Diabetes and Insulin Resistance Research Papers (original) (raw)

2025, Biology

This study aimed to understand how dietary curcumin influences metabolic abnormalities induced by a high-fat high-sugar diet (HFHSD) in aged female mice. We observed that curcumin effectively reduced body fat accumulation, steatosis of liver, and insulin resistance caused by a nutritional challenge, suggesting its potential in mitigating age-related metabolic disturbances. These findings highlight curcumin supplementation as a potential strategy to address metabolic issues associated with female aging.

2025, Jorjani Biomedicine Journal

Background: Obesity leads to neuronal apoptosis and cognitive impairment by increasing inflammation and oxidative stress. Although the beneficial role of exercise and antioxidant supplements have been reported separately, their interactive effect on neuronal apoptosis in obesity is still not well known. Therefore, this study aimed to investigate the effect of eight weeks of HIIT with Sp supplementation on apoptotic markers in the hippocampal tissue of high-fat diet-(HFD) induced obese rats.
Methods: In this experimental study, 24 obese male Sprague-Dawley rats (60% fat, 20% protein, and 20% carbohydrates) were randomly divided into four groups of six rats, including 1) HFD, 2) HFD+Sp, 3) HFD+HIIT, and 4) HFD+HIIT+Sp. Also, six healthy rats were selected as the HC group to investigate the effects of HFD on research variables. Subsequently, HIIT was performed for eight weeks, three sessions per week with an intensity of 80-110% of maximum running speed and 2-8 high-intensity intervals. Also, Sp supplement was taken orally during this period with a dose of 100 mg/kg/day. Bax and BCL-2 levels were measured with qRT-PCR method. One-way analysis of variance and Tukey's post-hoc tests were used for statistical analysis of data (p ≤0.05).
Results: In the HFD+HIIT and HFD+HIIT+Sp groups, Bax levels and Bax/BCL-2 ratio were lower and BCL-2 levels were higher than the HFD group (p=0.001). In the HFD+Sp group, BCL-2 levels were higher and Bax/BCL-2 ratios were lower than HFD group (p=0.008). Also, in the HFD+HIIT and HFD+HIIT+Sp groups, Bax levels and Bax/BCL ratio were lower and BCL-2 levels were higher than HFD+Sp group (p≤0.05). In addition, in the HFD+HIIT+Sp group, Bax levels were lower and BCL-2 levels were higher than in the HFD+HIIT group (p≤0.05).
Conclusion: It seems that although HIIT and Sp supplement separately have an anti-apoptotic effect, their interactive effect on inhibiting neuronal apoptosis in brain tissue in obesity conditions is more obvious than the effect of each one alone.

2025, Bioimpacts

The biological actions of oestrogen are mediated by the oestrogen receptor α or β (ERα or ERβ), which are members of a broad nuclear receptor superfamily. Numerous in vivo and in vitro studies have demonstrated that loss of circulating oestrogen modulated by classical ERα and ERβ led to rapid changes in pancreatic β-cell and islet function, GLUT4 expression, insulin sensitivity and glucose tolerance, dysfunctional lipid homeostasis, oxidative stress, and inflammatory cascades. Remarkably, 17β-oestradiol (E2) can completely reverse these effects. This review evaluates the current understanding of the protective role of classical ER in critical pathways and molecular mechanisms associated with insulin resistance and type 2 diabetes mellitus (T2DM). It also examines the effectiveness of menopausal hormone therapy (MHT) in reducing the risk of developing T2DM in menopausal women. Clinical trials have shown the protective effects of MHT on glucose metabolism, which may be useful to treat T2DM in perimenopausal women. However, there are concerns about E2's potential side effects of obesity and hyperlipidaemia in menopausal women. Further studies are warranted to gain understanding and find other oestrogen alternatives for treatment of insulin resistance and T2DM in postmenopausal women.

2025, Life Sciences

Endoplasmic reticulum (ER) is a crucial single membrane organelle that acts as a quality control system for cellular proteins as it is intricately involved in their synthesis, folding and trafficking to the respective targets. Type 2 diabetes is characterized by enhanced blood glucose level that promotes insulin resistance and hampers cellular glucose metabolism. Hyperglycemia provokes mitochondrial ROS production and glycation of proteins which exert a tremendous load on ER for conventional refolding of misfolded/unfolded and nascent proteins that perturb ER homeostasis resulting in apoptotic cell death. Impairment in ER functions is suspected to be through specific ER membrane-bound proteins known as Unfolded Protein Response (UPR) sensor proteins. Conformational changes in these proteins induce oligomerization and cross-autophosphorylation which facilitate processes required for the restoration of ER homeostatic imbalance. Multiple studies have reported the involvement of UPR mediated autophagy and apoptotic pathways in the progression of metabolic disorders including diabetes, cardiac ischemia/reperfusion injury and hypoxia-mediated cell death. In this review, the involvement of UPR pathways in the progression of diabetes associated complications have been addressed, which underscores molecular crosstalks during neuropathy, nephropathy, hepatic injury and retinopathy. A better understanding of these molecular interventions may reveal advanced therapeutic approaches for preventing diabetic comorbidities. The article also highlights the importance of phytochemicals that are emerging as novel ER stress inhibitors and are being explored for targeted interaction in preventing cell death responses during diabetes.

2025, Medical Laboratory Journal

Background: The ABO and Rh blood group systems have been associated with variations in disease susceptibility. This study aimed to assess the variability in blood parameters, including red cell parameters and metabolic parameters (Renal function, hepatic function, blood glucose, lipid profile, and thyroid function), by ABO and Rh blood grouping systems.
Methods: A secondary data analysis was conducted among patients who underwent a preventive health check-up at a private tertiary care hospital in Coimbatore, India. The laboratory database contained records of 62,808 adult participants who reported for master health check-ups between January 2017 and February 2024. Among these patients, those who reported for the first time were included.
Results: Blood grouping and typing data were available for 50,368 and 56,155 participants, respectively, with a mean age range of 52.6 to 53.0 years across all blood groups. The most prevalent blood group was O, followed by B, A, and AB, with a similar distribution across genders. The mean hemoglobin level was highest in the B group (13.7 ± 13.9 g/dl). MCH and MCV values were elevated in the A and O groups, while MCHC and ESR were higher in the B and AB groups. Renal and liver parameters mostly did not vary by blood group or Rh type, except for elevated urea levels in the A group and higher ALP levels in the O and Rh-positive groups. LDL and total cholesterol were highest in the A group, while HDL was highest in the AB group.
Conclusion: The results underscore the importance of considering blood group variations when interpreting blood parameters in clinical practice.

