Inverse association between high-density lipoprotein cholesterol and bone mineral density in patients with diabetes results from a nationally representative survey
Higher HDL levels were consistently and independently associated with lower BMD in US adults with diabetes, challenging the traditional view of HDL as universally protective and suggesting that in the diabetic context, elevated HDL may exert detrimental effects on bone health.
Abstract
Diabetes mellitus substantially increases the risk of osteoporosis and fractures, but the mechanisms remain unclear. Dyslipidemia, particularly the role of high-density lipoprotein (HDL), may influence bone mineral density (BMD), yet evidence in diabetic patients is limited. This study aimed to explore the association between HDL and BMD in US adults with diabetes using a nationally representative dataset. We analyzed data from 5 National Health and Nutrition Examination Survey cycles (2005–2018). A total of 5014 diabetic participants with available HDL and dual-energy X-ray absorptiometry (DXA)-measured BMD were included. Weighted multivariable linear regression models, smooth curve fitting, and 2-piecewise linear regression were employed to examine linear and nonlinear associations. Subgroup and sensitivity analyses were also conducted to assess robustness. Among 5014 participants (mean age 40.1 ± 31.2 years; 50.8% male), mean femoral neck and lumbar spine BMD were 0.81 and 1.03 g/cm2, respectively, with a mean HDL of 48.9 mg/dL. Higher HDL levels were inversely associated with BMD at both the femoral neck (β = −0.0011, 95% CI: −0.0015 to −0.0007) and lumbar spine (β = −0.0012, 95% CI: −0.0018 to −0.0007) after full adjustment. Participants in the highest HDL quartile had significantly lower BMD compared with those in the lowest quartile (femoral neck: −0.0294 g/cm2; lumbar spine: −0.0378 g/cm2). Smooth curve fitting indicated nonlinear, negative associations. Subgroup analyses revealed stronger inverse associations in men, participants with hypertension, those <60 years at the femoral neck, and those ≥60 years at the lumbar spine. Sensitivity analyses confirmed the robustness of the results. Higher HDL levels were consistently and independently associated with lower BMD in US adults with diabetes. These findings challenge the traditional view of HDL as universally protective, suggesting that in the diabetic context, elevated HDL may exert detrimental effects on bone health. Further longitudinal and mechanistic studies are warranted to clarify causal pathways and guide osteoporosis prevention strategies in this high-risk population.
To investigate the association between the Metabolic Score for Insulin Resistance (METS-IR) and bone mineral density (BMD) and trabecular bone score (TBS) in adult cancer patients.
This cross-sectional study enrolled 127 patients (median age 63 years, 44.9% female) with histopathologically confirmed malignancies. BMD at the lumbar spine, femoral neck, and total hip and lumbar spine TBS were measured by dual-energy X-ray absorptiometry. METS-IR was calculated using fasting glucose, triglycerides, high-density lipoprotein cholesterol, and body mass index. Multivariable linear regression was used to identify independent associations.
After adjustment for confounders, METS-IR was independently and positively associated with BMD at lumbar spine (β = 0.006, 95% CI 0.002–0.011, P = 0.007), femoral neck (β = 0.007, 95% CI 0.003–0.011, P < 0.001), and total hip (β = 0.007, 95% CI 0.003–0.010, P < 0.001). Age was inversely associated with lumbar spine and femoral neck BMD, but not with total hip BMD; bone metastasis was linked to higher lumbar spine and total hip BMD. In contrast, METS-IR showed no significant association with lumbar spine TBS (P = 0.374). For TBS, age and male sex, but not METS-IR, were independent determinants.
In cancer patients, higher METS-IR is independently associated with greater BMD but not with better trabecular microarchitecture. This discordance between bone quantity and quality suggests that insulin resistance may mask impaired bone quality despite preserved BMD. Clinicians should consider bone quality assessments when evaluating fracture risk in metabolically compromised cancer patients. Longitudinal studies are warranted to confirm these findings.
