Endocrine and Metabolic Science最新文献

Introduction

Primary aldosteronism (PA) is the most common endocrine cause of hypertension. Untreated PA carries a high cardiovascular morbidity and mortality. Subtyping with adrenal venous sampling (AVS) is essential for tailoring the therapeutic management. Mineralocorticoid receptor antagonists (MRA) are recommended to be discontinued prior to AVS but it entails a risk of worsening of hypertension and occurrence of hypokalemia. Literature is sparse regarding successful subtyping with AVS without discontinuing MRA. We report a case of PA highlighting successful subtyping with AVS followed by a positive response to adrenalectomy without discontinuing MRA (in a dose of >200 mg/day).

Case report

A 50 year old gentleman, known case of PA was requiring six classes of antihypertensive drugs, including 300 mg Eplerenone. In view of age >35 years and bilateral adrenal masses, he was planned for subtyping with AVS. It was deemed difficult to stop MRA prior to AVS. Renin levels were low, despite taking MRA, which indicated incomplete mineralocorticoid receptor blockade. AVS was done on concurrent MRA usage which indicated lateralization of excess aldosterone production to the right side. Patient underwent robot assisted right adrenalectomy. Post-surgery, there was a partial clinical success and complete biochemical success.

Conclusion

In patients with severe PA, hypertension and/or hypokalemia might be difficult to control without MRA. Successful lateralization with AVS can be done in patients with suppressed renin levels, even on MRA treatment.

Zinc transporter ZnT8, encoded by SLC30A8, is expressed highly in pancreatic β-cells that effluxes Zn²⁺ into insulin granules which is required to secret insulin from the granules. Genome-wide association study identified twelve loss of function mutations in SLC30A8 that play protective role against type 2 diabetes (T2D). This study aimed to find genetic association of a protein truncating variant rs200185429 in Bangladeshi healthy individuals (n = 184), patients with prediabetes (n = 130) and patients with T2D (n = 179). Genetic association study with respect to rs200185429 was performed using TaqMan® probe followed by allelic discrimination plots. Wild type CC genotype was found to be evenly distributed in healthy individuals (96.2 %), patients with prediabetes (95.38 %) and patients with T2D (94.41 %). CT genotype was more prevalent in T2D (5.59 %), less in healthy individuals (3.38 %). However, TT genotype was absent in the study participants. Mutant T allele was neither associated with prediabetes (OR = 1.22, χ² = 0.12, p = 0.72) nor with T2D (OR = 1.42, χ² = 0.52, p = 0.47). Similarly, none of the genetic inheritance models showed statistically significant association with T2D. Thus, a large-scale study is warranted to establish our finding regarding the association of rs200185429 with prediabetes and T2D in Bangladeshi population.

Background

Studies reported an association between rheumatoid arthritis and Diabetes mellitus. We sought to assess the causal association between rheumatoid arthritis and Diabetes mellitus risk using a two-way two-sample Mendelian randomization (MR) analysis.

Methods

Data on Diabetes mellitus and rheumatoid arthritis were obtained from the GWAS genome-wide database, and the MR method was used to explore the bidirectional causal association, the inverse variance weighted (IVW) method was used as the primary analysis method, and sensitivity analysis was performed.

Results

IVW results and MR-Egger method indicate that there is a significant correlation between Diabetes mellitus and rheumatoid arthritis (IVW: P = 0.002, OR = 1.057, 95%CI: 1.02–1.096, MR-Egger: P = 0.037, OR = 1.096, 95%CI: 1.006–1.194), MR-Egger intercept analysis shows that the P-value is 0.362 (>0.05), IVW results showed a significant association between rheumatoid arthritis and Diabetes mellitus (IVW: P = 2.65 × 10–9, OR = 1.797, 95%CI: 1.481–2.180), MR-Egger intercept analysis shows that the P-value is 0.221 (>0.05).

Conclusion

The results confirm that Diabetes mellitus and rheumatoid arthritis have a two-way causal chain, and it is necessary to strengthen bidirectional surveillance.

