scholarly journals Estrogen Deficiency Exacerbates Type 1 Diabetes–Induced Bone TNF-α Expression and Osteoporosis in Female Mice

Endocrinology ◽  
2017 ◽  
Vol 158 (7) ◽  
pp. 2086-2101 ◽  
Author(s):  
Sandi Raehtz ◽  
Hayley Bierhalter ◽  
Daniel Schoenherr ◽  
Narayanan Parameswaran ◽  
Laura R. McCabe
Keyword(s):  
Type 1 Diabetes ◽  
Bone Loss ◽  
Fracture Risk ◽  
Volume Fraction ◽  
Estrogen Deficiency ◽  
Bone Volume Fraction ◽  
Number Of Patients ◽  
Tnf Α

Abstract Estrogen deficiency after menopause is associated with rapid bone loss, osteoporosis, and increased fracture risk. Type 1 diabetes (T1D), characterized by hypoinsulinemia and hyperglycemia, is also associated with bone loss and increased fracture risk. With better treatment options, T1D patients are living longer; therefore, the number of patients having both T1D and estrogen deficiency is increasing. Little is known about the mechanistic impact of T1D in conjunction with estrogen deficiency on bone physiology and density. To investigate this, 11-week-old mice were ovariectomized (OVX), and T1D was induced by multiple low-dose streptozotocin injection. Microcomputed tomographic analysis indicated a marked reduction in trabecular bone volume fraction (BVF) in T1D-OVX mice (~82%) that was far greater than the reductions (~50%) in BVF in either the OVX and T1D groups. Osteoblast markers, number, and activity were significantly decreased in T1D-OVX mice, to a greater extent than either T1D or OVX mice. Correspondingly, marrow adiposity was significantly increased in T1D-OVX mouse bone. Bone expression analyses revealed that tumor necrosis factor (TNF)–α levels were highest in T1D-OVX mice and correlated with bone loss, and osteoblast and osteocyte death. In vitro studies indicate that estrogen deficiency and high glucose enhance TNF-α expression in response to inflammatory signals. Taken together, T1D combined with estrogen deficiency has a major effect on bone inflammation, which contributes to suppressed bone formation and osteoporosis. Understanding the mechanisms/effects of estrogen deficiency in the presence of T1D on bone health is essential for fracture prevention in this patient population.

scholarly journals Estrogen Deficiency Plus Type 1 Diabetes: A Double-Dip for Bone Loss

Endocrinology ◽  
2017 ◽  
Vol 158 (7) ◽  
pp. 2066-2067 ◽  
Author(s):  
Suresh Mishra ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Type 1 Diabetes ◽  
Bone Loss ◽  
Estrogen Deficiency

scholarly journals Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri

Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3169-3182 ◽  
Author(s):  
Jing Zhang ◽  
Katherine J. Motyl ◽  
Regina Irwin ◽  
Ormond A. MacDougald ◽  
Robert A. Britton ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Health ◽  
Lactobacillus Reuteri ◽  
Diabetic Mice ◽  
Tnf Α ◽  
Marrow Adiposity ◽  
Probiotic Lactobacillus ◽  
Osteoblast Maturation

Type 1 diabetes (T1D)–induced osteoporosis is characterized by a predominant suppression of osteoblast number and activity, as well as increased bone marrow adiposity but no change in osteoclast activity. The fundamental mechanisms and alternative anabolic treatments (with few side effects) for T1D bone loss remain undetermined. Recent studies by our laboratory and others indicate that probiotics can benefit bone health. Here, we demonstrate that Lactobacillus reuteri, a probiotic with anti-inflammatory and bone health properties, prevents T1D-induced bone loss and marrow adiposity in mice. We further found that L. reuteri treatment prevented the suppression of Wnt10b in T1D bone. Consistent with a role for attenuated bone Wnt10b expression in T1D osteoporosis, we observed that bone-specific Wnt10b transgenic mice are protected from T1D bone loss. To examine the mechanisms of this protection, we focused on TNF-α, a cytokine up-regulated in T1D that causes suppression of osteoblast Wnt10b expression in vitro. Addition of L. reuteri prevented TNF-α–mediated suppression of Wnt10b and osteoblast maturation markers. Taken together, our findings reveal a mechanism by which T1D causes bone loss and open new avenues for use of probiotics to benefit the bone.

scholarly journals Effect of Coxsackievirus B4 Infection on the Thymus: Elucidating Its Role in the Pathogenesis of Type 1 Diabetes

2021 ◽  
Vol 9 (6) ◽  
pp. 1177
Author(s):  
Abdulaziz Alhazmi ◽  
Magloire Pandoua Nekoua ◽  
Hélène Michaux ◽  
Famara Sane ◽  
Aymen Halouani ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Viral Infections ◽  
Lymphoid Organ ◽  
Thymic Epithelial Cells ◽  
Central Tolerance ◽  
Coxsackievirus B4

The thymus gland is a primary lymphoid organ for T-cell development. Various viral infections can result in disturbance of thymic functions. Medullary thymic epithelial cells (mTECs) are important for the negative selection of self-reactive T-cells to ensure central tolerance. Insulin-like growth factor 2 (IGF2) is the dominant self-peptide of the insulin family expressed in mTECs and plays a crucial role in the intra-thymic programing of central tolerance to insulin-secreting islet β-cells. Coxsackievirus B4 (CVB4) can infect and persist in the thymus of humans and mice, thus hampering the T-cell maturation and differentiation process. The modulation of IGF2 expression and protein synthesis during a CVB4 infection has been observed in vitro and in vivo in mouse models. The effect of CVB4 infections on human and mouse fetal thymus has been studied in vitro. Moreover, following the inoculation of CVB4 in pregnant mice, the thymic function in the fetus and offspring was disturbed. A defect in the intra-thymic expression of self-peptides by mTECs may be triggered by CVB4. The effects of viral infections, especially CVB4 infection, on thymic cells and functions and their possible role in the pathogenesis of type 1 diabetes (T1D) are presented.

scholarly journals Development of a Bioartificial Vascular Pancreas

2021 ◽  
Vol 12 ◽  
pp. 204173142110277
Author(s):  
Edward X Han ◽  
Juan Wang ◽  
Mehmet Kural ◽  
Bo Jiang ◽  
Katherine L Leiby ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Pancreatic Islets ◽  
Vascular Graft ◽  
Term Treatment ◽  
Diffusion Limitations ◽  
Human Scale ◽  
Arterial Blood ◽  
Long Term Treatment

Transplantation of pancreatic islets has been shown to be effective, in some patients, for the long-term treatment of type 1 diabetes. However, transplantation of islets into either the portal vein or the subcutaneous space can be limited by insufficient oxygen transfer, leading to islet loss. Furthermore, oxygen diffusion limitations can be magnified when islet numbers are increased dramatically, as in translating from rodent studies to human-scale treatments. To address these limitations, an islet transplantation approach using an acellular vascular graft as a vascular scaffold has been developed, termed the BioVascular Pancreas (BVP). To create the BVP, islets are seeded as an outer coating on the surface of an acellular vascular graft, using fibrin as a hydrogel carrier. The BVP can then be anastomosed as an arterial (or arteriovenous) graft, which allows fully oxygenated arterial blood with a pO2 of roughly 100 mmHg to flow through the graft lumen and thereby supply oxygen to the islets. In silico simulations and in vitro bioreactor experiments show that the BVP design provides adequate survivability for islets and helps avoid islet hypoxia. When implanted as end-to-end abdominal aorta grafts in nude rats, BVPs were able to restore near-normoglycemia durably for 90 days and developed robust microvascular infiltration from the host. Furthermore, pilot implantations in pigs were performed, which demonstrated the scalability of the technology. Given the potential benefits provided by the BVP, this tissue design may eventually serve as a solution for transplantation of pancreatic islets to treat or cure type 1 diabetes.

scholarly journals Prevalence of bone fracture and its association with severe hypoglycemia in Japanese patients with type 1 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002099
Author(s):  
Yuji Komorita ◽  
Masae Minami ◽  
Yasutaka Maeda ◽  
Rie Yoshioka ◽  
Toshiaki Ohkuma ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 1 Diabetes ◽  
Fracture Risk ◽  
Bone Fracture ◽  
Severe Hypoglycemia ◽  
Japanese Patients ◽  
Anatomic Site ◽  
Cross Sectional ◽  
History Of

