Endocrine Research[JOURNAL]
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200 papers
Osteonecrosis of Femoral Head is Associated with Congenital Multiple Pituitary Hormone Deficiency: Report of Three Cases and Literature Review.
Li S, Mao J, Wang X … +2 more , Nie M, Wu X
Endocr Res · 2019 Nov · PMID 30966827 · Publisher ↗
: Pituitary hormones are critical for bone development and maturation. It is currently unknown whether congenital multiple pituitary hormone deficiency (CMPHD) is associated with osteonecrosis of femoral head (ONFH). : C...
: Pituitary hormones are critical for bone development and maturation. It is currently unknown whether congenital multiple pituitary hormone deficiency (CMPHD) is associated with osteonecrosis of femoral head (ONFH). : Clinical presentations and hormonal profiles of three patients with CMPHD and ONFH were retrospectively described. The incidence of ONFH in this population was studied. : (1) Congenital hypopituitarism was diagnosed in three patients. Femoral epiphyseal fusion in these patients was markedly delayed, and they had very low bone mineral density. (2) Hip pain, which is the main presentation of ONFH, occurred at the age of 20-30 years. ONFH induced by excessive glucocorticoids was excluded. (3) The estimated incidence of ONFH was approximately 694:100,000. : CMPHD, especially a lack of growth and sex hormones, may contribute to ONFH.
Action of Reverse T3 on Cancer Cells.
Lin HY, Tang HY, Leinung M … +3 more , Mousa SA, Hercbergs A, Davis PJ
Endocr Res · 2019 Nov · PMID 30943372 · Publisher ↗
: Reverse T3 (rT3; 3,3',5'-triiodo-L-thyronine) is widely regarded as an inactive naturally occurring analog of thyroid hormone. rT3 is known to bind to the thyroid hormone analog receptor on plasma membrane integrin αvβ...
: Reverse T3 (rT3; 3,3',5'-triiodo-L-thyronine) is widely regarded as an inactive naturally occurring analog of thyroid hormone. rT3 is known to bind to the thyroid hormone analog receptor on plasma membrane integrin αvβ3. This integrin is generously expressed by tumor cells and is the initiation site for the stimulation by L-thyroxine (T4) at physiological free concentrations on cancer cell proliferation. : In the present studies, we show that rT3 caused increases of proliferation of 50% to 80% (P < 0.05-0.001) of human breast cancer and glioblastoma cells. : rT3 may be a host factor supporting cancer growth.
White Blood Cell Count and C-Reactive Protein Independently Predicted Incident Diabetes: Yuport Medical Checkup Center Study.
Kashima S, Inoue K, Matsumoto M … +1 more , Akimoto K
Endocr Res · 2019 Nov · PMID 30895902 · Publisher ↗
: White blood cell (WBC) count or C-reactive protein (CRP) level alone may not fully indicate the chronic inflammation causing type 2 diabetes. We examined both WBC count and CRP level, independently and in combination,...
: White blood cell (WBC) count or C-reactive protein (CRP) level alone may not fully indicate the chronic inflammation causing type 2 diabetes. We examined both WBC count and CRP level, independently and in combination, as predictive markers for type 2 diabetes and also considered the influence of obesity and other individual characteristics on the relationship. : In total, 9,706 participants were enrolled with WBC < 10*10/L and CRP < 10 mg/L using data from the Yuport Medical Checkup Center Study. The cumulative incidence of type 2 diabetes [defined either as known diabetes, fasting plasma glucose ≥ 7.0 mmol/L, or HbA1c ≥ 6.5% (47.5 mmol/mol)] was measured. Hazard ratios (HRs) were estimated using a Cox proportional hazards model. : During study period, 272 men (5.5%) and 113 women (2.4%) progressed to diabetes. The progression to diabetes was predicted by both increased baseline levels of WBC count [adjusted HR = 1.29 (95% CI: 1.04-1.60)] and CRP level [1.39 (1.10-1.74)], even after adjusting for possible confounders. The combined presence was more predictive of diabetes than either alone in a four-groups analysis [1.75 (1.28-2.40)]. In addition, the elevated HRs of either or both higher WBC and CRP levels were observed across four subgroups of body mass index (BMI), including low BMI, and people who had at least one occurrence of dyslipidemia. : Increased WBC counts and CRP levels were predictive for type 2 diabetes and the combination augmented the risk of diabetes, regardless of whether the BMI was high or low.
