Journal of Clinical Endocrinology & Metabolism最新文献

Context: Lifestyle intervention reduces the incidence of type 2 diabetes (T2D) in people with impaired glucose tolerance (IGT).

Objective: This work aimed to find out whether participation in an earlier lifestyle intervention had an effect on the occurrence of clinically diagnosed diabetic retinopathy (DR) during a median of 22 years of follow-up time.

Methods: The study included 505 individuals from the Finnish Diabetes Prevention Study (DPS) (mean age 55; range, 40-64 years at the onset of the study) with IGT who were originally randomly assigned to the intervention (weight loss, healthy diet, and physical activity) (N = 257) and usual care control groups (N = 248). The median follow-up was 22 years. Clinical retinopathy diagnoses were obtained from the Finnish national hospital Care Register for Health. Data on glycemic parameters, serum lipids, and blood pressure were available from both the intervention (median 4 years) and postintervention period (until year 7).

Results: No significant difference was found in the cumulative incidence of clinically diagnosed DR between the original intervention (N = 23, 8.9%) and control groups (N = 19, 7.7%) during the extended follow-up (odds ratio: 1.15; 95% CI, 0.61-2.21). A higher cumulative glycated hemoglobin A1c (HbA1c) was significantly associated with a higher risk of retinopathy (hazard ratio 1.4; 1.02-1.88, 95% posterior interval, adjusted for group, age, and sex). Furthermore, the incidence of retinopathy diagnosis was numerically more common among individuals who had developed diabetes during the follow-up (33/349) compared with those who had not (9/156); however, the comparison was not statistically significant (odds ratio: 1.86, 95% CI, 0.89-4.28, adjusted for group, age, and sex).

Conclusion: A higher cumulative HbA1c was significantly associated with a higher risk of retinopathy. No evidence was found for a beneficial effect of a 4-year lifestyle intervention on the long-term occurrence of clinical DR during a median of 22-year follow-up.

Background: Whether testosterone replacement therapy (TRT) conveys additional cardiometabolic benefit to an intensive lifestyle therapy (LT) in older men with obesity and hypogonadism remains unclear.

Objective: To determine whether TRT augments the effect of LT on metabolic outcomes in older men with obesity and hypogonadism.

Design: Secondary analysis of a randomized, double-blind, placebo-controlled trial.

Setting: Veterans Affairs Medical Center.

Participants: Eighty-three older (age ≥ 65 years) men with obesity (body mass index ≥ 30 kg/m2) and persistently low Am testosterone (< 10.4 nmol/L) associated with frailty.

Interventions: LT (weight management and exercise training) plus either testosterone (LT + TRT) or placebo (LT + Pbo) for 6 months.

Outcome measures: The primary outcome was change in glycated hemoglobin (HbA1c). Secondary outcomes included changes in other glucometabolic and lipid profile components, liver enzymes, inflammatory markers, and adipokines; subcutaneous, visceral, intramuscular, and hepatic fat; blood pressure; and metabolic syndrome score.

Results: HbA1c decreased similarly in LT + TRT and LT + Pbo groups (-0.5 ± 0.1 vs -0.6 ± 0.1%, respectively; P = 0.35). While TRT showed no synergistic effect with LT on ameliorating secondary outcomes, it eliminated the augmentative effect of LT on high-density lipoprotein cholesterol concentration (5.4 ± 1.0 mg/dL in the LT + Pbo group vs 0.2 ± 1.1 mg/dL in the LT + TRT group, P = .01) and adiponectin levels (-408 ± 489 ng/mL in LT + TRT group vs 1832 ± 468 ng/mL in LT + Pbo group, P = .02).

Conclusion: In older men with obesity and hypogonadism, adding TRT for 6 months to LT does not result in further improved cardiometabolic profiles and could potentially blunt some of the metabolic benefits induced by LT.

Context: The endocannabinoid system and its extension, the endocannabinoidome (eCBome), are involved in numerous biological processes, notably energy homeostasis, across virtually all tissues. While the circulating eCBome mediator profile is associated with dietary intakes and metabolic status, an important knowledge gap resides in the identification of the precise determinants of these mediators in the gut lumen.

Objective: We aimed at establishing the profile of eCBome mediators in human feces and investigating their association with circulating eCBome mediators, dietary intakes, metabolic status, and gut microbiota composition.

Methods: N-acyl-ethanolamines (NAEs) and 2-monoacyl-glycerols (2-MAGs) were profiled by liquid chromatography coupled to tandem mass spectrometry in plasma and feces of a cross-sectional cohort (n = 195) and a short-term dietary intervention trial (n = 21) with comprehensive dietary intakes and gut microbiota measures.

