is a rare endocrine disorder characterized by hyperphagia and abnormal food-related behaviors that contribute to severe morbidity, early mortality, and significant burdens for patients and caregivers. Dysregulation of acylated ghrelin (AG) and unacylated ghrelin (UAG) in people with PWS and hyperphagia has led to the hypothesis that replacing the relative deficit of UAG observed in this population will reduce hyperphagia. Livoletide is a cyclic, 8 amino acid analogue of UAG being developed as a potential treatment for hyperphagia and food-related behaviors associated with PWS. In a previous Phase 2a study (n=47) in people with PWS, livoletide improved food-related behaviors and hyperphagia scores relative to placebo. An extensive nonclinical safety program to support clinical development of livoletide has been conducted. Here we report the results of study of livoletide in juvenile rats.

Methods: Male and female juvenile Wistar rats were administered livoletide (10, 25, or 75 mg/kg/day, subcutaneous) once daily from the age of weaning (postnatal day 21) until 12 weeks of age (n=32/sex/group). Subgroups were sacrificed at the end of the dosing period or after a recovery period. Toxicity was assessed based on local tolerance, clinical observations, body weights, food consumption, tibia length, bone densitometry, behavioral tests, IGF1 (insulin-like growth factor-1), LH (luteinizing hormone), and other endpoints. Macroscopic (necropsy), microscopic/histopathological, and caesarean examinations were also performed. Toxicokinetic (TK) evaluations were performed at various time-points after dosing to assess exposure.

Results: Livoletide was not associated with treatment-related clinical signs or any relevant changes in hematological, coagulation, clinical chemistry parameters or urine analysis. Body weight and food consumption were unaffected. Livoletide did not affect systemic concentrations of IGF-1 or LH. No adverse effects of livoletide on bone growth, mating performance, or fertility were observed. Pups delivered by caesarian section did not exhibit abnormalities. Results were consistent with a lack of effect of livoletide on growth hormone signaling. Histological changes were limited to minimal local reversible reactions at injection sites that were non-adverse and observed at low incidence and severity.

Conclusions: Livoletide was well-tolerated and not associated with evidence of overt systemic toxicity. The no observed adverse effect level (NOAEL) of 75 mg/kg/day was associated with Cmax and AUC0-24h values of 72.6/83.2 μg/mL and 169/144 μg.h/mL (males/females), respectively. These exposures are >100-fold above the anticipated clinical exposures in the Phase 2b/3 ZEPHYR study, which is enrolling people ages 4 to 65 with PWS.

<![CDATA[SUN-594 Pubertal Timing and Hormonal Correlates in Male Obesity]]> An early, normal or delayed pubertal onset have been described in overweight/ obese males(1). A greater prepubertal adiposity has been associated with a greater risk for delayed puberty in males, but an underlying mechanism was not explored(2). We investigated whether an increased testosterone aromatization or an higher degree of low-grade inflammation might be more prevalent in obese males with a delay in genital development. Pubertal status assessment by Tanner staging and measurement of morning serum testosterone, estradiol, leptin, and hSCRP by standard laboratory methods were performed in 191 male adolescents, aged between 10 and 18.6 yr (median 12.8 yr) with overweight (BMI z-score > 1.3), starting an ambulatory (n = 138) or a residential weight loss program (n = 55). Their median (range) BMI z-score was 2.32 (1.34 – 3.38). Delayed / slow and early / rapid genital development was defined by a Tanner genital stage respectively above the 90th or below 10th percentile age distribution (national Flemish standards of 2004). In 3 males pubertal development was advanced, while in 34 it was delayed. In the remaining 154 adolescents genital stage was normally timed. Males with a delayed timing or progression of genital development were older (median(range) age:14.8 (11.6-18.6) yr vs 12.3 (10-18.6) yr; p< 0.005) and shorter (height sds: -0.55 (-1.90- 1.48) vs 0.49 (-3 – 3.19); p < 0.005), and had a higher birthweight (birthweight z-score: 0.15(-3.51-2.75) vs -0.34(-4.7-3.30); p = 0.058), but a similar BMI and waist z-score in comparison with males with a normally timed puberty. Median serum estradiol, leptin, and hSCRP concentrations did not differ significantly between those with a normal or a delayed pubertal onset or progression. In conclusion, pubertal delay is more frequently observed than early puberty in males referred to obesity clinics. Neither low grade inflammation nor increased estradiol production appear to be associated with a later onset of slower progression of genital development in male obesity. References (1) Li W et al. Int J Environ Res Public Health. 2017 Oct 24;14(10) (2) Lee JM et al. Arch Pediatr Adolesc Med. 2010 Feb;164(2):139-44.

