Daily Endocrinology Research Analysis

INTRODUCTION: We comprehensively investigated whether serum acylcarnitine levels are associated with and predict the decline of glomerular filtration rate (GFR) in type 2 diabetes. RESEARCH DESIGN AND METHODS: Two cohorts of patients with type 2 diabetes were investigated: a subset of the aggregate Gargano Mortality Study (aGMS, n=575; 9 years of median follow-up; mean age=60.9±9.8; mean diabetes duration=11.6±9.3) as a discovery set from Italy. A sample from the Joslin Kidney Study (JKS, n=252; 10 years of median follow-up; mean age=57.8±5.6; mean diabetes duration=14.2±7.6) was used as an independent validation set with different environmental and ethnic background for some associated metabolites in the aGMS. MAIN OUTCOME: estimated GFR (eGFR) change over time (mL/min/1.73 m RESULTS: Eleven out of the 40 acylcarnitines (by the AbsoluteIDQTM p180 Kit, BIOCRATES) were significantly associated with the rate of eGFR decline after Bonferroni correction. All 11 molecules were internally validated (p<0.05). Most of these associations survived the adjustment for several confounders, including age, sex, smoking habit, body mass index, glycated hemoglobin, disease duration, albumin excretion rate, triglycerides, low-density lipoprotein and statins treatment (p<0.05). Tiglylcarnitine and methylglutarylcarnitine, but not tetradecenoylcarnitine and hexadecenoylcarnitine, were also associated with eGFR decline in the JKS (p<0.05). Using multivariable least absolute shrinkage and selection operator regression analysis, methylglutarylcarnitine, hydroxyvalerylcarnitine, hexenoylcarnitine, decadienylcarnitine, dodecanedioylcarnitine, tetradecadienylcarnitine were independently associated with kidney function decline. The pairwise correlation among these ranged from -0.02 to 0.55. An acylcarnitine score comprising these six molecules improved discrimination (p<0.01) and reclassification (p<0.001) of two clinical prediction models of GFR decline in diabetes. CONCLUSIONS: In patients with type 2 diabetes, four short, three medium and four long-chain acylcarnitines are associated with the rate of kidney function decline. Adding the acylcarnitine score to clinical prediction models improves the identification of individuals who are at greater risk of progression to kidney failure.

OBJECTIVE: Osteoporosis in men is a common but often neglected health problem. We aim to compare the efficacy and safety of denosumab, zoledronic acid and alendronate in men with osteoporosis. METHODS: In this randomized, comparative, open-label study, 390 men with osteoporosis or osteopenia were included. They were randomized to receive the treatment of denosumab, alendronate, or zoledronic acid for 12 months. The percentage changes in bone mineral density (BMD), trabecular bone score (TBS) and bone turnover biomarkers (BTMs) during the treatment were evaluated. Safety parameters were observed. RESULTS: The baseline characteristics were well balanced among the three groups. After 12 months of treatment, denosumab, alendronate and zoledronic acid significantly increased BMD by 4.83 ± 0.89%, 4.32 ± 0.77%, 5.18 ± 0.73% at lumbar spine, by 2.75 ± 0.51%, 2.50 ± 0.61% and 2.83 ± 0.59% at total hip, TBS was significantly increased by 2.44 ± 0.52%, 2.00 ± 0.64%, 2.29 ± 0.55%, respectively, without significant differences among the three groups. Serum levels of BTMs decreased significantly and similarly in all three groups (all P < .05 vs. baseline). Denosumab and alendronate group had fewer adverse events than zoledronic acid group. Denosumab had similar efficacy in patients with different gonadal functions. In patients previously receiving bone resorption inhibitors, denosumab continued to increase BMD and TBS, but the increments were reduced by approximately 30% in BMD at lumbar spine compared with treatment-naive patients. CONCLUSION: Denosumab, alendronate and zoledronic acid significantly and similarly reduced BTMs, increased BMD and TBS in men with osteoporosis, whether the gonadal function of patients was normal or decreased. Previous anti-bone resorption therapy may partially diminish the efficacy of denosumab.

BACKGROUND AND AIM: Obesity has reached epidemic proportions worldwide, with large differences across regions. European data on obesity trends among ethnic groups is scarce, particularly regarding the influence of age and socioeconomic status on these trends, which is crucial for guiding targeted interventions. In this study, we assessed the prevalence of obesity and changes in body mass index (BMI) and waist circumference (WC) over time and the effects of key sociodemographic factors on these changes using longitudinal data from a large multi-ethnic cohort. METHODS: Using baseline and follow-up data from 10 484 participants in the HEalthy Life in an Urban Setting (HELIUS) study, representing Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Moroccan and Turkish populations; age-adjusted obesity prevalence; BMI and WC changes over an average follow-up of 6.3 (SD 1.2) years were calculated. Linear mixed models were used to assess changes in BMI and WC over time, adjusting for age, sex and socio-economic position. Key analyses were stratified by age (younger <50 years, older ≥50 years). RESULTS: Median age of the baseline population was 48.0 years (IQR 38.0, 56.0), with 56.7% being women. Age-adjusted prevalence of obesity increased from 23.6% at baseline to 28.7% at follow-up, with steeper increases in ethnic minority groups compared with the Dutch origin group. The steepest increase in BMI and WC was observed in younger migrants, especially in those of Ghanaian and African-Surinamese descent. In older participants, only individuals of Ghanaian and Turkish descent showed a further increase in BMI over time. CONCLUSION: Obesity is increasingly prevalent in ethnic minority groups under 50 years, potentially raising obesity-related health risks and underscoring the need for targeted interventions to prevent further complications.