Endocrinology, Diabetes, and Metabolism Commons^™

Role Of Serum Amyloid A In Abdominal Aortic Aneurysm And Related Cardiovascular Diseases, Preetha Shridas, Avery C. Patrick, Lisa R. Tannock

Internal Medicine Faculty Publications

Epidemiological data positively correlate plasma serum amyloid A (SAA) levels with cardiovascular disease severity and mortality. Studies by several investigators have indicated a causal role for SAA in the development of atherosclerosis in animal models. Suppression of SAA attenuates the development of angiotensin II (AngII)-induced abdominal aortic aneurysm (AAA) formation in mice. Thus, SAA is not just a marker for cardiovascular disease (CVD) development, but it is a key player. However, to consider SAA as a therapeutic target for these diseases, the pathway leading to its involvement needs to be understood. This review provides a brief description of the pathobiological …

Macrophages Expressing Uncoupling Protein 1 Increase In Adipose Tissue In Response To Cold In Humans, Brian S. Finlin, Hasiyet Memetimin, Amy L. Confides, Beibei Zhu, Philip M. Westgate, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the …

Bone Quality In Chronic Kidney Disease Patients: Current Concepts And Future Directions – Part Ii, Kamyar Asadipooya, Mohamed Abdalbary, Yahya Ahmad, Elijah Kakani, Marie-Claude Monier-Faugere, Amr El-Husseini

Internal Medicine Faculty Publications

Background: Patients with chronic kidney disease (CKD) have an increased risk of osteoporotic fractures, which is due not only to low bone volume and mass but also poor microarchitecture and tissue quality. The pharmacological and nonpharmacological interventions detailed, herein, are potential approaches to improve bone health in CKD patients. Various medications build up bone mass but also affect bone tissue quality. Antiresorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the ability to repair bone microdamage and cause an increase in bone brittleness. On the other hand, some osteoporosis therapies may cause a redistribution …

Bone Quality In Ckd Patients: Current Concepts And Future Directions – Part I, Kamyar Asadipooya, Mohamed Abdalbary, Yahya Ahmad, Elijah Kakani, Marie-Claude Monier-Faugere, Amr El-Husseini

Internal Medicine Faculty Publications

Background: There is ample evidence that patients with CKD have an increased risk of osteoporotic fractures. Bone fragility is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in general population and CKD patients. Although bone mineral density (BMD) is a very useful clinical tool in assessing bone strength, it may underestimate the fracture risk in CKD patients. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures …

Adrenal Vein Cortisol To Metanephrine Ratio For Localizing Acth-Independent Cortisol-Producing Adenoma: A Case Report, Rishi Raj, Philip A. Kern, Neelima Ghanta, Edilfavia M. Uy, Kamyar Asadipooya

Internal Medicine Faculty Publications

Context: Finding the source of adrenocorticotropic hormone (ACTH)-independent cortisol-producing adenoma in the patients with subclinical Cushing syndrome (SCS) and bilateral adrenal nodules is sometimes challenging. Computed tomography (CT) and positron emission tomography are helpful, but adrenal venous sampling (AVS) is the gold standard approach. However, interpretation of AVS is important to improve the accuracy of decision-making for surgery. We report a case and review of the literature to assess the benefit of using adrenal vein cortisol to metanephrine ratio to determine the source of cortisol production in SCS and bilateral nodules.

Evidence Acquisition: Three authors searched PubMed for data on …

Postoperative Hypocalcemia Following Parathyroidectomy For Giant Parathyroid Adenoma, Rishi Raj, Adele Amine, Demetrios Herodotou

Internal Medicine Faculty Publications

Objective
Giant parathyroid adenomas (GPAs) are a rare type of parathyroid adenoma (PA) weighing > 2 to 3 g. The objective of this manuscript is to report a case of giant parathyroid adenoma and highlight the risk of postoperative hypocalcemia.

Methods
We describe the presentation and work-up of a woman with GPA confirmed with histopathology as well as management of postoperative hypocalcemia.