<![CDATA[SUN-609 Livoletide (AZP-531), an Unacylated Ghrelin Analogue, Improves Hyperphagia and Food-Related Behaviors Both in Obese and Non-Obese People with Prader-Willi Syndrome]]> Prader-Willi syndrome (PWS) is a rare, complex neuro-developmental genetic disorder characterized by hyperphagia and abnormal food-related behaviors that contribute to severe morbidity and early mortality and to significant burden on patients and caregivers. While a majority of people with PWS is obese, hyperphagia is observed in both obese and non-obese people with PWS. There is currently no approved treatment for hyperphagia in PWS. People with PWS have increased circulating levels of the orexigenic hormone acylated ghrelin (AG) with a relative deficit of unacylated ghrelin (UAG), a hormone which counteracts many of AG’s effects. Livoletide (AZP-531) is a first-in-class UAG analogue previously shown to improve hyperphagia, food-related behaviors, and metabolic parameters, and to be well-tolerated in a Phase 2a trial in PWS. [Allas S et al. (2018) PLoS ONE 13(1): e0190849] Here we present additional analyses that examine the effects of livoletide in obese vs non-obese people with hyperphagia in PWS.

Methods: The Phase 2a trial was a randomized, double-blind, placebo-controlled study which included 47 people with PWS. Participants received a daily subcutaneous injection of livoletide (n=23) or placebo (n=24) during a 2-week treatment period. The study population was divided based on the body mass index (BMI) into obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) groups. The effect of livoletide on hyperphagia and food-related behaviors was assessed by the change from baseline in the 9-item Hyperphagia Questionnaire (HQ).

Results: There was a total of 34 obese and 13 non-obese subjects in the study. As expected, baseline BMI, body weight (BW) and waist circumference (WC) were significantly higher in obese vs. non-obese PWS subjects (BMI: 42.6 ± 6.0 vs 26.1 ± 2.8, BW: 103.5 ± 23.0 vs 68.5 ± 9.1 and WC: 118.3 ± 15.5 vs 91.8 ± 7.7, respectively, p<0.0001). There was no significant difference with respect to the ratios of males to females or of deletion to non-deletion between the 2 populations. Hyperphagia scores were similar at baseline for obese and non-obese participants (HQ score adjusted for 0 to 36 scale to reflect 9-item HQ-CT: 12.8 ± 7.0 vs 14.0 ± 7.8, p=0.6083, respectively). Fasting AG and UAG levels were lower in the obese vs. non-obese groups (AG: 93.6 ± 72.6 vs 122.1 ± 54.4, p=0.0275, UAG: 123.9 ± 87.2 vs 154.1 ± 62.6, p=0.0219, respectively). Livoletide-treated participants experienced similar improvements in hyperphagia and food-related behaviors as measured by the HQ whether they were obese or non-obese.

Conclusions: These results highlight the potential of livoletide for treating hyperphagia in both obese and non-obese people with PWS and hyperphagia. Livoletide is being investigated further in the ZEPHYR Phase 2b/3 trial, an ongoing pivotal study on the long-term safety and efficacy of livoletide in the treatment of hyperphagia and food-related behaviors in people with PWS.

