Clinical Medicine Insights-Endocrinology and Diabetes最新文献

Background: Single nucleotide polymorphisms (SNPs) in the low-density lipoprotein receptor-related protein 5 (LRP5) and the low-density lipoprotein receptor-related protein 5 (LRP6) genes have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity (OB). This study aimed to evaluate the polymorphisms in LRP5 and LRP6 genes in postmenopausal patients with T2DM and OB.

Methods: Participants were categorized into the Non-T2DM group (n = 53) and the T2DM group (n = 89) based on glycemic levels. Baseline data and biochemical indices were collected, Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry, and SNPs at the LRP5 and LRP6 loci were assessed by time-of-flight mass spectrometry.

Results: 1. There was a statistical difference in the distribution of genotypes (CC/CT) at locus rs4988331 (χ2 = 67.940, P = .000) and in the distribution of alleles (C/T) between the T2DM and non-T2DM groups (χ2 = 50.506, P = .000). Additionally, there were significant differences in the allele (G/A) at locus rs11054704, and both allele (G/T) and genotype (GG/GT) distributions at locus rs1181334 between the OB group and the normal weight group (P < .05). 2. OB was identified as a risk factor for T2DM in individuals with the wild-type at locus rs1181334, and the interaction between wild-type and mutant was significant (P < .05). 3. Multifactorial logistic regression analysis revealed that BMD (OR 3.755; 95% CI, 1.215-11.608) and triglyceride-glucose (TyG) index (OR 2.855; 95% CI, 1.361-5.986) were risk factors for T2DM in postmenopausal women, whereas alkaline phosphatase (ALP; OR 0.970; 95% CI, 0.945-0.995) and rs4988331 mutation (OR 0.018; 95% CI, 0.006-0.060) were protective factors.

Conclusion: Mutations at the LRP5-rs4988331 locus, as well as the LRP6-rs11054704 and rs1181334 loci, may be associated with the development of T2DM and OB in postmenopausal women.

Background: Diabetic ketoacidosis (DKA) is a rare but serious complication that can develop during pregnancy, with up to 30% of patients presenting with euglycemia, making prompt recognition challenging. It is associated with increased perinatal mortality rates, although the exact risk of maternal mortality remains unclear. The purpose of this systematic review was to examine the available literature and provide an overview of reported cases of DKA during pregnancy.

Methods: PubMed, Web of Science and Scopus library databases were screened from inception until January 2024. Included studies provided data on classic or euglycemic DKA during pregnancy. All study designs were considered eligible for inclusion.

Results: We identified 66 eligible articles, which included 57 case reports and case series with individual patient data, and 9 studies without individual patient data. The mean age at diagnosis was 28.8 years, and the average gestational age at diagnosis was 29.5 weeks. The majority of women had type 1 diabetes mellitus (T1DM) (45.9%), followed by gestational diabetes (GDM) (40.5%). Most cases were classified as classic DKA (70.3%), with nearly one-third developing euglycemic DKA (29.7%). The most common trigger factors were infections (28%), followed by poor adherence to treatment (13.5%). The most frequent symptoms included nausea (32.4%), vomiting (32.4%), osmotic symptoms (21.6%), and abdominal pain (20.2%). All cases were treated with intravenous insulin and fluids. The vast majority (98.9%) of women eventually fully recovered, with only 1 reported death due to organ failure (1.3%). Intrauterine death or stillbirth occurred in one-third of cases (35.2%), including 1 instance of a twin pregnancy.

Conclusions: DKA is a condition that clinicians may encounter during pregnancy. Although rare, increased awareness and early recognition are crucial for optimal management and improved maternal and neonatal outcomes.

Objective: The main objective was to assess the therapeutic efficacy of selenium alone versus a combination of myo-inositol and selenium (MI + Se) in treating patients with autoimmune thyroiditis (AIT). The study aims to determine which treatment option is more effective in restoring euthyroid state, as indicated by changes in thyroid-stimulating hormone (TSH), T3, T4, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb).

