Frailty and risk of microvascular complications in patients with type 2 diabetes : a population-based cohort study

Background Cross-sectional studies found that frailty was associated with prevalent diabetic microvascular complications (DMC). Longitudinal evidence in this regard is inconclusive and insufficient. We aimed to prospectively evaluate the association of pre-frailty and frailty with DMC in patients with type 2 diabetes (T2D). Methods We included 18,062 adults (mean age 59.4 ± 7.2 years, 37.4% female) with T2D at baseline in the UK Biobank. Frailty was defined using the frailty phenotype according to five components (weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength). DMC, defined as diabetic nephropathy, diabetic neuropathy, or diabetic retinopathy, was identified using hospital inpatient records and death registries. Cox proportional hazard regression models considering competing risks were used to evaluate the associations of frailty phenotype with overall DMC events and subtypes. Results Among all participants, 6101 (33.8%) were classified as non-frail, 10,073 (55.8%) were classified as pre-frail, and 1888 (10.4%) were classified as frail. During a median follow-up of 12.0 years, 3678 DMC cases were documented, including 2213 diabetic nephropathy, 1520 diabetic retinopathy, and 673 diabetic neuropathy events. In the multivariable-adjusted model, compared with participants with non-frail, both pre-frailty and frailty were significantly associated with increased risk of overall DMC (HR 1.10, 95% CI: [1.02, 1.18] for pre-frailty and HR 1.52 [95% CI: 1.36, 1.69] for frailty). Similar results were observed in the subtypes of DMC. For each one-point increase in frailty phenotype score, the risk of overall DMC, diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy event increased by 13%, 16%, 10%, and 20%, respectively. Conclusions Both pre-frailty and frailty were associated with an increased risk of DMC in patients with T2D. These findings have important implications for integrating early assessment and surveillance of frailty in diabetes and may favor the identification of at-risk patients

Association of serum uric acid with all-cause and cardiovascular mortality in diabetes: prospective cohort study and meta-analysis

   Objective: To investigate whether serum uric acid (SUA) level was associated with all-cause and cardiovascular disease (CVD) mortality among individuals with diabetes.  Research design and methods: In this prospective cohort, we included the patients with diabetes from the National Health and Nutritional Examination Survey (NHANES) 1999-2018. Mortality and underlying causes of death were ascertained by linkage to national death records through December 31, 2019. Weighted Cox proportional hazards regression models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CVD mortality. We further performed a meta-analysis of available cohort studies to combine the association between SUA and mortality in diabetes. Results: Among the 7,101 diabetes from NHANES 1999-2018, the weighted mean of SUA level was 5.7 mg/dL. During 57,926 person-years of follow-up, 1,900 deaths (674 deaths from CVD) occurred. In the fully adjusted model, when compared to patients with diabetes in the lowest SUA quintile, those in the highest SUA quintile had the HRs (95% CIs) of 1.28 (1.03, 1.58) for all-cause mortality and 1.41 (1.03, 1.94) for CVD mortality. We included 13 cohort studies in the meta-analysis, and found that the pooled HRs (95% CIs) were 1.08 (1.05, 1.11) for all-cause mortality and 1.05 (1.03, 1.06) for CVD mortality, with per 1 mg/dL increment of SUA level in diabetes.  Conclusions: This study indicated that higher SUA levels were associated with increased risks of all-cause and CVD mortality in diabetes. Interventional studies are needed to elucidate the health effect of lowering uric acid treatments.</p

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis

Background: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. Objective: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. Methods: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose–response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. Results: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07–2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36–0.84). Longitudinal analysis indicated that the annual change of SUA was from −4.80 (β, 95%CI: −10.74, 1.13) to −9.00 (β, 95%CI: −15.03, −2.99) and then to −6.77 (β, 95%CI: −12.83, −0.71, p for trend = 0.0212) μmol/L when increasing the quartile of vitamin D3. Conclusions: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism