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Objective
Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions.
Methods
Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis.
Results
The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered.
Conclusion
Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.
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Faculty of Medicine, University of Latvia, Riga, Latvia
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The increasing prevalence of ‘diabesity’, a combination of type 2 diabetes and obesity, poses a significant global health challenge. Unhealthy lifestyle factors, including poor diet, sedentary behaviour, and high stress levels, combined with genetic and epigenetic factors, contribute to the diabesity epidemic. Diabesity leads to various significant complications such as cardiovascular diseases, stroke, and certain cancers. Incretin-based therapies, such as GLP-1 receptor agonists and dual hormone therapies, have shown promising results in improving glycaemic control and inducing weight loss. However, these therapies also come with certain disadvantages, including potential withdrawal effects. This review aims to provide insights into the cross-interactions of insulin, glucagon, and GLP-1, revealing the complex hormonal dynamics during fasting and postprandial states, impacting glucose homeostasis, energy expenditure, and other metabolic functions. Understanding these hormonal interactions may offer novel hypotheses in the development of ‘anti-diabesity’ treatment strategies. The article also explores the question of the antagonism of insulin and glucagon, providing insights into the potential synergy and hormonal overlaps between these hormones.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Aim
We investigated whether a high-intensity interval training (HIIT) protocol could restore beta-cell function in type 2 diabetes compared with sedentary obese and lean individuals.
Materials and methods
In patients with type 2 diabetes, and age-matched, glucose-tolerant obese and lean controls, we examined the effect of 8 weeks of supervised HIIT combining rowing and cycling on the acute (first-phase) and second-phase insulin responses, beta-cell function adjusted for insulin sensitivity (disposition index), and serum free fatty acid (FFA) levels using the Botnia clamp (1-h IVGTT followed by 3-h hyperinsulinemic–euglycemic clamp).
Results
At baseline, patients with type 2 diabetes had reduced insulin sensitivity (~40%), acute insulin secretion (~13-fold), and disposition index (>35-fold), whereas insulin-suppressed serum FFA was higher (⁓2.5-fold) compared with controls (all P < 0.05). The HIIT protocol increased insulin sensitivity in all groups (all P < 0.01). In patients with type 2 diabetes, this was accompanied by a large (>200%) but variable improvement in the disposition index (P < 0.05). Whereas insulin sensitivity improved to the degree seen in controls at baseline, the disposition index remained markedly lower in patients with type 2 diabetes after HIIT (all P < 0.001). In controls, HIIT increased the disposition index by ~20–30% (all P < 0.05). In all groups, the second-phase insulin responses and insulin-suppressed FFA levels were reduced in response to HIIT (all P < 0.05). No group differences were seen in these HIIT-induced responses.
Conclusion
HIIT combining rowing and cycling induced a large but variable increase in beta-cell function adjusted for insulin sensitivity in type 2 diabetes, but the disposition index remained severely impaired compared to controls, suggesting that this defect is less reversible in response to exercise training than insulin resistance.
Trial registration
ClinicalTrials.gov (NCT03500016).
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Chronic inflammation induced by obesity plays a crucial role in the pathogenesis of insulin resistance. The infiltration of macrophages into adipose tissues contributes to adipose tissue inflammation and insulin resistance. Kaempferol, a flavonoid present in various vegetables and fruits, has been shown to possess remarkable anti-inflammatory properties. In this study, we used leptin receptor-deficient obese mice (db/db) as an insulin-resistant model and investigated the effects of kaempferol treatment on obesity-induced insulin resistance. Our findings revealed that the administration of kaempferol (50 mg/kg/day, for 6 weeks) significantly reduced body weight, fat mass, and adipocyte size. Moreover, it effectively ameliorated abnormal glucose tolerance and insulin resistance in db/db mice. In the adipose tissue of obese mice treated with kaempferol, we observed a reduction in macrophage infiltration and a downregulation of mRNA expression of M1 marker genes TNF-α and IL-1β, accompanied by an upregulation of Arg1 and IL-10 mRNA expression. Additionally, kaempferol treatment significantly inhibited the STING/NLRP3 signaling pathway in adipose tissue. In vitro experiments, we further discovered that kaempferol treatment suppressed LPS-induced inflammation through the activation of NLRP3/caspase 1 signaling in RAW 264.7 macrophages. Our results suggest that kaempferol may effectively alleviate inflammation and insulin resistance in the adipose tissue of db/db mice by modulating the STING/NLRP3 signaling pathway.