Methods: Google Scholar and PubMed databases were searched for randomized controlled trials (RCTs) and observational studies that reported outcomes of combined treatment (MI + Se) in restoring a euthyroid state, specifically comparing it with selenium-only (Se-only) treatment. Changes in TSH, T3, T4, TPOAb, and TgAb levels from baseline were defined as indicators to compare the effect of combined versus selenium-only treatment in restoring euthyroid levels. The Cochrane risk of bias tool and Newcastle Ottawa Scale were used to assess the quality of the randomized control trials included in the study. Review Manager (version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark) was used for statistical analysis.

Result: We pooled three studies, enrolling 151 participants in the MI + Se group and 137 participants in the Se group. Supplementation of Se with MI demonstrated a significant reduction in TSH levels compared to Se alone (SMD = -1.15, 95% CI: -1.60 to -0.69, P < .00001). MI + Se treatment also significantly reduced TgAb levels compared to Se (SMD = -0.51, 95% CI: -0.78 to -0.24, P = .0002). In contrast, TPOAB, T3 and T4 levels were non-significantly reduced from baseline in patients treated with MI + Se when compared to Se alone (SMD = -0.81, 95% CI: -0.44 to 0.09, P = .20), (SMD = 0.16, 95% CI: -0.09 to 0.42, P = .22), and (SMD = 0.30, 95% CI: -0.23 to 0.83, P = .26) respectively.

Conclusion: Supplementation of Se with MI showed a significant reduction in TSH and TgAb levels compared to selenium-only treatment, with a non-significant reduction in TPOAB, T3, and T4 levels. This entails the need for powered clinical trials and observational studies with longer follow-ups to critically assess the role of combined therapy in restoring euthyroid state in patients with AIT.

Background: Pre-diabetes, characterized by elevated glycemic indices, poses a high risk of diabetes development, and is increasingly linked to non-specific low back pain. While mechanisms remain incompletely understood, metabolic, inflammatory, and neurological factors are implicated. Dietary interventions, including low-glycemic and anti-inflammatory diets, alongside weight management, may improve outcomes in this population.

Objectives: In this non-randomized controlled trial, we aim to evaluate the influence of decreasing HbA1c levels on reducing chronic non-specific low back pain in pre-diabetic, non-obese individuals, as well as emphasizing the importance of such a study in supporting the literature.

Methods: A non-randomized controlled single-blind clinical trial was conducted among 82 participants with chronic non-specific low back pain and pre-diabetes at an outpatient clinic in Baghdad from the 30th of January to the 22nd of September. The intervention methods aimed at reducing HbA1c levels to assess the reduction impact on alleviating chronic non-specific low back pain included dietary adjustments, sleep optimization, and correction of vitamins and minerals deficiencies. The follow-up process was conducted individually for each participant, with a monthly assessment over a period of six months.

Results: At 12 weeks a significant decrease in chronic non-specific low back pain severity was observed in patients with lower HbA1C levels yielding a P-value of .021. Similarly, at 24 weeks there was a decline in the number of patients who reported chronic non-specific low back pain, and the association to lower HbA1C levels was significant with a p-value of .005.

Conclusion: This study suggests the presence of a statistically significant association between reduction of HbA1C levels and ensuing improvement in chronic non-specific low back pain symptoms in non-obese prediabetic patients.

Background: Globally, a rising trend has been observed in the prevalence of thyroid disorders, with many demographic and geographic factors influencing its epidemiology. Nonetheless, some cases often go undetected due to the inconsistent and non-specific nature of the clinical symptoms. Therefore, we aimed to determine the trend and relationship between various pathological findings in thyroid disease patients and their demographic factors to aid clinicians in making a prompt diagnosis and treatment plan.

Methods: A descriptive correlational study was conducted from January 2020 to May 2022 at Jinnah Postgraduate Medical Center, Karachi. We collected data via random sampling from 258 patients suffering from thyroid disorders. We evaluated baseline patient characteristics, along with, thyroid scan and fine needle aspiration cytology (FNAC) reports, and local thyroid gland examination findings.

Results: Out of 258 participants, 192 (74.4%) were females, whereas 66 (25.6%) were males, giving a female: male ratio of 2.9: 1. On local examination, 167 (64.7%) were found to have a solitary nodule, 79 (30.6%) had multinodular goiter. Findings revealed that benign follicular lesions had the highest prevalence (35.3%). Moreover, among the cancerous growth, papillary carcinoma presented the highest cases (12.4%). Of 258 cases, 24 patients had non-surgical interventions, while most (234) had surgical interventions. Total thyroidectomy was the most common procedure opted for by 45.3% (n = 117) of the participants, followed by lobectomy 70 (27.1%), near total thyroidectomy 43 (13.2%), modified radical neck dissection 5 (1.9%).