IntroductionType 1 diabetes (T1D) is associated with higher fracture risk. However, few studies have investigated the relationship between severe hypoglycemia and fracture risk in patients with T1D, and the results are controversial. Besides, none has investigated the risk factors for fracture in Asian patients with T1D. The aim of the present study was to investigate the prevalence of bone fracture and its relationship between severe hypoglycemia and other risk factors in Japanese patients with T1D.Research design and methodsThe single-center cross-sectional study enrolled 388 Japanese patients with T1D (mean age, 45.2 years; women, 60.4%; mean duration of diabetes, 16.6 years) between October 2019 and April 2020. The occurrence and circumstances of any fracture after the diagnosis of T1D were identified using a self-administered questionnaire. The main outcomes were any anatomic site of fracture and fall-related fracture. Severe hypoglycemia was defined as an episode of hypoglycemia that required the assistance of others to achieve recovery.ResultsA total of 92 fractures occurred in 64 patients, and 59 fractures (64%) were fall-related. Only one participant experienced fracture within the 10 years following their diagnosis of diabetes. In logistic regression analysis, the multivariate-adjusted ORs (95% CIs) of a history of severe hypoglycemia were 2.11 (1.11 to 4.09) for any fracture and 1.91 (0.93 to 4.02) for fall-related fracture. Fourteen of 18 participants with multiple episodes of any type of fracture had a history of severe hypoglycemia (p<0.001 vs no fracture).ConclusionsWe have shown that a history of severe hypoglycemia is significantly associated with a higher risk of bone fracture in Japanese patients with T1D.

scholarly journals Differential Expression of Inflammatory Markers in Hypoglycemia Unawareness Associated with Type 1 Diabetes: A Case Report

2020 ◽  
Vol 11 (1) ◽  
pp. 17
Author(s):  
Yousef Al Zoubi ◽  
Bashair M. Mussa ◽  
Ankita Srivastava ◽  
Abdul Khader Mohammed ◽  
Elamin Abdelgadir ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Case Report ◽  
Differential Expression ◽  
Insulin Pump ◽  
Mrna Level ◽  
Insulin Injection ◽  
Hypoglycemia Unawareness ◽  
Tnf Α ◽  
Ifn Γ

The recurrence of hypoglycemic episodes leads to attenuation of the normal counter-regulatory mechanisms that are controlled by the hypothalamus, which results in hypoglycemia unawareness (HU). In this case report, we described for the first time the differential expression of TNF-α, IL-1β, IL-6, and IFN-γ in a blood sample that was taken from a 27-year-old patient with type 1 diabetes mellitus (T1DM) who was diagnosed with HU. The anti-diabetic regimen is currently based on insulin injection, but the patient is planning to start the use of an insulin pump to have better control of glucose levels. Our results showed a trend toward an increase in the expression of IL-1β, IL-6, and IFN-γ in T1DM patient with HU. However, the mRNA level of TNF-α showed a significant decrease. These observations suggest that systemic inflammation could be an underlying cause of HU.

THYROID PATHOLOGY IN CHILDREN WITH TYPE 1 DIABETES

Vestnik ◽  
2021 ◽  
pp. 107-111
Author(s):  
С.И. Сабирова ◽  
С.Г. Надырова ◽  
А.Б. Жанзак ◽  
А.Е. Манасбаева ◽  
Ж.Ж. Нургалиева
Keyword(s):  
Type 1 Diabetes ◽  
Thyroid Gland ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Development Indicators ◽  
Clinical Hospital ◽  
Number Of Children ◽  
Thyroid Pathology ◽  
Number Of Patients

