Background: Postsurgical hypoparathyroidism (hypoPT) is associated with hypocalcemia and musculoskeletal complaints, yet its longterm impact on muscle function and quality of life remains poorly defined. This study aimed to evaluate muscle function, physical performance, and quality of life in patients with long-standing postsurgical hypoPT, in comparison with individuals with hypothyroidism (hypoT) and healthy controls. Methods: The study included 90 participants: 30 with postsurgical hypoparathyroidism and hypothyroidism (hypoPT + T), 30 with postsurgical hypothyroidism alone (hypoT), and 30 healthy controls. Muscle strength was evaluated using BIODEX concentric isokinetic dynamometry and handgrip testing. Functional performance was assessed with the timed up and go (TUG) and repeated chair stand (RCS) tests. Body composition was measured by bioimpedance analysis, and quality of life was evaluated using the short form questionnaire-36 version 2 (SF-36v2) and World Health Organization Five Welfare Index questionnaire (WHO-5) questionnaires. Results: Fat-free mass (FFM) was lower in the hypoPT + T group compared with controls (P < 0.01), although objective muscle strength did not differ significantly between groups. HypoPT + T patients exhibited prolonged TUG and RCS times and significantly lower SF-36v2 physical function scores (P < 0.01) compared with both hypoT patients and controls. WHO-5 scores were also reduced in the hypoPT + T group (P < 0.01), indicating impaired well-being independent of hypoT. Conclusions: Long-standing postsurgical hypoPT is associated with impaired functional performance and reduced quality of life, despite preserved objective muscle strength. These findings highlight the need for management strategies that address patient-reported outcomes and physical function, beyond conventional biochemical control.
Background: Imeglimin is a novel drug shown to improve mitochondrial function in patients with diabetes. This study was undertaken to evaluate the efficacy and safety of imeglimin in patients with poorly controlled type 2 diabetes. The effect of aging on the efficacy and safety of this drug was also evaluated. Methods: Imeglimin (2,000 mg/kg) was administered for 3 months to 52 patients. HemoglobinA1c (HbA1c) and other blood biochemical parameters were measured before and after the 3-month treatment period. Regression analysis was performed to determine the influence of age on the effects of the drug on these parameters. Results: Significant reduction of HbA1c and serum lipids were noted after the treatment. Regression analysis to determine the influence of age on relevant biochemical parameters in patients receiving imeglimin revealed that the biochemical effects of this drug on the serum levels of the hepatic function parameters (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (gamma-GTP)) and the serum uric acid level were influenced by interactions between the patient's age and the pre-treatment baseline levels of the parameters. Older patients with higher baseline levels of these parameters demonstrated greater reduction in hepatic biomarkers following treatment with imeglimin. Conclusions: This study confirmed imeglimin as a useful drug for individuals with type 2 diabetes who exhibit poor glycemia control. The effects of imeglimin in reducing the serum levels of hepatic function parameters were reinforced by aging, indicating that imeglimin is a particularly useful drug for patients with type 2 diabetes who are elderly and/or have hepatopathy.
Background: Hyperthyroidism is a disorder characterized by excessive thyroid hormone production. Methimazole is widely considered the first-line treatment due to its efficacy and favorable safety profile. However, there is limited contemporary local data on its clinical outcomes and adverse effects in Saudi Arabia. The aim of the study was to evaluate the efficacy and adverse effect profile of methimazole in adult patients with hyperthyroidism across varying treatment durations. Methods: This retrospective case-crossover study was conducted at King Abdullah Specialized Children's Hospital (KASCH). A total of 277 adult patients diagnosed with hyperthyroidism and treated with methimazole between January 2015, and December 2022 were included. Data were collected through chart review and analyzed using SAS version 9.4. A P value < 0.05 was considered statistically significant. Results: The majority of patients were female (70.4%) and had Graves' disease (71.5%). Treatment duration ranged from less than 6 months to more than 24 months. Gastrointestinal adverse effects, particularly sore throat, were significantly associated with longer treatment duration (P = 0.0067). Other adverse effects included dermatological reactions (30% rash), musculoskeletal symptoms (18.1% arthralgia), and hematological abnormalities (16.2% leukopenia), none of which showed significant variation across treatment durations. Older age was significantly associated with increased rates of anemia (P = 0.0340) and thrombocytopenia (P = 0.0019). Biochemical response was achieved in the majority of patients, with normalization of thyroid-stimulating hormone (TSH) in 73.7% and thyroxine (T4) in 55.5% of cases; however, a substantial proportion demonstrated low T4 levels post-treatment, suggesting potential overtreatment. Conclusions: Methimazole is an effective and generally well-tolerated treatment for hyperthyroidism. However, prolonged therapy and older age are associated with an increased risk of adverse effects. These findings highlight the importance of individualized dose titration and regular monitoring to optimize treatment outcomes and minimize complications.