2025, Journal of Biotechnology Research

This paper attempts to review available pertinent scientific and medical literature that the current global epidemic of obesity and diabetes has increased simultaneously or contemporaneously with adverse metabolic events. There is widespread established evidence that the type of carbohydrate consumed is important in the development or prevention of insulin resistance, obesity, and the metabolic syndrome. There is scarcity of published data on the combined effects of interactions between micronutrients, carbohydrates and lipids. However, there are extensive data supporting the benefits of the effects of both carbohydrates and lipids on various mechanisms of energy balance and diseases. Adequate measure is necessary to control carbohydrate-lipid interactions as they impact on obesity and diabetes.

2025

The present study was carried out to evaluate alpha-glucosidase inhibitory activity of abraga chendhooram which is a Siddha drug being used to treat diabetes mellitus. The ingredient of abraga chendhooram includes biotite (K(Mg,Fe)3AlSi3O10(F,OH)2), Sesbania grandiflora, Calotropis gigantea and Momordica charantia. In-vitro alpha-glucosidase inhibitory assay was performed by standard procedure. Different concentrations of abraga chendhooram and miglitol (standard drug) were used. Abraga chendhooram exhibited a dose dependent alphaglucosidase inhibitory activity, but it was less than standard drug. Further studies are warranted to look other possible mechanisms for its antidiabetic claim and to assess its safety

2025, Mathews Journal of Diabetes and Obesity

Certain modifications or alterations concomitant with ageing include diminished glucose tolerance due to increased insulin resistance from receptor and/or post-receptor perturbations and decrement in pancreatic islet B-cell sensitivity to glucose. Insulin has effects on ageing and lifespan, and provides a mechanism for gene manipulations for people to have prolonged and healthier lives, and as preserved insulin sensitivity is associated with longevity. The insulin function is dependent on mechanisms which are determinants of its circulating abundance, secretion, clearance and sensitivity in its target tissues. Ageing enhances deranging impacts on these processes which debilitate insulin functionality, resulting in augmented risk for morbidity, untoward sequelae and mortality. Certain models of impaired insulin signaling are associated with prolonged longevity or resistance to lifethreatening factors, such as oxidative stress. Insulin and insulin signaling is associated with successful ageing and longevity. This entry enunciates the importance of insulin sensitivity versus secretibility as being critical to the clinical strategy in the treatment, lifestyle changes, early interventions and control of type 2 diabetes. Calorie restriction enhances lifespan in numerous species. Diet manipulation that affects the glucoseinsulin system ostensibly benefits lifespan and diminishes the incidence of ageing-related chronic diseases. During ageing, augmented circulating abundance of glucose and other reducing sugars secondary to agetriggered insulin resistance nonenzymatically reacts with proteins and nucleic acids to debilitate tissue elasticity. Adequate control of factors associated with risks for obesity, diabetes, cardiovascular disease, and other insulin and ageing sequelae can be retarded in the elderly with optimum sustenance of their lifestyles.

2025, International Journal of Diabetes

Insulin has effects on ageing and lifespan, and provides a mechanism for gene manipulations for people to have prolonged and healthier lives and as preserved insulin sensitivity is associated with longevity. The insulin function is dependent on mechanisms which are determinants of its circulating abundance, secretion, clearance and sensitivity in its target tissues. Ageing enhances deranging impacts on these processes which debilitate insulin functionality, resulting in augmented risk for morbidity, untoward sequelae and mortality. Certain models of impaired insulin signaling are associated with prolonged longevity or resistance to life-threatening factors, such as oxidative stress. Insulin and insulin signaling are associated with successful ageing and longevity. Calorie restriction enhances lifespan in numerous species. Adequate control of factors associated with risks for obesity, diabetes, cardiovascular disease, and other insulin and ageing sequelae can be retarded in the elderly with optimum sustenance of their lifestyles.

2025

High environmental and demographic factors. The level of endog may be a critical risk factor in hypertensive diseases effect on the endothelium and smooth muscle cells in the vascular wall, where they this study is (HTN between 2011 to 2012) at Karkuk Teaching Hospital/Karkuk governora Parameters measured Index BMI) in premenopausal women with HTN. The results of this study shows a total of 100 Premenopausal women with HT were involved in this study who were included as controls (n=100), Serum estradiol was significantly reduced in Premenopausal women with HT G1 when compared with controls (p < 0.05); a significant negative correlation was found between estradiol and HT were estradiol was negatively correlated with body mass index. The above results suggest importance of hormone therapy

2025, Austin Journal of Biotechnology & Bioengineering

Asx is a fat-soluble xanthophyll carotenoid, one of its most relevant properties is its antioxidant activity. Depending on the dose and environment, it participates in an adequate regulation of ROS/RNS at optimal levels, either directly scavenger or indirectly through the stimulation of “antioxidant” pathways such as NRF2. This regulation and interactions within the signaling pathways are studied here in order to find information that provides data to elucidate the effects that may influence the processes of obtaining IPC and the study of the effect of molecules that increase the efficiency of the cellular response during the trans differentiation process. We found that adding Asx to a cocktail of differentiation molecules to obtain IPC from DPSC increases the efficiency of insulin production, as well as the expression of important markers for the maturity and identity of pancreatic β-type cells (NGN3, PDX1, MAFA). It was also revealed that Asx favors the proper regulation of oxidative stress caused during the process of cellular trans differentiation of DPSC towards IPC, through the direct inactivation of ROS and the increase in the expression of NRF2 as well as the decrease of their principal inhibitor KEAP1, favoring the maturity of the IPC. These results suggest the potential use of Asx to deepen the knowledge of its interaction with other signaling pathways that favor the generation of IPC and other cells sensitive to oxidative stress, and thereby lay the foundations for a possible cell replacement therapy as in DM.

