Endocrine and Metabolic Science最新文献

Background

Hyperuricemia in dyslipidemic patients has been addressed as a potential risk factor for cardiovascular disease, because of its association with atherosclerosis and elevated oxidative stress. Hence, the main objective of the present study was to evaluate the effect of statins on blood uric acid level in patients being treated for dyslipidemia at a tertiary care hospital.

Methods

The study comprised 120 patients with dyslipidemia who were treated at UCMS-TH's outpatient medicine department over a six-month period from December 2022 to May 2023. Participants who met the inclusion criteria for this interventional longitudinal study had their serum uric acid and lipid parameters measured at the start of the study and again after 6 weeks of statin therapy. Using a dependent t-test, we compared the effects of statin on uric acid reduction in the serum.

Results

Statin significantly reduced serum uric acid levels from 6.36 ± 1.02 mg/dL baseline to 5.12 ± 0.43 mg/dL (P < 0.001) after 6 weeks of treatment. The lipid markers LDL-C, TG, TC, and VLDL were all lowered, whereas the HDL level was raised (P < 0.05) after 6 weeks of statin medication.

Conclusion

Because of the association between elevated serum uric acid levels and an increased risk of cardiovascular disease, statins like atorvastatin may be prescribed to dyslipidemic individuals at high risk for cardiovascular mortality due to hyperuricemia.

Background

Diabetes is a common condition that often requires increasing intensity of glucose lowering regimens. We describe the population trends in the intensity of regimens, and associations of achieved HbA1c and treatment persistence.

Methods

We performed an episode-based analysis of the EXTEND-45 dataset, assessing trends in glucose lowering therapy and the associated outcomes of HbA1c and treatment persistence. Trends from 2009 to 2014 were assessed for each intensity level of a glucose lowering therapy regimen, according to the year prescribed. Episodes were defined as the length of time that an individual adhered to a regimen through ongoing prescription, and this was used as to define persistence. Mean HbA1c were calculated for each episode. Persistence and HbA1c were compared across the different regimens of treatment intensity.

Results

The intensity of glucose lowering therapy remained stable over time with around one third of episodes utilising a single glucose lowering agent. Mean HbA1c was higher for insulin-based treatment (mean 7.9 % SD = 1.3 %), and lowest for episodes of no glucose lowering treatment (mean 6.3 % (SD = 0.8 %). Around half of participants achieved glycemic targets of 7 %. While there was considerable variation in persistence, the median persistence was around 3 months (94 days, IQR 51–201 days).

Conclusions

Therapeutic intensity for diabetes has remained stable over 9 years. Whilst there was considerable variability in persistence with glucose lowering regimens, the mean duration of all regimens was less than a year. Requirement for higher intensity treatment with insulin was related to poorer glycemic control.

Introduction

Diabetes mellitus (DM) is considered as a group of metabolic diseases with a global distribution and severe complications. It is caused by insulin deficiency, which with time leads to development of pathological changes in the cardiovascular, respiratory, and other systems. Several studies have shown some features and the connection of structural changes of the lungs with DM, however very little is known regarding ultrastructural changes of type 2 alveolocytes (AT2).

Materials and methods

The study involved 24 white non-linear male laboratory rats which were divided into two groups (experimental and intact). The experimental group was further divided into two subgroups depending on the duration of study: the first group with hyperglycemia for 30 days, and the second with hyperglycemia for 60 days. For the experimental modeling of hyperglycemia, the rats were injected once subcutaneously with solution of alloxan monohydrate hyperglycemia.

Results

AT2 of the intact group had a high degree of differentiation with plates of high electron density. In AT2 of rats with hyperglycemia for 30 days, there were signs of vacuolation, mass accumulation of primary and secondary lysosomes, and lamellar bodies were grouped as conglomerates. In AT2 of the rats with 60 days of hyperglycemia, nuclei with scalloped contour, karyoplasmic outgrowths and intussusception, and condensation of heterochromatin were observed.

Conclusion

Under conditions of experimental chronic hyperglycemia, proliferation and destruction of AT2 are observed, which is the morphological basis for the violation of surfactant synthesis and immunocompetent properties in lung tissues of young rats.

Introduction

Diabetic wounds are highly susceptible to a range of pathogens, particularly bacteria, due to the immunocompromised state of diabetic patients. Although diabetic wound isolates are typically polymicrobial, S. aureus is the most common bacteria found in such isolates.

Objective

The objectives of this study were to identify the different bacterial isolates present in each sample of diabetic foot ulcers, determine the minimum inhibitory concentration of the identified bacterial strains to various antibiotics, and identify the genes responsible for drug resistance in multidrug-resistant bacterial strains.

Materials and methods

A cross-sectional prospective study was conducted at the Endocrinology Unit, Hayatabad Medical Complex, Peshawar, Pakistan, from November 2019 to March 2020. A total of n = 140 samples from diabetic foot ulcers were aseptically collected and evaluated for their sensitivity to antibacterial drugs commonly used in the study area. The samples were inoculated into various media and cultured, and biochemical and molecular analyses were conducted according to the Clinical Laboratory Institute Guidelines.