Background: Low-grade inflammation is believed to be an integral component and key marker of obesity and metabolic syndrome. Among various plant sources, the common bean (Phaseolus vulgaris) is a promising source of bioactive peptides, which could be effective in mitigating the negative effects of obesity. Methods: Using an enzyme-linked immunosorbent assay procedure, we evaluated the relative levels of hypoxia inducible factor 1 subunit alpha (HIF-1 alpha), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 1 beta (IL-1(3), tumor necrosis factor alpha (TNF-alpha), and resistin in the serum, visceral adipose tissue, liver, and kidneys of obese rats that either consumed P. vulgaris husk-derived peptides as a dietary supplement or did not. Results: In the serum of obese rats, the results revealed increased levels of all assessed cytokines (except IL-8 and TNF-alpha), mainly resistin, IL-6, and IL-1(3. In adipose tissue, the main changes were observed in the levels of resistin, IL-6, and TNF-alpha. In the liver and kidneys, alterations were primarily noted in the levels of HIF-1 alpha and IL-8. Conclusions: These cytokine profile patterns are indicative of the development of low-grade inflammation, insulin resistance, metabolic dysfunction-associated steatotic liver disease, and chronic kidney disease, which are inherent in obesity. At the same time, in animals that consumed peptides, cytokine levels were slightly above or at control levels, indicating the effectiveness of common bean husk peptides against obesity-induced low-grade inflammation.
Background: Although thyroid dysfunction has been increasingly reported in coronavirus disease 2019 (COVID-19), the mechanisms linking severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to thyroid hormonal disturbances remain incompletely understood. The study aimed to examine the relationship between inflammatory status and thyroid function in patients with active COVID-19 and in post-COVID individuals, compared with healthy individuals. Methods: An observational study with a cross-sectional analytical approach was conducted in 101 participants allocated into three groups: patients with active COVID-19 (group 1, n = 33), individuals with thyroid dysfunction following recovery from COVID-19 (group 2, n = 35), and a non-infected reference group (group 3, n = 33). Thyroid parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin (Tg), and thyroid peroxidase (TPO); selected cytokines, including interleukin-17A (IL-17A), interleukin-10 (IL-10), interleukin-7 (IL-7), and interferon-gamma (IFN-gamma); and markers related to hypoxia and antioxidant defense, including hypoxia-inducible factor 1-alpha (HIF-1 alpha) and nuclear factor erythroid 2-related factor 2 (NFE2L2), were assessed. Results: Significant between-group differences were observed for FT3 and TSH, with the lowest FT3 levels detected in the active COVID-19 group. Reduced FT3 was the most frequent abnormality in group 1, identified in 36.4% of patients, supporting a pattern consistent with euthyroid sick syndrome. TSH levels were significantly lower in group 1 than in group 3, while FT3 levels differed significantly between group 1 and both group 2 and group 3. HIF-1 alpha and NFE2L2 levels were highest in active COVID-19, indicating marked intracellular hypoxia together with activation of the antioxidant defense response. Receiver operating characteristic analysis showed good discriminatory performance of HIF-1 alpha for distinguishing active COVID-19 from the reference group (area under the curve = 0.771). Post-COVID patients showed the lowest median levels of IL-17A, IL-10, IL-7, and IFN-gamma, together with a high frequency of autoimmune thyroid disorders, most commonly Hashimoto's thyroiditis, present in 65.7% of patients. Conclusion: SARS-CoV-2 infection appears to induce transient thyroid hormonal alterations primarily through inflammatory and hypoxia-related mechanisms. These findings support the concept of virus-induced euthyroid sick syndrome during acute infection and highlight the potential for post-infectious thyroid dysfunction.
