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Kristen E Syring, Travis J Cyphert, Thomas C Beck, Charles R Flynn, Nicholas A Mignemi, Owen P McGuinness
Bile acids are involved in the emulsification and absorption of dietary fats as well as acting as signaling molecules. Recently, bile acid signaling through farnesoid X receptor (FXR) and G Protein-Coupled Bile Acid Receptor (TGR5) has been reported to elicit changes in not only bile acid synthesis but also metabolic processes including altering gluconeogenic gene expression and energy expenditure. A role for bile acids in glucose metabolism is also supported by a correlation between changes in the metabolic state of patients (i...
February 19, 2019: American Journal of Physiology. Endocrinology and Metabolism
Ying Xiong, Shuoqi Zhang, Jingjing Shi, Yang Fan, Qiang Zhang, Wenzhen Zhu
BACKGROUND: Diffusion-tensor-imaging (DTI) is sensitive in detecting white matter changes in type-2 diabetes mellitus (T2DM). However, DTI indices can be affected by either neurite density or spatial variation. A novel diffusion MRI technique, termed neurite orientation dispersion and density imaging (NODDI), can provide distinct indices of fiber density and dispersion. PURPOSE: To characterize brain microstructural alterations in T2DM patients with mild cognitive impairment (MCI) using the NODDI model...
February 19, 2019: Journal of Magnetic Resonance Imaging: JMRI
Douglas C Chang, Xiaoyuan Xu, Anthony W Ferrante, Jonathan Krakoff
Background: Plasma albumin is reduced during inflammation. Obesity, a strong risk factor for type 2 diabetes (T2D), is associated with adipose tissue inflammation. However, whether albumin is associated with adipose tissue inflammation and whether it predicts T2D are unclear. Methods: Adults (predominantly American Indian) from a longitudinal study were included. Macrophage content and gene expression related to recruitment/activation were measured from subcutaneous adipose tissue (n = 51)...
2019: Diabetology & Metabolic Syndrome
Ferran Comas, Cristina Martínez, Mònica Sabater, Francisco Ortega, Jessica Latorre, Francisco Díaz-Sáez, Julian Aragonés, Marta Camps, Anna Gumà, Wifredo Ricart, José Manuel Fernández-Real, José María Moreno-Navarrete
Background: Nrg4 expression has been linked to brown adipose tissue activity and browning of white adipocytes in mice. Here, we aimed to investigate whether these observations could be translated to humans by investigating NRG4 mRNA and markers of brown/beige adipocytes in human visceral (VAT) and subcutaneous adipose tissue (SAT). We also studied the possible association of NRG4 with insulin action. Methods: SAT and VAT NRG4 and markers of brown/beige ( UCP1, UCP3, and TMEM26 )-related gene expression were analyzed in two independent cohorts ( n = 331 and n = 59)...
2019: Frontiers in Physiology
Yuliya Lytvyn, Petter Bjornstad, Julie A Lovshin, Sunita K Singh, Genevieve Boulet, Mohammed A Farooqi, Vesta Lai, Josephine Tse, Leslie Cham, Leif E Lovblom, Alanna Weisman, Hillary A Keenan, Michael H Brent, Narinder Paul, Vera Bril, Andrew Advani, Etienne Sochett, Bruce A Perkins, David Z I Cherney
AIMS: Higher plasma uric acid (PUA) concentrations are associated with renal vasoconstriction, renin angiotensin aldosterone system (RAAS) activation and vascular stiffness, however the timeline for these associations in type 1 diabetes (T1D) is not clear. We aimed to compare the changes in such associations over a wide range of T1D duration. MATERIALS AND METHODS: PUA, glomerular filtration rate (GFRINULIN ), effective renal plasma flow (ERPFPAH ), vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), plasma renin and aldosterone were measured during a euglycemic clamp in participants with T1D: 27 adolescents (age 16...
