Clinical Medicine Insights-Endocrinology and Diabetes最新文献

Background: Matrix Gla protein (MGP) is a robust innate suppressor of the detrimental process of vascular calcification in the human body.

Objectives: The interrelationship between circulating MGP levels and renal and cardiac dysfunction, besides echocardiographic calcification score (ECS) was investigated in a sample of type 2 diabetes (T2D) patients.

Methods: The study included 130 subjects. They were 95 patients with T2D and 35 age- and sex-matched healthy controls. Patients were further subdivided into 52 T2D patients without DKD (eGFR ⩾ 60 ml/minute/1.73 m²) and 43 T2D persons with DKD (eGFR > 60 ml/minute/1.73 m²). Serum MGP levels, determined by ELISA, renal function tests, lipid profile, and echocardiography were studied in all participants.

Results: Significantly elevated circulating inactive MGP level was noted in individuals having T2D compared to controls. It correlated negatively with eGFR and left ventricular (LV) diastolic and systolic functions and positively with indices of LV hypertrophy. ECS was significantly increased in both T2D groups compared to controls and in DKD group compared to the diabetic group without DKD. A significant positive correlation was observed between inactive MGP and ECS.

Conclusion: Serum inactive MGP may contribute to the development of DKD and to the associated process of cardiac valvular calcification. It may be a beneficial diagnostic marker for early prediction of cardiac calcification and preclinical LV systolic and diastolic dysfunction in T2D patients, especially in those complicated with DKD.

Background: Artificial intelligence (AI) appears capable of detecting diabetic retinopathy (DR) with a high degree of accuracy in adults; however, there are few studies in children and young adults.

Methods: Children and young adults (3-26 years) with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) were screened at the Dhaka BIRDEM-2 hospital, Bangladesh. All gradable fundus images were uploaded to Cybersight AI for interpretation. Two main outcomes were considered at a patient level: 1) Any DR, defined as mild non-proliferative diabetic retinopathy (NPDR or more severe; and 2) Referable DR, defined as moderate NPDR or more severe. Diagnostic test performance comparing Orbis International's Cybersight AI with the reference standard, a fully qualified optometrist certified in DR grading, was assessed using the Matthews correlation coefficient (MCC), area under the receiver operating characteristic curve (AUC-ROC), area under the precision-recall curve (AUC-PR), sensitivity, specificity, positive and negative predictive values.

Results: Among 1274 participants (53.1% female, mean age 16.7 years), 19.4% (n = 247) had any DR according to AI. For referable DR, 2.35% (n = 30) were detected by AI. The sensitivity and specificity of AI for any DR were 75.5% (CI 69.7-81.3%) and 91.8% (CI 90.2-93.5%) respectively, and for referable DR, these values were 84.2% (CI 67.8-100%) and 98.9% (CI 98.3%-99.5%). The MCC, AUC-ROC and the AUC-PR for referable DR were 63.4, 91.2 and 76.2% respectively. AI was most successful in accurately classifying younger children with shorter duration of diabetes.

Conclusions: Cybersight AI accurately detected any DR and referable DR among children and young adults, despite its algorithms having been trained on adults. The observed high specificity is particularly important to avoid over-referral in low-resource settings. AI may be an effective tool to reduce demands on scarce physician resources for the care of children with diabetes in low-resource settings.

Background: Diabetic foot ulcers (DFUs) are debilitating to the patient and costly for the healthcare system. We set up the Diabetic Rapid Evaluation and lower limb Amputation Management (DREAM) clinic with the aim of providing early directed specialist care to patients with DFUs. With early management, we hope to treat DFUs in its early stages, reducing the need for and associated morbidity of major and minor lower limb amputations.

Objectives: We evaluated the outcomes of the fast-access DREAM clinic with multi-disciplinary evaluation for patients with DFUs. Outcomes include time from the point of referral to DREAM clinic evaluation, amputation rates and wound healing rates.

Design: Patients presenting with DFU to the DREAM clinic were enrolled. A podiatrist made the first assessment, followed by immediate specialist consultation with Endocrinologists, Vascular surgeons or Orthopaedic surgeons as required.

Methods: Data on baseline demographics and DFU characteristics were collected. Outcomes evaluated were wound healing at 12 weeks, wound salvage rates, time to DREAM clinic access and time to specialist referral.