2024, Leibniz Online

Endocrine diseases convey far-reaching consequences for individual health, ranging from a reduced quality of life over an increased risk of serious secondary diseases to acutely lifethreatening conditions. In recent decades, endocrinology has faced considerable progress, for example in molecular biological research, assay technology and therapeutic options. However, serious gaps remain open that prevent the derivation of a unified endocrine theory and the development of a predictive, preventive, personalised and participatory medicine (P4 medicine). As a possible brick for a solution, we have developed the universal non-linear "MiMe-NoCoDI" platform for formulating cybernetic models of endocrine networks. It allows the development of mathematical "high fidelity" descriptions as well as the implementation of simulations on digital and analog computers. In addition, it provides the basis for new diagnostic procedures in the form of calculated biomarkers (structure parameter inference approach-SPINA) and approaches to therapy planning (set point optimisation and targeting-SPOT), which are superior to previous methods of clinical endocrinology. This progress paves the way for a future precision endocrinology with applications ranging from vertically integrated physiology over individually planned patient treatment to macro-strategies in the public healthcare system.

2024, Jorjani Biomedicine Journal

Background: Insufficiency of omentin-1 and 25-hydroxyvitamin D serum levels is associated with obesity, which is known as a threat to health. Therefore, the aim of the present study was to examine the effect of eight weeks of Pilates exercise on the serum levels of 25-hydroxyvitamin D, omentin-1, and lipid profile in overweight women.
Methods: In the present clinical study, 26 young overweight women were divided (block randomization method) into the Pilates exercise (PT, n= 13) and control group (CG, n= 13). The PT group performed Pilates exercises for eight weeks (three 60-min sessions per week). The movements started from simple and then increased in intensity and complexity based on the Borg index. The CG group had no training session for eight weeks. Blood samples were taken before the first training session and 48 hours after the last training session. Analysis of covariance was used for between-group comparisons.
Results: Findings showed a significant increase in the serum levels of 25-hydroxyvitamin D (p=0.008, SD= 4.78±0.12 ng/ml, effect size= 0.243) and HDL-C (p=0.04, SD= 6.44±1.05 mg/dl, effect size= 0.168), but a significant decrease in HOMA-IR (p=0.001, SD= 1.54±0.09, effect size=0.199), cholesterol (p=0.001, SD= 16.72±3.24 mg/dl, effect size= 0.326), and triglyceride (p=0.001, SD= 2.46±0.07 mg/dl, effect size= 0.209), and no significant change in omentin-1 (p=0.65, SD= 3.01±0.08 ng/ml) and LDL-C (p=0.58, SD= 2.46±0.07 mg/dl) serum levels in the PT group compared to the CG group.
Conclusion: It seems that this type of exercise training may play a critical role in controlling the health parameters and physiological status of the overweight women by having positive effects on serum levels of 25-hydroxyvitamin D and lipid profile, which are affected by body composition, weight, and fat.

2024, NILES Journal forGeriatric and Gerontology/NILES Journal for Geriatric and Gerontology

Background: Cryolipolysis is a non-invasive procedure designed to target subcutaneous adipose tissue in obese patients that has emerged as a potential therapeutic approach for modifying insulin resistance(IR) in T2DM individuals. Aim: to evaluate the efficacy of cryolipolysis in reducing IR among patients diagnosed with T2DM patients exhibiting abdominal obesity. Research design: Randomized, two-group pre-post-test, controlled design. Patients and Methods: sixty females with T2DM exhibiting abdominal obesity were enrolled. The participants were randomly and equally divided either in Group A (cryolipolysis in combination with aerobic exercise), or in Group B (aerobic exercise therapy alone) for three months. All variables measured Pre-and post-study, including (HbA1c, FBG, fasting insulin level, HOMA testing). Results: there was statistically significant decrease in all measured parameters of groups A and B post-treatment compared with pre-treatment with a significant increase in water content, muscle mass, and a significant decrease in fat content and visceral fat of groups A and B post-treatment compared with pre treatment. Following the intervention, Group A significantly reduced fat content and visceral fat compared to Group B. However, there were no significant differences in waist-hip ratio, water content, and muscle mass between the two groups post-treatment. Significant improvements in metabolic parameters were observed in Group A compared to Group B. Group A showed a significant decrease in FBG, insulin levels, HbA1c, and HOMA-IR. Conclusions: Cryoliopolysis is one of the effective strategies for addressing localized fat deposits that enhance glucose absorption and favorable changes in HbA1c and HOMA-IR, that improve insulin sensitivity.

2024, Turkiye Klinikleri Journal of Cardiology

Đnsülin Rezistansı (IR), hipertansif hastalardaki sol ventrikül hipertrofisi ve disfonksiyonunun en önemli belirleyici olarak gösterilmektedir. ĐR'nın hipertansif hastalarda, bir çok hastalığın gelişimine zemin hazırlaması nedeni ile, antihipertansif tedavide sadece kan basıncının düzenlenmesi değil, var olan ĐR'nında engellemesi gereği ön plana çıkmıştır. Amacımız bir AT 1 reseptör antagonisti olan valsartan'ın, ĐR saptanan hipertansif vakalarda ĐR üzerine etkisini göstermekti. Materyel ve Metod: Fırat Üniversitesi Tıp Fakültesi Kardiyoloji AD'da, hipertansif ve insülin tolerans testi ile ĐR saptanan 32 hastaya (ortalama yaş 56.21±10); 80 mg/gün dozunda valsartan 8 hafta süre ile verildi. Sonuç: Sekiz haftanın sonunda, valsartan verilen hastalar da sistolik, diyastolik ve ortalama kan basıncı anlamlı şekilde azalırken (178.66±18.33mmHg'dan 146.66±16.47 mmHg'a; 104.66±10.08mmHg'dan 88±7.14mmHg'a; 128.64±11.19mmHg'dan 107.87±8.36mmHg'a) (p=0.0001), KĐTT değeri %2.46 ± 0.78'dan, %1.92 ± 0.67'a düştü (p=0.001). Bu düşme insülin direncinde anlamlı bir artış olarak yorumlandı. Sonuçda, AT1 reseptör antagonisti olan valsartan, kan basıncı kontrolünde etkili bulunurken, insülin rezistansı üzerine olumsuz etkisi gözlendi.