Aims

To determine the risk factors associated with amputations in hospitalized patients with diabetic foot infection.

Methods

this is a prospective study conducted at a tertiary care hospital in Panama between January 2010 and December 2016. We included all patients admitted to the hospital with diabetes and diabetic foot infection. A total of 351 patients were included, and a survey to assess for demographic and clinical factors was completed prospectively until discharge. The outcome was lower limb amputation.

Results

Sixty-one participants (17.4 %) required a lower limb amputation, and 22 (36.1 %) were major amputations. Several factors were associated with amputation in the univariate analysis: history of foot infection, history of amputation, peripheral arterial disease, a major index ulcer area, duration of the index ulcer >30 days, Grade III 3D severity according to Texas scale, a greater IDSA classification, the presence of necrosis and osteomyelitis. Nevertheless, multiple logistic regression revealed significant relationships between amputations and necrosis (P < 0.0001), osteomyelitis (P < 0.0001), and a severe IDSA classification (P = 0.008).

Conclusion

In patients with diabetes foot infection, the presence of osteomyelitis, necrosis and a severe IDSA classification were strongly associated with amputation.

Clinical relevance

The rates of lower limb amputations in diabetic foot infections are higher in Hispanics than Caucasians, moreover, data on risk factors for amputation from diabetic foot infection in Latin American countries and specially Central American countries is scarce and there is no data in Panama.

Previous observations suggest that strong social stressors, that is, repeated social defeat, could initiate functional changes in the hypothalamic-pituitary-adrenal (HPA) axis in social mammals. Here, we examine whether exposure to such stress in rats causes persistent alterations in gene expression associated with hypo-and/or hyper-methylation in the adrenal tissue, i.e., the interface between the HPA axis and the circulating hormones. Our integrated analyses of RNA-sequencing (RNAseq) and whole genome bisulfite sequencing (WGBS), suggested that adrenal mitochondrial membrane transport necessary for corticosterone (CORT) synthesis, are affected by repeated social defeat. The increased CORT levels observed in blood in the stressed rats further suggested that corticosterone synthesis might be influenced by this form of social stress. The cellular mechanisms underlying these changes, i.e., the enriched gene ontology (GO)-terms and increased levels of circulating CORT, remain to be investigated.

Background

The efficacy of insulin and C-peptide suppression (ICPS) test using a rapid-acting insulin analog to induce hypoglycemia in the diagnosis of insulinoma has never been studied.

Objective

To compare the efficacy of using plasma C-peptide (PCP) and plasma insulin (PI) responses to the ICPS test using insulin aspart and the supervised prolonged fast (SPF) test in the diagnosis of insulinoma.

Methods

The ICPS test was performed in 15 patients with insulinoma (IN) and 6 patients with non-insulinoma causes of hypoglycemia (non-IN) by intravenous infusion of insulin aspart to induce hypoglycemia. Plasma glucose (PG), C-peptide (PCP), and insulin (PI) levels were measured before and at the end of the test (end-ICPS) when the patients had hypoglycemia, defined by the presence of either PG ≤50 mg/dL with hypoglycemic symptoms or PG ≤40 mg/dL regardless of hypoglycemic symptoms. PCP and PI were measured by an immunoassay system that does not cross-react to insulin aspart (Cobas Modular Analytics e801). The SPF test was also performed in IN.

Results

IN had a higher median end-ICPS PI (34.77 versus 0.58 μIU/mL, p < 0.001), lower magnitude of PI suppression (−24.28 % ± 35.5 % versus −93.67 % ± 2.7 %, p < 0.001), higher mean end-ICPS PCP (4.62 ± 3.02 versus 0.49 ± 0.21 ng/mL, p < 0.001), and lower magnitude of PCP suppression (−25.51 % ± 22.2 % versus −70.28 % ± 19.4 %, p < 0.001) than non-IN. In IN, end-ICPS PI was significantly correlated to end-ICPS PCP (r = 0.724, p = 0.002). There were high correlations between end-ICPS PCP and end-SPF PCP (r = 0.882, p < 0.001) and between end-ICPS PI and end-SPF PI (r = 0.794, p < 0.001). The ICPS had a sensitivity and specificity of 93 % and 83 %, respectively, when using an end-ICPS PCP cut-off level of 0.6 ng/mL and 93 % and 100 %, respectively, when using an end-ICPS PI cut-off level of 3 μIU/mL. The ICPS test was terminated in a shorter time than the SPF test (1.01 ± 0.58 versus 7.80 ± 4.10 h, p < 0.001).