Results: Sixty-eight patients were enrolled, with 57.3% males, and mean age of 63 ± 13.0 years. Majority of ulcers were classified as neuropathic (41.3%) and located at the digits (40%). At 12-weeks follow-up, 1 had undergone major amputation, 9 minor amputations and 4 surgical debridements. The median time to DREAM clinic evaluation from first presentation was 3 days (IQR 7). Eleven (16.2%) required >1 specialist consult. Twenty (29.4%) were hospitalised for treatment. Twelve underwent revascularisation within 4 days (IQR 3.5). Twenty-four patients (35.3%) continued podiatry follow-up, having 28 DFUs in which 20 (71.4%) healed within 12 weeks.

Conclusion: The fast-access multidisciplinary DREAM clinic shows promising outcomes with lower major amputation rates and exemplary DFU healing outcomes.

Background: It is still unelucidated how hormonal alterations affect developing organisms and their descendants. Particularly, the effects of androgen levels are of clinical relevance as they are usually high in women with Polycystic Ovary Syndrome (PCOS). Moreover, it is still unknown how androgens may affect males' health and their descendants.

Objectives: We aimed to evaluate the multigenerational effect of prenatal androgen excess until a second generation at early developmental stages considering both maternal and paternal effects.

Design and methods: This is an animal model study. Female rats (F0) were exposed to androgens during pregnancy by injections of 1 mg of testosterone to obtain prenatally hyperandrogenized (PH) animals (F1), leading to a well-known animal model that resembles PCOS features. A control (C) group was obtained by vehicle injections. The PH-F1 animals were crossed with C males (m) or females (f) and C animals were also mated, thus obtaining 3 different mating groups: Cf × Cm, PHf × Cm, Cf × PHm and their offspring (F2).

Results: F1-PHf presented altered glucose metabolism and lipid profile compared to F1-C females. In addition, F1-PHf showed an increased time to mating with control males compared to the C group. At gestational day 14, we found alterations in glucose and total cholesterol serum levels and in the placental size of the pregnant F1-PHf and Cf mated to F1-PHm. The F2 offspring resulting from F1-PH mothers or fathers showed alterations in their growth, size, and glucose metabolism up to early post-natal development in a sex-dependent manner, being the females born to F1-PHf the most affected ones.

Conclusion: androgen exposure during intrauterine life leads to programing effects in females and males that affect offspring health in a sex-dependent manner, at least up-to a second generation. In addition, this study suggests paternally mediated effects on the F2 offspring development.

Background: The Republic of the Marshall Islands (RMI) faces a high prevalence of type 2 diabetes (T2DM).

Objectives: The aim of the study is to document the health of Marshallese with and without a T2DM diagnosis to inform future interventions.

Design: Data are from screenings collected in preparation for a diabetes education intervention. Data, including HbA1c, random glucose, cholesterol, weight, and self-rated health, were collected.

Methods: Kruskal-Wallis and Fisher's exact tests were used to identify differences in participants with and without T2DM diagnosis.

Results: There were significant differences in both HbA1c level (P ⩽ .0001) and glucose level (P ⩽ .0001) between the diagnosed T2DM and non-diagnosed T2DM groups, as well as diastolic blood pressure (P = .0179), systolic blood pressure (P = .0003), and pulse pressure (P = .0023). There were no differences in weight, body mass index (BMI), high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol, or self-rated health. Marshallese without a T2DM diagnosis have signs of insulin resistance, including elevated glucose and triglyceride levels.

Conclusion: The results indicate a need for a socioecological approach to T2DM interventions, and interventions in the RMI should consider inclusion of blood pressure and cholesterol management. There is a need for interventions to prevent prediabetes and its progression to T2DM.

Graves' disease (GD) is the most common cause of hyperthyroidism in children. A common GD symptom is a goiter. The usual biochemical profile in children with GD is a decreased thyroid hormone stimulating hormone (TSH) level and high free thyroxine (FT4) and free triiodothyronine (FT3) concentrations. The presence of thyroid receptor antibodies (TRAb) is the most important specific immunological sign for diagnosing GD. The treatment choices for pediatric GD are anti-thyroid drugs (ATDs), radioiodine, and thyroidectomy, but the risks and benefits of each modality are different. Management recommendations include the first-line use of a prolonged course of ATDs for at least 3 years and potentially 5 years or more. Rituximab and Teprotumumab are new novel alternative medications for the treatment of adult patients with GD and Graves' orbitopathy respectively, but evidence of the efficacy and safety of these drugs in pediatric patients with GD is lacking.

Background: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder. The aim of the present investigation was to identify gene signature specific to T2DM.