2024, Journal of Pharmacy & Pharmacognosy Research

Context: Polycystic ovary syndrome (PCOS) and thyroid are the most common endocrine disorders affecting women of childbearing age, causing anovulation and infertility. There is an increased prevalence of thyroid dysfunction reported among... more

2024, MAT JOURNALS

Diabetes mellitus, a chronic metabolic disorder characterized by elevated blood glucose levels, has reached epidemic proportions worldwide. This review provides a comprehensive assessment of the current landscape of diabetes therapies and outlines future prospects for improving the management and treatment of this condition. The current scenario highlights a multifaceted approach to diabetes management, with a focus on lifestyle interventions, oral antidiabetic drugs, insulin therapy, and emerging technologies like continuous glucose monitoring and closed-loop systems. While these approaches have significantly improved the lives of people with diabetes, several challenges persist. These include medication adherence, hypoglycemia risk, and the financial burden of diabetes care. Novel therapies, such as GLP-1 receptor agonists and SGLT-2 inhibitors, have shown promise in addressing these challenges by providing better glucose control, cardiovascular benefits, and weight reduction. The future prospects for diabetes therapies are exciting, with ongoing research into cell-based therapies, including pancreatic islet transplantation and stem cell-derived beta cells. Personalized medicine approaches, driven by genetics and artificial intelligence, hold the potential to optimize treatment regimens and predict individual responses to various therapies. Furthermore, advancements in telemedicine and digital health technologies will enhance patient selfmanagement and remote monitoring.

2024

2024, Advanced Biomedical Research

Background: Hypercholesterolemia that can increase stress oxidative has destructive effects on brain functions. Vitamin E is a powerful antioxidant and its effects on decrement of oxidative stress in the diseases such as Alzheimer's and hypercholesterolemia are demonstrated. The aim of this study was evaluation of the effects of vitamin E on the level of neuronal apoptosis in granular layer of dentate gyrus in the rabbits that fed with high-cholesterol diet. Materials and Methods: Male New Zealand white rabbits were divided into the control, the Vitamin E (50 mg/kg; gavage), the high-cholesterol diet (containing 2% cholesterol), and the high-cholesterol dietvitamin E groups. Serum levels of cholesterol, LDL, and HDL, before and after the regimen for 6 weeks, were measured. Then, the rabbits for immunohistochemical staining (TUNEL Test) and evaluation of neuronal apoptosis in dentate gyrus of hippocampal formation were anesthetized and brains were dissected. Results: Results showed that after the regimens, serum levels of cholesterol, LDL, and HDL in the cholesterol receiving groups were increased significantly (P < 0.05). Histological results demonstrated that neuronal apoptosis in the dentate gyrus of the high-cholesterol diet group was increased significantly (P < 0.05) comparing to the control group; however, vitamin E decreased apoptosis as there wasn't any significant differences between the high-cholesterol diet-vitamin E and control groups. Conclusions: Present results showed that consumption of high-cholesterol diets through hypercholesterolemia and its complication can induce neuronal death in hippocampus and probable resulting cognition disorders; however, vitamin E has neuroprotective effects and prevents neuronal apoptosis significantly.

2024, Bangabandhu Sheikh Mujib Medical College Journal

COVID-19 and diabetes mellitus have a dynamic and bidirectional relationship. Diabetes is a risk factor for COVID19. Diabetes mellitus is linked to hypercoagulability, inflammation, hyperglycemia, and other conditions (obesity, hypertension, cardiovascular disease, chronic kidney disease). Hyperglycemia may worsen SARS-CoV-2 infection. As a result of direct pancreatic damage caused by COVID-19, the stress response is triggered response to infection (including cytokine storm), including the use of hyperglycemic prescription medications such as corticosteroids for severe COVID-19, new-onset hyperglycemia and diabetes have been linked to the virus, as well as rapidly deteriorating blood glucose control in pre-existing diabetes. Insulin resistance and decreased b-cell secretion cause hyperglycemia. Challenges still remain in establishing the connection between COVID-19 and diabetes, whilst the pandemic progresses. Bangabandhu Sheikh Mujib Med. Coll. J. 2022;1(2):99-103

2024, Pharmacological Reviews

G protein-coupled receptors (GPCRs) continue to be important discovery targets for the treatment of type 2 diabetes mellitus (T2DM). Many GPCRs are directly involved in the development of insulin resistance and b-cell dysfunction, and in the etiology of inflammation that can lead to obesityinduced T2DM. This review summarizes the current literature describing a number of well-validated GPCR targets, but also outlines several new and promising targets for drug discovery. We highlight the importance of understanding the role of these receptors in the disease pathology, and their basic pharmacology, which will pave the way to the development of novel pharmacological probes that will enable these targets to fulfill their promise for the treatment of these metabolic disorders.

2024, European journal of nutrition

reactive oxygen species were elevated in the neonatal hearts of IDM/W compared with that seen in the offspring born from non-diabetic control animals. Similarly, the receptor of AGEs (RAGE) mRNA levels, reactive oxygen species and the amount of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) mRNA were higher in the hearts from the IDM/W when compared to that observed in the hearts of offspring born to non-diabetic animals. These deleterious effects of gestational diabetes were significantly decreased in the offspring of diabetic mothers receiving EPA supplementation. Conclusions Taken together, our data suggest that the EPA in fish oil may improve the impaired signalling and the excessive protein glycation in the cardiac muscles of infants exposed to intrauterine hyperglycemia.