Results: Six NAEs and 7 2-MAGs were identified in fecal samples, but some, especially omega-3-derived mediators, were undetectable in the majority of samples. Fecal NAEs, and to a lower extent 2-MAGs, were positively albeit weakly correlated with the circulating levels of eCBome mediators. Fecal 2-arachidonoyl-glycerol, N-palmitoyl-ethanolamine, and N-docosahexaenoyl-ethanolamine levels were positively associated with visceral adiposity and with some parameters of the metabolic profile. Dietary intakes of foods rich in fibers were associated with lower fecal levels of several eCBome mediators, while intakes of unsaturated fatty acids were associated with fecal 2-oleoyl-glycerol and 2-linoleoyl-glycerol. Interestingly, gut microbiota diversity and composition were a strong correlate of the fecal eCBome profile.

Conclusion: The fecal eCBome profile is associated with gut microbiota composition and dietary intakes, more than with the circulating profile. These results strengthen the hypothesis of an interrelation between the gut microbiome and eCBome signaling involved in the regulation of numerous host biological processes.

Context: Papillary thyroid cancer (PTC) is an endocrine malignancy with rapidly increased rate. The relationship between lipids and PTC recurrence need further investigate.

Objective: The objective of this study is to investigate the association between preoperative serum lipids levels and the outcomes of PTC patients.

Methods: A retrospective cohort study including 3575 patients with PTC from 2012 to 2016 with follow-ups in our institute were enrolled. Preoperative serum lipids were divided into categorical variables by receiver operating curves. Univariable and multivariable Cox regression models were developed and independent risk factors were used to construct a nomogram to predict disease-free survival (DFS) rate.

Results: Among the 3575 patients, the mean follow-up time was 56.7 months. Comparing with the patients with high levels of triglyceride (TAG ≥ 0.605 mmol/L) and high-density lipoprotein (HDL ≥ 0.935 mmol/L), those with low levels of TAG (hazard ratio [HR] 2.20, 95% CI 1.30-3.72) and HDL (HR 1.60, 1.00-2.57) had a significantly higher risk of recurrence in PTCs. The 5-year DFS rate of patients with low levels of TAG was 94.4%, which was much lower than that in the high-level group (97.2%, P < .001). While cholesterol (P = .13), low-density lipoprotein (P = .07), and very low-density lipoprotein (P = .15) were not statistically correlated with recurrence of PTCs. The nomogram model showed clinical predictive value with a c-index of 0.80 (95% CI 0.73-0.87) and 0.82 (95% CI 0.73-0.90) for 3- and 4-year DFS in the training cohorts.

Conclusion: In the present study, we provide initial evidence that low levels of TAG and HDL were independently associated with the recurrence of PTC, indicating that preoperative serum concentrations of lipids are helpful in predicting the prognosis for patients with PTC in clinical practice.

Context: Romosozumab, a monoclonal sclerostin antibody, is a recently approved highly potent antiosteoporotic agent with osteoanabolic properties. Clinical use of romosozumab is hindered by the fear of adverse cardiovascular (CV) events raised following the pivotal ARCH trial.

Objective: This work aimed to assess real-world CV safety of romosozumab vs alternative osteoanabolic therapies used for treatment of severe osteoporosis.

Methods: Data were obtained from TriNetX, a global federated health research network including real-time electronic medical records from 113 health care organizations with 136 460 930 patients across 16 countries at time of analysis. Inclusion criteria were age 40 years or older, a diagnosis of osteoporosis and prescription of romosozumab or a parathyroid hormone (PTH) analogue (teriparatide/abaloparatide) during August 2019 through August 2022. Propensity-score-matched cohorts were created 1:1 using demographic variables, comorbidities, and medications. Kaplan-Meier analysis was used to estimate the probability of the outcomes. Outcome measures included incident 3-point major adverse CV event or death (3P-MACE) during 1-year of follow-up after the initial prescription.

Results: A total of 5626 and 15 986 patients met the criteria for romosozumab and PTH analogue cohorts, respectively, with 5610 patients per group following propensity score matching. 3P-MACE was significantly less frequent in the romosozumab vs PTH analogue cohort (158 vs 211 patients with an outcome; P = .003) with reductions in the individual components of the composite outcome: myocardial ischemic events (31 vs 58; P = .003); cerebrovascular events 56 vs 79; P = .037; deaths (83 vs 104; P = .099).

Conclusion: In a diverse, real-world setting, prescription of romosozumab for osteoporosis is associated with fewer adverse CV events when compared to PTH analogue therapy.

Context: Progestins have recently been used as an alternative for gonadotropin-releasing hormone (GnRH) analogues to prevent premature luteinizing hormone surge due to the application of vitrification technology. However, the long-term efficacy and safety of a progestin-primed ovarian stimulation (PPOS) regimen, including oocyte competence, cumulative live birth rate (LBR), and offspring outcomes, remain to be investigated.

Objective: To compare cumulative LBR of preimplantation genetic testing (PGT) cycles between a PPOS regimen and GnRH analogues.

Methods: This was a retrospective cohort study at a tertiary academic medical center. A total of 967 patients with good prognosis were categorized into 3 groups: 478 patients received a long GnRH agonist, 248 patients received a GnRH antagonist, and 250 received a PPOS regimen. Medroxyprogesterone 17-acetate was the only progestin used in the PPOS regimen. The primary outcome was cumulative LBR. Secondary outcomes included time to live birth, cumulative rates of biochemical and clinical pregnancy and pregnancy loss, and perinatal outcomes.