Conclusion: Our study showed that nearly all thyroid-related pathologies were more prevalent amongst females than males, with the majority having an acute to sub-acute clinical presentation. Multinodular goiter was a prominent finding indicating a greater need for screening tools and access to healthcare facilities, especially in rural areas, to allow future studies to compare provinces accurately.

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women at various stages of life, presenting a wide range of symptoms and health implications. The term "Polycystic Ovary Syndrome" can be misleading, prompting many within the medical community and advocacy groups to advocate for a name change. Critics argue that this terminology can complicate understanding and awareness of the disease among patients. The primary concern is that PCOS emphasizes the ovarian aspect, fostering the misconception that PCOS is merely a gynecological disorder. In reality, PCOS impacts multiple organ systems, particularly metabolic health. Patients frequently experience insulin resistance, weight gain, irregular menstrual cycles, and hirsutism-symptoms that extend beyond ovarian dysfunction. In light of these issues, there is increasing support for renaming PCOS to better reflect its systemic implications and minimize confusion. The current name may hinder understanding and potentially lead to inadequate disease management. Alternative names have been proposed, including "Ovarian Dysmetabolic Syndrome," which our team supports, as well as "Metabolic Reproductive Syndrome" and "Hyperandrogenic Persistent Ovulatory Dysfunction Syndrome." These alternatives aim to highlight the hormonal imbalances and metabolic disturbances associated with the condition, fostering inclusivity and reducing stigma for all affected individuals. This narrative review provides a historical overview of PCOS, tracing its recognition from early descriptions to contemporary guidelines. We discuss the evolving understanding of its pathophysiology and the rationale behind the proposed name change. By adopting a new nomenclature, we can enhance understanding among healthcare professionals, increase inclusivity for affected women, reduce the stigma and anxiety linked to the diagnosis, and offer a more accurate representation of the condition's complex pathophysiology.

Background: Transcription factor 7-like 2 (TCF7L2) variants seem to affect diabetes susceptibility through β-cell dysfunction, underlying basis of which has been considered to be β-cell dedifferentiation rather than apoptotic β-cell death. The Extracellular regulated protein kinases/Mitogen-activated protein kinase signaling pathway (ERK/MAPK signaling pathway) has been confirmed to be significantly associated with multiple cellular process, including cellular dedifferentiation. However, the effects of TCF7L2 on β-cell function and ERK/MAPK signaling pathway are poorly understood.

Objectives: This study aimed to elucidate the regulation of TCF7L2 in β-cell function and ERK/MAPK signaling pathway, which further participate in glucose metabolism and diabetes progression.

Methods: After transfection of TCF7L2 siRNA and lenti-TCF7L2 plasmids, the activation of ERK/MAPK signaling and β-cell dedifferentiation were evaluated respectively. Six week-old male db/db mice were randomly grouped and fed a normal or high-fat diet, and then pancreatic level of TCF7L2 protein were measured respectively when the mice were fed to 8, 12, and 16 weeks of age. Furthermore, the contributions of TCF7L2 to ERK/MAPK signaling and glucose metabolism were investigated in a β-cell-specific TCF7L2 deletion mice model (TCF7L2^β-/-).

Results: The results demonstrated that impaired TCF7L2 induces β-cell dedifferentiation and decreases insulin secretion of MIN6 cells via ERK/MAPK signaling pathway. Consistently, decreased pancreatic TCF7L2 protein in parallel with reduced functional β-cells were observed in db/db mice after weeks of normal or high-fat diet. However, the differences between were only significant when the mice were fed to 12 weeks of age. After weeks of high-fat diet feeding, impaired glucose tolerance and increased activation of ERK/MAPK signaling were simultaneously observed in TCF7L2^β-/- mice.

Conclusion: The study indicate that the induction of β-cell dedifferentiation mediated by ERK/MAPK signaling pathway might be an essential component of TCF7L2 variants in the development of diabetes.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic agents widely prescribed in India despite safety concerns. However, studies focused on their safety profile are scarce, especially in South India.

Objective: To evaluate the prevalence and predictors of adverse events (AEs) with DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM).