Results
A 66-year-old Caucasian female with chronic fatigue was found to have elevated calcium levels at 13.7 mg/dL (normal, 8.9 to 10.2 mg/dL) and elevated parathyroid hormone levels at 1,240 pg/mL (normal, 12 to 72 pg/mL). Contrast enhanced computed …

Hereditary Hypophosphatemic Rickets With Hypercalciuria (Hhrh) Presenting With Genu Valgum Deformity: Treatment With Phosphate Supplementation And Surgical Correction, Juan M. Colazo, Seth A. Reasoner, Ginger Holt, Marie-Claude M. Faugere, Kathryn M. Dahir

Internal Medicine Faculty Publications

We describe a case of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) in a 32-year-old female with short stature, chronic pathologic genu valgum deformity, and knee pain who was referred to endocrinology clinic after previous inconclusive workups. We present imaging spanning 10 years of untreated disease. Biochemical studies showed hypophosphatemia with undetectable fibroblast growth factor 23 (FGF23.) Renal ultrasound revealed bilateral medullary nephrocalcinosis despite no apparent hypercalciuria. Due to concern for HHRH, genetic testing was performed that determined this patient to be homozygous in the SLC34A3 gene for a previously described missense variant (c.1402C > T, p.Arg468Trp). There was no known family …

The Β3-Adrenergic Receptor Agonist Mirabegron Improves Glucose Homeostasis In Obese Humans, Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.

METHODS. Before and after β3-AR agonist treatment, oral glucose tolerance tests and euglycemic clamps were performed, and histochemical analysis and gene expression profiling were performed on fat and muscle biopsies. PET-CT scans quantified brown adipose tissue volume and …

Candidemia Following Ureteric Stent Placement In A Patient With Type 2 Diabetes Treated With Canagliflozin, Rishi Raj, Jon Hendrie, Aasems Jacob, Derick Adams

Internal Medicine Faculty Publications

A 38-year-old female patient with well-controlled type 2 diabetes mellitus treated with canagliflozin underwent ureteral stent placement for obstructive renal calculi. Ten days following ureteroscopy and ureteral stenting, she developed fevers and blood cultures grew Candida glabrata (C. glabrata). The patient was successfully treated with an extended course of broad-spectrum antibiotics and antifungal agents. The clinical presentation of candidemia is indistinguishable from bacteremia resulting in delay in diagnosis and treatment. Candiduria is commonly seen in patients with type 2 diabetes, however it rarely leads to candidemia in an otherwise healthy person following a relatively simple urologic procedure. Sodium-glucose …

A Case Of Co-Secreting Tsh And Growth Hormone Pituitary Adenoma Presenting With A Thyroid Nodule, Laura Hamilton Adams, Derick Adams

Internal Medicine Faculty Publications

Co-secreting TSH and growth hormone pituitary adenomas are rare. We present a case of a 55-year-old woman who presented with symptoms of neck fullness. Ultrasound revealed multiple thyroid nodules and examination revealed several clinical features of acromegaly. She was found to have a co-secreting TSH and growth hormone pituitary macroadenoma. She underwent surgical resection followed by gamma knife radiation, which resulted in complete remission of her TSH and GH-secreting adenoma.

Telotristat Ethyl In Carcinoid Syndrome: Safety And Efficacy In The Telecast Phase 3 Trial, Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R. P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero

Internal Medicine Faculty Publications

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥ 4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with < 4 BMs/day on SSAs (or ≥ 1 symptom or ≥ 4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. …

The Influence Of A Kdt501, A Novel Isohumulone, On Adipocyte Function In Humans, Brian S. Finlin, Beibei Zhu, Bernard P. Kok, Cristina Godio, Philip M. Westgate, Neile Grayson, Robert Sims, Jeffrey S. Bland, Enrique Saez, Philip A. Kern

Internal Medicine Faculty Publications

Objective: In a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, a novel isohumulone drug, increased total and high-molecular weight (HMW) adiponectin in plasma. The objective was to determine whether KDT501 increased adiponectin secretion from subcutaneous white adipose tissue (SC WAT) and the underlying mechanism(s).

Methods: Nine obese participants with either prediabetes or with normal glucose tolerance plus three features of metabolic syndrome were part of the study. SC WAT biopsies were performed before and after 28 days of KDT501 treatment in a clinical research setting. In addition, a cold stimulus was used …

Use Of Dark Chocolate For Diabetic Patients: A Review Of The Literature And Current Evidence, Syed Raza Shah, Richard Alweis, Najla Issa Najim, Amin Muhammad Dharani, Muhammad Ahmed Jangda, Maira Shahid, Ahmed Nabeel Kazi, Syed Arbab Shah