A Multicenter Large-Scale Retrospective Analysis of the Correlation between Body Mass Index and All-Cause Mortality in Patients with Type 2 diabetes Mellitus: A Seven-Year Real-World Study.
Ma J, Wang X, Zheng M … +5 more , Yu H, Ma J, Li X, Pan J, Huang Y
Endocr Res · 2019 Aug · PMID 30773948 · Publisher ↗
: To investigate the association between body mass index (BMI) and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and to determine any sex-specific differences in this association. : We retrospectiv...
: To investigate the association between body mass index (BMI) and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and to determine any sex-specific differences in this association. : We retrospectively enrolled patients with T2DM and investigated the annual death data for seven years starting from 2010. All-cause mortality was calculated using Life Tables analysis. Multivariate Cox proportional hazards analysis was performed to identify the association between BMI and mortality. : During a mean survey period of 7.33 ± 1.42 years (X± SD), 996 of the 17259 patients enrolled died, resulting in an all-cause mortality rate of 5.77%, with no significant difference between women and men (6.04% . 5.56%; = 1.766, = 0.184). The top three causes of death were ischemic heart disease, cerebrovascular disease, and chronic kidney failure. A total of 87, 266, 332, and 311 patients with a BMI of <18.5, 18.5-23.99, 24.0-27.99, and ≥28.0 kg/m, respectively, died, with the corresponding mortality rate calculated at 15.45%, 3.30%, 5.80%, and 10.70%, respectively. The BMI value associated with the highest all-cause mortality was <18.5 kg/m, but this association was only significant in women aged <50 years (HR: 3.12; 95% CI, 1.62-4.34; < 0.001). : In patients with T2DM, a low BMI in women aged <50 years predicted high all-cause mortality.
Factors Influencing Serum Homocysteine Levels in Postmenopausal Osteoporotic Females - Comparison to Urinary Collagen Crosslinks.
Ohishi T, Fujita T, Nishida T … +4 more , Asukai M, Suzuki D, Sugiura K, Matsuyama Y
Endocr Res · 2019 Aug · PMID 30760054 · Publisher ↗
: The correlation between serum levels of homocysteine and bone mineral density remains controversial. The aim of this study was to identify the potential factors associated with the levels of serum total homocysteine (S...
: The correlation between serum levels of homocysteine and bone mineral density remains controversial. The aim of this study was to identify the potential factors associated with the levels of serum total homocysteine (S-Hcy) and urinary N-terminal telopeptide of type I collagen (U-NTX) in female osteoporotic patients. : This cross-sectional study included 163 female osteoporotic patients, aged between 48 and 91 years, who had never been treated with anti-osteoporosis therapy. Background data including spine and hip bone mineral density, ongoing therapy for the metabolic disease, aortic calcification score as evaluated by lateral lumbar X-ray film, and recent fragility fracture history were obtained. S-Hcy, U-NTX levels, and creatinine clearance were measured. : Multiple linear regression analysis revealed a significant correlation between S-Hcy levels and aortic calcification score ( = 0.022), creatinine clearance ( = 0.004), and recent fracture history (within 1 year after fracture) ( = 0.028); conversely, U-NTX levels correlated significantly with total hip bone mineral density ( < 0.0001) and recent fracture history (p = 0.0007). : S-Hcy levels had no correlation with bone mineral density, but were associated with the degree of aortic calcification, renal function, and fracture events. These confounding factors should be taken into consideration when the relationship between S-Hcy and bone mineral density is discussed.
Expression Is Regulated by Cell Differentiation and Overfeeding in Human Adipose Tissue.
Justesen L, Ribel-Madsen R, Gillberg L … +4 more , Hansen NS, Wulff AL, Grunnet LG, Brøns C
Endocr Res · 2019 Aug · PMID 30721637 · Publisher ↗
: The gene variant rs7903146 has the largest effect on type 2 diabetes risk reported in genome-wide association studies, however its role in adipose tissue development and function is unknown. We investigate the associa...
