Endocrine and Metabolic Science最新文献

Objective

Adrenal insufficiency (AI) is diagnosed with morning cortisol but ACTH stimulation test is usually needed to confirm the diagnosis. In this study we investigated different morning cortisol thresholds that can safely rule out AI without requiring a confirmatory ACTH stimulation test.

Design

Retrospective cohort study.

Methods

We included patients aged 18 and above who underwent the 250 mcg ACTH stimulation test from June 2018 to June 2022. Basal and post-ACTH serum cortisol values at 30 and 60 min were documented. Sensitivity, specificity and logistic regression analysis were employed to assess morning cortisol level's ability to predict AI as confirmed by ACTH stimulation test.

Results

237 patients were included, 66 diagnosed with AI and 171 had normal ACTH results. Hypertension and type 2 Diabetes correlated with lower AI incidence. Median morning cortisol was 138.0 nmol/L for AI group and 286.0 nmol/L for non-AI patients. A morning cortisol of 285 nmol/L had 90.6 % sensitivity, 50.3 % specificity, and a negative predictive value of 93.3 % for ruling out AI. A threshold of 306 nmol/L increased sensitivity to 95.3 % with 40 % specificity.

Conclusion

Morning cortisol is an effective diagnostic tool for ruling out AI. Using multiple thresholds based on clinical suspicion and the integration of predictive pre-test probability can reduce the need for excessive ACTH stimulation tests. This study contributes to the growing evidence of utilizing morning serum cortisol in the diagnosis of adrenal insufficiency.

Clinical relevance statement

Diagnosing Adrenal Insufficiency (AI) can be challenging due to debate regarding the cortisol cut-off value that can exclude AI without additional tests. The confirmatory short synacthen test has certain limitations including financial implications and time restrictions. We investigated the performance of various morning cortisol levels that can diagnose AI without additional testing.

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.

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

Objective

Methods

Results

Conclusion

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.

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.

Objective

Metabolic health and longevity are influenced by numerous factors including the growth hormone (GH) – insulin-like growth factor I (IGFI) axis and ketone bodies (KB). However, data on the impact of KB exposure on GH and IGF-I levels are few.

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Objective

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Trial registration