Background: This study aimed to comprehensively examine the effects of participation in a dietary intervention program on body composition and multiple hematological and biochemical markers in middle-aged and older women, particularly identifying the biomarkers that fluctuate in conjunction with changes in body composition. Methods: A 6-month dietary intervention program was conducted involving 33 middle-aged and older women (mean age 60.9 +/- 11.0 years, mean body mass index (BMI) 24.8 +/- 3.2 kg/m2). The body composition and nonfasting blood parameters were measured before and after the intervention. In this study, pre-or post-intervention changes and correlated changes in body composition were compared with blood parameters. Results: Participation in the dietary program led to significant reductions in body weight, BMI, body fat mass, body fat percentage, and waist circumference. The blood parameters showing significant decreases were white blood cell count, red blood cell count, aspartate aminotransferase, alanine aminotransferase, and cholinesterase. The change in body fat mass (Delta body fat mass) was positively correlated with the change in cholinesterase (Delta cholinesterase, r = 0.483). Multiple regression analysis identified Delta cholinesterase ((3 = 0.505) as an independent explanatory variable for Delta body fat mass. In addition, Delta cystatin C ((3 = 0.500) was considered an independent explanatory variable for the change in waist circumference (Delta waist circumference). Conclusions: The findings of this study indicate that cholinesterase and cystatin C may capture fluctuations in body composition earlier than conventional inflammatory markers. Consequently, they may be useful, simple, and objective indicators for evaluating the effectiveness of lifestyle interventions.
Background: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age and a major cause of anovulatory infertility. L-carnitine, a naturally occurring compound involved in energy metabolism and mitochondrial function, has gained attention for its potential role in enhancing ovarian function and improving reproductive outcomes. However, evidence regarding its efficacy during controlled ovarian stimulation remains limited and inconsistent. Methods: A comprehensive literature search was conducted across multiple electronic databases from inception to May 2025 to identify eligible randomized controlled trials (RCTs) evaluating L-carnitine supplementation compared with placebo in women with PCOS undergoing controlled ovarian stimulation. Data were extracted and analyzed using RevMan software. Primary outcomes included ovulation rate and clinical pregnancy rate; secondary outcomes were endometrial thickness and number of mature follicles. Results: Six RCTs comprising 485 participants met the inclusion criteria. Pooled analysis demonstrated that L-carnitine supplementation significantly improved ovulation and clinical pregnancy rates compared with placebo. Additionally, women receiving L-carnitine ex- hibited greater endometrial thickness and a higher number of mature follicles than those in the control group. Conclusions: L-carnitine supplementation during controlled ovarian stimulation appears to enhance reproductive outcomes in women with PCOS by improving ovulation, endometrial receptivity, and follicular development. These findings suggest that L-carnitine may serve as a valuable adjunct therapy in fertility treatment protocols for women with PCOS.
