المؤلفون: Jason Bini, Lisa Parikh, Cheryl Lacadie, Janice J. Hwang, Saloni Shah, Samuel B. Rosenberg, Dongju Seo, Katherine Lam, Muhammad Hamza, Renata Belfort De Aguiar, Todd Constable, Robert S. Sherwin, Rajita Sinha, Ania M. Jastreboff

المصدر: NeuroImage: Clinical, Vol 36, Iss , Pp 103202- (2022)

مصطلحات موضوعية: fMRI, Glucocorticoids, Cortisol, Stress, Hunger, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429

الوصف: Context: The neural regulation of appetite and energy homeostasis significantly overlaps with the neurobiology of stress. Frequent exposure to repeated acute stressors may cause increased allostatic load and subsequent dysregulation of the cortico-limbic striatal system leading to inefficient integration of postprandial homeostatic and hedonic signals. It is therefore important to understand the neural mechanisms by which stress generates alterations in appetite that may drive weight gain. Objective: To determine glucocorticoid effects on metabolic, neural and behavioral factors that may underlie the association between glucocorticoids, appetite and obesity risk. Methods: A randomized double-blind cross-over design of overnight infusion of hydrocortisone or saline followed by a fasting morning perfusion magnetic resonance imaging to assess regional cerebral blood flow (CBF) was completed. Visual Analog Scale (VAS) hunger, cortisol and metabolic hormones were also measured. Results: Hydrocortisone relative to saline significantly decreased whole brain voxel based CBF responses in the hypothalamus and related cortico-striatal-limbic regions. Hydrocortisone significantly increased hunger VAS pre-scan, insulin, glucose and leptin, but not other metabolic hormones versus saline CBF groups. Hydrocortisone related increases in hunger were predicted by less reduction of CBF (hydrocortisone minus saline) in the medial OFC, medial brainstem and thalamus, left primary sensory cortex and right superior and medial temporal gyrus. Hunger ratings were also positively associated with plasma insulin on hydrocortisone but not saline day. Conclusions: Increased glucocorticoids at levels akin to those experienced during psychological stress, result in increased fasting hunger and decreased regional cerebral blood flow in a distinct brain network of prefrontal, emotional, reward, motivation, sensory and homeostatic regions that underlie control of food intake.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2213158222002674Test; https://doaj.org/toc/2213-1582Test

الوصول الحر: https://doaj.org/article/93e4e657a1f4425ea9d0eb74f343c7d5Test

المؤلفون: Janice J. Hwang, Christina S. Han, Renata B. DeAguiar, Lisa Parikh, Denis Snegovskikh, Andrea Johnson

المصدر: American Journal of Perinatology. 37:1094-1101

مصطلحات موضوعية: Adult, Blood Glucose, Leptin, medicine.medical_specialty, medicine.medical_treatment, Overweight, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Internal medicine, Diabetes mellitus, Birth Weight, Humans, Insulin, Medicine, Obesity, 030212 general & internal medicine, Glycated Hemoglobin, 030219 obstetrics & reproductive medicine, business.industry, Infant, Newborn, Obstetrics and Gynecology, Type 2 Diabetes Mellitus, Fetal Blood, medicine.disease, Pregnancy Complications, Diabetes, Gestational, Endocrinology, Cord blood, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, business, Body mass index

الوصف: Objective In this study, we assess the impact of obesity and diabetes on maternal brain and periphery, as well as fetal exposure to insulin and leptin, and two hormones that play an important role in regulating energy homeostasis. Study Design Fasting maternal plasma, fetal cord vein and artery plasma, and maternal cerebrospinal fluid (CSF) were collected in 37 women (12 lean, nondiabetic [prepregnancy body mass index (BMI): 22.9 ± 1.7 kg/m2]; 12 overweight/obese nondiabetic [BMI: 37.8 ± 7.3 kg/m2]; 13 gestational/type 2 diabetes mellitus [BMI: 29.8 ± 7.3 kg/m2]) with uncomplicated singleton pregnancies undergoing elective Cesarean delivery. HbA1C, insulin, glucose, and leptin levels were measured. Results Compared with lean mothers, mothers with obesity and diabetes mellitus (DM) had significantly lower CSF-to-plasma ratios of insulin. Moreover, mothers with obesity and DM had significantly lower cord arterial and cord venous to maternal plasma ratios of insulin, but not leptin, compared with lean mothers. There were no differences in CSF and cord blood insulin and leptin levels between obese and DM mothers. Conclusion Compared with lean individuals, mothers with obesity and DM have relative deficiencies in insulin exposure. The patterns observed in mothers with obesity and diabetes were similar highlighting the importance of the maternal metabolic environment in obesity and suggesting obese patients warrant further clinical focus.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8e9a165ef0bb3cdd627bf3ab889c91ceTest
https://doi.org/10.1055/s-0040-1702988Test