2024, book chapter

In the early 1940's, the US Food and Drug Administration (FDA) approved marketing of synthetic estrogens; non steroidal Diethylstilbestrol (DES) and Ethinylestradiol (EE) as well as Conjugated Equine Estrogens (CEEs) for medical purposes. High Dose Estrogen (HDE) therapy using DES and EE was introduced into the treatment of advanced breast cancer in postmenopausal women. Oral contraceptives (OCs) comprising EE were developed in the early 1960s and EE became a standard component of near all combined forms of contraceptive pills. Use of exclusively synthetic estrogens for both HDE therapy of breast cancer and contraception ensured a possibility for clear evaluations of the risks and benefits of synthetic hormone use. HDE therapy for breast cancer induced serious toxicity affecting near all organs, suggesting a genome-wide disturbance in cellular mechanisms. OCs comprising low doses of EE which may induce arterial and venous thromboembolic events and show ambiguous correlations with cancer risk at different sites by means of altered regulation of Estrogen Receptors [ERs]. In contrast, for menopausal Hormone Replacement Therapy [HRT] both synthetic and natural estrogens extracted from biological samples were prescribed. Among postmenopausal women, the use of estrogens with different origin and even their combinations with synthetic progestins resulted in a chaos of quite controversial clinical experiences concerning the risks for arterial and venous thromboembolism and for cancers of breasts and endometrium. Analysis of the effects of specific HRT types in postmenopausal women justified that horse urine derived CEE without synthetic progestin is a highly beneficial formula against breast cancer, coronary heart disease and bone loss. The presented study reveals that an 80 year period of synthetic hormone prescription may be blamed for the misbelief that ERs exposed to elevated endogenous estrogen concentrations may be deregulated and drive cancer promoting changes. In tumors constitutively upregulating ER alpha expression, recent patents disclose amplifying ESR1 mutations.

2024, Annals of Internal Medicine

Background: Hashimoto disease is a chronic autoimmune thyroiditis. Despite adequate hormone substitution, some patients have persistent symptoms that may be the result of immunologic pathophysiology. Objective: To determine whether thyroidectomy improves symptoms in patients with Hashimoto thyroiditis who still have symptoms despite having normal thyroid gland function while receiving medical therapy. Design: Randomized trial. (ClinicalTrials.gov: NCT02319538) Setting: Secondary care hospital in Norway. Patients: 150 patients aged 18 to 79 years with persistent Hashimoto-related symptoms despite euthyroid status while receiving hormone replacement therapy and with serum antithyroid peroxidase (anti-TPO) antibody titers greater than 1000 IU/mL. Intervention: Total thyroidectomy or medical management with hormone substitution to secure euthyroid status in both groups. Measurements: The primary outcome was general health score on the Short Form-36 Health Survey (SF-36) at 18 months. Secondary outcomes were adverse effects of surgery, the other 7 SF-36 subscores, fatigue questionnaire scores, and serum anti-TPO antibody titers at 6, 12, and 18 months. Results: During follow-up, only the surgical group demonstrated improvement: Mean general health score increased from 38 to 64 points, for a between-group difference of 29 points (95% CI, 22 to 35 points) at 18 months. Fatigue score decreased from 23 to 14 points, for a between-group difference of 9.3 points (CI, 7.4 to 11.2 points). Chronic fatigue frequency decreased from 82% to 35%, for a between-group difference of 39 percentage points (CI, 23 to 53 percentage points). Median serum anti-TPO antibody titers decreased from 2232 to 152 IU/mL, for a between-group difference of 1148 IU/mL (CI, 1080 to 1304 IU/mL). In multivariable regression analyses, the adjusted treatment effects remained similar to the unadjusted effects. Limitation: Results are applicable only to a subgroup of patients with Hashimoto disease, and follow-up was limited to 18 months. Conclusion: Total thyroidectomy improved health-related quality of life and fatigue, whereas medical therapy did not. This improvement, along with concomitant elimination of serum anti-TPO antibodies, may elucidate disease mechanisms.

2024, Revista de la Facultad de Ciencias Médicas de Córdoba

Introduction. Levothyroxine (LT4) has been considered the standard of care for treatment of hypothyroidism. Current recommendations suggest a LT4 dose between 1.6–1.8 µg/kg/day. The aim of this study was to evaluate the LT4 dose for adult patients with primary hypothyroidism of different etiologies who reached euthyroidism. Methods. A cross-sectional study was performed from the retrospective review of the charts of patients with primary hypothyroidism in treatment with LT4. Subjects were classified according to TSH level in overtreated (TSH < 0.4 µIU/ml), euthyroid (TSH 0.40-4.20), and undertreated (TSH >4.2) and according to the etiology of hypothyroidism. A stepwise logistic regression model was performed to evaluate the variables associated with TSH<0.4 µIU/ml. Results. 955 patients were included. 75.13% of the patients had an adequate LT4 replacement. LT4 dose to achieve euthyroidism was higher in patients with a history of radioiodine therapy (1.92 μg/kg) and thyroid ...

2024, IJIRAE:: AM Publications,India

Diabetes is a serious complaint that affects the maturity of the population. Now a days its play a major role on human life. Imbalance in insulin processing by the body which leads to varieties of disorder. The main aim of this work is to make an early prediction of diabetes more precisely by using Auto Machine Learning Tools. Auto Machine learning Tools provide better results in diabetes detection by constructing models from patient datasets. This model automates the training, tuning, and deploying machine learning models. Recent developments in Machine learning show that Automatic Diabetic detection using Random Forest Algorithm models can be very beneficial in such problems. The proposed Random forest model predicts the diabetes at early stage. We use Decision tree classifier to predict whether a patient has diabetes based on diagnostic measurements. Performance and accuracy of the applied algorithm is discusses and compared.

2024, Nature genetics

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P…

2024, Annals of Human Genetics

SummaryGenome‐wide association (GWA) studies have identified around 20 common genetic variants influencing the risk of type 2 diabetes (T2D). Likewise, a number of variants have been associated with diabetes‐related quantitative glycaemic traits, but to date the overlap between these genes and variants has been low. The majority of genetic studies have focused on fasting plasma glucose levels; however, this measure is highly variable. We have conducted a GWA meta‐analysis of glycated haemoglobin (HbA1C) levels within three healthy nondiabetic populations. This phenotype provides an estimate of mean glucose levels over 2–3 months and is a more stable predictor of future diabetes risk. Participants were from three isolated populations: the Orkney Isles in the north of Scotland, the Dalmatian islands of Vis, and Korčula in Croatia (total of 1782 nondiabetic subjects). Association was tested in each population and results combined by meta‐analysis. The strongest association was with the...