: The gene variant rs7903146 has the largest effect on type 2 diabetes risk reported in genome-wide association studies, however its role in adipose tissue development and function is unknown. We investigate the association between gene variant rs7903146 and metabolic parameters and examine in vitro and ex vivo gene expression of in human adipose tissue and progenitor cells from two independent populations of young healthy men with increased risk of type 2 diabetes due to low birth weight (LBW). : Adipose tissue biopsies were excised from 40 healthy young men with low and normal birth weights (NBW) after a control and 5-day high-fat overfeeding diet. In another cohort including 13 LBW and 13 NBW men, adipocyte progenitor cells were isolated and cultivated. Transcriptome-wide expression was performed on RNA extracted from biopsies or cell cultures. : Diet-induced peripheral insulin resistance is more pronounced in carriers of the T-risk allele rs7903146, whereas no association with hepatic insulin resistance was shown. expression increased during adipogenesis in isolated preadipocytes from both LBW and NBW men (p < 0.001) and correlated positively with markers of progenitor cell proliferation and maturation capacity. In the mature adipose tissue, LBW men had lower expression of compared to NBW men at baseline (p = 0.03) and expression was suppressed by short-term overfeeding in NBW men (p = 0.005). : The results suggest a regulation of expression during adipogenesis and in mature adipose tissue upon overfeeding, and further that young men exposed to an adverse intrauterine environment have reduced mature adipose tissue expression.
The Non-Aromatic Δ5-Androstenediol Derivative of Dehydroepiandrosterone Acts as an Estrogen Agonist in Neonatal Rat Osteoblasts through an Estrogen Receptor α-related Mechanism.
Langley E, Velazquez-Cruz R, Parra-Torres A … +1 more , Enríquez J
Endocr Res · 2019 Aug · PMID 30580653 · Publisher ↗
: It has been proposed that DHEA influences bone formation through, bioconversion to 17β-estradiol; however, DHEA is converted to Δ5-androstenediol (Δ5-Adiol), a metabolite with estrogenic potential involved in diverse b...
: It has been proposed that DHEA influences bone formation through, bioconversion to 17β-estradiol; however, DHEA is converted to Δ5-androstenediol (Δ5-Adiol), a metabolite with estrogenic potential involved in diverse biological process. To gain new insight into the role of Δ5-Adiol in bone cells, we examined DHEA and Δ5-Adiol effects in neonatal rat and human hFOB1.19 osteoblasts. : Osteoblast activity was assessed by analyzing proliferation, alkaline phosphatase activity, and expression of and . We also examined binding affinities for osteoblast-ER and transcriptional activation of human (h)ERα, hERβ or hAR in U2-OS cells. : The most striking finding was that Δ5-Adiol had greater stimulatory effect than DHEA on rat osteoblast proliferation and differentiation, as well as expression in human osteoblasts. Interestingly, the Δ5-Adiol or DHEA-induced effects were not precluded with letrozole or trilostane, consistent with bioconversion of DHEA to Δ5-Adiol due to elevated expression of in neonatal rat osteoblasts, suggesting a high level of 17β-hydroxysteroid dehydrogenase type 1 activity. Conversely, Δ5-Adiol and DHEA-induced proliferative effects were inhibited with ICI 182780 alone or combined with trilostane, which correlates with the higher binding affinity of Δ5-Adiol for ER compared to DHEA. Furthermore, Δ5-Adiol showed a greater relative agonist activity for hERα than for hERβ or hAR. : This study is the first to show that a bioactive DHEA derivative stimulates E-dependent osteoblast activities, including proliferation and differentiation in rat and human osteoblasts, through ERα-related mechanisms.
Rates and Causes of Death among Adult Diabetes Patients in Romania.
Ioacara S, Guja C, Ionescu-Tirgoviste C … +3 more , Martin S, Tiu C, Fica S
Endocr Res · 2019 Aug · PMID 30424683 · Publisher ↗
: To study the age and sex-dependent mortality rates and causes of death in a large Romanian diabetes cohort as compared with the general population. : All adult patients aged 20-64 years, receiving a free diabetes presc...
