[Posted 8/Oct/2026]

AUDIENCE: Endocrinology, Ob/Gyn, Internal Medicine

KEY FINDINGS: Higher circulating ferritin levels were associated with increased T2D risk in both men and women, with a stronger association observed in women in the primary sex-specific analysis after exclusion of a heterogeneous study. These findings suggest that ferritin may provide additional information for sex-specific diabetes risk assessment.

However, the meta-analysis establishes an association rather than causation. Differences in study populations, substantial between-study heterogeneity, and insufficient information on menopausal status limit interpretation. Further prospective research is needed to determine whether ferritin improves diabetes risk prediction beyond established clinical factors and whether the observed sex difference is consistent across diverse populations.

BACKGROUND: Iron metabolism has been implicated in glucose regulation and the development of type 2 diabetes (T2D). Ferritin, a marker of iron stores, has been associated with diabetes risk in observational studies, although findings have varied across populations. Because circulating ferritin concentrations differ between men and women, investigators conducted a dose-response meta-analysis to examine whether the association between ferritin levels and incident T2D varies by sex.

DETAILS: Researchers systematically searched PubMed, Web of Science, and EMBASE for prospective studies published through August 1, 2018. Fifteen studies involving 77,352 participants aged 20 to 80 years and 18,404 incident T2D cases were included. Follow-up ranged from approximately 3 to 17 years. The investigators assessed the relationship between circulating ferritin concentrations and T2D risk using pooled relative risk estimates and dose-response analyses. Sex-specific analyses were conducted to evaluate potential differences in the association between ferritin levels and diabetes development.

Across all participants, each 100-microgram-per-liter increase in circulating ferritin was associated with a 22% higher risk of T2D (RR, 1.22; 95% CI, 1.14-1.31). In sex-specific analyses, after excluding a study contributing substantial heterogeneity, each 100-microgram-per-liter increase in ferritin was associated with a 53% higher T2D risk in women (RR, 1.53; 95% CI, 1.29-1.82), compared with a 21% increase in men (RR, 1.21; 95% CI, 1.15-1.27). The difference between sexes was statistically significant (P=0.020).

Nonlinear dose-response analyses also indicated that the association between ferritin and T2D risk was stronger in women than in men at comparable ferritin concentrations. The association remained evident after adjustment for several potential confounders, including inflammatory markers, body mass index, liver enzymes, and metabolic factors.

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Source: Jiang, L., Wang, K., Lo, K., et al. ex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies. The Journal of Clinical Endocrinology & Metabolism. 2026; 104(10): 4539-4551. Published: August 22, 2026. DOI: 10.1210/jc.2019-00495.

[Posted 12/Oct/2026]

AUDIENCE: Cardiology, Endocrinology, Internal Medicine

KEY FINDINGS: This study found that HF was associated with increased visceral adiposity, reduced muscle volume, and greater muscle fat infiltration, even when patients were compared with controls matched for BMI. The differing patterns across HF phenotypes suggest that body composition abnormalities are not uniform among patients with heart failure.

The findings indicate that BMI and conventional anthropometric measures may underestimate clinically relevant metabolic and muscular abnormalities. Advanced imaging and more consistent definitions of sarcopenia may improve characterization of these abnormalities, although further research is needed to determine their prognostic value and implications for treatment.

BACKGROUND: Heart failure (HF) is associated with metabolic and musculoskeletal abnormalities that may not be adequately captured by body mass index (BMI). Excess visceral fat, reduced skeletal muscle volume, and increased fat infiltration within muscle can coexist and may differ across HF phenotypes. This study used advanced imaging to characterize body composition in patients with HF compared with matched controls and to examine differences among HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF).

DETAILS: Researchers analyzed participants in the UK Biobank Imaging Study. A total of 185 individuals with HF and available ejection fraction measurements were matched in a 1:5 ratio with 925 controls matched for age, sex, and BMI. Whole-body magnetic resonance imaging (MRI) was used to quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, liver fat, thigh fat-free muscle volume, and muscle fat infiltration (MFI). Dual-energy x-ray absorptiometry (DXA) was used to measure total fat and appendicular lean mass. Personalized z-scores adjusted for sex and body size were calculated. Adverse muscle composition (AMC) was defined by the combination of low muscle volume and high muscle fat infiltration. The investigators also assessed sarcopenia using grip strength and DXA-derived lean mass criteria.