Hong-Dan Yao, Cheng Niu, Lin Zhu et al.· Frontiers in Endocrinology· 0 citations
OBJECTIVE
To gain insight into higher fracture risk in individuals with type 2 diabetes, we determined the association of type 2 diabetes glycemic status and severity with longitudinal changes in peripheral bone density and microarchitecture.
RESEARCH DESIGN AND METHODS
We conducted a longitudinal study of 769 participants from the Framingham Study who underwent high-resolution, peripheral, quantitative computed tomography (HR-pQCT) at the tibia and radius, in 2012-2016 and 2021-2023 (mean 8-year follow-up). Linear regression models estimated mean 8-year percent changes in bone measures, across indicators of diabetes severity, adjusting for age, sex, weight, and height.
RESULTS
The mean age was 67 ± 7 years, and 59% of participants were women. More than half (57%) were normoglycemic (fasting plasma glucose [FPG] <100 mg/dL, not on any treatment), 31% had prediabetes (100 ≤ FPG ≤125 mg/dL), and 12% had type 2 diabetes (FPG >125 mg/dL or on treatment). Adjusted mean percent changes in HR-pQCT bone measures were similar across diabetes severity, including glycemic status, use of diabetes medications, duration of diabetes, and HbA1c. For example, cortical volumetric bone mineral density at the radius changed by -1.50% (95% CI -2.43, -0.56) in type 2 diabetes and -1.96% (-2.53, -1.39), in prediabetes, compared with -2.42% (-2.86, -1.97) in normoglycemia (reference group; all P > 0.05).
CONCLUSIONS
The magnitude of peripheral bone loss over 8 years did not differ between individuals with type 2 diabetes and those with normoglycemia, suggesting that bone deterioration alone does not explain the higher fracture risk in older adults with type 2 diabetes. Future studies should address other contributors to skeletal fragility.
A. Dufour, M. Bouxsein, Mu-Song Gao et al.· Diabetes Care· 0 citations
Increases in ECF, ICF, and TBW were significantly linked to a lowered osteoporosis risk and enhanced BMD, which may aid clinicians in the early identification and intervention of patients at risk for bone loss.
Wanxin Su, Sizhe Xiao, Yanhui Li et al.· American Journal of the Medi...· 0 citations
Lipid metabolism is recognized as a key player in carcinogenesis, but the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and overall cancer prevalence remains unclear in the US population. This study aimed to investigate the association between NHHR and cancer prevalence based on self-reported lifetime cancer diagnoses in a nationally representative US population. We utilized data from the National Health and Nutrition Examination Survey from 2007 to 2016. The primary exposure was NHHR, and the primary outcome was self-reported lifetime cancer diagnosis. Associations were assessed using weighted multivariable logistic regression models, with NHHR modeled as both a continuous variable and tertiles. Model 1 was unadjusted; Model 2 adjusted for age, sex, race/ethnicity, education level, marital status, and family income-to-poverty ratio; and Model 3 further adjusted for total cholesterol, glycated hemoglobin, physical activity, and drinking status. The analysis included adults aged 18 years or older with available NHHR and cancer-related information. Exploratory cancer-specific analyses were performed for prostate, breast, colorectal, and lung cancers. Among 26,416 participants, 2451 (9.0%) reported a lifetime cancer diagnosis. The mean age of the participants was 49.48 ± 17.67 years, and the mean NHHR was 2.96 ± 1.48. In the fully adjusted model, each unit increase in NHHR corresponded to 7% higher odds of cancer prevalence (odds ratio: 1.07 [95% confidence interval: 1.01–1.13]). NHHR tertiles were defined as T1 (0.45–2.11), T2 (2.11–3.11), and T3 (3.11–15.03). Compared with participants in the lowest tertile, those in the highest tertile had 22% higher odds of cancer prevalence (odds ratio: 1.22 [95% confidence interval: 1.04–1.48], P = .035). Subgroup analyses suggested potential effect modification by sex. Elevated NHHR levels were positively associated with cancer prevalence in US adults, suggesting that NHHR may be a potential biomarker warranting further investigation.