Results: The PPOS regimen was negatively associated with cumulative LBR compared with GnRH antagonists and GnRH agonists (28.4% vs 40.7% and 42.7%). The average time to live birth was significantly shorter with GnRH antagonists than with the PPOS regimen. The cumulative biochemical and clinical pregnancy rates were also lower in the PPOS regimen than GnRH analogues, while cumulative pregnancy loss rates were similar across groups. Furthermore, the number and ratio of good-quality blastocysts were significantly reduced in the PPOS regimen compared with GnRH analogues. In addition, perinatal outcomes were comparable across 3 groups.

Conclusion: A PPOS regimen may adversely affect cumulative LBR and blastocyst quality in women with good prognosis compared with GnRH analogues in PGT cycles.

The current classification of diabetes had its genesis over 85 years ago, when individuals with diabetes were first subclassified into insulin sensitive and insulin insensitive states based on the response to an oral glucose tolerance test. About 35 years later, the contemporary classifications of type 1 and type 2 diabetes were coined. Today's evidence, however, suggests that multiple etiologic and pathogenic processes lead to both type 1 and type 2 diabetes, reflecting significant heterogeneity in factors associated with initiation, progression, and clinical presentation of each disorder of glucose homeostasis. Further, the current classification fails to recognize what is currently defined as "atypical" diabetes. Heterogeneity of diabetes continues through the life-course of an individual, with modification of prognosis risk (eg, diabetic complications) altered by genetics, life experience, comorbidities, and therapy. Understanding the sources of heterogeneity in diabetes will likely improve diagnosis, prevention, treatment, and prediction of complications in both the medical and public health settings. Such knowledge will help inform progress in the emerging era of precision diabetes medicine. This article presents NIDDK's Heterogeneity of Diabetes Initiative and a corresponding roadmap for future research in type 2 diabetes heterogeneity.

Context: Dysbetalipoproteinemia (DBL) is a multifactorial disorder that disrupts the normal metabolism of remnant lipoproteins, causing increased risk of cardiovascular disease. However, establishing a proper diagnosis is difficult, and the true prevalence of the disease in the general population remains unknown.

Objective: The objectives were to study the prevalence of the disease and to validate the performance of different clinical diagnostic criteria in a large population-based cohort.

Methods: This study included 453 437 participants from the UK Biobank. DBL was established in participants having an ε2ε2 genotype with mixed dyslipidemia or lipid-lowering therapy use (n = 964). The different diagnostic criteria for DBL were applied in individuals without lipid-lowering medication (n = 370 039, n = 534 DBL), to compare their performance.

Results: Overall, 0.6% of participants had an ε2ε2 genotype, of which 36% were classified as DBL, for a disease prevalence of 0.2% (1:469). The prevalence of DBL was similar between the different genetic ancestries (≤0.2%). Several diagnostic criteria showed good sensitivity for the diagnosis of DBL (>90%), but they suffered from a very low positive predictive value (0.6-15.4%).

Conclusion: This study reported for the first time the prevalence of DBL in the UK Biobank according to genetic ancestry. Furthermore, we provided the first external validation of different diagnostic criteria for DBL in a large population-based cohort and highlighted the fact that these criteria should not be used to diagnose DBL alone but should rather be used as a first screening step to determine which individuals may benefit from genetic testing to confirm the diagnosis.

Context: The relationship between the consumption of different beverages and the risk of microvascular complications in individuals with type 2 diabetes (T2D) is unclear.

Objective: To investigate the association of individual beverage consumption, including artificially sweetened beverages (ASBs), sugar-sweetened beverages (SSBs), tea, coffee, natural juice, and yogurt, with the risk of microvascular complications in adults with T2D.

Methods: This cohort study included 6676 participants with T2D who were free of macrovascular and microvascular complications at baseline in the UK Biobank. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: During a median follow-up of 11.7 years, 1116 cases of composite microvascular complications were documented. After multivariable adjustment, a linear dose-response relationship was demonstrated between the consumption of ASBs and SSBs and the risk of microvascular complications. Compared with nonconsumers, those who consumed ≥2.0 units/day of ASBs and SSBs had an HR (95% CI) of 1.44 (1.18-1.75) and 1.32 (1.00-1.76) for composite microvascular complications, respectively. In addition, higher tea consumption was associated with a lower risk of diabetic retinopathy, with an HR (95% CI) of 0.72 (0.57-0.92) for whom consuming ≥4.0 units/day. There was no significant association between individual beverage consumption and the risk of diabetic neuropathy. No significant association was observed between the consumption of coffee, natural juice, or yogurt and the risks of microvascular complications. Moreover, substituting half units/day of ASBs or SSBs with tea or coffee was associated with a 16% to 28% lower risk of microvascular complications.

Conclusion: Higher consumption of ASBs and SSBs was linearly associated with an increased risk of microvascular complications in adults with T2D.