Conclusion

In the diagnosis of insulinoma, the ICPS test using insulin aspart is practical, safe, less time-consuming, and as effective as the SPF test. The responses of PI to hypoglycemia are more obvious and consistent, without overlap, than the responses of PCP in IN and non-IN. The use of end-ICPS PI is better than end-ICPS PCP in the evaluation of the ICPS test. The ICPS test using a rapid-acting insulin analogue such as insulin aspart can be used instead of the conventional CPS test using recombinant human insulin and should be considered an alternative first-line test to the SPF test.

Objective

To investigate the association between glycemic levels and mortality in patients without diabetes hospitalized for COVID-19 in Perú.

Methods

In a retrospective study conducted from April to June 2020 in Cayetano Heredia hospital, 529 patients were admitted with a positive SARS-CoV-2 laboratory result or a computed tomography chest scan with suggestive images of COVID-19 pneumonia. Patients were classified into three groups according to their first blood glucose measure. Group 1: glucose level lower than 100 mg/dL; Group 2: glucose level between 100 mg/dL and 126 mg/dL, and Group 3: glucose level over 126 mg/dL. Demographical characteristics, concomitant diseases, laboratory data, and treatment received during hospitalization were also described. Regression-adjusted models were used to analyze association of interest.

Results

The number of patients who met inclusion criteria was 289. Mortality occurred in 137 cases (47 %). Group 1, group 2 and group 3 had 29/77 (38 %), 58/120 (48 %), and 50/92 (54 %) mortality/severe cases, respectively. After all available confounding factors were adjusted, the group of patients with blood glucose levels over 126 mg/dL had a 73 % increased mortality hazard compared to the ones lower than 100 mg/dL (aHR: 1.73 [95%CI: 1.05–2.84]; p = 0.032).

Conclusion

Hyperglycemia (≥ 126 mg/dL) at baseline in patients without a previous history of diabetes is associated with mortality in admitted patients with COVID-19. Routine laboratory testing should never miss a baseline measure of glycemia as this allows for timely blood glucose management, thereby minimizing its negative impact on COVID-19 patients' outcomes.

Exposure to a stressor can alter energy intake, potentially resulting in overall changes to body weight. However, our understanding of the relationship between stress and food intake remains incomplete. In these studies, we evaluated whether the type of food available for consumption after stress exposure may be an important determinant of plasma corticosterone (CORT) and ghrelin levels after restraint stress in male rats. Male rats were exposed to 1 h restraint stress or handling control, then given access to a test food to assess how access to different types of food impacted plasma CORT and ghrelin post-stressor. Our results indicated that the type of test food did not impact the plasma CORT response after restraint stress. In contrast, plasma ghrelin levels were differentially altered by the type of test food available in the experiment. These findings suggest the importance of considering the type of test food available in studies examining interactions between stress and feeding, and may also point to a crucial role of the timing of prior palatable food access in such experiments.

