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Introduction: Albuminuria, an early marker of kidney damage, is a risk factor for chronic kidney disease (CKD) progression, cardiovascular disease (CVD), and death. Dietary sodium is a risk factor for elevated blood pressure, CVD, and all cause-mortality. It is particularly important in patients with CKD due to increased salt-sensitivity. It is unclear if dietary sodium reduction is associated with reduced albuminuria. Hypothesis: A low sodium diet will reduce albuminuria in patients with CKD. Methods: The Sodium Lowering and Urinary Protein Reduction (SUPER) Trial was a randomized, parallel trial testing the effect of a 24-week dietary sodium reduction intervention compared to usual diet on albuminuria in 151 CKD patients with albuminuria. Participants were eligible if they had an estimated glomerular filtration rate (eGFR) of 30-90 mL/min/1.73 m 2 and an albumin-to-creatinine ratio (ACR) of 30-1,500 mg/g. Intervention group participants received a dietician-led behavioral change intervention targeting sodium intake Results: Study participants were an average of 65.6 years old, 72% African American, and 48% women. Median baseline ACR was 180.3 mg/g in the intervention and 157.4 mg/g in the control group, respectively. Urinary sodium excretion was reduced by 15.5% and 0.0% in the intervention and control groups, respectively. Results for the primary and key secondary outcomes are presented in the Table. Conclusions: The dietician-led dietary sodium reduction intervention succeeded in significantly reducing dietary sodium and BP in patients with CKD and albuminuria. However, no significant differences were observed in ACR, albuminuria, or eGFR between treatment groups.

Introduction: Low-carbohydrate diets lead to weight loss and improvement in hemoglobin A1c and other cardiometabolic outcomes. However, there is limited research on how much of the glycemic effects of low-carbohydrate diets are mediated by weight loss. Hypothesis: The effect of a low-carbohydrate dietary intervention on hemoglobin A1c would be mediated by weight loss. Methods: We conducted a 6-month randomized clinical trial on the effects of a low-carbohydrate diet intervention (target Results: 150 participants (mean [SD] age 59 [8] years; 108 [72%] female; 88 [59%] Black) were randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) arm. Mean (SD) HbA1c was 6.16% (0.30%) at baseline. Six-month data was collected on 142 participants (95%). Compared with the usual diet arm, the low-carbohydrate diet intervention arm had significantly greater 6-month reduction in HbA1c (net difference, -0.23% [95% CI, -0.32 to -0.14%]) and body weight (-5.9 kg [95% CI, -7.4 to -4.4 kg]). In mediation analyses, 59% of the total effect of intervention on 6-month change in hemoglobin A1c was mediated by weight measured at 3 months (Table). Conclusions: In mediation analyses, a substantial proportion (59%) of the total effect of intervention on 6-month change in hemoglobin A1c was mediated through weight measured at 3 months. Future research should further explore contributions of weight loss to reductions in glycemia in other populations.

Introduction Although hyperkalemia and metabolic acidosis often co-occur in patients with chronic kidney disease (CKD), the prevalence of metabolic acidosis among patients with CKD and hyperkalemia is understudied. Therefore, we used medical record data from the Research Action for Health Network to estimate this prevalence. Methods Adult patients with CKD stage 3–5, ≥ 1 outpatient potassium value > 5.0 mEq/l, and ≥ 1 outpatient bicarbonate value available were identified. Patients with end stage kidney disease (ESKD) in the prior year were excluded. The prevalence of metabolic acidosis in each calendar year from 2014 to 2017 among patients with CKD and hyperkalemia was estimated using two definitions of hyperkalemia (potassium > 5.0 mEq/l and > 5.5 mEq/l) and metabolic acidosis (bicarbonate 5.0 mEq/l and ranged from 33 to 39% when hyperkalemia was defined by potassium > 5.5 mEq/l. Conclusion Results demonstrated that prevalence estimates of metabolic acidosis varied based on the definition of hyperkalemia and metabolic acidosis utilized.

Background: Low-carbohydrate diets decrease hemoglobin A1c among patients with type 2 diabetes mellitus. However, evidence on effects of low-carbohydrate diets on hemoglobin A1c among individuals with prediabetes is limited. Methods: We conducted a randomized parallel-group trial of 150 adults aged 40-70 years with untreated hemoglobin A1c from 6.0-6.9%. Participants were assigned to a healthy low-carbohydrate diet (target Results: Mean age was 59 years; 72% were female and 59% were Black. 95% completed the study. Participants in the low-carbohydrate arm had significantly greater 6-month decrease in hemoglobin A1c (net difference, -0.23% [95% CI, -0.32 to -0.14%]) , fasting plasma glucose (net difference, -10.3 mg/dL [95% CI, -15.7 to -4.9 mg/dL]) , and body weight (net difference, -5.9 kg [95% CI, -7.2 to -4.7 kg]) compared with usual diet arm. At 6 months, 53% in the low-carbohydrate arm and 32% in the usual diet arm had hemoglobin A1c Conclusion: A healthy low-carbohydrate diet led to improvements in glycemic and other cardiometabolic outcomes in adults with elevated hemoglobin A1c and could be recommended for prevention of type 2 diabetes mellitus. Disclosure K.S.Dorans: None. M.J.O'brien: None. G.I.Uwaifo: None. J.He: None. L.A.Bazzano: None. L.Qi: None. H.He: None. J.Chen: None. L.J.Appel: n/a. F.Hu: None. J.Samet: None. K.T.Mills: None. Funding National Institute of General Medical Sciences (1P20GM109036-01A1) . The California Walnut Commission (Folsom, CA) supported the study by providing walnuts. Shakes and bars were donated by The Simply Good Foods Company (Denver, CO) . Sugar replacement samples were provided by Swerve LLC (New Orleans, LA) .

Recent reports suggest a potential relationship between COVID-and onset of diabetes (DM) . We present the case of a 35 yr old female with type 1 DM (T1DM) who following COVID-pneumonia (COVP) developed worsening insulitis suggesting a potential direct effect of COVID-on beta cell function. The patient is a 35 yr old Caucasian female with T1DM first diagnosed 5 yrs ago. She had some residual beta cell secretory function with fasting C-peptide; 0.51 (0-8-3.85ng/ml) . She also has hemochromatosis, thyroiditis with thyroid nodular disease and +ve history of T1DM in her older brother and maternal cousin. Since diagnosis she has been on insulin pump therapy and a CGMS device with excellent glycemic control and HBA1c of 6.7-7.1. She had not received the COVID-vaccine and had COVP in July 2021 requiring inpatient care but not intubation. She received oral steroids and Remdesivir with salutary response. She has not had post-acute sequelae of SARS-CoV (PASC) but ˜ 2 months post discharge had acute thyroiditis with no thyroid abscess, elevated sed rate, leucocytosis and peak thyroglobulin; 158 (3-40ng/ml) . Since discharge she noted persistent global hyperglycemia requiring increased basal and bolus insulin therapy with peak HBA1c of 8.3. Further evaluation showed active insulitis with reduced C-peptide 0.and increase in islet related antibodies compared to titers obtained at the time of initial diagnosis 5 yrs prior. The clinical presentation of our patient suggests a potential role of COVID-in inducing insulitis with significant implications for at risk patients including T1DM patients with preserved islet function but also type 2 DM and LADA patients. This case provides another compelling reason for advocating COVID-vaccination in at risk patients. The duration of this effect on islet function and whether beta cell functional recovery is possible over time remains to be seen. The insulitis manifests with worsening glycemic profiles as well as possibly impacting islet mediated counterregulatory glycemic responses. Disclosure G.I.Uwaifo: None.