February 13, 2019: Diabetes, Obesity & Metabolism
Melanie Cree-Green, Anne-Marie Carreau, Haseeb Rahat, Yesenia Garcia-Reyes, Bryan C Bergman, Laura Pyle, Kristen J Nadeau
Polycystic Ovarian Syndrome (PCOS) is associated with insulin resistance (IR) and altered muscle mitochondrial oxidative phosphorylation. IR in adults with obesity and diabetes is associated with changes in amino acid, free fatty acid (FFA) and mitochondrial acylcarnitine (AC) metabolism. We sought to determine if these metabolites are associated with IR and/or androgens in youth-onset PCOS. We enrolled obese girls with PCOS [n = 15, 14.5 ± 1.6 years, BMI %ile 98.5 ± 1.0] and without PCOS [n = 6, 13.2 ± 1...
February 12, 2019: American Journal of Physiology. Endocrinology and Metabolism
Brian G Engelhardt, Ujjawal Savani, Dae Kwang Jung, Alvin C Powers, Madan Jagasia, Heidi Chen, Jason J Winnick, Robyn A Tamboli, James E Crowe, Naji N Abumrad
New-onset post-transplant diabetes mellitus (PTDM) occurs frequently following allogeneic hematopoietic cell transplant (HCT). Although calcineurin inhibitors and corticosteroids are assumed the cause for hyperglycemia, patients developing PTDM have elevated fasting C-peptide levels before HCT and prior to immunosuppressive medications. To determine if PTDM results from established insulin resistance present before transplant, we performed oral glucose tolerance tests (OGTT) and measured whole-body, peripheral, and hepatic insulin sensitivity with euglycemic hyperinsulinemic clamps before and 90 days after HLA-identical sibling donor HCT in 20 patients without pre-transplant diabetes...
February 6, 2019: Biology of Blood and Marrow Transplantation
Dane M Horton, David A Saint, Kathryn L Gatford, Karen L Kind, Julie A Owens
Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in programming of insulin resistance later in life. Spontaneous IUGR in the guinea pig, due to natural variation in litter size, produces offspring with asymmetric IUGR and neonatal catch-up growth. We hypothesized that spontaneous IUGR and/or accelerated neonatal growth would impair insulin sensitivity in adult guinea pigs. Insulin sensitivity of glucose metabolism was determined by hyperinsulinemic-euglycemic clamp (HEC) in 38 (male=21, female=17) young adult guinea pigs from litters of two to four pups...
February 8, 2019: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Yoko Koike, Shin-Ichiro Shirabe, Hajime Maeda, Ayako Yoshimoto, Keiko Arai, Atsushi Kumakura, Koichi Hirao, Yasuo Terauchi
AIMS: Information on the clinical efficacy of SGLT2 inhibitors in the Japanese population is limited. The aim of this single-arm, single-center, open-label study was to confirm the body weight- and fat mass-lowering effects of canagliflozin (CANA) and the accompanying improvement in insulin resistance in Japanese patients with Type 2 diabetes mellitus (T2DM). METHODS: Thirty-eight patients were enrolled and administered 100 mg CANA once daily for 24 weeks. Blood and anthropometric parameters were examined before and after treatment...
February 1, 2019: Diabetes Research and Clinical Practice
Rachel J Perry, Aviva Rabin-Court, Joongyu D Song, Rebecca L Cardone, Yongliang Wang, Richard G Kibbey, Gerald I Shulman
Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and to increase both glucose production and glucagon secretion. The mechanisms behind these alterations are unknown. Here we show that the SGLT2 inhibitor (SGLT2i) dapagliflozin promotes ketoacidosis in both healthy and type 2 diabetic rats in the setting of insulinopenia through increased plasma catecholamine and corticosterone concentrations secondary to volume depletion...