Methods: The next generation sequencing (NGS) dataset GSE81608 was retrieved from the gene expression omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) between T2DM and normal controls. Then, Gene Ontology (GO) and pathway enrichment analysis, protein-protein interaction (PPI) network, modules, miRNA (micro RNA)-hub gene regulatory network construction and TF (transcription factor)-hub gene regulatory network construction, and topological analysis were performed. Receiver operating characteristic curve (ROC) analysis was also performed to verify the prognostic value of hub genes.

Results: A total of 927 DEGs (461 were up regulated and 466 down regulated genes) were identified in T2DM. GO and REACTOME results showed that DEGs mainly enriched in protein metabolic process, establishment of localization, metabolism of proteins, and metabolism. The top centrality hub genes APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1 were screened out as the critical genes. ROC analysis provides prognostic value of hub genes.

Conclusion: The potential crucial genes, especially APP, MYH9, TCTN2, USP7, SYNPO, GRB2, HSP90AB1, UBC, HSPA5, and SQSTM1, might be linked with risk of T2DM. Our study provided novel insights of T2DM into genetics, molecular pathogenesis, and novel therapeutic targets.

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) use is associated with an increased risk of diabetic ketoacidosis (DKA).

Objective: This study evaluated and compared the DKA characteristics and outcomes of users and non-users of SGLT2i.

Methods: We retrospectively studied patients with type 2 diabetes mellitus (T2DM) admitted with DKA to Tawam Hospital, Al Ain City, UAE between January 2017 and March 2021. Demographic data, clinical, and laboratory findings were extracted from the electronic medical records.

Results: A total of 55 patients with T2DM (62% UAE nationals, 50% women) were admitted with DKA. The average age was 54.0 ± 18.9 years and average diabetes duration of 15.7 ± 15.1 years. Seventeen patients (31%) were using SGLT2i. Infection was the main precipitating factor for DKA in (8 out of 17) SGLT2i users. Compared to non-users, SGLT2i users had lower systolic blood pressure (119.9 vs 140 mmHg; P = .012) and serum glucose levels (16.2 vs 24.9 mmol/L; P < .001) and higher Na level (137.5 vs 132.6 mmol/L; P = .005). Additionally, 56.3% of SGLT2i users had euglycemic DKA compared to 2.6% of nonusers (P < .001). Acute kidney injury (AKI) occurred more in SGLT2i users compared to non-users (94.1% vs 67.6%, P = .043). Further analysis revealed that SGLT2i users were about five times more likely to have prolonged hospital length of stay (⩾14 days) when compared with non-users (adjusted OR: 4.84; P = .035). Overall, there was no difference between the two groups with regards to DKA complications and mortality.

Conclusions: SGLT2i related DKA is associated with lower blood glucose levels, lower SBP, worse hypovolemia, increased risk of AKI, and longer hospital stay when compared to non SGLT2i related episodes. Since the benefits of SGLT2 inhibitors far outweigh potential risks, there is a need to raise healthcare professionals and patients' awareness about this potential association.

Background: Both hormonal and genetic data reveal that the stress hormone cortisol and its regulating genes may affect the level of testosterone in humans. It is uncertain whether type 2 diabetes mellitus would manifest similarly. Furthermore, a genetic strategy to screen out the stress system genes that may contribute to testosterone decline in humans is less understood.

Objectives: In this study, we aimed to elucidate the link between stress and testosterone levels, both hormonally and genetically.

Method: This study comprised 37 individuals with type 2 diabetes mellitus and 50 healthy individuals. For the analysis of hormones and the targeted genes, we used the RIA system and bioinformatics expertise.

Results: The patients had significantly elevated cortisol and lower testosterone readings, according to data from hormonal analyses. The bioinformatics approach reveals that SHBG was intracellularly suppressed by 2 defined stress system genes: FKB5 and CYP17. TCF4/TCF8, ATRX, and AR in skeletal muscle were inversely related to stress system genes. Furthermore, all testosterone regulated genes were positively linked with SHBG in the current study. A strong relationship between GNAS and PKA with CYP17 and FKBP5 reveals that the Gαs-cAMP/PKA signaling pathway may be one of the regulatory pathways through which the suppression of testosterone system genes happens. In conclusion, this study demonstrated that beyond stress, the key stress system genes might affect cortisol levels, which in turn affect testosterone figures via the Gαs-cAMP/PKA signaling pathway.

Lipoid congenital adrenal hyperplasia (LCAH) is characterized by disturbance of adrenal and gonadal steroidogenesis (OMIM:201710). It is caused by mutation in the Steroidogenic Acute Regulatory Protein (StAR). We report a classic case of LCAH in a neonate (46, XY) with phenotypic female genitalia who presented with significant salt loss with a novel homozygous variant mutation c.745-1G>C p. in StAR gene.