ImportanceLow-carbohydrate diets decrease hemoglobin A1c (HbA1c) among patients with type 2 diabetes at least as much as low-fat diets. However, evidence on the effects of low-carbohydrate diets on HbA1c among individuals with HbA1c in the range of prediabetes to diabetes not treated by diabetes medications is limited.ObjectiveTo study the effect of a behavioral intervention promoting a low-carbohydrate diet compared with usual diet on 6-month changes in HbA1c among individuals with elevated untreated HbA1c.Design, Setting, and ParticipantsThis 6-month randomized clinical trial with 2 parallel groups was conducted from September 2018 to June 2021 at an academic medical center in New Orleans, Louisiana. Laboratory analysts were blinded to assignment. Participants were aged 40 to 70 years with untreated HbA1c of 6.0% to 6.9% (42-52 mmol/mol). Data analysis was performed from November 2021 to September 2022.InterventionsParticipants were randomized to a low-carbohydrate diet intervention (target Main Outcomes and MeasuresSix-month change in HbA1c was the primary outcome. Outcomes were measured at 0, 3, and 6 months.ResultsOf 2722 prescreened participants, 962 underwent screening, and 150 were enrolled (mean [SD] age, 58.9 [7.9] years; 108 women [72%]; 88 Black participants [59%]) and randomized to either the low-carbohydrate diet intervention (75 participants) or usual diet (75 participants) group. Six-month data were collected on 142 participants (95%). Mean (SD) HbA1c was 6.16% (0.30%) at baseline. Compared with the usual diet group, the low-carbohydrate diet intervention group had significantly greater 6-month reductions in HbA1c (net difference, –0.23%; 95% CI, –0.32% to –0.14%; P P P Conclusions and RelevanceIn this randomized clinical trial, a low-carbohydrate dietary intervention led to improvements in glycemia in individuals with elevated HbA1c not taking glucose-lowering medication, but the study was unable to evaluate its effects independently of weight loss. This diet, if sustained, might be a useful dietary approach for preventing and treating type 2 diabetes, but more research is needed.Trial RegistrationClinicalTrials.gov Identifier: NCT03675360

Introduction The progression of mild hyperkalemia and the predictors of progression have not been well characterized. In this study we aimed to characterize the progression of hyperkalemia and identify the risk factors for hyperkalemia progression. Methods Adults with mild hyperkalemia (at least one serum potassium measure > 5.0 and ≤ 5.5 mEq/L) were identified using electronic medical records from the Research Action for Health Network (2012–2018). Progression to moderate-to-severe and progression to severe hyperkalemia were defined as the first occurrences of a serum potassium measure > 5.5 and > 6.0 mEq/L, respectively. Kaplan–Meier analyses were conducted to estimate progression rates for all patients and by pre-specified patient subgroups. Hazard ratios (HR) of moderate-to-severe and severe hyperkalemia progression were estimated using Cox models. Results Of 35,369 patients with mild hyperkalemia, 16.9% and 8.7% progressed to moderate-to-severe and severe hyperkalemia, respectively. Rates of hyperkalemia progression elevated with the severity of chronic kidney disease (CKD). The highest progression rates were seen in patients with CKD stage 5 (stage 5 vs. no CKD: moderate-to-severe, 50.2% vs. 12.0%; severe, 31.3% vs. 3.9%; p

Energy drinks are widely used and very popular. They are touted as "harmless" energy boosters for use in professional, recreational and domestic settings. They are typically high in monosaccharides, and caffeine with other assorted products like ginseng. Careful study of the potential risks of their use is nonexistent while rigorous documentation of their touted energy boosting capacity is also meagre. We present the cautionary case of a 46-year-old Caucasian man with well-controlled type 2 diabetes and nonalcoholic fatty liver disease who developed a toxic triad syndrome of gastritis, hepatitis and pancreatitis within 4 months of commencing daily consumption of 2-3 160z cans of the energy drink Monster Energy. His clinical symptoms and biochemical derangements promptly resolved with stopping the beverage. We discuss the potential risks inherent in unsupervised liberal consumption of energy drinks and the need for both caution and vigilance among clinicians and patients.

With the increased prevalence of obesity, the phenotype of T1DM has changed. The prevalence of obesity in pts with T1DM is increasing, but there is limited data on how it compares to pts with T2DM. Bariatric surgery is effective for glycemic, weight and cardiometabolic risk surrogate amelioration in T2DM with obesity. However, the role of bariatric surgery in T1DM with obesity is largely unexplored. Retrospective chart review was done of patients with T1DM seen in Ochsner clinic system from January 2015 to January 2018. Obesity prevalence was quantified. Pts with bariatric surgery (BS) history were identified and their cardiometabolic surrogates pre and post BS were obtained. This was compared to pts with T2DM over the same time period. More in depth chart analysis of 300 pts from this cohort of T1DM pts was done to better characterize features of these pts 10, 282 pts with T1DM were identified over the observation period vs. 146,617 pts with T2DM. The prevalence of obesity in the T1DM cohort was 48.3% vs. 59.7% in the T2DM cohort while the prevalence of morbid obesity was 14.5% vs. 19% in the T1DM vs. T2DM groups. The number of pts who had bariatric surgery was 25 vs. 307 in the T1DM vs. T2DM groups. The percentage utilization of bariatric surgery as an intervention for obesity was very low in both cohorts (0.5 vs. 0.35 % in the T1DM vs. T2DM groups). Of the 300 pts with detailed chart review, actual diabetes subtypes were 163 (54%) T1DM, 43 (14.3%) as LADA, 1 (0.3%) as maturity-onset diabetes of the young, 2 (0.7%) as type 1.5 (essentially LADA), 8 (2.7%) as type 1+2 (T1DM with obesity and insulin resistance), 11 (3.7%) deceased, 71 (23.7%) as T2DM that had been miscoded as T1DM. For subsequent analyses, T1DM, LADA, type 1.5, and type 1+2 were included in the T1DM cohort. The weight and cardiometabolic surrogate changes in T1DM subjects were inconsistent and less marked than in T2DM subjects. Obesity prevalence in T1DM is close to that in T2DM and the use of bariatric surgery as an intervention remains very low both in T1DM and T2DM pts with obesity. Disclosure W. A. West: None. K. G. Romo: None. G. I. Uwaifo: None.

Obesity prevalence in T1DM is increasing. While T1DM is typically treated exclusively with insulin, the changing obesity trends and T1DM heterogeneity has raised interest in use of various oral hypoglycemic agents (OHA) as adjunctive therapy. The extent and impact of OHA “off label” use in “real world” settings is not well studied. We report on the extent, distribution, glycemic and cardiometabolic impact of OHA use in a T1DM cohort. Retrospective chart review of 300 patients with health record coded T1DM seen between January 2015 and January 2018 was done. OHA use, comorbidities, demographics, vital signs, and cardiometabolic risk surrogates were extracted for analyses.. The chart review showed actual DM subtypes were :163 (54%) T1DM, 43 (14.3%) Latent Autoimmune Diabetes of Aging (LADA), 1 (0.3%) maturity-onset diabetes of the young, 2 (0.7%) type 1.5 (essentially LADA), 8 (2.7%) type 1+2 (T1DM with obesity and insulin resistance), 11 (3.7%) deceased, and 71 (23.7%) T2DM that had been miscoded as T1DM. All subsequent analyses included T1DM, LADA, type 1.5, and type 1+2 in the verified T1DM cohort. 16% of the T1DM cohort were on at least one OHA and most common were sulphonylureas (16%), DPP-4 blockers (15.3%), SGLT-2 blockers (11%) and metformin (9.2%). OHA use in T1DM was not associated with any significant change in weight, BMI nor blood pressure. There was however a statistically significant decline in total cholesterol, LDL and HBA1c but not fasting triglycerides. No significant differences were found in hypoglycemia related admissions or DKA admissions with OHA use including among SGLT-2 users. Off label use of OHAs is quite prevalent in the studied population of patients with T1DM (16%) and their use was associated with improvements in HBA1c and aspects of lipid metabolism despite no significant changes in weight, BMI or blood pressure. OHAs may have utility as adjunctive therapy and require more structured study to enable development of therapeutic algorithms for their use in T1DM therapeutics. Disclosure K. G. Romo: None. W. A. West: None. G. I. Uwaifo: None.