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Objective
Hashimoto’s thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis.
Methods
Forty patients with Hashimoto’s thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months.
Results
After 6 months of a low-carbohydrate diet, patients with Hashimoto’s thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63–614.62) vs 89.45 (15.9–215.67); TgAb: 17.05 (1.47–81.64) vs 4.1 (0.51–19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto’s thyroiditis following a normal diet after 6 months (P < 0.05).
Conclusion
Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto’s thyroiditis.
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In this review, we discuss the definition, prevalence, and etiology of sporadic multiglandular disease (MGD), with an emphasis on its preoperative and intraoperative predictors. Primary hyperparathyroidism (PHPT) is the third-most common endocrine disorder, and multiglandular parathyroid disease (MGD) is a cause of PHPT. Hereditary MGD can be definitively diagnosed with detailed family history and genetic testing, whereas sporadic MGD presents a greater challenge in clinical practice, and parathyroidectomy for MGD is associated with a higher risk of surgical failure than single gland disease (SGD). Therefore, it is crucial to be able to predict the presence of sporadic MGD in a timely manner, either preoperatively or intraoperatively. Various predictive methods cannot accurately identify all cases of sporadic MGD, but they can greatly optimize the management of MGD diagnosis and treatment and optimize the cure rate. Future research will urge us to investigate more integrative predictive models as well as increase our understanding of MGD pathogenesis.
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Department of Medicine, Copenhagen University Hospital – Amager and Hvidovre, Hvidovre, Denmark
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Imperial College Healthcare NHS Trust, St Mary’s Hospital, London, UK
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Post-bariatric hypoglycaemia (PBH) is typically a post-prandial hypoglycaemia occurring about 2–4 h after eating in individuals who have undergone bariatric surgery. PBH develops relatively late after surgery and often after discharge from post-surgical follow-up by bariatric teams, leading to variability in diagnosis and management in non-specialist centres.
Aim
The overall aim was to improve and standardise clinical practice in the diagnosis and management of PBH. The objectives were: (1) to undertake an up-to-date review of the current literature; (2) to formulate practical and evidence-based guidance regarding the diagnosis and treatment of PBH; (3) to recommend future avenues for research in this condition.
Method
A scoping review was undertaken after an extensive literature search. A consensus on the guidance and confidence in the recommendations was reached by the steering group authors prior to review by key stakeholders.
Outcome
We make pragmatic recommendations for the practical diagnosis and management of PBH, including criteria for diagnosis and recognition, as well as recommendations for research areas that should be explored.
Plain English summary
Post-bariatric hypoglycaemia (PBH) is a condition that commonly affects people who have undergone weight loss surgery. In this condition, people develop low blood sugar occurring about 2–4 h after meals, leading to debilitating symptoms such as hunger, sweating, anxiety, palpitations and even blackouts and fainting. PBH is becoming more common as weight loss surgery is being taken up by more people to help with their weight and to help with diabetes. The condition often develops after the patient has been discharged from follow-up after their surgery, which can lead to inconsistent diagnosis and treatment in non-specialist healthcare centres. The lack of clear information and evidence in the existing scientific literature further contributes to the variation in care. To address this problem, the Society for Endocrinology has created new guidelines to help healthcare professionals accurately diagnose and manage this condition. The guidelines were developed with input from dietitians, surgeons and doctors specialising in weight loss, and hormone specialists.
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Background
The most important part of the follow-up of differentiated thyroid carcinoma (DTC) is the measurement of serum thyroglobulin (Tg). An increase of Tg levels indicates likely tumor recurrence. According to the guidelines of the European Society of Medical Oncology (ESMO), the follow-up should consist of serum Tg assays and a neck ultrasound, while the American Thyroid Association (ATA) recommends serum Tg assays, neck ultrasounds, and a diagnostic radioiodine whole-body scan (WBS) if non-stimulated Tg is greater than 10 ng/mL or if Tg is rising. This study questions the necessity of a diagnostic WBS in patients with low stimulated Tg levels during the initial follow-up.
Design
This study is a retrospective data analysis.
Methods
The data of 185 patients, who were in regular treatment and aftercare between 2015 and 2018 at the Department of Nuclear Medicine in Vienna, as well as the data of 185 patients who were treated in Tbilisi between 2015 and 2019, were analyzed.