2024, Journal of diabetes

Cinnamomum cassia (Family: Lauraceae) is an Ayurvedic medicinal plant used traditionally for the treatment of a number of diseases, including diabetes. The hypoglycemic effect of this plant has been established in vivo. However, the effects of cinnamic acid, isolated from C. cassia, on the insulin signaling cascade in an in vitro model have not been elucidated. Hence, the aim of the present study was to evaluate the anti-diabetic effect of cinnamic acid on glucose transport by L6 myotubes. The mechanism of action of cinnamic acid was determined using specific targets in the insulin signaling pathway, including protein tyrosine phosphatase (PTP) 1B, phosphatidylinositol 3-kinase (PI3-K) and the glucose transporter GLUT4. After differentiation of myoblast to myotubes, the cells were serum deprived for 5 h and then treated with 1 ng/mL cinnamic acid and 50 μmol/L rosiglitazone for 18 h and 100 nmol/L insulin for 20 min for gene expression studies. Expression of GLUT4 mRNA was increased...

2024, American journal of human genetics

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyse...

2024, Srpski arhiv za celokupno lekarstvo

Introduction/Objective. Hypothyroidism is a common disease and treatment with levothyroxine (LT4) is effective. However, variations in management are frequent. The aim of this study was to identify practices and attitudes of Serbian physicians relating to the treatment of hypothyroidism. Methods. An anonymized questionnaire was distributed electronically to members of the Serbian Thyroid Society, Serbian Association of Endocrine Surgeons, and Section for Endocrinology of the Serbian Medical Society. Results. Out of 170 invitations, 99 responses were received. LT4 was the first choice for the treatment of hypothyroidism in 90% of patients. After starting LT4 replacement therapy most respondents would recheck thyroid-stimulating hormone (TSH) in 4?6 weeks (n = 51, 62%) and in eight weeks (n = 29, 35%). In total, 61% of respondents (n = 60) indicated that they would consider treating euthyroid patients with LT4, the commonest indication being female infertility with high levels of thyr...

2024, Medical Laboratory Journal

Background: Omentin-1 plays an important role in insulin function. Despite numerous studies, the effect of interval training on this adipokine is still vague. This study aimed to elucidate the effect of high-intensity interval training (HIIT) on serum glucose, insulin, insulin resistance (IR), omentin-1 serum levels, and gene expression in the visceral adipose tissue in type 2 diabetic (T2D) rats.
Methods: In an experimental study, 20 male rats (8-10 weeks, weight: 250-270 g) were randomly divided into 2 groups: diabetic control (N=10) and diabetic training (N=10). The training protocol was 30 minutes of HIIT (1-min run, 2-min rest) performed 5 days a week for 4 weeks. Fasting blood glucose, insulin resistance, omentin-1 serum level, and gene expression were measured in the visceral fat 48 hours after the last exercise for both groups.
Results: The HIIT resulted in lower serum glucose and insulin resistance (P = 0.001), higher serum omentin-1 levels (P = 0.001), and higher visceral fat gene expression (P = 0.004) in the training group compared to the control group.
Conclusion: Lower serum glucose and insulin resistance and higher omentin-1 serum levels and gene expression in the training group can prove the effectiveness of HIIT training in T2D, although further research is required.

2024, Archives of Iranian Medicine

The coronavirus infection is an evolving pandemic with high morbidity and mortality, especially in people with comorbidities. The case fatality rate (CFR) is 9.2% in the presence of diabetes, while it is 1.4% in those without any comorbidity. Diabetes is a prevalent disease globally; hence, healthcare professionals are highly concerned about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic progression. Current evidence does not support higher incidence of coronavirus disease 2019 (COVID-19) in people with diabetes (PWD). However, people with diabetes are considered high risk for developing complications. Optimal metabolic control is a challenging concept, especially in the presence of an acute and severe respiratory viral infection. In this consensus, we considered the challenging issues in management of patients with diabetes during the COVID-19 pandemic. The consensus covers various aspects of outpatient as well as inpatient care based on the current evidence.

2024, American Journal of Health Promotion

2024, Diabetes, Metabolic Syndrome and Obesity

Diabetes Mellitus (DM) is a significant global health concern, with Type 2 DM (T2DM) being highly prevalent. Glucagon-Like Peptide 1 receptor agonists (GLP-1RA), such as Danuglipron, offer potential benefits in T2DM management. This meta-analysis examines the safety and efficacy of Danuglipron, focusing on adverse outcomes and glycemic parameters. Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane Library for RCTs involving Danuglipron till August 2023, following PRISMA guidelines. The Cochrane risk-of-bias tool was used for quality assessment. Adverse outcomes (diarrhea, nausea, vomiting, headache, decreased appetite, dyspepsia, dizziness) and glycemic parameters like changes in HbA1C, fasting plasma glucose (FPG), and body weight were analyzed.

2024, Current Developments in Nutrition

Objectives Investigate the impact of dietary linoleic acid (LA) on whole-body energy metabolism, fatty acid uptake, oxylipin metabolites, and energy production machinery in skeletal muscle. Methods Mice were fed modified AIN-93 M diets containing 6% wt of LA or palmitic acid (PA) for 5 weeks. To address energy balance, grip strength, blood glucose, and body composition were measured weekly and indirect calorimetry was performed after 4.5 weeks of diet. To address skeletal muscle architecture, cross-sectional area was quantified in quadriceps. To determine the effect of LA diet on skeletal muscle lipids, fatty acid composition was measured in quadriceps using GC. Targeted lipidomics using LC-MS/MS was utilized to measure LA-derived oxylipins in mitochondria isolated from gastrocnemius. Results No difference in food intake, body weight, blood glucose, or body composition were observed between diet groups. Mice fed the LA diet exhibited higher heat production and lower respiratory exch...