BACKGROUND
To examine the association between the serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) and peripheral arterial disease (PAD) among U.S. adults.
METHODS
This cross-sectional study used data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). PAD was defined as ABI <0.90 in either leg. Weighted multivariable logistic regression was used to estimate odds ratios (ORs) for PAD according to UHR modeled continuously and by quartiles. Restricted cubic spline (RCS) regression, subgroup analyses, interaction tests, sensitivity analyses, stratified receiver operating characteristic (ROC) analyses and propensity score matching (PSM) were performed.
RESULTS
A total of 6149 participants were included, among whom 459 had PAD (7.5%).Each one-unit increase in UHR was associated with higher odds of PAD (OR 1.04, P = 0.004). The highest UHR quartile (≥14.47) was associated with 52% higher odds of PAD compared with the lowest quartile (<7.78) (P = 0.036). RCS analysis showed an overall association (P for overall = 0.006) without evidence of a statistically significant nonlinear pattern (P for nonlinearity = 0.375). Stratified ROC analysis identified optimal cut-offs of 10.69 for the overall population (AUC = 0.577), 12.55 for statin users (AUC = 0.602), and 9.82 for non-statin users (AUC = 0.554). PSM confirmed the overall association (P = 0.027) , with significance retained only among statin users (P = 0.002).Subgroup and sensitivity analyses generally supported the robustness of the findings.
CONCLUSIONS
Higher UHR is independently associated with PAD. UHR may serve as an adjunctive screening marker, particularly for statin users (cut-off ≥12.55).
Chunhong Ding, Qiliang Chai, Li-Fang Jin et al.· Annals of Vascular Surgery· 0 citations
Background Diabetic kidney disease (DKD) is a major complication of type 2 diabetes (T2D) and is closely linked to metabolic dysregulation. The uric acid-to-high-density lipoprotein cholesterol ratio (UHR) integrates urate-related purine metabolism and high-density lipoprotein cholesterol (HDL-C)-related lipid metabolism, two metabolic signals potentially related to kidney injury. This study examined the cross-sectional association between UHR and prevalent DKD in patients with T2D. Methods This study included a primary clinical cohort of 912 patients with T2D and an external validation cohort from the National Health and Nutrition Examination Survey (NHANES; n = 2,738). Multivariable logistic regression was used to assess the association between UHR and prevalent DKD. Restricted cubic spline (RCS) analyses evaluated exposure-response patterns. Subgroup, interaction, and joint analyses were performed to examine the association across clinical strata. Results In the primary cohort, DKD prevalence increased from 20.52% in the lowest UHR quartile to 55.26% in the highest quartile (P < 0.001). After full adjustment, each 1-SD increase in UHR was associated with more than 2-fold higher odds of DKD (OR, 2.22; 95% CI, 1.80–2.77; P < 0.001). Compared with Q1, the adjusted ORs for Q2, Q3, and Q4 were 1.29, 2.32, and 6.73, respectively. The trend across quartiles was significant (P for trend < 0.001). RCS analyses showed positive overall associations between UHR and DKD. The positive association was generally observed across predefined subgroups, with nominal evidence of interaction by body mass index (BMI) and insulin use. In NHANES, 1,067 of 2,738 participants had DKD. External validation showed directionally consistent results. Higher odds of DKD were observed per 1-SD increase in UHR (OR, 1.44; 95% CI, 1.23–1.68; P < 0.001) and in Q4 vs. Q1 (OR, 2.61; 95% CI, 1.79–3.79; P < 0.001). Survey-weighted RCS showed a positive association without significant non-linearity. Conclusion Higher UHR was associated with greater odds of prevalent DKD in the hospital-based T2D cohort, with directionally consistent findings in the NHANES validation cohort.
Yong-Jun Ma, Xinyi Huang, Guangming Chen et al.· Frontiers in Nutrition· 0 citations
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