February 1, 2019: Nature Communications
Debabrata Ghosh, Jun Peng, Katherine Brown, Shashank Sirsi, Chieko Mineo, Philip W Shaul, Kenneth Hoyt
OBJECTIVES: To evaluate the use of super-resolution ultrasound (SR-US) imaging for quantifying microvascular changes in skeletal muscle using a mouse model of type 2 diabetes. METHODS: Study groups were young, standard chow-fed male C57BL/6J mice (lean group) and high fat diet-fed older mice (obese group). After an overnight fast, dynamic contrast-enhanced US imaging was performed on the proximal hind limb adductor muscle group for 10 minutes at baseline and again at 1 and 2 hours during administration of a hyperinsulinemic-euglycemic clamp...
January 31, 2019: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
Marie-Christine Simon, Akiko Möller-Horigome, Klaus Strassburger, Bettina Nowotny, Birgit Knebel, Karsten Müssig, Christian Herder, Julia Szendroedi, Michael Roden
Context and Objective: Not only type 2, but also type 1 diabetes can associate with insulin resistance, as assessed from insulin-stimulated whole body glucose disposal (M-value). We hypothesized that different factors affect the M-value at the onset of type 1 and type 2 diabetes. Design and Patients: We examined 132 patients with type 1 or type 2 diabetes matched for sex, age, and body mass index with known diabetes duration of less than 12 months. Multivariable linear regression analyses were applied to test the associations between glycemic control, blood lipids, adiponectin, pro-inflammatory immune mediators and M-value, obtained from from hyperinsulinemic-euglycemic clamps...
January 28, 2019: Journal of Clinical Endocrinology and Metabolism
Daisuke Sugimoto, Yoshifumi Tamura, Kageumi Takeno, Hideyoshi Kaga, Yuki Someya, Saori Kakehi, Takashi Funayama, Yasuhiko Furukawa, Ruriko Suzuki, Satoshi Kadowaki, Miho Nishitani-Yokoyama, Kazunori Shimada, Hiroyuki Daida, Shigeki Aoki, Akio Kanazawa, Ryuzo Kawamori, Hirotaka Watada
Context: Adipose tissue insulin resistance is observed in obese subjects and is considered an early metabolic defect preceding insulin resistance in muscle and liver. While Asians readily develop metabolic disease without obesity, the clinical features of non-obese, apparently healthy Asians with reduced adipose tissue insulin sensitivity (ATIS) have not been elucidated. Objective: To investigate the clinical parameters associated with reduced ATIS in non-obese, apparently healthy (body mass index <25 kg/m2) Japanese men...
January 23, 2019: Journal of Clinical Endocrinology and Metabolism
Stephan Siebel, Alfonso Galderisi, Neha S Patel, Lori R Carria, William V Tamborlane, Jennifer L Sherr
OBJECTIVE: We have shown that "euglycemic DKA" in patients with type 1 diabetes receiving a sodium-glucose cotransporter 2-inhibitor (SGLT2i) is due to normal increases in rates of ketogenesis but blunted increases in plasma glucose levels. In this analysis, we assessed whether rescue treatment of early ketoacidosis with insulin is altered by SGLT2i use. RESEARCH DESIGN AND METHODS: Participants received 0.2 U/kg of aspart insulin after two 6-h interruptions of basal insulin that increased beta-hydroxybutyrate (BHB) by 1...
January 28, 2019: Diabetes Technology & Therapeutics
Christian Tronstad, Ole Elvebakk, Odd Martin Staal, Håvard Kalvøy, Jan Olav Høgetveit, Trond Geir Jenssen, Kåre Inge Birkeland, Ørjan G Martinsen
Over the last four decades, there has been a pursuit for a non-invasive solution for glucose measurement, but there is not yet any viable product released. Of the many sensor modalities tried, the combination of electrical and optical measurement is among the most promising for continuous measurements. Although non-invasive prediction of exact glucose levels may seem futile, prediction of their trends may be useful for certain applications. Hypoglycemia is the most serious of the acute complications in type-1 diabetes highlighting the need for a reliable alarm, but little is known about the performance of this technology in predicting hypoglycemic glucose levels and associated trends...