Background: Primary hyperparathyroidism (PHPT) is an important but under-recognized cause of nephrolithiasis. Despite clinical guidelines recommending biochemical screening for PHPT in stone-forming patients, especially those with hypercalcemia, screening and referral patterns remain inconsistent in routine practice. This study aimed to evaluate adherence to PHPT screening recommendations among adult stone-forming patients and to determine the prevalence and characteristics of confirmed PHPT cases in a tertiary Saudi center. Methods: A retrospective cohort study was conducted at King Abdulaziz Medical City (KAMC), Riyadh, including adult Saudi patients diagnosed with nephrolithiasis between January 2019 and December 2023. Data were extracted from the BestCare electronic health record system. Patients were classified according to serum calcium status and parathyroid hormone (PTH) testing. PHPT was defined as persistent hypercalcemia with inappropriately elevated PTH after exclusion of secondary causes. Statistical analysis was performed using SPSS version 26. Results: A total of 1,229 patients were included (800 males, 429 females). Females had a significantly higher body mass index (BMI) (P < 0.001) and were more likely to have kidney stones >= 10 mm (P = 0.004), while males had significantly higher creatinine levels (P < 0.001) and more ureteral stones (P < 0.001). PTH screening was performed more frequently in females (53.2%) than males (46.8%) (P < 0.001). Although PHPT was diagnosed more frequently in females, the gender difference in PHPT prevalence was not statistically significant (P = 0.336). Referral to endocrinology was significantly more common among those diagnosed with PHPT (P = 0.046), yet overall referral rates remained low. Conclusion: There is significant under-screening for PHPT among patients with nephrolithiasis, particularly among hypercalcemic individuals. Gender-based disparities in evaluation and referral patterns were observed. These findings emphasize the need for improved clinician awareness and systematic screening protocols to enhance early detection and management of PHPT in stone-forming patients.
Background: Diabetic peripheral neuropathy (DPN) is a prevalent, severe diabetic consequence. Exploring relationship between biomarker levels and DPN may help improve understanding disease mechanisms and support future biomarker-oriented research. Meanwhile, fibroblast growth factor 1 (FGF1) and heat shock protein 27 (HSP27) indicated nerve protection; whereas, semaphorin3A (Sema3A) and nerve filament light chain (NFL) indicated damage to a nerve. This study was designed to assess the association between biomarker levels and occurrence of DPN. Methods: A case-control study comprised 45 DPN patients diagnosed by nerve conduction studies (NCS), 48 diabetic without neuropathy (DWN) patients, and 45 healthy controls. The participants' ages ranged from 35 to 60 years. Serum FGF1, HSP27, Sema3A, and NFL concentrations were measured using sandwich and competitive enzyme linked immunosorbent assay (ELISA) techniques. Results: DPN group showed elevation in HSP27 and Sema3A levels relative to DWN group (P = 0.016 and P = 0.027, respectively). The receiver operating characteristic (ROC) curve showed the area under the curve (AUC) values between DPN and DWN groups, which were 0.469 for FGF1, 0.746 for HSP27, 0.783 for Sema3A, and 0.625 for NFL. Besides, the results indicate that there is an association between FGF1, Sem3A and neuropathy (beta = -0.010, P < 0.001 for FGF1; beta = 3.007, P <= 0.001 for Sema3A), and a significant elevation was found in age and duration of injury with disease (beta = 0.129, P < 0.001 for age; beta = 0.589, P < 0.001 for duration). Conclusion: The results indicate that HSP27 and Sema3A are linked to DPN and show a capacity to differentiate between DPN and DWN patients. A notable correlation is observed between age, duration, and disease progression. Further studies are needed.