<![CDATA[SUN-600 Presence of LMNA p.R582H Pathogenic Variant in Homozygous State Demonstrates Gene Dosage Effect on the Severity of Fat Loss in Lipodystrophy]]> Background Classical heterozygous pathogenic variants of the lamin A/C (LMNA) gene cause familial partial lipodystrophy type 2 (FPLD2). However, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants, and a few patients have been associated with generalized fat loss. Clinical Case Here, we report a patient with lamin A specific pathogenic variant at exon 11 LMNA p.R582H present in homozygous state. Fat distribution was compared radiographically to a heterozygote LMNA p.R582H patient from another pedigree, female healthy control, a series of adult female subjects with congenital generalized lipodystrophy type 1 (CGL1, n = 9) and typical FPLD2 (n = 8). The whole body MRI of the index case confirmed near-total loss of subcutaneous adipose tissue with well-preserved fat in the retroorbital area, palms and soles, mons pubis, and external genital region. This pattern resembled the fat loss pattern observed in CGL1 with only one difference: strikingly more fat was observed around mons pubis and the genital region. Also, homozygous p.R582H LMNA variant was associated with lower leptin level and earlier onset of metabolic abnormalities compared to heterozygous p.R582H variant and typical FPLD2 cases. On the other hand, heterozygous LMNA p.R582H variant was associated with partial fat loss which was similar to typical FPLD2 but less severe than the patients with the hot-spot variants at position 482. Conclusions Our observations and radiological comparisons demonstrate a gene dosage effect of LMNA variants on the severity of fat loss and add to the body of evidence that there may be complex genotype-phenotype relationships in this interesting disease known as FPLD2. Although the pathological basis for fat loss is not well understood in patients harboring pathogenic variants in the LMNA gene, our observation suggests that genetic factors modulate the extent of fat loss in LMNA associated lipodystrophy.

<![CDATA[SUN-605 Mediastino-Abdominal Lipomatosis: Deep Accumulation of Fat Mimicking a Respiratory Disease]]> Introduction: Multiple systemic lipomatosis (MSL) is a rare disorder with unknown etiology. It is characterized by the massive development of non-encapsulated lipomas in subcutaneous tissues. Lipomatosis of the face, head, neck, extremities, abdomen, and pelvis have been reported in the literature. Case: We report a case of a 65 years old female (BMI: 34 kg/m2) with past medical history of hypertension, hyperlipidemia(DLD) diabetes mellitus type 2 and sleep apnea that was brought into emergency room (ER) for worsening shortness of breath. In the ER, she was having an oxygen saturation of 75% and required intubation. The patient was afebrile, with a BP of 120/75 mm Hg and a heart rate of 70/minute. Trans-thoracic echocardiogram revealed normal ejection fraction and normal pulmonary pressure with no wall motion abnormality. CXR showed no infiltration or consolidation. CT angiogram (CTA) ruled out pulmonary embolism but it was notable for large deposits of fat involving the abdomen and thorax, with invasion into the mediastinum and the space between the liver and diaphragm. Mesenteric fat was increased. Tissue was biopsied, which confirmed the diagnosis of fatty invasion. Discussion: Abdominal lipomatosis is characterized by massive enlargement of the abdomen due to intraperitoneal and retroperitoneal fatty deposits. Phenotypically patients can appear to be thin or obese, however, it is more common in the overweight population like our patient. Mediastinal lipomatosis is a benign cause of mediastinal widening, however patients can develop respiratory symptoms like exertional dyspnea due to compression of airways. MSL affects white caucasian between 25-60 years old and it is associated with DLD, impaired glucose tolerance, hyperuricemia, macrocytic anemia, and peripheral neuropathy. The pathophysiology is not fully understood, some theories stated that it is related to defective lipid mobilization in lipomatocytes, other suggested disorder in the mitochondria of brown fat. Conclusion: CT and MRI of the abdomen and chest are very helpful in the diagnosis of MSL but a tissue biopsy is what makes the final diagnosis. There is no definitive treatment; the recommendations are a healthy lifestyle including a low-fat diet, abstinence from alcohol and exercise. In severe cases, surgery is recommended.