Objectives Patients with hyperkalemia are commonly treated in the inpatient setting; however, real-world evidence is limited. The purpose of this study was to describe the inpatient management and post-discharge outcomes among patients with hyperkalemia. Methods Electronic medical record data (2012-2018) were used to analyze US adult patients with an inpatient stay with hyperkalemia (≥1 potassium value >5.0mEq/L). Patient characteristics, treatments, and monitoring six months prior to and during the inpatient stay, and hyperkalemia recurrence and inpatient readmissions post-discharge were summarized and compared among patients with mild (>5.0-5.5mEq/L), moderate (>5.5-6.0), and severe (>6.0) hyperkalemia. Results Of the 21,793 patients, 69.2% had mild, 19.0% had moderate, and 11.8% had severe hyperkalemia during inpatient care. The most common inpatient treatments were temporizing agents (mild: 28.9%; moderate: 46.0%; severe: 73.0%), diuretics (32.7%; 37.1%; 34.6%), and sodium-polystyrene sulfonate (11.7%; 27.8%; 45.3%). Almost no patients (0.1%) received a potassium binder at discharge. Most patients (86.8%) had their potassium levels return to ≤5.0mEq/L during the inpatient stay. Death during the inpatient stay occurred in 12.3% of mild, 15.5% of moderate, and 19.5% of severe hyperkalemic patients. Within 30 days of discharge, hyperkalemia recurred in 13.3%, 15.4%, and 18.4% of patients with mild, moderate, and severe hyperkalemia, respectively. Additionally, 19.7%, 21.5%, and 19.6% of patients were readmitted to inpatient care within 30 days post-discharge. Conclusion Among patients with hyperkalemia in the inpatient setting, treatment and normalization of serum potassium levels were common. However, death, readmission, and hyperkalemia recurrence were also fairly common across all cohorts. Future studies examining measures to reduce inpatient death, readmission, and hyperkalemia recurrence among patients with hyperkalemia in inpatient care are warranted.

Background Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality globally. Strong evidence supports the importance of diet and other lifestyle factors in preventing T2DM. Among individuals with T2DM, low-carbohydrate diets lead to decreases in hemoglobin A1c (HbA1c). However, research on the effects of low-carbohydrate diets on glycemic outcomes among individuals not currently on glucose-lowering medications who have elevated HbA1c is limited. Methods The objective of this randomized controlled trial is to study the effect of a healthy low-carbohydrate diet achieved through behavioral intervention and key food supplementation compared with usual diet on HbA1c and other metabolic risk factors among individuals with HbA1c from 6.0 to 6.9% who are not on glucose-lowering medications. In this parallel trial, 150 participants will be randomized to the intervention or control group for 6 months. The healthy low-carbohydrate diet target is Discussion We expect that the results from this study will lead to new approaches for developing and implementing dietary approaches (other than the most commonly used reduced fat diet) that will substantially reduce risk of cardiometabolic disease among adults with or at high risk of T2DM. The study intervention involves behavioral counseling and promotes consumption of dietary components thought to reduce risk of cardiometabolic disease and has expected applicability in clinical practice. Trial registration ClinicalTrials.gov NCT03675360. Registered on September 18, 2018 (prior to enrolment of the first participant).

Since the early animal lesional and electric brain stimulation experiments of Hetherington and Ranson, it has been appreciated that lesions in certain parts of the hypothalamus can induce profound phenotypes of morbid obesity or dramatic wasting. These and other findings led to the postulation of hypothalamic “satiety” and “feeding” centers. Subsequent clinical observations in humans including characterization of children with morbid obesity associated with entities such as the Prader-Willi and Frohlich syndromes as well as Simmonds’ cachexia demonstrated that similar hypothalamic dysfunction phenotypes existed in human hypothalamic disease. The discovery of leptin and the subsequent better characterization of the hypothalamic basis for modulation of satiety, hunger, and energy balance as well as the discovery of various adipo- and enterocytokines with central hypothalamic modulatory effects crystallized hypothalamic obesity and wasting as distinct and important clinical entities. This manuscript seeks to provide a comprehensive overview of the causes, presentation, and basic pathophysiology of these two disparate but functionally related clinical syndromes.

The hypothalamus and pituitary gland which are, respectively, the approximate sizes of an almond and a bean seed form an integral part of the interface between the endocrine system and the central nervous system. The hypothalamus in addition is central in coordinating various metabolic, autonomic, and behavioral responses to environmental stimuli. These effects are mediated to less degree by neuronal connections with the rest of the brain and more so via the synthesis and secretion of myriad neurohormones which include stimulatory (releasing) and inhibitory hormones. These hormones and the secondary humoral factors whose secretion they modulate have central roles in the homeostatic control of processes as diverse as hunger, appetite, energy balance, temperature control, sleep regulation, other circadian rhythms, reproductive function, and social behavioral activities including affection and aggression. This chapter highlights the neuroendocrine functional relationships of the hypothalamic and pituitary axes to the rest of human systemic function.

To assess risk factors and incidence of diabetes complications in women with type 1 diabetes (T1D) based on parity.Data were collected from women (16-40 years old) in the T1D Exchange completing pregnancy/childbirth questionnaires during 2011-2013 and 2016-2018. Incidence of risk factors and diabetes complications were compared between women with a first pregnancy at/within 1-year of enrollment (There was a trend for lower HbA1c (adjustedFour-5 years after delivery, parous women with T1D tended to have lower HbA1c levels despite higher body mass indices and more frequent adverse lipid profiles and hypertension compared with nulliparous women. Further studies based on these trends are warranted.

• Background: Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality globally. Strong evidence supports the importance of diet and other lifestyle factors in preventing T2DM. Among individuals with T2DM, low-carbohydrate diets lead to decreases in hemoglobin A1c (HbA1c). However, research on the effects of low-carbohydrate diets on glycemic outcomes among individuals not currently on glucose-lowering medications who have elevated HbA1c is limited.• Methods: The objective of this randomized controlled trial is to study the effect of a healthy low-carbohydrate diet achieved through behavioral intervention and key food supplementation compared with usual diet on HbA1c and other metabolic risk factors among individuals with HbA1c from 6.0 to 6.9% who are not on glucose-lowering medications. In this parallel trial, 150 participants will be randomized to the intervention or control group for 6 months. The healthy low-carbohydrate diet target is Discussion: We expect that the results from this study will lead to new approaches for developing and implementing dietary approaches (other than the most commonly used reduced fat diet) that will substantially reduce risk of cardiometabolic disease among adults with or at high risk of T2DM. The study intervention involves behavioural counselling and promotes consumption of dietary components thought to reduce risk of cardiometabolic disease and has expected applicability in clinical practice.• Trial registration: Clinicaltrials.gov registry: https://clinicaltrials.gov/ct2/show/NCT03675360. Registered on September 18, 2018 (prior to enrolment of the first participant).

Objectives: To examine changes in device use and glycemic outcomes for pregnant women from the T1D Exchange Clinic Registry between the years 2010-2013 and 2016-2018. Methods: Participant-reported device use and glycemic outcomes were compared for women aged 16-40 years who were pregnant at the time of survey completion, comparing 2010-2013 (cohort 1) and 2016-2018 (cohort 2). Hemoglobin A1c results within 30 days prior to survey completion were obtained from medical records. Results: There were 208 pregnant women out of 5,236 eligible participants completing the questionnaire in cohort 1 and 47 pregnant women out of 2,818 eligible participants completing the questionaire in cohort 2. Continuous glucose monitor (CGM) use while pregnant trended upward among cohort 2 (70% vs 37%, P = .02), while reported continuous subcutaneous insulin infusion (CSII) use while pregnant declined (76% vs 64%, P = .04). HbA1c levels trended downward (6.8% cohort 1 vs 6.5% cohort 2, P = .07). Conclusions: Self-reported CGM use while pregnant increased over the studied intervals whereas CSII use decreased. Additional evaluation of device use and the potential benefits for T1D pregnancies is needed.