المؤلفون: Wai Lam, Janice J. Hwang, Robert S. Sherwin, Muhammad Hamza, Cheryl Lacadie, R. Todd Constable, Feng Dai, Dongju Seo, Renata Belfort-DeAguiar, Rajita Sinha, Anne-Sophie Sejling, Christian P. Schmidt, Lisa Parikh

المصدر: Journal of Clinical Investigation. 128:1485-1495

مصطلحات موضوعية: Adult, Blood Glucose, Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, endocrine system diseases, Brain activity and meditation, Hypoglycemia, Angular gyrus, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Diabetes mellitus, Internal medicine, Humans, Medicine, Prefrontal cortex, Cerebral Cortex, Type 1 diabetes, business.industry, nutritional and metabolic diseases, General Medicine, Awareness, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, Female, Clinical Medicine, business, Insula, 030217 neurology & neurosurgery

الوصف: Background Among nondiabetic individuals, mild glucose decrements alter brain activity in regions linked to reward, motivation, and executive control. Whether these effects differ in type 1 diabetes mellitus (T1DM) patients with and without hypoglycemia awareness remains unclear. Methods Forty-two individuals (13 healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM-Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp for assessment of neural responses to mild hypoglycemia. Results Mild hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and insula changes, but showed altered activation patterns in the prefrontal cortex and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes in brain activity. These findings were also associated with blunted hormonal counterregulatory responses and hypoglycemia symptom scores during mild hypoglycemia. Conclusion In T1DM, and in particular T1DM-Unaware patients, there is a progressive blunting of brain responses in cortico-striatal and fronto-parietal neurocircuits in response to mild-moderate hypoglycemia. These findings have implications for understanding why individuals with impaired hypoglycemia awareness fail to respond appropriately to falling blood glucose levels. Funding This study was supported in part by NIH grants R01DK020495, P30 DK045735, K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported by an NIH Clinical Translational Science Award (UL1 RR024139).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36737dec8c9326f32c9e7d19e4698156Test
https://doi.org/10.1172/jci97696Test

المؤلفون: Lisa Parikh, Renata Belfort-DeAguiar, Christian Schmidt, Fangyong Li, Qinxin Wang, Janice Hwang, Wai Lam, Ahmed Elshafie, Elizabeth Sanchez-Rangel, Janice Kim

المصدر: J Clin Endocrinol Metab

مصطلحات موضوعية: medicine.medical_specialty, Meal, Food intake, business.industry, Endocrinology, Diabetes and Metabolism, Biochemistry (medical), Clinical Biochemistry, digestive, oral, and skin physiology, medicine.disease, Biochemistry, Obesity, Low glucose, Endocrinology, Normal weight, Internal medicine, Healthy individuals, medicine, Interstitial glucose, Group interaction, business, Clinical Research Articles

الوصف: Purpose Changes in blood glucose levels have been shown to influence eating in healthy individuals; however, less is known about effects of glucose on food intake in individuals who are obese (OB). The goal of this study was to determine the predictive effect of circulating glucose levels on eating in free-living OB and normal weight (NW) individuals. Methods Interstitial glucose levels, measured with a continuous glucose monitor (CGM) system, were obtained from 15 OB and 16 NW volunteers (age: 40 ± 14 and 37 ± 12 years; weight: 91 ± 13 and 68 ± 12 kg; hemoglobin A1c: 5.1% ± 0.7% and 5.2% ± 0.4%, respectively). While wearing the CGM, participants filled out a food log (mealtime, hunger rating, and amount of food). Glucose profiles were measured in relation to their meals [macro program (CGM peak and nadir analysis) using Microsoft® Excel]. Results OB and NW individuals showed comparable CGM glucose levels: mean [OB = 100 ± 8 mg/dL; NW = 99 ± 13 mg/dL; P = nonsignificant (NS)] and SD (OB = 18 ± 5 mg/dL, NW = 18 ± 4 mg/dL; P = NS). Obesity was associated with slower postprandial rate of changing glucose levels (P = 0.04). Preprandial nadir glucose levels predicted hunger and food intake in both groups (P < 0.0001), although hunger was associated with greater food intake in OB individuals than in NW individuals (P = 0.008 for group interaction). Conclusions Premeal glucose nadir predicted hunger and food intake in a group of free-living, healthy, nondiabetic NW and OB individuals; however for a similar low glucose level stimulus, hunger-induced food intake was greater in OB than NW individuals.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8877e9b92817e5b9f0b13d1313e447a4Test
https://europepmc.org/articles/PMC6667277Test/