Compared with matched controls, participants with HF had significantly greater visceral adipose tissue (z-score, 0.46 ± 1.1 vs 0.07 ± 1.0; P < 0.001) and muscle fat infiltration (8.4% ± 2.3% vs 7.6% ± 2.0%; P < 0.001). Adverse muscle composition was present in 36% of participants with HF compared with 17% of controls (P < 0.001). Muscle volume was also lower in the HF group (z-score, −0.7 ± 1.0 vs −0.1 ± 0.9; P < 0.001). Body composition patterns differed across HF phenotypes. HFmrEF was associated with the highest visceral adipose tissue levels and lowest muscle volume. HFpEF showed greater overall fat and muscle fat infiltration, whereas HFrEF had the highest prevalence of adverse muscle composition and the weakest grip strength.

Despite the MRI-detected muscle abnormalities, the estimated prevalence of sarcopenia varied considerably according to the diagnostic criteria applied, highlighting inconsistencies among current definitions.

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Source: Butler, J., Fioretti, F., Anker, S. D., et al. Body Composition in Heart Failure: A Magnetic Resonance Imaging and Dual X-Ray Absorptiometry Assessment in the UK Biobank Study. JACC: Heart Failure. 2026; 14(10): 103242. Published: October, 2026. DOI: 10.1016/j.jchf.2026.103242.

A Paradigm for Healthy Aging

[Posted 6/Oct/2026]

AUDIENCE: Ob/Gyn, Endocrinology, Internal Medicine

KEY FINDINGS: Key Information The FIGO-IMS position paper reframes hormone therapy in POI and early menopause as replacement of prematurely lost ovarian hormones, with potential implications for healthy aging. Treatment decisions should consider age at ovarian insufficiency, symptoms, bone health, cardiovascular risk, uterine status, reproductive goals, and individual contraindications.

The evidence supports a comprehensive, individualized approach rather than assuming that regimens used for typical-age menopause are sufficient for younger women with prolonged estrogen deficiency. The authors also acknowledge important evidence gaps, particularly regarding long-term cardiovascular outcomes and comparative effectiveness of different hormone regimens.

BACKGROUND: Premature ovarian insufficiency (POI) and early menopause are associated with prolonged estrogen deficiency during years when ovarian hormone production would ordinarily continue. Beyond vasomotor symptoms and reproductive consequences, estrogen deficiency may affect skeletal, cardiovascular, metabolic, cognitive, and genitourinary health. Hormone therapy (HT) has traditionally been considered primarily for symptom control, but its role in replacing deficient ovarian hormones and supporting long-term health warrants broader clinical consideration.

A joint position paper from FIGO and the International Menopause Society (IMS) reviews current evidence and proposes a more comprehensive approach to hormone therapy in women with POI or early menopause.

DETAILS: The position paper examines the physiological rationale for estrogen replacement, the timing and duration of treatment, hormone formulation and route of administration, and the potential implications for bone and cardiovascular health. It discusses the distinction between hormone replacement in younger women with premature estrogen loss and conventional menopausal hormone therapy initiated around the usual age of menopause. The authors review evidence supporting physiological estradiol replacement, including transdermal 17β-estradiol at 100 micrograms per day or oral 17β-estradiol at 2-4 mg per day. The paper also addresses the need for progestogen protection in women with an intact uterus, individualization of treatment, fertility considerations, and the limitations of available evidence concerning long-term cardiovascular outcomes and comparisons between HT and combined oral contraceptives.

The position paper emphasizes that hormone therapy in women with POI or early menopause should be considered an important component of long-term health management, rather than solely a treatment for vasomotor symptoms. Physiological estrogen replacement may help maintain bone mineral density and address consequences of premature estrogen deficiency. The authors discuss evidence that transdermal estradiol at 100 micrograms per day can restore lumbar spine and femoral neck bone mineral density to normal levels in women with POI. However, evidence regarding the superiority of higher estrogen doses for all skeletal outcomes remains inconsistent, and comparative data on major cardiovascular outcomes are limited.

The paper also highlights the need for further research comparing hormone therapy with combined oral contraceptives and evaluating long-term health outcomes, treatment acceptability, and optimal regimens.