Some patients with type 2 diabetes (T2DM) and/or pancreatogenous diabetes have exocrine pancreatic insufficiency (EPI). The impact of pancreatic enzyme replacement (PER) on diabetes (DM) control is largely undocumented and unknown. We present 4 cases suggesting PER may positively impact DM glycemic and lipids. Case 1 is a 46 yr Caucasian (C) man with T2DM and recurrent gall stone pancreatitis. Prior to onset his HBA1c was between 6.3-7.4 but with recurrent episodes reached peak of 10.8. He was diagnosed with chronic pancreatitis with EPI and commenced PER. After 3 mths on PER his HBA1c was 6.7 with resolution of hypertriglyceridemia (HTG) and improved total cholesterol (TC). Case 2 is a 57 yr old C man with T2DM and episodic HTG related pancreatitis. He had erratic medication access due to insurance limitations. He was recently diagnosed with EPI but initially could not afford PER. HBA1c at diagnosis of EPI was 9.7 with elevated TC and HTG. When he secured PER, within 8 wks of use HBA1c reduced to 7.6 with improved HTG and TC. Case 3 is a 24 yr old C man with known cystic fibrosis and cystic fibrosis related DM. Initial HBA1c was 8.6 and he had been of PER voluntarily for yrs. He had features of EPI and was urged to resume PER which he did. At 4 mth follow up after restarting PER his HBA1c was 6.4 with improvement in HTG. Case 4 is a 36 yr old C man with prior well controlled T2DM and known MEN-1. His prior mean HBA1c was 6.7. Due to recurrent bouts of severe hypoglycemia in the prior 2 yrs work up revealed multiple pancreatic insulinomas for which he had partial pancreatectomy. His DM control declined with peak HBA1c of 11.3. He developed symptoms of EPI and was commenced on PER. 3mths after starting PER his HBA1c was 7.1 with resolution of HTG and improved TC. Early recognition of EPI in patients with DM is important. Commencement of PER in such patients may positively impact glycemia and dyslipidemia especially HTG. Further study of the relationship of PER to DM metabolic control is warranted. Disclosure G.I. Uwaifo: None.

BACKGROUND: PCOS is the most common cause of hirsutism in women of reproductive age. The presence of virilization in addition to hirsutism should alert to the possibility of less common causes of hyper-androgenization (HA) in this population including otherwise uncommon functional ovarian neoplasms (FON). We present 3 cases of women initially thought to have PCOS in whom virilization was the prime clue to the correct diagnosis of FON. Clinical Case series: Case 1 is a 40yr old woman with obesity and dysmetabolic syndrome referred for hirsutism presumed due to PCOS. She had noted symptoms over 2–3 yrs with amenorrhea and associated infertility. Examination revealed marked hirsutism and virilization with Ferriman-Galleway score (FGS) of 20. Lab tests confirmed marked male range HA. Multiple imaging tests revealed no adrenal or ovarian mass lesions. FDG-PET scan finally revealed a left ovarian focus for which she has left oophorectomy that revealed a 1cm Leydig cell tumor, Her HA resolved post-op and spontaneous periods resumed. Case 2 is a 45yr old woman referred with possible PCOS who had 5 mth history of progressive hirsutism and generalized hypertrichosis, dull lower abdominal pain and amenorrhea. Examination revealed marked hirsutism with generalized hypertrichosis and virilization. FGS was 25 and clitoral index was 935mm2. Lab tests confirmed marked male range HA and abdominopelvic imaging show no adrenal lesions but a 5.2cm left ovarian mass. Left salpingo-oophorectomy revealed a steroid cell tumor and postoperatively her androgen levels normalized. Case 3 is 37 yr old woman with SLE and obesity with prior gastric bypass referred with presumed PCOS but presenting with 1 yr history of progressive hirsutism. She was initially thought to have non classical CAH and treated with oral glucocorticoids with no symptom improvement. Examination revealed marked hirsutism, virilization with elevated FGS and clitoromegaly. Lab tests showed marked male range HA but multiple imaging studies revealed no apparent adrenal or ovarian lesions. Patient had no fertility interests and so had elective total hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed a 2.5cm left ovarian Leydig cell tumor not apparent at surgery and post op her androgen levels normalized. Conclusion: The distinction between PCOS which is ubiquitous and FON which is rare hinges on careful history and examination. Rapid onset hirsutism with virilization should prompt suspicion of FON. Marked male range HA (total serum testosterone >250ng/dl) is another “red flag” finding. Persistent radiologic search for such lesions should continue as they may not be immediately apparent on routine abdominopelvic imaging.

BACKGROUND: Primary hyperparathyroidism (pHT) is one of the most common causes of hypercalcemia. About 10% of these patients have a familial cause of which MEN and the hyperparathyroid-jaw tumor syndrome (HJTs) are most common. Familial hypocalciuric hypercalcemia (FHH) due to loss of function mutations of the calcium sensing receptor (CASR) gene is an important familial mimic of this that needs to be distinguished. Beyond this are still a group of patients with familial isolated primary hyperparathyroidism (FIpHT). Recognition of this entity is important because of the different prognostic and surgical treatment strategy for their management compared to regular sporadic pHT. Clinical Case: A 58 yr old postmenopausal lady on topical HRT was referred for thyroid nodular disease. Her initial lab tests showed primary hyperparathyroidism with mild hypercalcemia. Her initial neck sonogram showed multiple benign appearing nodules that did not warrant biopsy. There was a history of hypothyroidism in her mother and thyroid cancer in a maternal cousin. In addition, her father and two sons have history of hypercalcemia that required repeated hospital admissions for treatment. Her two daughters to date have had no hypercalcemia, nephrolithiasis nor thyroid problems. There was no family history of jaw, renal nor brain or pituitary tumors and no history of severe dyspeptic disease nor familial cancers. She had hypercalciuria, normal bone density and non-obstructive nephrolithiasis. MEN-1 gene testing was normal. Parathyroid scan suggested a possible right sided parathyroid lesion and she had elective parathyroidectomy of an ectopic right parathyroid that was hypercellular on histology. The intra-operative PTH dropped following the lesion extraction by ~ 51%. Post operatively the patient’s mild pHT and hypercalcemia persists but imaging studies have been unrevealing. Further genetic testing for other possible etiologies of familial pHT were -ve for HJTs but revealed a novel somatic mutation of the CASR gene; c.1868G>A (p.Gly623Asp) whose present significance is unclear. This variant has been described in one family with FHH but In silico predictive analyses of the mutation suggests a possible deleterious effect. Given her known family history of symptomatic hypercalcemia this novel mutation appears to be a hitherto unrecognized cause for FIpHT. The patient is presently being conservatively managed and monitored. Conclusion: While familial pHT is relatively uncommon its recognition is important as it can inform planned surgical intervention and expected prognosis for anticipated cure. While MEN and HJTs are the most common etiologies for familial pHT other possibilities need to considered when the history suggests possible FIpHT and our case highlights a novel CASR mutation as diagnostic consideration.

BACKGROUND: Insulin induces intracellular shift of phosphorus, causing hypophosphatemia. This is mild, transient and quiescent in normal persons. Persistent hyperinsulinemia in patients with depleted phosphorus stores can cause profound symptomatic hypophosphatemia. Clinical Case: A 36yr old man with MEN 1 presented in follow-up. His original manifestation of MEN 1 was familial primary hyperparathyroidism (pHPT) for which he had parathyroidectomy in 2009. At one of his endocrine clinic visits, he was noted to have asymptomatic hypophosphatemia with serum phosphorus of 2.4 (2.7–4.5 mg/dL) and mildly elevated PTH of 89 (9–77 pg/mL). This was presumed to be due to mild persistent/recurrent pHPT, and he was advised to increase dietary phosphorus intake. About a year later, he presented to the emergency room (ER) with palpitations and marked asthenia. Serum phosphorus was 1.0. He was treated with intravenous phosphorus and discharged on oral phosphorus replacement with advice to increase his dietary phosphate intake. Despite this, he continued to have recurrent spells of dizziness, weakness, palpitations, and marked hypophosphatemia several requiring repeat ER visits. His degree of mild pHPT remained stable and imaging studies to identify a possible cause for tumor induced osteomalacia with phosphate wasting was unrevealing. He volunteered at a follow up visit that he had a long history of low blood sugar spells (confirmed by fingerstick) that he had learnt to manage with frequent carbohydrate rich snacks. This prompted the consideration of a possible insulinoma as the cause for his persistent hypophosphatemia. Despite significant hypoglycemia on an abbreviated supervised fast, an OGTT and mixed meal test showed profound severe insulin mediated hypoglycemia. CGMS also showed multiple extended early morning severe hypoglycemic spells