Internal Medicine Faculty Publications

Dietary changes are a major lifestyle factor that can influence the progression of chronic diseases such as diabetes. Recently, flavanols, a subgroup of plant-derived phytochemicals called flavonoids, have gained increasing attention, due to studies showing an inverse correlation between dietary intake of flavanols and incidence of diabetes. Flavanoids in the cocoa plant may ameliorate insulin resistance by improving endothelial function, altering glucose metabolism, and reducing oxidative stress. Oxidative stress has been proposed as the main culprit for insulin resistance. The well-established effects of cocoa on endothelial function also points to a possible effect on insulin sensitivity. The relationship between insulin …

Temperature As A Circadian Marker In Older Human Subjects: Relationship To Metabolic Syndrome And Diabetes, Brianna D. Harfmann, Elizabeth A. Schroder, Jonathan H. England, Natalie J. Senn, Philip M. Westgate, Karyn A. Esser, Philip A. Kern

Internal Medicine Faculty Publications

Background: Circadian rhythms are characterized by approximate 24-hour oscillations in physiological and behavioral processes. Disruptions in these endogenous rhythms, most commonly associated with shift work and/or lifestyle, are recognized to be detrimental to health. Several studies have demonstrated a high correlation between disrupted circadian rhythms and metabolic disease. The aim of this study was to determine which metabolic parameters correlate with physiological measures of circadian temperature amplitude (TempAmp) and stability (TempStab).

Methods: Wrist skin temperature was measured in 34 subjects (ages 50 to 70, including lean, obese, and diabetic subjects) every 10 minutes for 7 consecutive days. Anthropometric measures and …

Effects Of Kdt501 On Metabolic Parameters In Insulin-Resistant Prediabetic Humans, Philip A. Kern, Brian S. Finlin, Dorothy Ross, Tania Boyechko, Beibei Zhu, Neile Grayson, Robert Sims, Jeffrey S. Bland

Internal Medicine Faculty Publications

Context: KDT501 is an isohumulone drug that has demonstrated beneficial effects on metabolic parameters in mice.

Objective: This study was intended to examine potential improvements in metabolism in humans.

Design and Setting: Changes in carbohydrate and lipid metabolism, along with inflammatory markers, were evaluated in prediabetic humans in a clinical research center.

Participants: Nine obese patients participated. All had prediabetes or normal glucose tolerance plus three features of metabolic syndrome.

Intervention: All participants were treated with escalating doses of KDT501 to a maximum dose of 1000 mg every 12 hours for a total of 28 days.

Outcome Measures: Changes in …

Rising Thyroid Cancer Incidence In Southern India: An Epidemic Of Overdiagnosis?, Indu Elizabeth Mathew, Aju Mathew

Internal Medicine Faculty Publications

Background: Thyroid cancer incidence is rising in high-income countries. This increase in disease burden is attributed to the phenomenon of overdiagnosis.

Objective: We aimed to investigate trends in thyroid cancer rates in India, focusing on the state of Kerala in southern India, which has reported a high incidence of the disease.

Design: Population-based study using data from the National Cancer Registry Program.

Participants: We used data from the Population Based Cancer Registries for Thiruvananthapuram (capital of Kerala state), Delhi, Mumbai, Bangalore, and Chennai. We used data for three reporting periods from 2005 to 2014 (represented as 2006, 2009, and 2012). …

A Case Of Pituitary Abscess Presenting Without A Source Of Infection Or Prior Pituitary Pathology, Derick Adams, Philip A. Kern

Internal Medicine Faculty Publications

Pituitary abscess is a relatively uncommon cause of pituitary hormone deficiencies and/or a suprasellar mass. Risk factors for pituitary abscess include prior surgery, irradiation and/or pathology of the suprasellar region as well as underlying infections. We present the case of a 22-year-old female presenting with a spontaneous pituitary abscess in the absence of risk factors described previously. Her initial presentation included headache, bitemporal hemianopia, polyuria, polydipsia and amenorrhoea. Magnetic resonance imaging (MRI) of her pituitary showed a suprasellar mass. As the patient did not have any risk factors for pituitary abscess or symptoms of infection, the diagnosis was not suspected …

Pioglitazone Treatment Reduces Adipose Tissue Inflammation Through Reduction Of Mast Cell And Macrophage Number And By Improving Vascularity, Michael L. Spencer, Lin Yang, Akosua Adu, Brian S. Finlin, Beibei Zhu, Lindsey Rae Shipp, Neda Rasouli, Charlotte A. Peterson, Philip A. Kern

Internal Medicine Faculty Publications

Context and Objective

Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.

Design, Setting and Participants

Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting.

Results

Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01), and also increased …