2024, Journal of Clinical and Basic Research (JCBR)

Background: Insulin resistance plays a significant role in the pathogenesis of type 2 diabetes mellitus (T2DM). Irisin, an adipo-myokine, is found to increase insulin sensitivity by adaptive thermogenesis. Various studies have found that endocrine and exocrine functions of the pancreas are affected in T2DM. This case-control study with 180 participants aimed to find any association of serum irisin with insulin resistance and pancreatic profile in newly diagnosed T2DM.
Methods: Fasting blood sugar (FBS) and pancreatic profile were measured by Auto Analyzer, serum insulin by chemiluminescence assay, serum irisin by Enzyme-Linked Immunoassay (ELISA) kit, and insulin resistance by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
Results: Significantly lower irisin levels were observed in T2DM patients compared to healthy individuals (p =0.001*). A positive correlation was found between serum irisin and insulin resistance in T2DM patients, whereas a negative correlation was found in healthy controls. In some cases, serum amylase and lipase positively correlated with irisin, whereas a negative association was observed in controls.
Conclusion: This study concludes a protective role for irisin in combating insulin resistance and improving pancreatic function in T2DM, but more extensive studies are required to prove it.

2024, Journal of Drug Targeting

Diabetes is on the rise across the globe affecting more than 463 million people and crucially increasing morbidities of diabetes-associated diseases. Urgent and immense actions are needed to improve diabetes prevention and treatment. Regarding the correlation of diabetes with many associated diseases, inhibition of the disease progression is more crucial than controlling symptoms. Currently, anti-diabetic drugs are accompanied by undesirable side-effects and target confined types of biomolecules. Thus, extensive research is demanding to identify novel disease mechanisms and molecular targets as probable candidates for effective treatment of diabetes. This review discusses the conventional molecule targets that have been applied for their therapeutic rationale in treatment of diabetes. Further, the emerging and prospective molecular targets for the future focus of library screenings are presented.

2024, Middle East Current Psychiatry

Background Diabetes patients are at risk of developing mental health comorbidities such as depression and poor quality of sleep. These conditions can affect diabetic management, including glycemic and plasma lipid control to optimal levels. We investigated the association between diabetic control and the presence of depression and poor sleep quality in type 2 diabetes (T2DM) patients at Sunyani Government hospital in Ghana. Using a case–control design, we recruited 200 T2DM patients and compared them to 160 non-diabetic controls. The presence of depression was assessed using the Patient Health Questionnaire (PHQ)-9 and sleep quality using the Pittsburgh Sleep Quality Instrument (PSQI). Blood samples were collected to measure glycated hemoglobin (HbA1c) levels and plasma lipid profiles. Poor glycemic control was defined as HbA1c > 7%, depression as PHQ-9 score > 9 and poor sleep quality as PSQI score ≥ 5. Results T2DM patients had a higher prevalence of depression (31.5% vs 10....

2024, Expert Opinion on Investigational Drugs

Introduction: This manuscript describes 21 drug targets in the area of diabetes and related conditions that were discontinued in 2015. Areas covered: The material for this paper was obtained by contacting biopharmaceutical companies, reviewing their pipelines, press releases and annual reports. Additionally, the authors searched clinicaltrials.gov, PubMed and general Internet search engines. Majority of the compounds were in early stages of the development. Expert opinion: Business reasons for termination of the drug projects emerge more and more frequently over the years. Safety signals usually appear early in the development and are often associated with novel drugs. 2015 medicines with inadequate efficacy were unable to compete with existing approved members of the class they represented. List of Abbreviations 11β-HSD1-11β-hydroxysteroid dehydrogenase type ACC-acetyl-CoA carboxylase BIP-basal insulin peglispro CCR-CC Chemokine Receptor DPP-4-dipeptidyl peptidase-4 EMA-European medicines agency FDA-food and drug administration GR-glucagon receptor GLP-1-glucagon-like peptide-1 HbA1c-hemoglobin A1c Article Highlights • Due to national differences in the regulatory requirements for drug approval, it is challenging to develop a drug that can be concurrently approved in multiple countries. • The key reasons for the termination of drug projects are: lack of safety and/or efficacy, business decisions and/or strategic reevaluation. • Basal insulin peglispro was, perhaps, the largest anti-diabetes drug project terminated in 2015. • The risk for termination is very low for new members of existing classes. This has resulted in five glucagon-like peptide-1receptor agonists, four dipeptidyl peptidase-4 inhibitors, three sodium/glucose cotransporter 2 inhibitors and four different types of insulin glargine currently on the market. • For capital efficiency it is critical to identify a dug project that carries a high risk of imminent failure as early in the development as possible. • Opportunities for anti-diabetes drug development include an easy to take regimen that could reduce HbA1c without compromising safety, preserve/improve β cell function, and produce clinically significant cardiovascular risk reduction and weight loss. • Development of an oral glucagon-like peptide-1 receptor agonist would further advance therapeutic and commercial success of the class.

2024, Diabetologia

Aims/hypothesis MODY is believed to be caused by at least 13 different genes. Five rare mutations at the BLK locus, including only one non-synonymous p.A71T variant, were reported to segregate with diabetes in three MODY families. The p.A71T mutation was shown to abolish the enhancing effect of BLK on insulin content and secretion from pancreatic beta cell lines. Here, we reassessed the contribution of BLK to MODY and tested the effect of BLK-p.A71T on type 2 diabetes risk and variations in related traits. Methods BLK was sequenced in 64 unelucidated MODY samples. The BLK-p.A71T variant was genotyped in a Electronic supplementary material The online version of this article

2024, IOSR Journal of Pharmacy (IOSRPHR)

There is a debate about the relation between ghrelin and insulin. Many researchers have found low ghrelin level in diabetic patients while others claim that no correlation between them. Thus further investigations are needed to clarify the precise role of ghrelin in the development and/ or treatment of diabetes. To date and up to our knowledge, this is the first study to be conducted on Emirati people in the United Arab Emirates (UAE) to explore the relationship between ghrelin concentration and type 2 diabetes. This research aimed for better understanding about the role of ghrelin hormone in the pathogenesis process of diabetes disease, in an attempt to help patients who find it difficult to control their diabetes by studying the relation between serum total ghrelin levels; insulin and insulin resistance in patients with type 2 diabetes mellitus in the UAE and relate them to the glycemic condition. A cross sectional study was conducted at Rashid Centre for Diabetes and Research (RCDR) in Ajman, UAE. Thirty patients were selected from the outpatient clinic at RCDR and fifteen healthy controls were included in this study. The Blood sample was collected from each participant and analyzed for HbA1c, insulin, glucose and total ghrelin level. Ghrelin level was measured using the enzyme-linked immunosorbent assay (ELISA) technique. The results of this study showed that mean ghrelin level was low in both insulin-resistant and noninsulin resistant diabetic patients as compared to the control group. In conclusion, low ghrelin level is associated with poor diabetes control and bad prognosis parameters in type 2 diabetic patients.