Introduction: Mifepristone (MFP) aka RU-486/Korlym is a synthetic steroid analog originally developed in 1980 as an abortifacient that is now used in the management of Cushing’s syndrome (CS). It is both a progesterone (PG) and glucocorticoid (GC) receptor blocker. CS is often associated with reproductive functional anomalies including hypogonadism, menstrual irregularities and infertility. Due to its mode of action, measurement of serum PG and/or cortisol in patients on MFP are inaccurate indices of systemic PG and/or GC deficiency or excess. However, the potential impact of MFP use on other serum steroid assays has not been widely studied. We report the case of a 55 yr old man on treatment with MFP for adrenal CS found to have striking artefactual changes in serum androgen and estrogen levels. Case Summary: A 55 yr old African American man was referred with poorly controlled type 2 diabetes, hypertension, hyperlipidemia, obesity and untreated hypogonadism. He had a 3.2cm left adrenal incidentaloma associated with adrenal CS and he chose medical management rather than surgery. Upon starting MFP at 300mg QD serum total estrogen (by radio-immunoassay; RIA) and estradiol (by chemiluminescence immunoassay; CIA) were markedly elevated while serum total, free, bioavailable testosterone and dihydrotestosterone were all markedly reduced. His HBA1c, weight and energy levels improved on MFP despite these findings. The serum steroid levels normalized to pre-treatment levels after stopping MFP for ~ 4weeks but the changes recurred after restarting therapy. After MFP dose escalation to 300mg BID the serum steroid levels normalized after stopping MFP for ~ 6 weeks. The artefactual low testosterone levels also occured with measurement by equilibrium dialysis but “normal accurate” results were obtained when measured by liquid chromatography-Tandem mass spectrometry (LC-TMS). He remains on MFP 300mg BID without need for androgen repletion. Discussion: With increased use of MFP for CS, indices for tracking its clinical and biochemical effects assume great importance. There are few reports of the possible effects of MFP on estrogen and testosterone serum assays despite its touted low cross reactivity with sex steroids. Our case suggests that the significance, extent and prevalence of artefactual changes on serum sex steroid assays may be underestimated and under- appreciated. Conclusions: Our case of wide disparities in serum estrogen and androgen measures in a patient on MFP indicates that caution needs to be exercised in the interpretation of such results in patients on current MFP therapy. Our clinical observations suggest depending on the dose that a wash out period of 4–6 weeks is required to ensure accurate measures. Studies to ascertain the prevalence of this artefactual effect are needed and it appears testosterone measurement by LC-TMS obviates the testosterone assay artefact.

The prevalence of obesity and its complications and comorbidities continue to increase. It is well established that obesity is a major etiologic factor in the onset of type 2 diabetes (T2DM) and that bariatric surgery (BS) is an effective management strategy for both weight and glycemic control in obese T2DM patients. The relationship between obesity and type 1 diabetes (T1DM) is less clear though recent reports suggest a recent surge in the prevalence of obesity among T1DM patients. To explore the prevalence of obesity in T1DM and the impact of bariatric surgery in these patients a 1 year (2018) retrospective chart review of T1DM patients was done and the identified patients were compared to T2DM patients seen over the same time period in the Ochsner clinical network. Of 93,367 subjects with T2DM seen over the 1 year period, 62, 034 (66.4%) are obese and of these 18,670 (30%) are morbidly obese. The T1DM patients over the same period are 7,143 of which 3,728 (52%) are obese and 969 (26%) are morbidly obese. Over this period while 1,818 Obese T2DM patients (2.9% of the cohort) had BS only 6 obese T1DM patients (0.16%) of the cohort had BS. This group consists of mostly Caucasian (5/6) women (5/6) with 3 having gastric bypass and 4 having sleeve gastrectomy. While the prevalence of cardiometabolic comorbidities (hypertension, dyslipidemia, ESRD, CAD, and CVD) were essentially similar in both cohorts of obese diabetics, the effects of bariatric surgery on weight, HBA1c, blood pressure and lipids were more variable in the T1DM patient than the T2DM patients. Obesity is presently nearly as prevalent in T1DM as T2DM. Morbid obesity is just as prevalent in both diabetes cohorts. While BS remains underutilized as a management strategy in obese T2DM it remains a rarity in obese T1DM and the little data available suggests that its impact on cardiometabolic surrogates may be more variable in this unique cohort. More study is needed of the potential utility and impact of BS in weight management of obese T1DM. Disclosure G.I. Uwaifo: None.

We aimed to assess the association between pregnancy and occurrence of diabetes-related complications in women with type 1 diabetes (T1D). Females 16-40 years old in the T1D Exchange clinic registry completing an initial questionnaire during 2011-13 and repeating it between 2016-18 (N=497; age 22±5 years, duration 12 [6,17] years, 87% non-Hispanic White) were categorized into 2 cohorts: first pregnancy during 2011-13 (preg; n=28) and never pregnant (never; n=469). No participants had complications reported at baseline. Funduscopic exam data were not uniformly available. There was a trend for lower HbA1c 5 years after study enrollment in the preg group (7.3%±1.3%) compared with the never group (7.9%±1.4%), P=0.14 adjusted for age, race/ethnicity, and body mass index. Both albuminuria and nephropathy within 5 years of study enrollment were found at higher frequency in the women who had never been pregnant (Table). Rates of neuropathy within 5 years of enrollment were similar between the groups. While rates of cardiovascular disease within 5 years of study enrollment were low for both groups (0 in preg group and 2 participants in never group), the pregnant cohort despite having lower A1c had higher frequency of some cardiovascular disease risk factors (e.g., obesity). In persons with T1D without reported complications at enrollment, pregnancy was not associated with new complication development 5 years after delivery. Disclosure S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US. N.C. Foster: None. S. DuBose: None. S. Agarwal: None. S. Lyons: None. A.L. Peters: Advisory Panel; Self; Abbott, Becton, Dickinson and Company, Bigfoot Biomedical, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Livongo Health, MannKind Corporation, Medscape, Merck & Co., Inc., Omada Health, Inc., OptumRx, Inc., Sanofi US, Zafgen, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Jaeb Center for Health Research, MannKind Corporation, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc. G.I. Uwaifo: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Eli Lilly and Company, Insulet Corporation. Consultant; Self; Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi. Research Support; Self; Dexcom, Inc., Insulet Corporation. C.J. Levy: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Allergan. Funding The Leona M. and Harry B. Helmsley Charitable Trust