Целью научной работы является изучение структуры заболеваний щитовидной железы у больных сахарным диабетом 1 типа. В данной статье мы ретроспективно проанализировали 972 историй болезни больных детей с СД 1 типа, находившихся на стационарном лечении в ДГКБ №2 г. Алматы (Казахстан) в период с 2014 по 2019 гг. Были изучены и оценены показатели физического развития, объективные данные (кожные покровы, ЧСС, АД, пальпация ЩЖ), лабораторно - уровней гормонов ТТГ, свТ4, свТ3, а/т к ТПО, а/т к ТГ в сыворотки крови, инструментально - УЗИ ЩЖ. Всего за 2014-2019 гг. через отделение эндокринологии ДГКБ №2 прошли 972 детей с диагнозом СД 1 типа. Большинство детей (382 человек, 79,9%) имели стаж болезни СД до 5 лет. 88 детей (18,5%) со стажем от 5 до 10 лет, 8 человек (1,7%) страдали СД более 10 лет. СД1 в основном был диагностирован в возрасте 7-12 лет (245-51,3%), меньше всего выявили СД 1 типа у детей до 3 лет (21 - 4,4%). Из общего количества пациентов с СД1 (972) было обследовано на функцию ЩЖ 478 детей (49,2%). Среди них было выявлено 319 детей с дисфункцией ЩЖ, что составляет 66,7%. Так, за 2014 год из 92 детей - 7 (7,6%), обследованных на функцию щитовидной железы, в результате чего было выявлено 6 (85,7%) детей с дисфункцией щитовидной железы. С каждым годом росло количество детей, которых направляли на обследование ЩЖ, так в сравнении с 2014 годом, когда из 92 детей - 7 (7,6%) были обследованы на функцию щитовидной железы, в 2019 году были обследованы уже 222 (92,1%) детей из 241. Симптомы как гиперфункции, так и гипофункции ЩЖ, особенно их субклинические варианты протекают под маской других заболевании и не сразу обнаруживаются, исходя из этого следует сразу обследовать на функцию ЩЖ при поступлении и в дальнейшим их наблюдать в динамике. В ходе исследования дисфункция щитовидной железы диагностирована у 319 (67,7%) пациентов, что должно привлечь внимание не только эндокринологов, но и врачей общей практики, педиатров и настроить их на прицельный поиск этой патологии и своевременную коррекцию гипотиреоза или другой патологии ЩЖ при его наличии The purpose of this research is to study the structure of thyroid diseases in patients with type 1 diabetes. In this article, we retrospectively analyzed 972 case histories of sick children with type 1 diabetes who were treated in the children's city clinical hospital No. 2 in Almaty (Kazakhstan) in the period from 2014 to 2019. Physical development indicators, objective data (skin, heart rate, blood pressure, thyroid palpation), laboratory levels of TSH, thyroxine, triiodothyronine, antibodies to thyroperoxidase, antibodies to thyroglobulin in blood serum, instrumental ultrasound examination of the thyroid gland were studied and evaluated. In total, in 2014-2019, 972 children with a diagnosis of type 1 diabetes mellitus passed through the endocrinology Department of the children's city clinical hospital No. 2.The majority of children (382 people, 79.9%) had a history of diabetes up to 5 years. 88 children (18.5%) with experience from 5 to 10 years, 8 people (1.7%) had diabetes for more than 10 years. Type 1 diabetes was mainly diagnosed at the age of 7-12 years (245-51. 3%), the least detected type 1 diabetes in children under 3 years (21 - 4.4%). Out of the total number of patients with type 1 diabetes (972), 478 children (49.2%) were examined for thyroid function. Among them, 319 children with thyroid dysfunction were identified, which is 66.7%. So, in 2014, out of 92 children, 7 (7.6%) were examined for thyroid function, as a result of which 6 (85.7%) children had thyroid dysfunction. Every year, the number of children referred for thyroid examination increased, so compared to 2014, when out of 92 children - 7 (7.6%) were examined for thyroid function, in 2019, 222 (92.1%) children out of 241 were examined. Symptoms of both hyperfunction and hypofunction of the thyroid gland, especially their subclinical variants, occur under the guise of other diseases and are not immediately detected, so you should immediately investigate the function of the thyroid gland at admission and further observe them in dynamics. During the study, thyroid dysfunction was diagnosed in 319 (67.7%) patients, which should attract the attention of not only endocrinologists, but also General practitioners, pediatricians and set them up for a targeted search for this pathology and timely correction of hypothyroidism or other thyroid pathology if it is present.

The effect of the COVID-19 pandemic on metabolic control in children with type 1 diabetes: a single-center experience

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Emre Sarıkaya ◽  
Dilek Çiçek ◽  
Ebru Gök ◽  
Leyla Kara ◽  
Uğur Berber ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Metabolic Control ◽  
Glycosylated Hemoglobin ◽  
Emergency Admissions ◽  
Single Center Experience ◽  
Number Of Patients ◽  
Significant Difference ◽  
Before And After ◽  
One Year

Abstract Objectives Coronavirus disease 2019 has caused a major epidemic worldwide, and lockdowns became necessary in all countries to prevent its spread. This study aimed to evaluate the effects of staying-at-home practices on the metabolic control of children and adolescents with type 1 diabetes during the pandemic period. Materials and Methods Eighty-nine patients younger than 18 years old who were diagnosed with type 1 diabetes at least one year before the declaration of the pandemic were included in the study. The last visit data of the patients before and after the declaration of the pandemic, and the frequency of presentation of diabetes-related emergencies from one year after diagnosis of type 1 diabetes to the declaration of the pandemic, and from the declaration of the pandemic to the last visit after the pandemic declaration were compared. Results The total number of patients was 89, and 48 (53.9%) were boys. The mean (± standard deviation [SD]) age at diagnosis was 8.4 ± 3.7 years (boys 7.9 ± 3.6 years; girls 8.9 ± 3.9 years). There was no statistically significant difference when the SD values of the anthropometric measurements, and the glycosylated hemoglobin (HbA1c) and lipid profile tests were compared. However, the frequency of admission to the emergency service related to diabetes was significantly different. Conclusions Although the pandemic did not significantly affect the metabolic and glycemic controls of the children with type 1 diabetes included in this study, an increase in the frequency of diabetes-related emergency admissions was noted.

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