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder initiated by insulin resistance, leading to compensatory hyperinsulinemia, beta-cell exhaustion, and chronic hyperglycemia. It is a major global health burden associated with macrovascular and microvascular complications. Dysregulation of the renin-angiotensin system (RAS), Antioxidant pathway, inflammation, and vitamin D signaling interact in a self-perpetuating metabolic loop driving disease progression. Hepatic insulin resistance plays a central role, while glucotoxic pathways distinguish T2DM from obesity. This review aims to examine the molecular cross-talk among the RAS, antioxidant pathway, inflammation, and vitamin D signaling pathways in T2DM pathogenesis. It seeks to clarify how their interactions drive insulin resistance, beta-cell dysfunction, and complications, thereby supporting the development of more precise, mechanism-based therapeutic strategies. The RAS plays a central role in T2DM through overactivation of the angiotensin-converting enzyme/angiotensin II/angiotensin II receptor type 1 (ACE/Ang II/AT1R) axis, promoting insulin resistance, beta-cell apoptosis, oxidative stress (OS), inflammation, and vascular damage, while the ACE2/Ang-(1-7)/Mas axis offers protective effects. Ang II-induced ROS production disrupts antioxidant defenses and accelerates glucotoxicity. Chronic low-grade inflammation, marked by increased interleukin-6 (IL-6) and reduced interleukin-10 (IL-10), further worsens metabolic dysfunction. Vitamin D receptor (VDR) signaling counteracts these effects by suppressing renin, reducing Ang II activity, enhancing antioxidant enzymes, and modulating inflammation. The liver serves as a key site where these pathways converge. Therapeutic strategies-including ACE inhibitors, angiotensin II receptor blockers (ARBs), GLP-1 receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, antioxidants, and vitamin D-target these interconnected mechanisms, with responses influenced by disease stage and sex differences. T2DM develops through interconnected dysregulation of four key pathways: the RAS, OS-antioxidant imbalance, chronic inflammation, and vitamin D/VDR signaling. These pathways interact to promote insulin resistance, beta-cell dysfunction, and vascular complications, driving progression from prediabetes to overt disease. Therapeutic strategies targeting these mechanisms-including RAS inhibitors, antioxidant-based interventions, metformin, and vitamin D supplementation-offer complementary benefits but have limitations and potential adverse effects. Treatment responses may vary by biological factors such as sex and disease stage, highlighting the need for well-designed clinical trials to enable precise, mechanism-based management.
Background: The established detrimental effects of subclinical hypothyroidism (SCH) on the cardiovascular system have been well-documented; however, the association between SCH and cardio-ankle vascular index (CAVI) remains inconclusive. Methods: A retrospective, cross-sectional study was conducted to assess the association between SCH and CAVI. CAVI measurements were obtained using the VaSera VS-1000 vascular screening system. Multivariate logistic regression analysis was conducted to identify independent predictors of elevated CAVI. Results: The study included 247 subjects diagnosed with SCH and 1,749 age-and gender-matched control group. Individuals with SCH demonstrated lower basal metabolic rates, higher body weight and fat levels, as well as increased blood lipids and high-sensitivity C-reactive protein (hsCRP) levels. Additionally, individuals with SCH showed elevated CAVI values. CAVI showed a positive correlation with higher levels of thyroid-stimulating hormone (TSH) levels and a negative correlation with free triiodothyronine (FT3) levels, with no statistically significant correlation to free thyroxine (FT4) levels. Logistic regression analysis identified advanced age and hypertension as major independent risk factors associated with elevated CAVI. SCH and overweight were identified as independent risk factors for elevated CAVI. Furthermore, hyperlipidemia characterized by high total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and apolipoprotein B (apoB) is also correlated with an elevated risk of CAVI. Conclusions: This study offers epidemiological evidence supporting a correlation between elevated TSH and an increased risk of high CAVI in individuals with SCH. Individuals with SCH and elevated TSH levels appear to be at increased risk of arterial stiffness, suggesting a potential link between thyroid function and early vascular alterations.
Background: Obesity is a major public health issue caused by an abnormal increase in adipose tissue and is linked to increased insulin resistance and type 2 diabetes. Diabetes is a metabolic condition characterized by high glucose levels that is caused by insulin deficiency and alterations in insulin action mechanisms. Many of the genes associated with obesity are expressed in the central nervous system. Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor, has a single-nucleotide polymorphism (SNP), rs4684677, which is associated with insulin resistance and metabolic syndrome. Adipose tissue secretes hormones known as adipokines, which include resistin and adiponectin, encoded by the ADIPOQ gene. SNPs in the RETN gene (rs1862513) have been linked to obesity and diabetes. Adiponectin is a cytokine generated from adipose tissue, and its polymorphism (rs2241766) increases the incidence of type 2 diabetes. Ghrelin binds to its receptor and promotes the expression of neuropeptide Y (NPY), thereby increasing food intake. NPY (rs16147) polymorphism has been linked to diabetes and obesity. The melanocortin 4 receptor (MC4R) is a regulator of energy balance and appetite. MC4R (rs17782313) polymorphism was associated with an increased risk of obesity. Methods: Our study included 99 obese with diabetes and 99 non-obese patients with diabetes. RETN (rs1862513), GHRL (rs4684677), MC4R (rs17782313), NPY (rs16147), and ADIPOQ (rs2241766) genes were genotyped using real-time polymerase chain reaction. Results: As a result, the RETN, MC4R, and NPY polymorphisms showed statistically significant differences in genotype/allele distributions between groups. Conclusions: In conclusion, by representing data from the Turkish population for the first time, this study offers fresh insights and provides a unique perspective on the impact of the indicated genes on obesity, thereby contributing to the understanding of a hitherto unstudied ethnic group.