We examined characteristics of pregnant women aged 16-40 years with type 1 diabetes (T1D) enrolled in the T1D Exchange clinic registry. We compared characteristics of 3 cohorts of women with data collection periods from: 2010-12 (N=4651), 2011-13 (N=3355), and 2016-18 (N=2818). 2.9%, 2.2%, and 1.7% of women reported being pregnant during 2010-12, 2011-13, and 2016-18, respectively. For pregnant women, there was a trend for a decrease in HbA1c over the 3 time periods from 6.8% to 6.7% to 6.4% (P=0.13 adjusted for age, race/ethnicity, frequency of glucose monitoring, and use of CGM). Self-reported use of CGM while pregnant increased more than 2-fold over the time period (P=0.001 adjusted for age, duration, race/ethnicity, insurance status, and use of pump); conversely, self-reported pump use while pregnant remained unchanged (adjusted P=0.38) (Table). Severe hypoglycemia (seizure/loss of consciousness) was similar across cohorts (adjusted P=0.38).We found in a real-world population of pregnant women in the U.S., lower HbA1c levels compared to those pregnant 5-6 years ago. CGM use in pregnancy appears to have increased over time, with relatively low but stable participant-reported insulin pump use. Further explorations of these findings, ongoing assessment of real-world pregnancy outcomes and comparisons with data on T1D pregnant women from other large registries are needed. Disclosure C.J. Levy: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Allergan. N.C. Foster: None. S. DuBose: None. S. Agarwal: None. S. Lyons: None. A.L. Peters: Advisory Panel; Self; Abbott, Becton, Dickinson and Company, Bigfoot Biomedical, Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Livongo Health, MannKind Corporation, Medscape, Merck & Co., Inc., Omada Health, Inc., OptumRx, Inc., Sanofi US, Zafgen, Inc. Research Support; Self; AstraZeneca, Dexcom, Inc., Jaeb Center for Health Research, MannKind Corporation, National Institute of Diabetes and Digestive and Kidney Diseases. Speaker's Bureau; Self; Novo Nordisk Inc. G.I. Uwaifo: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J. Sherr: Advisory Panel; Self; Bigfoot Biomedical, Eli Lilly and Company, Insulet Corporation. Consultant; Self; Lexicon Pharmaceuticals, Inc., Medtronic, Sanofi. Research Support; Self; Dexcom, Inc., Insulet Corporation. S. Polsky: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Barbara Davis Center for Diabetes, Children's Diabetes Foundation, Dexcom, Inc., Eli Lilly and Company, JDRF, Leona & Harry Helmsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi US. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Background: Hypolipidemia and hypocholesterolemia are uncommon and because of the established risk of hypercholesterolemia for cardiovascular disease, reduced lipids and total cholesterol levels are often clinically desired and/or deemed clinically inconsequential. A finding of persistently low lipid levels and total cholesterol may however not be innocuous nor desirable. We describe the case of a 46 yr old man with persistently low total cholesterol levels

GLP-1 agonists are widely used antidiabetic agents. Among their potential associated side effects is acute pancreatitis (AP). Its exact prevalence is unknown as are known predictors for its incidence. We present two cases that suggest that carrier states for hemochromatosis (HC) and cystic fibrosis (CF) are risk factors for GLP-1 agonist associated AP. Case 1 is a 39 year old Caucasian lady with type 2 diabetes diagnosed 2 years ago. She has morbid obesity, hypothyroidism and NAFLD. She had a history of symptomatic AP to liraglutide (Victoza), exenatide (Byetta), dulaglutide and sitagliptin. She is currently managed with Degludec insulin, repagnilide, metformin and prn Lispro insulin with a current HBA1c of 6.5. Work up for mild transaminitis and prior elevated ferritin revealed she is a heterozygous carrier for the C282Y HC mutation despite currently having normal ferrokinetic profile. Her ongoing glycemic care is now without any further use of GLP-1 analogs nor DPP-4 inhibitors. Case 2 is a 62 year old Caucasian lady with type 2 diabetes diagnosed 8 years ago. She has hypertension, hypercholesterolemia and sleep apnea. She had a history of developing symptomatic AP to exenatide ER (Bydureon), dulaglutide and liraglutide (Victoza). Her current antidiabetic regime consists of Detemir insulin, Aspart insulin prn, metformin, repaglinide, and canagliflozin with a current HBA1c of 7.7. Because of a positive history of CF in several grand children she had genetic testing that showed she is a heterozygous carrier of the Delta F5deletion mutation of the CFTR gene. Her ongoing diabetes care is without any further use of GLP-1 analogs. Our case series present two patients with class associated predilection for GLP-1 analog associated AP. Heterozygous carrier states for CF and HC may represent at risk clinical phenotypes for GLP-1 AP. Consideration should be given to genetic screening for these carrier states prior to commencing diabetic patients on GLP-1 analogs and possibly also DPP-4 inhibitors. Disclosure W.A. West: None. G.I. Uwaifo: None.

Bariatric surgery is effective in reducing body weight and obesity-related comorbidities. This study examined differences in the short-term effect of Roux en Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on the hedonic rating of food. Predominantly black women with complicated obesity and a BMI>50 g/m(2) completed a validated food preference questionnaire before and 1-3 months following surgery. Analysis of preference scores indicated that the preference for fat decreased with both surgeries. VSG also decreased the preference for sugar. Further studies are needed to evaluate long term effects of surgery on food preferences and to elucidate physiological mechanisms.

Graves orbitopathy (GO) is an autoimmune disorder representing the most frequent extrathyroidal manifestation of Graves disease. It is rare, with an age-adjusted incidence of approximately 16.0 cases per 100,000 population per year in women and 2.9 cases per 100,000 population per year in men. GO is an inflammatory process characterized by edema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat. Despite recent progress in the understanding of its pathogenesis, GO often remains a major diagnostic and therapeutic challenge. It has become increasingly important to classify patients into categories based on disease activity at initial presentation. A Hertel exophthalmometer measurement of >2 mm above normal for race usually categorizes a patient as having moderate-to-severe GO. Encouraging smoking cessation and achieving euthyroidism in the individual patient are important. Simple treatment measures such as lubricants for lid retraction, nocturnal ointments for incomplete eye closure, prisms in diplopia, or botulinum toxin injections for upper-lid retraction can be effective in mild cases of GO. Glucocorticoids, orbital radiotherapy, and decompression/rehabilitative surgery are generally indicated for moderate-to-severe GO and for sight-threatening optic neuropathy. Future therapies, including rituximab aimed at treating the molecular and immunological basis of GO, are under investigation and hold promise for the future.

A multidisciplinary approach to weight loss is necessary to manage obesity. Medications are important in the management strategy, and pharmacists can enhance the care provided. This paper focuses on the integration of a clinical pharmacist into a multidisciplinary team at a weight management clinic serving medically indigent patients in New Orleans.

We present the case of a 43-year-old gentleman who presented to the emergency room with acute abdominal distension, confusion and vascular collapse. The emergent radiologic imaging obtained showed massive bilateral adrenal enlargement, but despite the initial clinical suspicion of possible overwhelming sepsis and/or massive abdominal/intralesional hemorrhage, lab tests based obtained rapidly confirmed the diagnosis of acute Addisonian crisis which responded dramatically to adrenocorticoid hormone replacement therapy and aggressive fluid resuscitation. The patient's established history of metastatic lung cancer confirmed this as a case of metastatic massive bilateral adrenal metastases with an initial presentation of acute adrenal insufficiency which is uncommon in the setting of metastatic carcinomatosis but more typically associated with lymphomas. Recognition of this clinical possibility is vital to enable rapid diagnosis and consequent life saving therapy.

Polymorphisms (SNP) in the glucocorticoid receptor (GR) gene can alter sensitivity to glucocorticoids. Previous studies of the N363S and BclI SNP in the GR gene have shown a metabolic syndrome phenotype in mostly non-African populations. The obesity phenotype of African Americans (AA) seems to be more severe than that of Caucasians.We aimed to assess the prevalence of N363S and BclI in obese and non-obese Caucasian (n=26) and African (n=23) Mississippians (age: 23-63 years) to investigate associations with body composition (body mass index/BMI, waist-to-hip ratio), metabolic parameters (salivary cortisol, fasting glucose and insulin, hemoglobin A1C, fructosamine, HOMA-IR index), and psychological stress perception (blood pressure/BP, perceived stress scale/PSS).All subjects were homozygous for wildtype N363N. BclI polymorphism genotype frequencies among the 23 AA were: homozygous CC (57%), GG (4%), and heterozygous CG (39%), and among the 26 white women: homozygous CC (35%), GG (19%), and heterozygous CG (46%). Linear and logistic regression analyses including a parsimonious model identified BMI as a statistically significant parameter between the two ethnic groups (BMI was 3.13 kg/m2 higher in AA). Within the AA group, BMI, waist-to-hip ratio, log (HOMA-IR), PSS scores, BP, and hyperlipidemia showed no statistically significant relationships for the BclI polymorphism. PSS scores were 15.2 for AA vs. 14.7 for white women (normal mean: 14.7 vs. 12.8).Black Mississippians have a higher BMI than whites, which may be related to the presence of the BclI polymorphism and increased glucocorticoid sensitivity. Although more blacks (52%) than whites (38%) had elevated BP, PSS scores in both groups suggest that a high BMI is not regarded as abnormal or stressful. This might negatively impact behavior change regarding lifestyle modifications with increased physical activity and healthier food choices. Larger studies, particularly in African populations, are needed to better define metabolic and psychological characteristics in relation to the N363S and BclI GR gene polymorphisms.