: To study the age and sex-dependent mortality rates and causes of death in a large Romanian diabetes cohort as compared with the general population. : All adult patients aged 20-64 years, receiving a free diabetes prescription in a major urban area during 2001-2008 were included and followed-up for death until December 31, 2011. Crude mortality rates and standardized mortality rate ratios (SMR) against general population (data from the National Institute of Statistics) were calculated. Years lost due to diabetes were computed assuming the general population mortality rates for ages below 20 and above 64 years. : During the 11 years study period, 49,328 diabetes patients (mean age at baseline 53.0 ± 8.8 years) contributed 297,370 person-years and 5,053 deaths. All cause mortality rates (per 1000 person years) increased with age and was 3.4 in 20-24 years age group and 25.7 in 60-64 year age group, while the corresponding SMR decreased from 6.0 to 1.5. Diabetes patients aged 20-24 years had a life expectancy of 48.6 years, which was 6.6 years less compared with the corresponding general population (55.2 years). The gap was 7.0 years in women and 5.8 years in men. Diabetes patients aged 20-24 years lost 196 minutes of life daily due to diabetes in women and 182 minutes in men. : Mortality rates increased, while mortality rate ratios against general population decreased with age. Men had higher mortality rates, but women had higher mortality rate ratios in the gender analysis.
Relationship between metabolic syndrome and metabolic syndrome score with -cell function by gender in non-diabetic Korean populations.
Yoon H, Yoon YS, Kim SG … +4 more , Oh HJ, Choi CW, Seong JM, Park J
Endocr Res · 2019 Aug · PMID 30339044 · Publisher ↗
: The present study was conducted to assess the association of metabolic syndrome (MetS) and the MetS score (MSS) with -cell function by gender in Korean non-diabetic populations. : This study used the data from the 2015...
: The present study was conducted to assess the association of metabolic syndrome (MetS) and the MetS score (MSS) with -cell function by gender in Korean non-diabetic populations. : This study used the data from the 2015 Korean National Health and Nutrition Examination Survey including 4380 adults, aged 20 or older. : After adjusting for related variables (with exception of body mass index [BMI]), MetS (< 0.001) and MSS (< 0.001) were positively associated with homeostasis model assessment of -cell function (HOMA-), in both men and women. When further adjusting for BMI, MetS (= 0.002) and MSS (= 0.006) were positively associated with HOMA- in women, whereas the association of MetS (= 0.140) or MSS (= 0.697) and HOMA- was no longer significant in men. : MetS and MSS increases were positively associated with -cell function in non-diabetic Korean women, but not in non-diabetic Korean men.
Effect of insulin on thyroid cell proliferation, tumor cell migration, and potentially related mechanisms.
Zhang X, Sheng X, Miao T … +2 more , Yao K, Yao D
Endocr Res · 2019 · PMID 30260725 · Publisher ↗
BACKGROUND: Diabetes has recently been identified as a risk factor for a variety of cancers, possibly due to hyperinsulinemia or exogenous insulin use. Thyroid cancer is the most common endocrine malignancy, and its inci...
BACKGROUND: Diabetes has recently been identified as a risk factor for a variety of cancers, possibly due to hyperinsulinemia or exogenous insulin use. Thyroid cancer is the most common endocrine malignancy, and its incidence has been exponentially increasing worldwide at an alarming rate. The aim of this study was to establish whether insulin use affects thyroid cancer development and progression, specifically cell proliferation and migration in vitro. METHODS: In this study, we investigated the effects of the insulin agents most commonly used in the clinic, regular human insulin (HI) and insulin glargine (IG), on the proliferation and migration of thyroid cells. RESULTS: Both HI and IG affected the thyroid cells in a dose-dependent manner and at high concentrations significantly promoted thyroid cell proliferation and tumor cell migration. The promoting effect might be elicited by activation of the insulin receptor and insulin-like growth factor-1 receptor and through the downstream Akt-signaling pathway, which inhibits the activity of the tumor-suppressor FoxO3a. In particular, MAPK-signaling cascades were activated in papillary thyroid carcinoma cell-1 cells but not in follicular rat thyroid-5 cells. CONCLUSION: The in vitro evidence demonstrated that HI and IG can promote thyroid cell proliferation and tumor cell migration at supraphysiological concentrations, but the effect was not significant at low concentrations. Whether high-dose insulins could affect diabetic patients with thyroid cancer or undetected (pre)cancerous lesions needs further in vivo study. ABBREVIATIONS: HI: human regular insulin; IG: insulin glargine; IR: insulin receptor; IGF-1R: insulin-like growth factor-1 receptor; Akt: protein kinase B (PKB); MAPK: mitogen-activated protein kinase; FoxO3a: the forkhead box-containing protein: class O 3a.