المؤلفون: Renata Belfort-DeAguiar, Wai Lam, Janice Hwang, Ahmed Elshafie, Christian P. Schmidt, Lisa Parikh, Robert S. Sherwin, Elizabeth Sanchez Rangel, Catherine W. Yeckel

المصدر: Diabetes. 67

مصطلحات موضوعية: medicine.medical_specialty, endocrine system diseases, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, nutritional and metabolic diseases, Type 2 diabetes, Carbohydrate metabolism, medicine.disease, Obesity, Metformin, Endocrinology, Insulin resistance, Diabetes mellitus, Internal medicine, Internal Medicine, Medicine, business, Glycemic, medicine.drug

الوصف: We evaluated the relationship between measurements of beta cell function and insulin resistance assessed from OGTT and 2-step glucose clamp data with indices of glucose variability (GV) obtained with a continuous glucose monitor (CGM) in obese subjects with and without type 2 diabetes (T2D). 17 healthy obese (OB) (FPG 91 ± 4.9mg/dl and A1c 5.2 ± 0.4%) and 8 age- and weight-matched participants with T2D treated with diet and/or metformin (FPG 131.5 ± 42.8 mg/dl and A1c 6.8 ± 0.8%) wore CGM (Dexcom®) for up to 5 days. EasyGV® software was used to calculate indices of GV: standard deviation (SD), mean amplitude of glycemic excursions (MAGE), J-Index, continuous overlapping net glycemic action (CONGA), and Glycemic Risk Assessment in Diabetes Equation (GRADE). Indices of glucose metabolism were determined with a 2 hour OGTT and a two-step hyperglycemic-euglycemic clamp. Insulin levels during the hyperglycemic-step of clamp (116 ± 126 vs. 40 ± 23 mU/mL) were equal in both groups, while glucose infusion rate (GIR) (7.7 ± 3.1 vs. 3.9 ± 2.4 mg/kg/minutes) during euglycemia was as expected significantly lower in the T2D subjects compared to OB subjects. GV indices (SD, CONGA, J-Index, GRADE) were statistically lower in OB vs. T2D (P Disclosure A. Elshafie: None. W. Lam: None. L. Parikh: None. E. Sanchez Rangel: None. C.P. Schmidt: None. J. Hwang: None. C.W. Yeckel: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc..

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::0898ea0407a54dd377cf832bde371558Test
https://doi.org/10.2337/db18-82-lbTest

المؤلفون: Renata Belfort-DeAguiar, Robert S. Sherwin, Christian P. Schmidt, Derek Groskreutz, Lisa Parikh, Jessica Leventhal, Ania M. Jastreboff, Todd Constable, Cheryl Lacadie, Rajita Sinha, Dongju Seo, Janice Hwang, Muhammad Hamza, Wai Lam, Samuel Rosenberg

المصدر: Diabetes. 67

مصطلحات موضوعية: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Putamen, Insulin, medicine.medical_treatment, Perfusion scanning, medicine.disease, Impulsivity, Obesity, medicine.anatomical_structure, Endocrinology, Cerebral blood flow, Internal medicine, Internal Medicine, medicine, Hyperinsulinemia, medicine.symptom, business, Anterior cingulate cortex

الوصف: Elevated insulin levels are often observed in obesity, but the effects of hyperinsulinemia on cerebral blood flow (CBF) are not known. While insulin acts as a satiety factor in lean humans, it is unclear if this CNS effect is maintained in the setting of hyperinsulinemia in obesity. This study aimed to isolate the effects of elevated insulin levels during euglycemia in lean (LN: n=6, BMI 21.1 kg/m2, age 32 years) and obese (OB: n=8, BMI 32, age 30) humans. Participants underwent a 2 hour oral glucose tolerance test [mean 120-min insulin LN 41 mU/ml vs. OB 113 mU/mL (p=.49) and glucose LN 101 mg/dL vs. OB 112 mg/dL (p=.72)] and on 2 separate days received either a saline infusion (control) or underwent a euglycemic-hyperinsulinemic clamp (insulin 2 mU/kg/min, glucose 90 mg/dL) during functional magnetic resonance imaging (fMRI). Whole-brain analyses comparing neural responses on hyperinsulinemic vs. saline control days demonstrated increased CBF in the putamen, insula, anterior cingulate cortex, and middle temporal gyrus in the OB group, but not in the LN group (p=.01, whole-brain corrected; Figure). We conclude that obesity invokes different CBF responses to hyperinsulinemia, specifically in regions implicated in impulsivity, reward processing, and interoceptive signaling. Thus, while in lean humans increased insulin levels signal satiety and reduce food-seeking behavior, this may not be the case in obese humans. Disclosure D. Groskreutz: None. R. Sinha: None. C. Lacadie: None. W. Lam: None. M. Hamza: None. C.P. Schmidt: None. D. Seo: None. J. Hwang: None. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc.. J. Leventhal: None. S. Rosenberg: None. L. Parikh: None. T. Constable: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc. A.M. Jastreboff: Consultant; Self; Novo Nordisk Inc., Rhythm Pharmaceuticals Inc., Medtronic.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e13d326e691f4e9c8417ee0ed4c2eeb8Test
https://doi.org/10.2337/db18-365-orTest