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Source: Benedetto, C., Khadilkar, S. S., Nappi, R. E., et al. Hormone therapy (HT) in women with premature ovarian insufficiency or early menopause: Time to think of a new paradigm for healthy aging. Journal of Gynecology & Obstetrics.. 2026; 175(1): 26-47. Published: October, 2026. DOI: 10.1002/ijgo.71217.

[Posted 5/Oct/2026]

AUDIENCE: Family Medicine, Endocrinology, Primary Care

KEY FINDINGS: Among adults older than 50 years initiating levothyroxine, an initial dose exceeding 1.0 μg/kg per day was associated with higher long-term risks of cardiovascular events, bone outcomes, and all-cause mortality compared with lower initial dosing. The findings support careful consideration of initial dose and subsequent titration in older patients. However, the observational design does not establish that higher dosing directly caused these outcomes, and prospective studies are needed to validate the findings.

BACKGROUND: Levothyroxine is commonly prescribed for hypothyroidism, but determining an appropriate initial dose in older adults remains challenging. Both insufficient and excessive thyroid hormone replacement may adversely affect cardiovascular health, bone integrity, and survival. This study used an emulated target trial approach to evaluate the association between initial weight-based levothyroxine dosing and long-term clinical outcomes in adults older than 50 years.

DETAILS: This observational study used data from The Health Improvement Network, a UK primary care database, covering January 1, 2006, through December 31, 2021. Eligible participants were adults older than 50 years with diagnosed hypothyroidism, at least one recorded thyroid-stimulating hormone (TSH) measurement exceeding 4.0 mU/L, and a new levothyroxine prescription during the study period. The investigators compared patients initiating levothyroxine at more than 1.0 μg/kg per day with those receiving 1.0 μg/kg per day or less. Dosing was assessed using both total bodyweight and lean bodyweight. Participants were followed for up to 10 years for cardiovascular events, bone outcomes, and all-cause mortality. Inverse probability of treatment weighting was used to adjust for baseline confounders, and weighted Cox proportional hazards models were applied to estimate outcome associations.

A total of 19,027 records were eligible, including 14,296 women (75%) and 4,731 men (25%). The cardiovascular analysis included 15,463 adults, the bone health analysis included 14,947, and all 19,027 participants were included in the mortality analysis. Unweighted event rates were higher among patients initiating levothyroxine at more than 1.0 μg/kg per day than among those receiving lower doses. Cardiovascular events occurred in 20% versus 18%, bone outcomes in 13% versus 9%, and all-cause mortality in 18% versus 17%, respectively. Higher initial dosing was associated with increased risk of cardiovascular events (adjusted hazard ratio [HR], 1.18; 95% CI, 1.08-1.29), bone outcomes (HR, 1.29; 95% CI, 1.16-1.43), and all-cause mortality (HR, 1.17; 95% CI, 1.09-1.25).

Using total bodyweight-based dosing, the weighted 10-year absolute risk differences between the higher- and lower-dose groups were 1.3% (95% CI, 0.3-3.0) for cardiovascular events, 3.0% (95% CI, 1.6-4.5) for bone outcomes, and 3.4% (95% CI, 1.7-5.1) for all-cause mortality. Similar associations were observed in analyses using lean bodyweight-based dosing.

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Source: Holley, M., Wilkes, S., Moss, E. D., et al. Weight-based levothyroxine dosing and long-term cardiovascular, bone, and mortality outcomes in older adults: an emulated target trial using UK primary care data. The Lancet Primary Care. 2026; 2(8): 100194. Published: August, 2026. DOI: 10.1016/j.lanprc.2026.100194.

[Posted 1/Oct/2026]

AUDIENCE: Nephrology, Endocrinology, Emergency Medicine

KEY FINDINGS: In this European cohort of older adults with ESKD, vascular access creation frequently did not coincide with the timing of hemodialysis initiation. More than 4 in 10 AVFs were created early, while approximately 1 in 4 were created late, resulting in substantial use of CVCs at dialysis initiation. The findings highlight the difficulty of predicting dialysis initiation in older adults and support the development of clinical prediction tools to better individualize vascular access planning.

BACKGROUND: Planning vascular access for older adults with end-stage kidney disease (ESKD) is challenging because the timing of hemodialysis initiation is difficult to predict. Arteriovenous fistulas (AVFs) created too early may remain unused, whereas delayed creation can result in hemodialysis being initiated through a central venous catheter (CVC). This study evaluated the timing of vascular access creation relative to hemodialysis initiation in older patients across Europe.