Results

A total of 122 bacterial isolates were obtained out of a total of 144. The results of antibiotics susceptibility testing showed that gram-positive isolates were more resistant to penicillin G (93.18 %), but exhibited sensitivity to vancomycin (100 %) and linezolid (LZD) (95 %). Gram-negative isolates were found to be 100 % resistant to penicillin, such as amoxicillin (AMC), and sulphonamides, such as sulphamethoxazole/trimethoprim (SXT) groups of antibiotics. A total of 36 (29.50 %) multidrug-resistant (MDR) isolates were identified. MDR isolates exhibited good sensitivity to meronem (MEM), i.e. 97 %, and were highly resistant to sulphamethoxazole/trimethoprim and clindamycin, i.e. 100 %.

Conclusion

Gram-positive isolates were resistant to penicillin G (93.18 %) but sensitive to vancomycin (100 %) and linezolid (95 %). Gram-negative isolates were resistant to penicillin and sulphonamides. Among the isolates, 29.50 % were multidrug-resistant (MDR), with high resistance to sulphamethoxazole/trimethoprim and clindamycin but good sensitivity to meronem (97 %).

Two sentence summary

This study highlights the emerging problem that world is facing right now in the form of antimicrobial resistance.

Our study showed increased antimicrobial resistance in wounds of diabetic foot ulcers.

Introduction

Insulin pumps serve as alternative insulin delivery methods with physiological similarity to the normal pancreas. The MiniMed 780G device is an advanced closed-loop hybrid system. Recent real-life studies have allowed reaching a higher percentage of time in range (TIR) (70 to 180 mg/dL). Being an emerging technology, it is of the utmost value to report on the early experience of use of this device.

Methods

This was an observational, descriptive, cross-sectional study that included patients older than 18 years with types 1 diabetes mellitus and other types switched to a Medtronic 780G insulin pump. Baseline clinical and glycemic control variables and those after 4 weeks of using the SmartGuard mode were evaluated.

Results

Thirty-nine patients (mean age, 33 years) were analyzed, 95 % of whom had type 1 diabetes with an average disease duration of 17 years. The values for time below range (TBR) <54 mg/dL, TBR <70 mg/dL, TIR, time above range (TAR) >180 mg/dL, and TAR >250 mg/dL were 0 %, 3 %, 72 %, 21 %, and 3 %, respectively, at baseline and 1 %, 2 %, 79 %, 14 %, and 2 %, respectively, after the intervention. The changes in TIR varied based on prior therapy: multiple daily injections of insulin, 13 % improvement; MiniMed Paradigm Veo/MiniMed 640G, 6 % improvement; and MiniMed 670G, −4 % improvement.

Conclusion

In conclusion, the application of a hybrid closed-loop system allowed for better glycemic control based on international standards. The average percentage improvement in TIR was lower than that in other studies and was dependent on the previous method of insulin administration, achieving lower performance with the migration from recent technologies such as the Minimed 670G.

Asthenospermia is a common cause of male infertility refers to semen samples with spermatozoa that move slowly or immotile. Recent research has implicated oxidative stress-induced ferroptosis in asthenospermia's pathophysiology. Peroxiredoxins are important players in the antioxidant defense to protect cells against oxidative stress. However, some aspects of the antioxidant response necessary for male fertility are not well understood. This case-control study aimed to elucidate the role of peroxiredoxins in regulating oxidative stress in male fertility via their correlation with ferroptosis. It included 90 fertile and 90 asthenospermic subfertile males from Hilla City, Iraq. Total peroxiredoxin activity, peroxiredoxin-6 level, and peroxiredoxin-4 level were measured alongside the ferroptosis biomarkers glutathione peroxidase-4, malondialdehyde, and the reduced/oxidized protein thiol ratio. Infertile males had significantly higher oxidized thiol and malondialdehyde levels than fertile males (p < 0.05). Total peroxiredoxin activities, peroxiredoxin-6 levels, peroxiredoxin-4 levels, glutathione peroxidase-4 levels, and reduced/oxidized protein thiol ratios were significantly lower in infertile males than in fertile males (p < 0.05). Therefore, peroxiredoxin activity and level correlate with reduced/oxidized protein thiol ratio. They are inversely associated with ferroptosis and directly associated with semen quality. These findings suggest that peroxiredoxins are crucial in preventing ferroptosis and have potential implications for treating asthenospermia.

Background

Weight loss is important to reduce the risk of metabolic complications in obese individuals, in whom dysregulated adipokines play a central role. This study aims to investigate whether dysregulated adipokines and postprandial triglycerides (TG) improve with a modest weight loss.