Endocrine complications of celiac disease: a case report and review of the literature.
Walker MD, Zylberberg HM, Green PHR … +1 more , Katz MS
Endocr Res · 2019 · PMID 30198791 · Publisher ↗
PURPOSE: The purpose of this article is to review recent literature regarding endocrine disorders related to celiac disease (CD). METHODS: We describe a case report and review existing literature on the endocrine manifes...
PURPOSE: The purpose of this article is to review recent literature regarding endocrine disorders related to celiac disease (CD). METHODS: We describe a case report and review existing literature on the endocrine manifestations of CD. RESULTS: CD is an autoimmune disorder characterized by intestinal inflammation in response to gluten. CD can cause a wide range of extra-intestinal complications, including endocrine manifestations. Metabolic bone disease including osteoporosis and osteopenia, vitamin D deficiency, secondary hyperparathyroidism and less frequently osteomalacia can be seen. In CD, fracture risk is increased by 30-40%, while risk for hip fracture is approximately doubled. The risk for other endocrine disorders, particularly autoimmune endocrinopathies, is also increased in those with CD compared to the general population. Epidemiologic data indicate the risk for hypothyroidism is 3-4 times higher among those with CD, while risk of type 1 diabetes is greater than double. Risk for primary adrenal insufficiency is a striking 11-fold higher in those with versus without CD, though the absolute risk is low. Fertility is reduced in women with CD before diagnosis by 37% while male fertility in the absence of hypogonadism does not appear to be affected. Other endocrine conditions including hyperthyroidism, ovarian failure, androgen insensitivity, impaired growth and growth hormone deficiency and autoimmune polyendocrine syndromes have also been associated with CD. CONCLUSIONS: CD is associated with a wide range of endocrine manifestations.
A subset of patients with acquired partial lipodystrophy developing severe metabolic abnormalities.
Ozgen Saydam B, Sonmez M, Simsir IY … +11 more , Erturk MS, Kulaksizoglu M, Arkan T, Hekimsoy Z, Cavdar U, Akinci G, Demir T, Altay CT, Mihci E, Secil M, Akinci B
Endocr Res · 2019 · PMID 30182761 · Publisher ↗
UNLABELLED: Purpose/Aim of the study: Acquired partial lipodystrophy (APL) is a rare disease characterized by selective loss of adipose tissue. In this study, we aimed to present a subset of patients with APL, who develo...
UNLABELLED: Purpose/Aim of the study: Acquired partial lipodystrophy (APL) is a rare disease characterized by selective loss of adipose tissue. In this study, we aimed to present a subset of patients with APL, who developed severe metabolic abnormalities, from our national lipodystrophy registry. MATERIALS AND METHODS: Severe metabolic abnormalities were defined as: poorly controlled diabetes (HbA1c above 7% despite treatment with insulin more than 1 unit/kg/day combined with oral antidiabetics), severe hypertriglyceridemia (triglycerides above 500 mg/dL despite treatment with lipid-lowering drugs), episodes of acute pancreatitis, or severe hepatic involvement (biopsy-proven non-alcoholic steatohepatitis (NASH)). RESULTS: Among 140 patients with all forms of lipodystrophy (28 with APL), we identified 6 APL patients with severe metabolic abnormalities. The geometric mean for age was 37 years (range: 27-50 years; 4 females and 2 males). Five patients had poorly controlled diabetes despite treatment with high-dose insulin combined with oral antidiabetics. Severe hypertriglyceridemia developed in five patients, of those three experienced episodes of acute pancreatitis. Although all six patients had hepatic steatosis at various levels on imaging studies, NASH was proven in two patients on liver biopsy. Our data suggested that APL patients with severe metabolic abnormalities had a more advanced fat loss and longer disease duration. CONCLUSIONS: We suggest that these patients represent a potential subgroup of APL who may benefit from metreleptin or investigational therapies as standard treatment strategies fail to achieve a good metabolic control.
Growth hormone therapy in children with idiopathic short stature - the effect on appetite and appetite-regulating hormones: a pilot study.
Yackobovitch-Gavan M, Gat-Yablonski G, Shtaif B … +4 more , Hadani S, Abargil S, Phillip M, Lazar L
Endocr Res · 2019 · PMID 29979896 · Publisher ↗
AIM: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure...