المؤلفون: Dongju Seo, Dustin Scheinost, Cheryl Lacadie, Janice Hwang, Rajita Sinha, Robert S. Sherwin, Todd Constable, Lisa Parikh, Renata Belfort-DeAguiar, Derek Groskreutz

المصدر: Diabetes. 67

مصطلحات موضوعية: Hypoglycemia unawareness, medicine.medical_specialty, Resting state fMRI, business.industry, Endocrinology, Diabetes and Metabolism, Audiology, Hypoglycemia, medicine.disease, Functional networks, Internal Medicine, medicine, Bold fmri, business, Default mode network

الوصف: The impact of hypoglycemia awareness (HA) on brain resting state connectivity remains unclear. To examine the impact of HA on the default mode network (DMN), a functional network in the brain that is active during wakeful rest and associated with introspection, 12 T1DM individuals with hypo unawareness (T1DM-UW) (by Clarke score) (7F/5M, age 44±12 years, BMI 26.4±4.2 kg/m2, HbA1c 7.1±0.7) and 15 T1DM-Aware (AW) (10F/5M, age 30±7, BMI 24.5±3.1, HbA1C 7.1±0.9) individuals underwent resting state BOLD fMRI scanning to assess the DMN during a two-step euglycemic (Eu)-hypoglycemic (Hypo) clamp (90-60 mg/dl). T1DM-AW individuals exhibited a hypoglycemia-induced decrease in DMN connectivity (P Disclosure D. Groskreutz: None. J. Hwang: None. D. Seo: None. C. Lacadie: None. L. Parikh: None. R. Belfort-DeAguiar: Research Support; Self; GlaxoSmithKline plc.. D. Scheinost: None. R. Sinha: None. T. Constable: None. R. Sherwin: Other Relationship; Self; QuintilesIMS, MannKind Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; ICON plc..

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::f826baf4a7862c2c86f715e7710c34c9Test
https://doi.org/10.2337/db18-11-lbTest

المؤلفون: Feng Dai, Douglas L. Rothman, Robert S. Sherwin, Graeme F. Mason, Brian B. Koo, Lihong Jiang, Lisa Parikh, Renata Belfort-DeAguiar, Janice J. Hwang, Elizabeth Sanchez Rangel, Muhammad Hamza

مصطلحات موضوعية: 0301 basic medicine, Adult, Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Carbohydrate metabolism, 03 medical and health sciences, Young Adult, Diabetes mellitus, Internal medicine, Medicine, Humans, Insulin, Obesity, business.industry, Fatty Acids, Glucose transporter, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, Brain, General Medicine, Human brain, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Glucose, Diabetes Mellitus, Type 2, Hyperglycemia, Female, business, Homeostasis, Research Article

الوصف: In rodent models, obesity and hyperglycemia alter cerebral glucose metabolism and glucose transport into the brain, resulting in disordered cerebral function as well as inappropriate responses to homeostatic and hedonic inputs. Whether similar findings are seen in the human brain remains unclear. In this study, 25 participants (9 healthy participants; 10 obese nondiabetic participants; and 6 poorly controlled, insulin- and metformin-treated type 2 diabetes mellitus (T2DM) participants) underwent 1H magnetic resonance spectroscopy scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-hour hyperglycemic clamp (glucose ~220 mg/dl). The change in intracerebral glucose was significantly different across groups after controlling for age and sex, despite similar plasma glucose levels at baseline and during hyperglycemia. Compared with lean participants, brain glucose increments were lower in participants with obesity and T2DM. Furthermore, the change in brain glucose correlated inversely with plasma free fatty acid (FFA) levels during hyperglycemia. These data suggest that obesity and poorly controlled T2DM progressively diminish brain glucose responses to hyperglycemia, which has important implications for understanding not only the altered feeding behavior, but also the adverse neurocognitive consequences associated with obesity and T2DM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8f7cf0c91791d3e56048e3ee9e259769Test
https://europepmc.org/articles/PMC5846903Test/