DETAILS: This secondary analysis used data from the EQUAL cohort, a prospective observational study involving patients aged 65 years or older with stage 4 or 5 chronic kidney disease in six European countries. Patients were included when their estimated glomerular filtration rate fell below 15 mL/min/1.73 m², provided they received a vascular access and had at least 6 months of follow-up. AVF timing was categorized as early when hemodialysis did not begin within 6 months after AVF creation, on time when hemodialysis was initiated with an AVF within 6 months, and late when hemodialysis was initiated with a CVC before or within 6 months after AVF creation.

A total of 332 patients were analyzed. An AVF was the first vascular access in 221 patients (67%), while 111 patients (33%) initially received a CVC. Among those initially receiving a CVC, 53 patients (48%) subsequently underwent AVF creation. At dialysis initiation, 158 patients (54%) were using an AVF and 136 (46%) were using a CVC. Among the 274 patients who underwent AVF creation, access was created on time in 88 patients (32%), early in 114 (42%), and late in 72 (26%). Despite the high proportion of early AVF creation, most fistulas were eventually used, with 90% of patients initiating hemodialysis within 3 years after AVF creation.

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Source: Heggen, B. D. C., Chesnaye, N. C., Dekker, F. W., et al. Vascular Access Surgery Timing: A Prospective European Cohort Study in Elderly Patients with ESKD. Kidney360. 2026; 7(9): 2066-2074. Published: September 22, 2026. DOI: 10.34067/KID.0000001180.

[Posted 28/Sep/2026]

AUDIENCE: Oncology, Endocrinology, Internal Medicine

KEY FINDINGS: The findings indicate that PTC overdiagnosis remained substantial even after accounting for a possible underlying increase in true disease incidence. The modeling suggests that limiting unnecessary ultrasonography referrals for nonpalpable thyroid nodules could reduce detection of cancers unlikely to affect population mortality, potentially reducing unnecessary diagnoses and treatment-related burdens without a meaningful modeled increase in overall mortality. Because these findings are based on a simulation model rather than observed outcomes from an intervention, they should be interpreted as population-level estimates rather than evidence that reducing imaging is appropriate for individual patients.

BACKGROUND: Papillary thyroid cancer (PTC) incidence in the United States has increased substantially over recent decades, largely driven by detection of small, early-stage tumors, while population-level mortality has remained relatively stable. This pattern has raised concern that some thyroid cancers detected through imaging may never have become clinically significant. This study used a validated simulation model to estimate the extent of PTC overdiagnosis in the United States and examine the potential effects of reducing thyroid ultrasonography for nonpalpable thyroid nodules.

DETAILS: Researchers used the Papillary Thyroid Carcinoma Microsimulation Model (PATCAM) to evaluate PTC incidence among US adults aged 18 years or older from 1991 through 2019. The model accounted for changes in underlying thyroid cancer risk and estimated the proportion and absolute number of PTC cases considered overdiagnosed, defined in the model as cancers whose detection and treatment did not affect population mortality. The investigators also modeled the potential effects of reducing thyroid ultrasonography referrals for nonpalpable thyroid nodules.

Between 1991 and 2019, the model estimated that 72% to 94% of diagnosed PTC cases were overdiagnosed. The estimated proportion was 75% to 95% among women and 63% to 90% among men. The corresponding absolute rate of overdiagnosis was 13 to 17 per 100,000 women and 3 to 5 per 100,000 men, translating to an estimated 443,212 to 573,705 women and 107,804 to 154,504 men overdiagnosed with PTC during the 28-year period. The model further estimated that reducing thyroid ultrasonography for nonpalpable nodules by 33% would reduce PTC incidence in 2019 by 17%, from 18 to 15 per 100,000 individuals. A 67% reduction in ultrasonography was associated with a modeled 41% reduction in incidence, from 18 to 11 per 100,000. In both scenarios, the modeled change in overall mortality was less than 0.1%.

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Source: Francis, D. O., Davies, L., Zhang, Y., et al. Overdiagnosis of Papillary Thyroid Cancer. JAMA Network Open. 2026; 9(2): e2559852. Published: February 24, 2026. DOI: 10.1001/jamanetworkopen.2025.59852