AIM: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure (REE). METHODS: Nine pre-pubertal children with idiopathic short stature underwent a standard meal test before and 4 months following initiation of GH treatment. Ghrelin, GLP-1, leptin, and insulin levels were measured; area under the curve (AUC) was calculated. Height, weight, body composition, REE, and insulin-like growth factor levels were recorded at baseline and after 4 and 12 months. RESULTS: Following 4 months of GH therapy, food intake increased, with increased height-standard deviation score (SDS), weight-SDS, and REE (p < .05). Significant changes in appetite-regulating hormones included a decrease in postprandial AUC ghrelin levels (p = .045) and fasting GLP-1 (p = .038), and an increase in fasting insulin (p = .043). Ghrelin levels before GH treatment were positively correlated with the changes in weight-SDS (fasting: r = .667, p = .05; AUC: r = .788, p = .012) and REE (fasting: r = .866, p = .005; AUC: r = .847, p = .008) following 4 months of GH therapy. Ghrelin AUC at 4 months was positively correlated with the changes in height-SDS (r = .741, p = .022) and fat-free-mass (r = .890, p = .001) at 12 months of GH treatment. CONCLUSIONS: The reduction in ghrelin and GLP-1 following GH treatment suggests a role for GH in appetite regulation. Fasting and meal-AUC ghrelin levels may serve as biomarkers for predicting short-term (4 months) changes in weight and longer term (12 months) changes in height following GH treatment. The mechanisms linking GH with changes in appetite-regulating hormones remain to be elucidated. ABBREVIATIONS: SDS: standard deviation score; REE: resting energy expenditure; SMT: standard meal test; AUC: area under the curve; ISS: idiopathic short stature; SGA: small for gestational age; FFM: fat-free-mass; FM: fat mass; EER: estimated energy requirements; DRI: dietary reference intakes; IQR: inter-quartile range.
Osteoprotegerin increases parallel to insulin resistance in obese adolescents.
Kotanidou EP, Kotanidis CP, Giza S … +5 more , Serbis A, Tsinopoulou VR, Karalazou P, Tzimagiorgis G, Galli-Tsinopoulou A
Endocr Res · 2019 · PMID 29877745 · Publisher ↗
UNLABELLED: Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL...
UNLABELLED: Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). MATERIAL AND METHODS: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. RESULTS: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents' subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. CONCLUSIONS: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation.
Correlation between thyroidal and peripheral blood total T cells, CD8 T cells, and CD8 T- regulatory cells and T-cell reactivity to calsequestrin and collagen XIII in patients with Graves' ophthalmopathy.
Al-Ansari F, Lahooti H, Stokes L … +2 more , Edirimanne S, Wall J
Endocr Res · 2018 Nov · PMID 29787340 · Publisher ↗
UNLABELLED: Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8 T cells and autoimmunity ag...
UNLABELLED: Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8 T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO. MATERIALS AND METHODS: Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method. RESULTS: We found a positive correlation between thyroidal CD8 T cells and CD8 T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves' Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII. CONCLUSIONS: Our observations provide further evidence for a possible role of thyroidal CD8 T cells, CD8 T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.
Endurance training alters YKL40, PERM1, and HSP70 skeletal muscle protein contents in men with type 2 diabetes mellitus.
Brinkmann C, Kuckertz A, Schiffer T … +3 more , Bloch W, Predel HG, Brixius K
Endocr Res · 2019 · PMID 29781744 · Publisher ↗
BACKGROUND: The fight against type 2 diabetes mellitus (T2DM) is tremendously challenging. This pilot study investigates whether endurance training (3 times per week for 3 months, moderate intensity) can change the skele...
BACKGROUND: The fight against type 2 diabetes mellitus (T2DM) is tremendously challenging. This pilot study investigates whether endurance training (3 times per week for 3 months, moderate intensity) can change the skeletal muscle protein contents of chitinase-3-like protein-1 (YKL40), peroxisome proliferator-activated receptor y coactivator-1 and estrogen-related receptor-induced regulator in muscle-1 (PERM1) and heat-shock protein-70 (HSP70), which have been discussed as novel therapeutically relevant targets. METHODS: Muscle biopsies were obtained from overweight/obese men with T2DM (n = 7, years = 63 ± 9) at T1 (6 weeks pre-training), T2 (1 week pre-training) and T3 (3 to 4 days post-training). The protein levels of YKL40, PERM1, and HSP70 were determined by immunohistochemistry. RESULTS: YKL40, PERM1, and HSP70 were significantly upregulated following endurance training (T2-T3: +103%, +61%, +89%, p = 0.012, p = 0.010, p = 0.028). There was a fiber type-specific distribution of HSP70 with increased protein contents in type I fibers. A significant change in the fiber type distribution with an increase in type I fibers and a decrease in type II fibers was observed post-training. There were no significant differences for YKL40, PERM1, HSP70, or the fiber type distribution between T1 and T2. CONCLUSION: The training-induced upregulation of YKL40, PERM1, and HSP70 could help manage the diabetic disease and reduce its complications.