Acromegaly is a rare chronic endocrine disorder caused by excessive secretion of growth hormone (GH), usually from a pituitary adenoma, leading to characteristic somatic changes and multiple systemic complications. A substantial proportion of patients with acromegaly develop endocrine comorbidities, most notably impaired glucose metabolism and diabetes mellitus, due to GH-induced insulin resistance and beta-cell dysfunction. We present a clinical case of a 37-year-old male, referred for diagnostic clarification in a specialized endocrine clinic due to an enlarged thyroid gland and distinct acromegaloid features, prompting further investigation. Biochemical testing confirmed the presence of hypersomatotropism, and magnetic resonance imaging (MRI) identified a pituitary macroadenoma, measuring 21 & times; 13 mm. The patient underwent successful transsphenoidal biportal adenomectomy. Given the positive family history-a sister previously diagnosed with acromegaly, genetic testing was initiated. The patient tested negative for common syndromic causes, including familial isolated pituitary adenomas (FIPA), multiple endocrine neoplasia type 1 and 4 (MEN1, MEN4). Whole exome sequencing revealed pathogenic variants in genes MT-ND5 and MT-ND4, associated with a genetic form of diabetes mellitus. While hyperglycemia may resolve in some patients after successful treatment of acromegaly, persistent diabetes mellitus was observed in our case, likely due to the alterations inMT-ND5 and MT-ND4 genes. This clinical case provides initial evidence suggesting a novel link between familial forms of acromegaly and mitochondrial diabetes, offering new perspectives on shared genetic pathways.
We present the case of a 24-year-old African-American woman who noticed an anterior cervical mass during self-examination 2 weeks prior. Although she experienced no compressive, local or systemic symptoms, she expressed aesthetic concerns. Ultrasound findings identified a single left thyroid nodule, cystic and with internal septations and eccentric solid areas (EU-TIRADS 2) measuring 22.9 mm in maximum diameter, warranting fine-needle aspiration (FNA) due to aesthetic concerns. Initial blood tests showed no inflammatory markers or thyroid axis abnormalities. Despite recommendations for therapeutic intervention, the patient declined the procedure after observing a reduction in the mass. Four months later, follow-up ultrasound revealed complete resorption of the nodule. This report reviews evidence on thyroid nodule disappearance/resorption, emphasizing the importance of individualized, patient-centered care.
Background: Tirzepatide, a dual glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist, effectively reduces weight and improves metabolic parameters in obesity. Its effects on thyroid function, particularly thyroid-stimulating hormone (TSH) and free thyroxine (fT4), in euthyroid patients are unclear. This study aimed to evaluate changes in thyroid function, along with anthropometric, glycemic, and lipid profiles in euthyroid adults with obesity after 1 month of tirzepatide therapy. Methods: In this single-center retrospective observational study, 38 euthyroid adults with obesity were evaluated after initiation of tirzepatide therapy. Exclusion criteria included prior thyroid disease or use of medications affecting thyroid function. Baseline and 1-month followup measurements included TSH, fT4, and selected metabolic parameters. Statistical analyses were performed using suitable parametric or non-parametric methods for within-group comparisons, with categorical variables analyzed via Chi-square tests. Correlation analyses were conducted to evaluate associations between variables. A P value of less than 0.05 was considered statistically significant. Results: After 1 month of therapy, body weight, body mass index, fasting blood glucose, low-density lipoprotein, triglycerides, and total cholesterol decreased significantly. TSH decreased and fT4 increased significantly, with both remaining within the euthyroid range. Conclusions: In this short-term retrospective analysis, tirzepatide therapy in euthyroid adults with obesity was associated with modest but statistically significant changes in TSH and fT4 levels, both of which remained within the established euthyroid reference range. These findings represent early biochemical observations and should be considered hypothesis-generating. Further prospective studies with longer follow up are required to determine the clinical relevance of these changes.