Vitamin D deficiency is widely prevalent across all ages, races, geographical regions, and socioeconomic strata. In addition to its important role in skeletal development and calcium homeostasis, several recent studies suggest its association with diabetes, hypertension, cardiovascular disease, certain types of malignancy, and immunologic dysfunction. Here, we review the current evidence regarding an association between vitamin D deficiency and hypertension in clinical and epidemiological studies. We also look into plausible biological explanations for such an association with the renin-angiotensin-aldosterone system and insulin resistance playing potential roles. Taken together, it appears that more studies in more homogeneous study populations are needed before a firm conclusion can be reached as to whether vitamin D deficiency causes or aggravates hypertension and whether vitamin D supplementation is safe and exerts cardioprotective effects. The potential problems with bias and confounding factors present in previous epidemiological studies may be overcome or minimized by well designed randomized controlled trials in the future.

Obesity has rapidly become a life-threatening epidemic worldwide. There are a plethora of obesity-related co-morbidities and complications that increase morbidity, mortality and cost of care associated with obesity. Orlistat is approved for the treatment of obesity and has been evaluated both in obesity and in the several obesity-related co-morbidities.The purpose of this article is to provide detail of the pharmacotherapeutic role of orlistat in obesity, describe orlistat and its pharmacological properties, critique the evidence for orlistat's use in obesity and obesity related co-morbidities, and define the role of orlistat in clinical practice.A thorough, all-inclusive literature search was conducted to isolate clinical trials, case reports and meta-analyses evaluating the safety and efficacy of orlistat in various patient populations.Orlistat's unique mechanism of action, beneficial effects on multiple co-morbidity surrogates and relatively mild adverse effect and drug interaction profile position it favorably as the first option for pharmacotherapy in comprehensive obesity management of adults and children.

Cardiovascular disease (CVD) burden remains the predominant cause of mortality and morbidity in the United States and in most of the developed world. The ongoing twin epidemics of obesity and type 2 diabetes mellitus provide a groundswell source for sustaining this trend for the foreseeable future (increasing the prevalence of CVD by 2-4 times), unless radical changes are made in public health policy. Oral hypoglycemic agents (OHAs) remain a mainstay for management of type 2 diabetes in most practice settings. Although these agents are primarily prescribed to achieve better glycemic control, it is important to evaluate what effects they have on cardiovascular risk and whether there are significant differences in effects among the different OHAs. This review presents the available data on the effects of the various OHAs on cardiovascular risk surrogates and actual events in retrospective and prospective study design settings.

To determine the prevalence and the metabolic characteristics of acanthosis nigricans (AN) in a group of 28 study subjects with biopsy-proven nonalcoholic steatohepatitis (NASH).The study participants (15 female and 13 male patients, 20 of whom were white subjects; mean body mass index, 32.7 +/- 5.7 kg/m2; mean age, 45.7 +/- 11.3 years) underwent an oral glucose tolerance test (OGTT), frequently sampled intravenous glucose tolerance test (FSIGT), and fasting metabolic panels. AN status was clinically determined, and fat mass was measured by dual-energy x-ray absorptiometry.All study subjects had insulin resistance (IR), and 15 (54%) had the metabolic syndrome (by Adult Treatment Panel III criteria). Of the 28 patients, 4 (14%) had AN (AN+) and 24 did not (AN-). AN+ subjects had a higher body mass index (37.7 +/- 5.6 versus 31.5 +/- 4.3 kg/m2), fat mass (38.9 +/- 4.0 versus 29.2 +/- 2.3 kg), and leptin levels (17.2 +/- 3.9 versus 9.3 +/- 1.6 ng/mL) (P0.05). They also had significantly higher indices of insulin secretion: fasting and stimulated insulin and C-peptide levels from OGTT and FSIGT. Metabolic syndrome prevalence was 40% in AN- versus 75% in AN+ subjects (not significantly different). Although the AN+ group had significantly lower fasting and OGTT-derived indices of insulin sensitivity in comparison with the AN- group, their FSIGT indices were similar. Waist circumference (a surrogate of visceral adiposity) and cytokine profiles were similar in the AN+ and AN- groups.AN was not highly prevalent in our study cohort with NASH, despite the high prevalence of IR. Hyperinsulinemia and total adiposity, rather than visceral adiposity and IR, were the indices most predictive of AN. The use of AN as an index of IR in patients with NASH appears to have limited diagnostic value.

After many decades of relative therapeutic stagnation since the initial discovery of insulin, followed by some modifications on its structure and only having sulfonylureas and biguanides for many years, the last decade has seen a surge in new therapeutic options for the management of diabetes. The results of the United Kingdom Prospective Diabetes Study and Kumamoto study indicate the need for aggressive glycemic control and the slow inexorable clinical deterioration associated with type 2 diabetes overtime. The propensity for weight gain and hypoglycemia are the two major limitations that subcutaneous insulin and sulfonylureas have been particularly prone to. The newer antidiabetic medications and those on the horizon attempt to address these limitations. GLP-1 agonists and the DPP-IV inhibitors exploit the innate incretin system to improve glycemia while promoting satiety and weight management. Like GLP-1 related compounds, pramlintide offers the potential to address postprandial hyperglucagonemia associated with type 2 diabetes only limited by the multiple injections and gastrointestinal side effects. The glitazars offer the hope ofa new approach to diabetes care addressing not just glycemia, but dyslipidemia and other components of the metabolic syndrome, though the side effect profile remains a major unknown. The INGAP peptide represents the holy grail of diabetes care as it offers the potential of a new paradigm: that of islet regeneration and potential for a cure. But at this stage, with no human data available, it remains highly speculative. Beyond these and other novel agents being developed to meet the challenge of the worldwide epidemic of diabetes, the central place of insulin in diabetes care cannot be forgotten. In view of this the continued efforts of improvement in insulin delivery, kinetics and action have spurred such innovations as the various inhaled insulins and new insulin analogues. There is cause for guarded optimism and excitement about the years ahead. There is reason to expect that despite the growing burden of diabetes worldwide, we will be better equipped to manage it and its comorbidities and prevent its onset and possibly even cure it.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease for which there is no known effective therapy. A proportion of patients with NASH progress to advanced fibrosis and cirrhosis. NASH is considered one of the clinical features of the metabolic syndrome in which insulin resistance plays a central role. This prospective study evaluates the role of insulin-sensitizing agent in treatment of NASH. Eighteen nondiabetic patients with biopsy-proven NASH were treated with pioglitazone (30 mg daily) for 48 weeks. Tests of insulin sensitivity and body composition as well as liver biopsies were performed before and at the end of treatment. By 48 weeks, serum alanine aminotransferase values fell to normal in 72% of patients. Hepatic fat content and size as determined by magnetic resonance imaging decreased, and glucose and free fatty acid sensitivity to insulin were uniformly improved. Histological features of steatosis, cellular injury, parenchymal inflammation, Mallory bodies, and fibrosis were significantly improved from baseline (all P < 0.05). Using strict criteria, histological improvement occurred in two-thirds of patients. Pioglitazone was well tolerated; the main side effects were weight gain (averaging 4%) and an increase in total body adiposity. In conclusion, these results indicate that treatment with an insulin-sensitizing agent can lead to improvement in biochemical and histological features of NASH and support the role of insulin resistance in the pathogenesis of this disease. The long-term safety and benefits of pioglitazone require further study.