April 4, 2019: Analytica Chimica Acta
Yao Lin, Zerong Liang, Liping He, Mengliu Yang, Dongfang Liu, Harvest F Gu, Hua Liu, Zhiming Zhu, Hongting Zheng, Ling Li, Gangyi Yang
BACKGROUND: Ghrelin modulates many physiological processes. However, the effects of intestinal ghrelin on hepatic glucose production (HGP) are still unclear. The current study was to explore the roles of intestinal ghrelin on glucose homeostasis and insulin signaling in the liver. METHODS: The system of intraduodenal infusion and intracerebral microinfusion into the nucleus of the solitary tract (NTS) in the normal chow-diet rats and pancreatic-euglycemic clamp procedure (PEC) combined with [3-3 H] glucose as a tracer were used to analyze the effect of intestinal ghrelin...
January 25, 2019: Cell Communication and Signaling: CCS
Dawei Shi, Eyal Dassau, Francis J Doyle
The long-term use of the artificial pancreas (AP) requires an automated insulin delivery algorithm that can learn and adapt with the growth, development, and lifestyle changes of patients. In this work, we introduce a data-driven AP adaptation method for improved glucose management in a home environment. A two-phase Bayesian optimization assisted parameter learning algorithm is proposed to adapt basal and carbohydrate-ratio profile, and key feedback control parameters. The method is evaluated on the basis of the 111-adult cohort of the FDA-accepted UVA/Padova type 1 diabetes mellitus simulator through three scenarios with lifestyle disturbances and incorrect initial parameters...
January 2019: Bioengineering & Translational Medicine
Timothy S Reid, John White, Luigi Meneghini
Pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs form the basis for the development of drugs used in everyday clinical practice, such as commonly used insulin products. PK measures the concentration of a drug in the body, and reflects the rates and amounts absorbed and processed. PD is the biologic effect of a drug in the body, including the time-course of when the biologic effect starts, peaks, and ends. While the determination of PK/PD parameters is important and foundational for the development of different insulin products, studies are often complex and can be difficult to translate into real-world clinical practice...
January 2019: Journal of Family Practice
Ranganath Muniyappa, Sri Harsha Tella, Shrayus Sortur, Reed Mszar, Shivraj Grewal, Brent S Abel, Sungyoung Auh, Douglas C Chang, Jonathan Krakoff, Monica C Skarulis
Context: Surrogate indices of muscle and hepatic insulin sensitivity derived from an oral glucose tolerance test (OGTT) are frequently used in clinical studies. However, the predictive accuracy of these indices has not been validated. Design: In this cross-sectional study, hyperinsulinemic-euglycemic glucose clamp with tritiated glucose infusion and a 75-g OGTT were performed in individuals (n = 659, aged 18 to 49 years, body mass index of 16 to 64 kg/m2 ) with varying degrees of glucose tolerance...
January 1, 2019: Journal of the Endocrine Society
Hilda E Ghadieh, Lucia Russo, Harrison T Muturi, Simona S Ghanem, Iyad H Manaserh, Hye Lim Noh, Sujin Suk, Jason K Kim, Jennifer W Hill, Sonia M Najjar
BACKGROUND: CEACAM1 regulates insulin sensitivity by promoting insulin clearance. Accordingly, global C57BL/6J.Cc1-/- null mice display hyperinsulinemia due to impaired insulin clearance at 2 months of age, followed by insulin resistance, steatohepatitis, visceral obesity and leptin resistance at 6 months. The study aimed at investigating the primary role of hepatic CEACAM1 in insulin and lipid homeostasis independently of its metabolic effect in extra-hepatic tissues. METHODS: Liver-specific C57BL/6J...
January 18, 2019: Metabolism: Clinical and Experimental
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