Research design and methods: This retrospective cross-sectional study analyzed data from medical records of T2DM patients prescribed DPP-4 inhibitors admitted to the medicine department from 2019 to 2021 at a South Indian tertiary care hospital. The causality of AEs was assessed using the WHO-Uppsala Monitoring Centre (WHO-UMC) criteria and the Naranjo scale, and severity using the Modified Hartwig and Seigel scale. We applied a Generalized model with a binary response and logit-link function to understand the factors that best explain the AE. The best-fit models were chosen based on least Akaike's information criterion and highest PseudoR ² and presented the odds ratio (OR) with a 95% confidence interval. The analyses were performed in R software version 4.2.1.

Results: Among the 796 patients included in the study, 26% experienced AEs. A total of 212 AEs were observed, and Saxagliptin-associated AEs were the most prevalent (66.6%). Hepatic AEs were predominant (37.7%), followed by gastrointestinal events (16.5%) and electrolyte imbalances (12.3%). Most AEs were possible based on WHO-UMC criteria (78.7%) and the Naranjo scale (86.7%), with 58% being of moderate severity and 42% mild. In the multivariate analysis, aspartate transaminase [OR: 1.013 (0.006-1.020)], alkaline phosphatase [OR: 1.004 (1.001-1.007)] and patients already on DPP-4 inhibitors [OR 1.191(1.012-1.366)] were significant predictors for AEs with DPP-4 inhibitors.

Conclusion: The study highlighted a high prevalence of AEs with DPP-4 inhibitors and identified significant predictors of these AEs. These findings underscore the necessity of vigilant monitoring and risk assessment while prescribing DPP-4 inhibitors to the Indian population.

Objectives: Type 2 diabetes mellitus (T2DM) is a persistent metabolic illness causing elevated glucose levels due to insulin resistance. Social media has been found to positively impact diabetes management by boosting motivation, adherence, emotional support, and sharing evidence-based information, thereby enhancing patients' glycemic control efforts and achieving HbA1c targets. Primarily to examine the influence of social media within a random sample Iraqi population of T2DM patients on the control of diabetes, as measured by HbA1c levels.

Methods: A multicentric cross-sectional study involves patients diagnosed with T2DM recruited between December 30, 2019 and November 8, 2023. Patients diagnosed with T2DM, who visited the outpatient clinic at least twice during the study period, were included. The sample size comprised 2921 patients. Various social media platforms available including, Facebook, WhatsApp, Instagram, Telegram, X (formerly known as Twitter), and Viber, were reported.

Results: The study involves 2921 participants with a mean age of 53.3 years, 56% of them successfully reached their HbA1c target within a mean of 18.17 months. A significant correlation was found between achieving the target and using social media (P = .0001), with a shorter average duration among social media users compared to non-users. A family history of diabetes also significantly correlated with achieving the desired outcome, suggesting a probable positive correlation (P = .019).

Conclusion: The study reveals a significant association between social media usage and glycemic control, introducing the importance of technology-based interventions in enhancing diabetes self-management, highlighting the relationships between social media engagement and HbA1c target achievement.

Carney Complex (CNC) is a rare syndrome characterized by spotty skin pigmentation and multiple neoplasms, notably cardiac myxomas, schwannomas, and endocrine tumours. It is often inherited in an autosomal dominant manner with PRKAR1A gene mutations found in the majority of cases. Male infertility is established as part of the CNC phenotype and is largely associated with Large cell calcifying Sertoli cell tumours (LCCSCT). We describe a case of a 30-year-old male patient with Carney Complex, presenting with severe oligoasthenozoospermia and primary pigmented nodular adrenocortical disease (PPNAD). During follow-up consults, the severe oligozoospermia and impaired semen motility persisted and the patient was also diagnosed with a recurring cardiac myxoma and LCCSCT. Molecular testing identified a novel PRKAR1A mutation involving a deletion of exons 4 to 7. Our findings suggest this mutation causes PRKAR1A haploinsufficiency, which may be directly linked to male infertility, irrespective of the presence of testicular tumours. Accordingly, in male patients with CNC, detection of a PRKAR1A gene mutation may serve as a predictive marker for infertility. This case report illustrates the importance of early consideration and management of infertility in male patients diagnosed with CNC.