Fibroblast growth factor 21, adiposity, and macronutrient balance in a healthy, pregnant population with overweight and obesity.
Sutton EF, Morrison CD, Stephens JM … +1 more , Redman LM
Endocr Res · 2018 Nov · PMID 29768065 · Full text
AIM OF THE STUDY: The regulation and actions of fibroblast growth factor 21 (FGF21) are responsive to energy status and macronutrient balance, and investigations of FGF21 in normal pregnancy, which could be informative f...
AIM OF THE STUDY: The regulation and actions of fibroblast growth factor 21 (FGF21) are responsive to energy status and macronutrient balance, and investigations of FGF21 in normal pregnancy, which could be informative for FGF21 biology, are seldom. The goal of our study was to examine FGF21 levels in a contemporary healthy, pregnant population. METHODS: We phenotyped 43 women with overweight and obesity during pregnancy for weight, body composition, and fasting blood. Serum FGF21 was measured during the first and third trimesters. Placentas were collected at delivery. RESULTS: Maternal FGF21 concentrations were positively correlated with body mass index and adiposity, but not lean mass or glucose homeostasis. FGF21 concentrations significantly increased from the first to third trimester of pregnancy (0.105 vs. 0.256 ng/mL, p < 0.0001). Changes in FGF21 concentrations across pregnancy were not associated with changes in body weight or composition but inversely with the change in fasting glucose. FGF21 mRNA levels in placenta were very low and do not likely contribute to FGF21 in the maternal circulation. CONCLUSIONS: FGF21 increases throughout pregnancy in our healthy cohort with overweight and obesity, independent of the placenta, and does not appear to be sensing the changes in energy balance (reflected in the change in maternal energy stores), but changes in macronutrient status. Thus, we propose FGF21 may be a potential signal of maternal nutrient status in pregnancy.
A new type of familial partial lipodystrophy: distinctive fat distribution and proteinuria.
Yurekli B, Ozdemir Kutbay N, Altay C … +5 more , Unlu SM, Sen S, Onay H, Atik T, Akinci B
Endocr Res · 2018 Nov · PMID 29733702 · Publisher ↗
PURPOSE: To describe an interesting subtype of familial partial lipodystrophy (FPLD). METHODS: The phenotype of this distinctive FPLD subtype was studied in three Turkish female siblings. RESULTS: Mutation testing was ne...
PURPOSE: To describe an interesting subtype of familial partial lipodystrophy (FPLD). METHODS: The phenotype of this distinctive FPLD subtype was studied in three Turkish female siblings. RESULTS: Mutation testing was negative for the genes associated with lipodystrophy syndromes. In MRI studies, fat loss was prominent in the posterior aspects of the proximal lower limbs, whilst some fat was preserved in the anterior, medial and lateral aspects. Remarkably, fat tissue was preserved in the distal part of the limbs. Local fat accumulation was observed in the mons pubis area. Asymmetrical fat loss was also remarkable in the upper extremities. All three patients had severe insulin resistance associated with diabetes mellitus, acanthosis nigricans, hypertriglyceridemia and hepatic steatosis. Abnormal amounts of proteinuria were detected in all three subjects. Renal biopsy showed mild tubular atrophy, interstitial fibrosis, irregular thickening and wrinkling of glomerular basal membranes, small areas of segmental sclerosis and pedicel effacement. CONCLUSIONS: We reported a form of FPLD characterized by a striking pattern of highly selective partial fat loss and proteinuria.
Age-associated increase of thyroid hormone receptor β gene promoter methylation coexists with decreased gene expression.