<![CDATA[SUN-607 Iron Parameters in Patients with Partial Lipodystrophy and Impact of Metreleptin Therapy]]> Introduction Intriguing rodent studies and epidemiological data suggest that iron metabolism and adipocytokines crosstalk to regulate glucose metabolism and fuel storage. Iron parameters have not been previously studied in patients with lipodystrophy whereas increased iron stores have been associated with type 2 diabetes. In this study, we sought to investigate the status of iron parameters in patients with partial lipodystrophy (PL) and to interrogate whether the adipocyte hormone leptin can modulate iron metabolism. Methods Serum samples of 19 patients with PL (age: 42, IQR: 34-57, M/F: 3/16) were used from an open-label study previously performed at the University of Michigan evaluating the efficacy of metreleptin in nonalcoholic steatohepatitis (NCT01679197) to measure ferritin, hepcidin, iron, and transferrin soluble receptor levels. High-sensitivity C-reactive protein (hs-CRP) levels were also determined as broader changes in inflammatory pathways may potentially impact circulating ferritin levels. Results were integrated into an existing database of metabolic parameters. Data are presented as median, IQR. Results At baseline, ferritin levels were positively correlated with fasting glucose (r = 0.533; p = 0.023) and HbA1c (r = 0.510; p = 0.031). During the 6 months of therapy period, HbA1c (9.2%, 7.3-10.3 vs. month-3: 8.6%, 7.7-9.6; p = 0.099; and month-6: 8.5%, 6.8-9.5; p = 0.264), triglyceride levels (346 mg/dL, 240-1771 vs. month-3: 346 mg/dl, 237-479; p = 0.047; and month-6: 295 mg/dl, 207-495; p = 0.091), and hepatic fat (12.7%, 9.8-20.6 vs. month-6: 8.9%, 7.0-11.0; p = 0.031)} decreased. Reductions were observed in serum ferritin after metreleptin treatment (83.23 ng/mL, 76.43-178.97 vs. month-3: 73.79 ng/ml, 68.30-78.59; p = 0.007; and month-6: 61.03 ng/mL, 46.45-157.74; p = 0.004). There was a tendency for hepcidin and iron to be decreased, but this did not reach statistical significance. On the other hand, there were notable reductions in hs-CRP levels at 6 months compared to baseline (2.94 mg/L, 1.30-4.80 vs. 1.6 mg/L, 1.00-6.30; p = 0.012). Baseline leptin level was inversely correlated with percent reduction in hs-CRP at month-6 (r = -0.685; p = 0.001). Also, modest correlations were observed between changes in serum iron and triglycerides (r = 0.491, p = 0.033) and hepatic fat (r = 0.412, p = 0.079). Conclusions We observed a significant relationship between ferritin and glucose control in a group of patients with PL. Metreleptin therapy was associated with improvements in triglycerides and hepatic fat and there were also significant decreases in ferritin and hs-CRP levels. These results raise the possibility that metreleptin therapy influences iron metabolism. However, whether the decrease in ferritin indicates a decrease in iron stores or is mediated by an effect on inflammation remains unknown.