The mainstays of therapy of familial dyslipoproteinemia (FDB) are diet and long-term niacin or fibrate therapy. Statins are progressively recognized as accepted alternatives for FDB. We hereby describe the case of a 32-year-old obese man with treated panhypopituitarism and FDB, whose hyperlipidemia improved significantly on atorvastatin therapy. In this patient, we also noted a marked discrepancy between the serum high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo-) AI levels, with HDL-C being disproportionately low in comparison to the corresponding apo-AI values. Although atorvastatin therapy resulted in a significant improvement of lipid metabolism parameters within 8 weeks, the aforementioned discrepancy between HDL-C and apo-AI levels persisted. This case buttresses the effectiveness of atorvastatin therapy in FDB, and highlights the occurrence of discrepancy between HDL-C and measured apo-AI levels in rare cases of dyslipidemia. We speculate that the latter phenomenon may be caused by allelic variation(s) in any of three genes: apo-AI, apo-CIII, and apo-AIV.

Study Objectives. To determine whether orlistat causes fat-soluble vitamin deficiencies in African-American and Caucasian adolescents. Design. Prospective, open-label pilot study. Setting. Warren Grant Magnuson Clinical Center of the National Institutes of Health. Patients. Seventeen adolescents with body mass indexes above the 95th percentile for age, race, and gender who also had at least one obesity-related comorbid condition. Intervention. Subjects received orlistat 120 mg 3 times/day and a daily multivitamin supplement containing vitamin A 5000 IU, vitamin D 400 IU, vitamin E 300 IU, and vitamin K 25 μg. Measurements and Main Results. During 3–6 months of orlistat treatment, acute absorption of retinol (vitamin A) was not significantly altered, but absorption of α-tocopherol (vitamin E) was significantly reduced compared with baseline levels (p

The euglycemic clamp is the gold standard for estimating insulin sensitivity. The hyperglycemic clamp is easier to perform and is the gold standard for estimating beta-cell secretion. Reports in adults suggest that hyperglycemic clamps can estimate insulin sensitivity with results equivalent to euglycemic clamps. We investigated whether insulin sensitivity measures from both clamps are equivalent in children. Thirty-one lean and obese children (mean body mass index, 25.1 +/- 4.9 kg/m(2); mean age, 8.7 +/- 1.4 yr; 15 girls and 16 boys; 12 black and 19 white) were studied. All subjects underwent hyperglycemic clamps, then euglycemic clamps 2-6 wk later. Body composition was estimated by dual energy x-ray absorptiometry. Visceral and sc abdominal fat was estimated by abdominal magnetic resonance imaging. Whole-body glucose disposal and insulin sensitivity (SI clamp) derived from both clamps and normalized for total or visceral fat and lean mass were significantly correlated (r, 0.45-0.65; P < 0.05). However, absolute SI clamp values were not equivalent. Bland-Altman comparisons found that SI clamp estimates from hyperglycemic clamps became less precise as SI clamp increased. There were significant correlations between indices of beta-cell secretion from the hyperglycemic clamp and mean C-peptide values from the euglycemic clamp (P < 0.05). However, no correlation was found between measures of total insulin clearance (derived from the euglycemic clamp) and surrogates of hepatic insulin clearance (derived from the hyperglycemic clamp). In this cohort of diverse children, SI clamp values from euglycemic and hyperglycemic clamps were significantly correlated but were not equivalent, whereas the insulin clearance measures were not correlated. It cannot be assumed that the hyperglycemic clamp obviates the need for euglycemic clamp studies to accurately estimate insulin sensitivity in children.

To investigate whether differences in body composition of African American children (AA) and Caucasian children (C) explain differences in insulin sensitivity and secretion.Prepubertal nondiabetic children (31 AA and 54 C) were studied; 84% were overweight. Participants underwent a 2-hour hyperglycemic clamp, to estimate insulin sensitivity (SI(clamp)) and secretion, and dual energy x-ray absorptiometry, to assess body composition.AA had greater total body fat mass (P =.01), fasting, 1st phase, 2nd phase, and steady state insulin levels (P.05). AA and C had similar glucose disposal rates, but AA had lower SI(clamp) (P.05). Fasting, 1st phase, and steady state C-peptide were less in C (P.05), whereas corresponding C-peptide/insulin ratios were higher (all P.005). Insulin levels and SI(clamp) remained different in AA and C after adjustment for body fat or lean mass differences. Analyses restricted to only overweight AA and C showed similar trends.Prepubertal African American children have higher baseline and glucose-stimulated insulin and C-peptide levels, as well as reduced insulin sensitivity that is not entirely explained by differences in adiposity. The lower C-peptide/insulin molar ratio in AA suggests that they probably have lower hepatic insulin clearance than Caucasian children.

Obesity is prevalent worldwide and associated with co-morbidities that result in increased cardiovascular risk. Hypertension is the most prevalent obesity comorbidity associated with increased cardiovascular risk. Obesity hypertension is a distinct subtype of essential hypertension. While endogenous Cushing's syndrome is an uncommon cause of both obesity and hypertension, the recent recognition of other hypercortisolemic states has raised the profile of hypercortisolism as an important contributor in obesity hypertension. The high prevalence of exogenous, iatrogenic, pseudo, and subclinical Cushing's syndromes makes hypercortisolism an important diagnostic consideration in the evaluation and management of patients with obesity hypertension who are resistant to conventional management. Available data suggest that the renin-angiotensin-aldosterone system modulating antihypertensives have the best efficacy in hypercortisolism-mediated obesity hypertension. Strategies aimed at reducing cortisol production and action also have utility. This review provides a comprehensive overview of the epidemiology, etiopathogenesis and management options available for glucocorticoid-mediated obesity hypertension.

African American children have earlier pubertal and skeletal maturation and a higher body mass index (BMI) than Caucasian children. We tested the hypothesis that advanced bone age in African American children is accounted for by their greater adiposity.We studied 252 African American (n = 97) and Caucasian (n = 155) children aged 5 to 12 years. Skeletal age was determined by a radiologist blinded to clinical details. The difference between bone age (BA) and chronological age (CA) (noted as BA - CA) and the ratio of bone age to chronological age (BA/CA) were determined. Analysis of covariance was used to adjust skeletal maturation for the effects of adiposity, as measured by BMI, BMI standard deviation score (BMI SDS), and fat mass by dual energy x-ray absorptiometry (DXA).African American children were significantly heavier than Caucasians (BMI SDS 2.7 +/- 3.4 vs 1.7 +/- 2.4, P.05). Both BA - CA (0.75 +/- 1.46 vs 0.28 +/- 1.38, P.05) and BA/CA (1.09 +/- 0.17 vs 1.03 +/- 0.16, P.05) were significantly greater in African Americans than Caucasians. BA - CA and BA/CA were significantly correlated with lean body mass, BMI, BMI SDS, and DXA fat mass (all r0.46, P.001). Neither BA - CA nor BA/CA of African Americans and Caucasians were significantly different after correction for lean body mass and measures of adiposity, including BMI, BMI SDS, or DXA fat mass.Skeletal age is more advanced in African American than Caucasian children and is significantly related to body mass. In large measure, the advancement in skeletal maturation of prepubertal and early pubertal African American children can be accounted for by their greater adiposity.

Background and Purpose. Little is known about the methods used to assess the physical fitness of adolescents who are overweight. We investigated the relationship between walk/run performance and cardiorespiratory fitness in adolescents who are overweight. Subjects. Eight African-American adolescents (5 female, 3 male) and 10 Caucasian adolescents (5 female, 5 male) who were overweight (mean age=14.5 years, SD=2.0, range=12–17; mean body mass index [BMI]=42.9 kg/m2, SD=11.5) participated in this study. Methods. Subjects performed a 12-minute walk/run test. The distances traveled at both 9 minutes (D9) and 12 minutes (D12) were recorded, and the distance traveled between 9 and 12 minutes (D9–12) was calculated. Subjects also completed a maximal cycle ergometry test, during which peak oxygen uptake (V̇o2peak), anaerobic threshold (AT), peak power (Wpeak), and power at the anaerobic threshold (Wat) were determined. Body composition was determined by air displacement plethysmography. Results. The mean percentage of body fat was 48.6% (SD=5.3%, range=40.3%–60.4%). Percentage of body fat and BMI were each inversely related to D9, D12, and V̇o2peak (all P