Daily Endocrinology Research Analysis

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by metabolic and inflammatory disturbances beyond hyperglycemia. Hepatokines such as adropin have emerged as regulators of insulin resistance and vascular function, yet the comparative metabolic effects of sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors on adropin remain unclear. This study compared the effects of empagliflozin versus sitagliptin, each added to metformin, on serum adropin, insulin resistance, glycemic control, lipid profile, and inflammation in adults with T2DM. METHOD: In this single-center, randomized, open-label, parallel-group superiority trial with blinded outcome assessment and blinded statistical analysis, 100 adults with inadequately controlled type 2 diabetes mellitus (HbA1c ≥ 7.5%) receiving stable metformin therapy were allocated in a 1:1 ratio to receive empagliflozin 10 mg once daily or sitagliptin 100 mg once daily for a 12-week intervention period. The co-primary outcomes were changes in circulating adropin concentrations and insulin resistance, assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). Secondary outcomes included changes in HbA1c, fasting insulin, lipid parameters, body weight, and tumor necrosis factor-α (TNF-α). All analyses were conducted according to the intention-to-treat principle. RESULT: Ninety‑four participants completed the intervention; all were included in analyses. Serum adropin increased from 291 ± 133 to 362 ± 124 pg/mL with empagliflozin and from 299 ± 98 to 358 ± 126 pg/mL with sitagliptin (time effect: F = 19.67, p < .001). HOMA‑IR declined from 10.08 ± 4.44 to 6.65 ± 2.50 with empagliflozin and from 9.28 ± 2.97 to 7.15 ± 1.80 with sitagliptin (interaction: F = 4.85, p = .032, partial η² = 0.09). HbA1c decreased from 8.10 ± 0.53 to 7.04 ± 1.18 with empagliflozin and from 8.29 ± 0.66 to 7.62 ± 0.68 with sitagliptin (interaction: F = 4.30, p = .043, η² = 0.081). TNF‑α fell from 44.12 ± 21.52 to 30.78 ± 15.93 in empagliflozin and from 43.93 ± 21.33 to 37.65 ± 17.96 in sitagliptin (time effect: F = 37.09, p < .001). Empagliflozin produced greater reductions in fasting insulin (- 3.43 ± 2.34 µIU/mL vs. - 2.13 ± 1.17 µIU/mL, interaction p = .036), triglycerides (- 42.5 ± 23.9 mg/dL vs. - 21.9 ± 14.5 mg/dL, interaction p = .005), and a larger HDL‑C increase (+ 5.8 ± 3.1 mg/dL vs. + 3.3 ± 2.5 mg/dL, interaction p = .017). Body weight and BMI decreased similarly in both groups (time effect p < .001, no interaction). No serious adverse events occurred. CONCLUSION: Both empagliflozin and sitagliptin improved metabolic and inflammatory markers and were associated with comparable increases in circulating adropin. Empagliflozin conferred broader metabolic benefits, particularly in insulin resistance, glycemic control, and lipid profile. The parallel rise in adropin across treatment groups highlights its potential role as a treatment-responsive biomarker rather than a drug-specific effect. TRIAL REGISTRATION: This trial was prospectively registered with the Iranian Registry of Clinical Trials (IRCT ID: IRCT20160625028627N8) on May 27, 2025 (Trial ID: 83720). The complete trial record is accessible at https://irct.behdasht.gov.ir/user/trial/83720/view.

PURPOSE: T1 signal intensity ratio (SIR) on MRI has not been rigorously evaluated as a noninvasive method to detect pancreatic fibrosis in patients undergoing surgery for recurrent acute (RAP) and chronic pancreatitis (CP). The aim of our study was to evaluate the association between histologic fibrosis score (FS) and T1 SIR and contrast enhancement of the pancreas on MRI among patients with RAP and CP undergoing total pancreatectomy with islet autotransplantation (TPIAT). METHODS: Patients who underwent MRI < 6 months before TPIAT between 2011 and 2023 were classified into 3 groups: definite CP (n = 23) and indeterminate CP (n = 11) by M-ANNHEIM criteria; and RAP defined as ≥ 2 episodes of imaging-documented acute pancreatitis (n = 22). The perilobular and intralobular fibrosis of each surgical biopsy was scored from 0 to 6. The FS was the sum of perilobular and intralobular fibrosis (0-12). We measured the T1 signal intensity of the pancreas and reference organs using pre-contrast T1-weighted fat-saturated (T1WFS) sequences to obtain the T1 SIR. We also measured the T1 signal intensity of the pancreas in the pre-contrast, arterial, venous, and delayed phases. RESULTS: A total of 56 patients were included. The median FS was 6.25 (range 0-12). Pancreas-to-spleen T1 SIR (p = 0.004) and pancreas-to-paraspinal T1 SIR (p = 0.03) were significantly associated with pancreatic fibrosis after adjusting for age, BMI, exocrine insufficiency, fat fraction, diabetes mellitus, and clinical diagnosis. Analysis of the enhancement curves showed that the venous phase of T1 signal intensity can differentiate between indeterminate CP, RAP and definite CP (p < 0.004 for all). CONCLUSION: Both the T1 SIR of the pancreas-to-spleen and pancreas-to-paraspinal muscle show an independent association with fibrosis. T1 SIR demonstrates a significant association with histologically quantified pancreatic fibrosis and may serve as a promising noninvasive imaging biomarker pending further validation.

BACKGROUND AND OBJECTIVE: Despite the consensus that diagnosis of male hypogonadism requires both biochemical and clinical criteria, important uncertainties remain regarding preanalytical conditions, assay selection, and the role of free testosterone (T) and sex hormone-binding globulin (SHBG) measurements. To address these issues, this study provides a summary of the European Association of Urology Guidelines on Sexual and Reproductive Health (SRH) recommendations for the measurement of total T and biochemical diagnosis of male hypogonadism. METHODS: For the 2026 guidelines on SRH, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Database searches included MEDLINE, EMBASE, and the Cochrane Library. Recommendations within the guidelines were developed by the panel to prioritize clinically important care decisions. The strength of each recommendation was determined according to a balance between the desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasize the importance of measuring total T in a fasting state and in the morning (7:00-10:00 AM). Immunoassays remain clinically acceptable for total T measurement when liquid chromatography-tandem mass spectrometry is unavailable. A T level of ≤12 nmol/l continues to be the recommended threshold for diagnosing symptomatic male hypogonadism in clinical practice. Emerging evidence supports broader use of SHBG to prevent misdiagnosis of male hypogonadism. Calculated free T, derived from total T, SHBG, and albumin levels, should be considered in conditions known to affect circulating SHBG levels. CONCLUSIONS AND CLINICAL IMPLICATIONS: Accurate biochemical confirmation of male hypogonadism requires standardized sampling procedures and validated assays. Total T remains the cornerstone of diagnosis; however, SHBG and calculated free T are essential in men with altered binding protein levels. Recent data, although based on limited evidence, support the use of calculated free T even in healthy individuals and not just in patients with conditions associated with potential alterations in SHBG levels. PATIENT SUMMARY: This paper explains how testosterone (T) should be measured to diagnose low T (male hypogonadism). Testing should be done in the morning and after fasting. In some cases, additional measurements such as SHBG and calculated free T may help improve diagnostic accuracy, although current evidence supporting their use is limited.