<![CDATA[SUN-606 Identification of NASH Using Data from NHANES III]]> Nonalcoholic steatohepatitis (NASH) is a serious liver condition marked by hepatic steatosis (HS), cell damage and inflammation. Patients with NASH are at risk for developing cirrhosis and hepatic cancer. Currently, the definitive method of diagnosing NASH is by liver biopsy. To avoid the costs and risks associated with biopsy procedures, there has been considerable effort to develop a non-invasive method of identifying patients with NASH. However, none of these methods has become accepted as a “gold standard.” Our objective was to compare three non-invasive methods of identifying NASH by using data from NHANES III (1988-1994) to determine variables associated with published formulas to identify NASH. We used ultrasound data to identify subjects with moderate - severe HS. Among those with HS, we identified the NASH population using either the HAIR score, the NASH liver fat score, or the Gholam score. The HAIR score was developed in a sample of obese patients, is based on hypertension, insulin resistance and alanine transaminase (ALT) levels, and had an AUROC of 0.9, a sensitivity of 0.8, and a specificity of 0.89. The NASH liver fat score was developed in a Finnish population undergoing gastric bypass, and validated in an Italian population of liver biopsy patients. This score incorporates metabolic syndrome, type 2 diabetes, serum insulin, AST, and ALT. In the Finnish and Italian populations, respectively, it had AUROCs of 0.73 and 0.74, sensitivities of 59.5 and 92.9, and specificities of 79.7 and 32.7. The Gholam score was developed in a sample of obese patients and uses aspartate aminotransferase (AST) and type 2 diabetes diagnosis. It had an AUROC of 0.82, a sensitivity of 0.76, and a specificity of 0.66. We performed multinomial logistic regression to compare each NASH population to the normal population (those with no or only mild HS). We identified 1236 subjects as having NASH by at least one method. 18% of these were identified by all 3 methods, while 20% were identified by 2 methods. All three methods identified significant risk factors for NASH (p<0.05) as being overweight or obese, having elevated AST or ALT levels, and having elevated C-peptide, serum glucose, or serum triglyceride levels. However, the HAIR and Gholam methods also identified being Mexican-American as a significant risk factor, with the NASH liver fat score did not. Being a former alcohol drinker and not meeting guidelines for physical activity were significant risk factors when using the NASH liver fat score. Further refinement of a noninvasive method for identifying NASH is required. Considerable care must be taken in interpreting risk factors, because the results differ depending which method is used. This could have implications in clinical practice as well, where patients and their risk factors may be mis-identified if formulas are used and not liver biopsy.

<![CDATA[SUN-598 Phenotypic Study of Meso-Somatous (Roch-Leri) Lipomatosis]]> 5 in 82% of LMS patients and lipomas were localized first to the forearms (82%), then the thighs (73%) and the abdomen (55%). At diagnosis, the age of LMS patients was 20 years old; 55% of the LMS patients had a BMI above 30 and 45% above 25. No patient had excessive alcohol consumption. Five had a history of auto-immuneor inflammatory disease: 1 hyperthyroidism, 1 hypothyroidism, 1 multiple sclerosis, 1 vitiligo, 1 Raynaud syndrome. Conclusion: LMS mainly affects overweight men and is associated with hypertension, hyperinsulinism, increased gammaGT and a decrease in CD3, CD4 and CD8 lymphocytes, suggesting an immune dysregulation, all the more so that 45% had an associated auto-immune/inflammatory disease. ]]> <![CDATA[SUN-595 Comparative Comorbidity Burden Among Patients with Prader-Willi Syndrome: A Population-Level Cohort Study]]> <![CDATA[SUN-597 Healthcare Utilization Patterns Among Commercially Insured Patients with Prader-Willi Syndrome: A Retrospective Analysis of Administrative Claims]]> <![CDATA[SUN-602 Weight Loss After Glucagon-Like Peptide-1 Receptor Agonist Treatment in Childhood Obesity with Diabetes and Cirrhosis Associated with a Homozygous MC4R Mutation]]> <![CDATA[SUN-603 Electronic Cigarette Exposure Induces Pro-Inflammatory Changes in Adipose Tissue in Apolipoprotein E (APOE) Knockout Mice]]> <![CDATA[SUN-604 U.S. Prevalence & Mortality of Prader-Willi Syndrome: A Population-Based Study of Medical Claims]]>