This review briefly summarizes imeglimin's discovery, development, properties, mechanisms, and core findings on efficacy and safety from major studies. Imeglimin is a first-in-class, orally available tetrahydro-triazine that was designed from the metformin scaffold to address the pathophysiological defects of f-cell dysfunction and insulin resistance in type 2 diabetes mellitus (T2DM). Pre-clinical work shows that imeglimin partially inhibits mitochondrial complex I, corrects complex III deficiency, lowers reactive oxygen species, and boosts NAD+-dependentATP generation. This enhances glucose-stimulated insulin secretion and preserves f-cell mass. Additionally, the compound augments endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) release and improves hepatic and skeletal-muscle insulin signaling, resulting in combined insulinotropic and insulin-sensitizing actions. Pharmacokinetic studies reveal rapid absorption, an elimination half-life of approximately 9-12 h, high oral bioavailability, and predominantly renal excretion with no clinically meaningful interactions with metformin or sitagliptin. In phase 2 and 3 trials, the optimized regimen of 1,000 mg twice daily consistently lowers glycated hemoglobin (HbA1c) by approximately 0.8-0.9% as monotherapy and provides additional reductions of 0.4-0.6% when combined with metformin or insulin. It maintains placebo-like tolerability and a minimal risk of hypoglycemia. Long-term data confirm durable glycemic efficacy, a neutral cardiovascular profile with no QT/QTc prolongation, and predominantly mild gastrointestinal adverse events. Real-world evidence supports sustained HbA1c lowering, modest weight loss, and lipid improvements over 12 months, independent of age, sex, body mass index, or renal function. Multivariate and cluster analyses suggest that older age, therapy-naive status, and lower baseline HbA1c predict a more pronounced response, highlighting the importance of patient stratification. Research on imeglimin for T2DM is constrained by small sample sizes, mainly Japanese data, lack of cardiovascular outcome trials, limited comparisons with other antidiabetic drugs, and insufficient long-term safety information. More studies are needed to clarify its efficacy and safety profiles.
Background: The aim of the study was to determine the prevalence of diabetic peripheral neuropathy and vitamin B12 deficiency, their associated factors, and impact on health-related quality of life in a sample from the Dominican Republic. Methods: A total of 367 patients with diabetes were recruited. The Toronto Clinical Scoring System (TCSS) was used to evaluate the presence of neuropathy symptoms, while the 36-Item Short Form Health Survey (SF-36) was used to assess health-related quality of life. Results: Of the participants, 33.5% had neuropathy according to TCSS scores. Only one participant reported having a previous diagnosis of neuropathy. Factors associated with neuropathy were age, chronic renal insufficiency, and history of stroke. The prevalence of vitamin B12 deficiency was 4.5%, and no association was found with neuropathy. The presence of neuropathy significantly affected (P < 0.05) all physical dimensions of the SF-36 and the vitality dimension. Factors associated with the Physical Component Score (PCS) were age, neuropathy, and total number of comorbidities; factors associated with Mental Component Score (MCS) were age, sex, and being widowed. Conclusions: The prevalence of neuropathy was high and its impact on QoL was significant. Almost none of the patients in which neuropathy was detected had a previous diagnosis. Considering this, the development of awareness and prevention interventions among both doctors and patients in the Dominican context is of utmost importance.