2024, Paediatrics and Child Health

BACK TO TABLE OF CONTENTS have been a consistent problem in the United States and the concern has led to a call for population-based screening. The CPSP study has shown that the experience of Canadian families affected by fragile X-related disorders is in many ways similar to American families, and that an improved approach to recognizing and diagnosing FXS would be of benefit.

2024, Medical Hypotheses

Primary hypothyroidism can affect lipid metabolism, cardiovascular (CV) function, and overall patients' quality of life (QoL). Decrease in serum nitric oxide (NO) levels could promote the atherosclerosis acceleration in hypothyroid patients. Our hypothesis is that serum NO level is altered in hypothyroidism; more specifically, we hypothesize that the early vascular changes that can be observed in hypothyroidism could be due to these alterations and that serum NO levels are associated with lipid levels in female patients diagnosed with subclinical hypothyroidism (SCH) or clinical hypothyroidism (CH). Furthermore, since serum NO level is an early marker of atherosclerosis and related CV disorders, which are commonly present and follow hypothyreosis and greatly contribute to overall QoL, we further hypothesized that NO level would correlate with Thyroid Symptom Questionnaire (TSQ) and General Health Questionnaire 12 (GHQ12) scores in hypothyroid patients. A collaterally of our hypothesis was that levothyroxine (LT4) treatment would affect serum NO levels as well as TSQ and GHQ12 scores. Therefore, we have analyzed lipid profile, the level of NO and QoL scores in female patients diagnosed with SCH and CH in order to determine the correlation between NO and generic and thyroid disease symptoms in treatment naïve SCH and CH patients and after LT4 treatment and laboratory euthyroidism achievement. As a consequence of our hypothesis is that measurement of serum NO level in SCH and CH patients may be an innovative way to improve LT4 treatment efficacy. This assumption could have a practical significance for future investigations regarding the management of hypothyroidism treatment protocols in current guidelines.

2024, Frontiers in Endocrinology

2023, International Journal of Molecular Sciences

We previously reported that glucokinase undergoes ubiquitination and subsequent degradation, a process mediated by cereblon, particularly in the presence of uridine diphosphate glucose (UDP-glucose). In this context, we hereby present evidence showcasing the resilience of variant glucokinase proteins of maturity-onset diabetes of the young type 2 (MODY2) against degradation and, concomitantly, their influence on insulin secretion, both in cell lines and in the afflicted MODY2 patient. Hence, glucose-1-phodphate promotes UDP-glucose production by UDP-glucose pyrophosphorylase 2; consequently, UDP-glucose-dependent glucokinase degradation may occur during fasting. Next, we analyzed glucokinase variant proteins from MODY2 or persistent hyperinsulinemic hypoglycemia in infancy (PHHI). Among the eleven MODY2 glucokinase-mutated proteins tested, those with a lower glucose-binding affinity exhibited resistance to UDP-glucose-dependent degradation. Conversely, the glucokinaseA456V-mutated p...

2023, Molecular and Cellular Endocrinology

Mifepristone is the only FDA-approved drug for glycaemia control in patients with Cushing's syndrome and type 2 diabetes. Mifepristone also has beneficial effects in animal models of diabetes and patients with antipsychotic treatment-induced obesity. However, the mechanisms through which Mifepristone produces its beneficial effects are not completely elucidated. Purpose: To determine the effects of mifepristone on insulin-stimulated glucose uptake on a model of L6 rat-derived skeletal muscle cells. Results: Mifepristone enhanced insulin-dependent glucose uptake, GLUT4 translocation to the plasma membrane and Akt Ser 473 phosphorylation in L6 myotubes. In addition, mifepristone reduced oxygen consumption and ATP levels and increased AMPK Thr 172 phosphorylation. The knockdown of AMPK prevented the effects of mifepristone on insulin response. Conclusions: Mifepristone enhanced insulin-stimulated glucose uptake through a mechanism that involves a decrease in mitochondrial function and AMPK activation in skeletal muscle cells.

2023, Frontiers in Endocrinology

Levothyroxine (LT4) is used to treat frequently encountered endocrinopathies such as thyroid diseases. It is regularly used in clinical (overt) hypothyroidism cases and subclinical (latent) hypothyroidism cases in the last decade. Suppressive LT4 therapy is also part of the medical regimen used to manage thyroid malignancies after a thyroidectomy. LT4 treatment possesses dual effects: substituting new-onset thyroid hormone deficiency and suppressing the local and distant malignancy spreading in cancer. It is the practice to administer LT4 in less-than-high suppressive doses for growth control of thyroid nodules and goiter, even in patients with preserved thyroid function. Despite its approved safety for clinical use, LT4 can sometimes induce side-effects, more often recorded with patients under treatment with LT4 suppressive doses than in unintentionally LT4-overdosed patients. Cardiac arrhythmias and the deterioration of osteoporosis are the most frequently documented side-effects of LT4 therapy. It also lowers the threshold for the onset or aggravation of cardiac arrhythmias for patients with pre-existing heart diseases. To improve the quality of life in LT4-substituted patients, clinicians often prescribe higher doses of LT4 to reach low normal TSH levels to achieve cellular euthyroidism. In such circumstances, the risk of cardiac arrhythmias, particularly atrial fibrillation, increases, and the combined use of LT4 and triiodothyronine further complicates such risk. This review summarizes the relevant available data related to LT4 suppressive treatment and the associated risk of cardiac arrhythmia.

2023, Circulation: Cardiovascular Genetics