Pawlik-Pachucka E, Budzinska M, Wicik Z … +5 more , Domaszewska-Szostek A, Owczarz M, Roszkowska-Gancarz M, Gewartowska M, Puzianowska-Kuznicka M
Endocr Res · 2018 Nov · PMID 29733698 · Publisher ↗
PURPOSE: It is not established if healthy aging of the thyroid axis is associated with alterations other than changes in hormone secretion. METHODS: The expression of thyroid hormone receptor β gene (THRB) was analyzed i...
PURPOSE: It is not established if healthy aging of the thyroid axis is associated with alterations other than changes in hormone secretion. METHODS: The expression of thyroid hormone receptor β gene (THRB) was analyzed in peripheral blood mononuclear cells (PBMC) obtained from young, elderly, and long-lived individuals. The interaction between the 3'UTR of TRβ1 mRNA and selected miRNAs was measured using pmirGLO reporter vector. Methylation of the THRB CpG island was analyzed using methylation-sensitive restriction/RT-PCR and bisulfite sequencing methods. RESULTS: Old age was associated with a significantly lower amount of total TRβ mRNA (p = 0.033) and of TRβ1 mRNA (p = 0.02). Older age was also associated with significantly higher methylation of the THRB promoter (restriction/RT-PCR: p = 0.0023, bisulfite sequencing: p = 0.0004). Higher methylation corresponded to a lower expression of the THRB mRNA, but this correlation did not reach the level of significance. miR-26a interacted with two sites in the 3'UTR of the TRβ1 mRNA leading to the decrease of the reporter protein activity (p < 0.0001 and p = 0.0005), and miR-496 interacted with one of the two putative binding sites which also decreased the reporter protein activity (p < 0.0001). Analysis of the expression of miR-21, miR-26a, miR-146a, miR-181a, miR-221, and miR-496 showed that the expression of miR-26a was significantly decreased in old subjects (p = 0.017), while the levels of other miRNAs were unaffected. CONCLUSIONS: Age-related decrease of THRB expression in PBMC of elderly and long-lived humans might be, in part, a result of the increased methylation of its promoter, but is unrelated to the activity of the miRNAs analyzed here.
Skeletal response to treatment with teriparatide (TPD) after bisphosphonate in post-menopausal women with osteoporosis and a high prevalence of secondary risk factors in real-life setting of a metabolic bone clinic; effect of age and vitamin D status.
Mok J, Brown C, Moore AEB … +2 more , Min SS, Hampson G
Endocr Res · 2018 Aug · PMID 29652557 · Publisher ↗
PURPOSE: Teriparatide (TPD) is a skeletal anabolic agent used in patients with severe post-menopausal osteoporosis (PMO) and steroid-induced osteoporosis who are at hish risk of fracture. Predictors of therapeutic respon...
PURPOSE: Teriparatide (TPD) is a skeletal anabolic agent used in patients with severe post-menopausal osteoporosis (PMO) and steroid-induced osteoporosis who are at hish risk of fracture. Predictors of therapeutic response to teriparatide in real-life setting are not well characterised. We investigated potential factors associated with teriparatide response in post-menopausal women with established osteoporosis. METHODS: We carried out a retrospective survey of 48 women, aged 73.2 [7.5] years with severe osteoporosis and prevalent fractures treated with TPD according to the NICE criteria. BMD was measured at baseline, 6-12 and 18-24 months at the lumbar spine (LS), total hip (TH) and femoral neck (FN). Bone turnover markers, serum 25 (OH)vitamin D were determined at 3-12 and 12-24 months. RESULTS: BMD increased at 6-12 months (% change mean [SEM] 6.5 [1.1] p = 0.004) and 18-24 months (8.45 % [1.2] p<0.001) at the LS. A significant increase in BMD was observed at FN (3.1 [1.3] % p = 0.02). Changes in BMD at the TH was higher in patients younger than 73 years compared to older women (% change in BMD 4.13 [1.64] % v/s -1.7 [1.1] p = 0.007). Baseline 25 (OH) vitamin D correlated with change in P1NP at 3-12 months (r = 0.45 p = 0.049). CONCLUSIONS: TPD-induced changes in BMD at the TH appears may be dependent on age. Vitamin D status may influence the early anabolic effect to TPD. Our data suggest that these factors may be important considerations when initiating and optimising treatment with TPD, although further larger studies are needed to confirm these findings.
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