Results
There was a highly significant relationship between low stimulated Tg levels (<0.5 ng/mL) and the outcome of the diagnostic WBS at the first follow-up (χ 2 = 14.7, P < 0.001). In total, 31 out of 370 patients (8.4%) had positive findings in the diagnostic WBS. Seventy-five of 370 patients (19.74%) had stimulated Tg levels >0.5 ng/mL.
Conclusion
Our data suggest that the first follow-up, 4–12 months after the initial therapy of DTC, including the measurement of basal and stimulated Tg levels and Tg antibody levels, does not mandate a diagnostic WBS on all patients.
Significance statement
In this study, we examined the still commonly used routine diagnostic radioiodine whole-body scan in the first follow-up of patients with differentiated thyroid carcinoma. We questioned the necessity of the scan in patients with low stimulated thyroglobulin levels. Therefore, we combined retrospective data from the University Hospital in Vienna and in Tbilisi to analyze 370 patients. We were able to demostrate a highly significant relationship between low stimulated thyroglobulin levels (<0.5 ng/mL) and the outcome of the diagnostic scan at the first follow-up (χ = 14.7, P < 0.001).
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Objective
The aim of this study was to investigate the relationship between weight-adjusted-waist index (WWI) and diabetic kidney disease in individuals afflicted with type 2 diabetes.
Methods
Comprehensive data were ascertained from the National Health and Nutrition Examination Survey in 2013–March 2020. Weighted univariate, multivariate logistic regression models, subgroup analyses and tests for interaction were performed. Additionally, we employed smooth curve fitting to assess linear correlations and the threshold effects were calculated by applying a binary linear regression model. Breakpoints are identified by a model with maximum likelihood ratio and a two-step recursive approach. Receiver operating characteristic curve (ROC) along with the area under the curve (AUC) value predict the capability of WWI and body mass index for diabetic kidney disease.
Results
A total of 10,661 individuals diagnosed with type 2 diabetes were included, and the overall prevalence of diabetic kidney disease was 20.74%. WWI exhibited a positive correlation with the likelihood of diabetic kidney disease in type 2 diabetes patients (OR: 1.17, 95% CI: 1.03–1.33). The results of subgroup analysis showed significant interaction for gender (P < 0.05). Among female patients, U-shaped correlations were observed with a breakpoint at 11.48. Additionally, weight-adjusted waist index (AUC = 0.664) proved to be a more effective predictor of diabetic kidney disease compared to body mass index (AUC = 0.555).
Conclusion
In patients with type 2 diabetes, increased weight-adjusted-waist index is implicated with an increased risk of diabetic kidney disease. WWI can be used as a new anthropometric index to predict diabetic kidney disease, and its predictive ability is stronger than body mass index.
National Institute of Endocrinology CI Parhon, Bucharest, Romania
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National Institute of Endocrinology CI Parhon, Bucharest, Romania
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National Institute of Endocrinology CI Parhon, Bucharest, Romania
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National Institute of Endocrinology CI Parhon, Bucharest, Romania
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Background
Pheochromocytomas (PHEOs) are rare catecholamine-secreting adrenal tumors. Approximately 60–90% of bilateral PHEOs are hereditary. We retrospectively analyzed the clinical characteristics of patients with bilateral PHEOs and the morbidity rate (malignancy, tumor recurrence and adrenal insufficiency (AI) rate) related to surgery technique and genetic status of the patients.
Results
Fourteen patients (12.5%, nine women, five men) had synchronous or metachronous bilateral PHEOs (out of 112 PHEO patients who underwent surgery between 1976 and 2021). The median age at diagnosis was 32 years (9–76) (three were children). Nine patients (64.2%) presented synchronous bilateral tumors, five (35.7%) contralateral metachronous tumors, 2–12 years after the first surgical intervention; three (21.4%) were metastatic. Median follow-up: 5 years (1–41), IQR 19 months. A total of 78.5% had a germline mutation (eight RET gene with MEN2A syndrome, three VHL syndrome, three not tested). Post-surgery recurrence was noted in 16.6% of patients (one with MEN2A syndrome and metastatic PHEOs, one with VHL syndrome), with similar rates after total adrenalectomy or cortical-sparing adrenal surgery. AI was avoided in 40% after cortical-sparing surgery.
Conclusion
Bilateral PHEOs are usually associated with genetic syndromes. The surgical technique for patients with hereditary bilateral PHEOs should be chosen based on a personalized approach, as they are at higher risk for developing new adrenal tumors requiring additional surgeries.