Methods

Individuals with obesity (BMI ≥ 30 kg/m²) were recruited among patients at the University Hospital of North Norway and the Stamina Health weight loss rehabilitation program. We measured resting energy expenditure (REE), and calculated the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), leptin to adiponectin (L:A) ratio, indirect leptin sensitivity (REE:leptin ratio), postprandial TG clearance at 6 h, and TG response before and after weight loss. The goal of the weight loss intervention was a loss of ≥5 % of initial total body weight.

Results

28 participants completed the study, of which 13 lost ≥ 5 % body weight and 18 lost <5 % body weight. HOMA-IR (−23.1 %), REE:leptin ratio (+80.1 %) and L:A ratio (−45.7 %) significantly improved with weight loss, whereas there was no improvement of postprandial TG response or clearance. No significant changes were observed in the non-weight loss group.

Conclusion

The data are consistent with the general concept that modest weight loss in obese patients may restore metabolic regulation by improving L:A ratio and insulin and leptin sensitivity.

Thyroid Hormone Receptor (THR) is a member of the nuclear receptor (NR) superfamily, best defined as intracellular ligand-modulated transcription factors. Thyroid hormone (TH), by binding to THR, regulates several physiological and metabolic processes, e.g., development, metabolism, homeostasis, reproduction, etc. THR primarily heterodimerizes with RXR and binds to its response element to modulate the expression of the target genes. THR has two different isoforms differentially expressed throughout the body, i.e., THRα and THRβ, encoded by two distinct genes, THRA and THRB, respectively. The indispensable roles of THRβ in the regulation of the hypothalamus-pituitary-thyroid in addition to biochemical processes, including metabolism, hepatic and kidney-related functions, etc., illustrate that receptor dysregulations are the underlying cause of the onset of several diseases, including diabetes, cardiac ailments, metabolic-related disorders, endocrine-related cancers, reproductive issues, etc. This also makes it a potential target for pharmacological interventions. In this context, the present review focuses mainly on the intrinsic mechanism of THRβ functioning and its contribution to disease progression. In addition, several genetic/polymorphic variations in the THRB gene that are primary driving factors in eliciting rare genetic disorder, i.e., resistance to thyroid hormone (RTH), have also been addressed in detail. We have also highlighted the implications of THR targetability by addressing the impact of TH analogs/modulators and thyroid hormone-disrupting chemicals in disease occurrence and its management.

The Wilms tumor suppressor gene (WT1) is a transcription factor with a wide array of functions, that affects the differentiation and survival of several cell types in different organs. It plays a special role in renal and gonadal development, organs in which WT1 deleterious variants determine well-established conditions, such as Wilms tumor, corticosteroid-resistant nephropathy with progression to loss of renal function, and a spectrum of gonadal development abnormalities (XX and XY gonadal dysgenesis, XX testicular and XX ovotesticular) and testicular tumors. Moreover, WT1 variants are also associated with urinary tract malformations, heart and nervous system diseases, diaphragmatic hernias, leukemia, and tumorigenesis. Consequently, an increasingly broad phenotypic spectrum has been associated with WT1 deleterious variants in 46,XX, and 46,XY individuals. The genotype-phenotype causal relationship involving WT1 pathogenic variants and their heterogeneous clinical manifestations is also discussed.

This review summarizes current knowledge regarding the clinical implications of WT1 disorders and highlights the importance of diagnosing deleterious variants of WT1 for the early identification of individuals at high risk of developing severe phenotypes, for the adequate planning of the therapeutic approach, and for familiar genetic counseling.

Introduction

It seems that the risk of developing diabetes cannot be predicted solely based on weight or BMI. Metabolic phenotypes might offer a more precise tool for identifying patients at higher risk of diabetes, thus enabling more effective and targeted preventive interventions.

Objective

To determine the association between these metabolic phenotypes and the risk of diabetes.

Materials

Systematic Review (SR) with a meta-analysis of cohort studies. The search was carried out in four databases: Pubmed/Medline, SCOPUS, Web of Science, and EMBASE. Metabolic states were classified into six groups: Metabolically Healthy Normal Weight (MHNW), Metabolically Unhealthy Normal Weight (MUNW), Metabolically Healthy Overweight (MHOW), Metabolically Unhealthy Overweight (MUOW), Metabolically Healthy Obesity (MHO), and Metabolically Unhealthy Obesity (MUO). Association measures were presented as odds ratios (OR) and hazard ratios (HR) along with their 95 % confidence intervals (CI95%).

Results

A total of six studies were evaluated. For the meta-analysis, only studies using OR as the measure of association were included. Compared with individuals with MHNW, a statistically significant association was found for MUNW (OR: 1.82; CI95% 1.62, 2.04), MHOW (OR: 1.19; CI95% 1.07, 1.32), MUOW (OR: 2.44; CI95% 2.19, 2.72), MHO (OR: 2.14; CI95% 1.52, 3.01), and MUO (OR: 3.94; CI95% 3.28, 4.74).

Conclusions

Metabolic phenotypes are significantly associated with the risk of diabetes, regardless of BMI. Further research in this field is required, and should be conducted in other regions of the world where obesity and diabetes rates are rapidly increasing.