Ovarian steroidogenesis is an essential process that modulates reproduction. In the cyclic rat, vasoactive intestinal peptide (VIP) stimulates the secretion of steroid hormones, and this is dependent on the superior ovarian nerve (SON). In a rat model of polycystic ovarian syndrome induced by an estradiol valerate injection (PCOS-EV), the increase in SON activity results in elevated levels of norepinephrine (NE) and VIP in the ovary, which in turn leads to a rise in androgen. To analyze whether a greater influx of NE to the ovary, due to the hyperactivity of the SON, modifies the response of the gonad to VIP, PCOS-EV or vehicle-treated rats (Vh) were subjected to: 1) stimulation of the left or right ovary with VIP (L-VIP or R-VIP), or 2) the left or right section of the SON (LSON or RSON) followed by injection of VIP into the denervated ovary. Animals were euthanized 1 h later, and the serum levels of steroid hormones were assessed. In Vh rats treated on estrus, VIP stimulation increased the serum levels of testosterone, irrespective of the ovary injected (Vh L-VIP: 17.3 ± 0.5 or Vh R-VIP: 11.3 ± 1.1 vs. Vh: 6.4 ± 1.3). Section of the SON prior to VIP stimulation did not modify testosterone secretion (Vh LSNO+L-VIP: 15.5 ± 2.7 vs. Vh L-VIP: 17.3 ± 0.5; Vh RSNO+R-VIP: 10.6 ± 0.9 vs. Vh R-VIP: 11.3 ± 1.1). In PCOS-EV rats, VIP stimulation of the left ovary lowered testosterone (EV L-VIP: 11.0 ± 4.0 vs. EV: 24.6 ± 2.5). On the other hand, the effects of VIP injection into the denervated ovary were asymmetric, i.e., treatment in the left ovary not modified testosterone levels (EV LSNO+L-VIP: 6.3 ± 1.3 vs. EV L-VIP: 11.0 ± 4.0), while it decreased testosterone when performed in the right ovary (EV RSNO+R-VIP: 6.9 ± 1.3 vs. EV R-VIP: 29.6 ± 7.6). These results show that, in estrus, VIP has a stimulating effect on testosterone secretion, which is amplified by SON signals. Contrary to this, in the PCOS-EV rat, VIP lowers the elevated levels of androgens that characterize this animal model. Based on present results, we suggest that VIP could be used as a treatment for PCOS.

Background

Studies have shown the importance of metabolic factors like BMI, waist circumference, and lipid profile in predicting knee osteoarthritis severity. However, their predictive ability in knee osteoarthritis patients with metabolic syndrome still needs to be explored.

Objectives

Evaluate the predictive ability of Body mass index (BMI), waist circumference, and triglyceride/ High-density lipoprotein cholesterol (HDL-c) ratio in determining the severity of knee osteoarthritis in patients with metabolic syndrome.

Materials and methods

A cross-sectional study at Ho Chi Minh City Hospital for Rehabilitation and Professional Diseases from January 2023 to January 2024 included 697 patients meeting ACR 1991 and NCEP-ATP III criteria for knee osteoarthritis and metabolic syndrome, respectively. Logistic regression analyzed the predictive ability of BMI, waist circumference, and triglyceride/HDL-C ratios. Six hundred ninety-seven patients were divided into two groups: severe and non-severe knee osteoarthritis. The criteria for severity were defined as the presence of both: (1) Kellgren-Lawrence grade 3 or higher on knee radiographs and (2) moderate or higher knee pain. Two models were constructed to analyze the predictive ability of severe knee osteoarthritis. Model 1 included univariate factors, while Model 2 incorporated multivariate models.

Results

Among the 697 patients who participated in the study, the average age was 58.7 ± 12.1 years, and females accounted for 71.3 %. The mean BMI and waist circumference were 24.8 ± 2.0 kg/m² and 86.2 ± 6.0 cm, respectively. In model 1 (univariate), the discriminative ability of BMI, waist circumference, and triglycerides/HDL-c in predicting severity was excellent, with respective AUCs of 0.90 (95 % CI: 0.87–0.92, p < 0.001), 0.81 (95 % CI: 0.78–0.85, p < 0.001), and 0.85 (95 % CI: 0.82–0.88, p < 0.001). In model 2 (combined model), the combination of all three factors resulted in an AUC of 0.93 (95 % CI: 0.91–0.95, p < 0.001) with a specificity of up to 90.2 %.

Conclusion

BMI, waist circumference, and triglyceride/HDL-C ratio are individual and combined predictors of knee osteoarthritis severity in patients with metabolic syndrome.