Geriatric nutritional risk index as a predictor for fragility fracture risk in elderly with type 2 diabetes mellitus: A 9-year ambispective longitudinal cohort study.

BACKGROUND & AIMS: The elderly are prone to fragility fractures, especially those suffering from type 2 diabetes mellitus (T2DM) combined with osteoporosis. Although studies have confirmed the association between GNRI and the prevalence of osteoporosis, the relationship between GNRI and fragility fracture risk and the individualized 10-year probability of osteoporotic fragility fractures estimated by FRAX remains unclear. This study aims to delve into the association between the GNRI and a fragility fracture and the 10-year probability of hip fracture (HF) and major osteoporotic fracture (MOF) evaluated by FRAX in elderly with T2DM. METHODS: A total of 580 patients with T2DM aged ≥60 were recruited in the study from 2014 to 2023. This research is an ambispective longitudinal cohort study. All participants were followed up every 6 months for 9 years with a median of 3.8 years through outpatient services, medical records, and home fixed-line telephone interviews. According to the tertiles of GNRI, all subjects were divided into three groups: low-level (59.72-94.56, n = 194), moderate-level (94.56-100.22, n = 193), and high-level (100.22-116.45, n = 193). The relationship between GNRI and a fragility fracture and the 10-year probability of HF and MOF calculated by FRAX was assessed by receiver operating characteristic (ROC) analysis, Spearman correlation analyses, restricted cubic spline (RCS) analyses, multivariable Cox regression analyses, stratified analyses, and Kaplan-Meier survival analysis. RESULTS: Of 580 participants, 102 experienced fragile fracture events (17.59%). ROC analysis demonstrated that the optimal GNRI cut-off value was 98.58 with a sensitivity of 75.49% and a specificity of 47.49%, respectively. Spearman partial correlation analyses revealed that GNRI was positively related to 25-hydroxy vitamin D [25-(OH) D] (r = 0.165, P < 0.001) and bone mineral density (BMD) [lumbar spine (LS), r = 0.088, P = 0.034; femoral neck (FN), r = 0.167, P < 0.001; total hip (TH), r = 0.171, P < 0.001]; negatively correlated with MOF (r = -0.105, P = 0.012) and HF (r = -0.154, P < 0.001). RCS analyses showed that GNRI was inversely S-shaped dose-dependent with a fragility fracture event (P < 0.001) and was Z-shaped with the 10-year MOF (P = 0.03) and HF (P = 0.01) risk assessed by FRAX, respectively. Multivariate Cox regression analysis demonstrated that compared with high-level GNRI, moderate-level [hazard ratio (HR) = 1.950; 95% confidence interval (CI) = 1.076-3.535; P = 0.028] and low-level (HR = 2.538; 95% CI = 1.378-4.672; P = 0.003) had an increased risk of fragility fracture. Stratified analysis exhibited that GNRI was negatively correlated with the risk of fragility fracture, which the stratification factors presented in the forest plot were not confounding factors and did not affect the prediction effect of GNRI on the fragility fracture events in this overall cohort population (P for interaction > 0.05), despite elderly females aged ≥70, with body mass index (BMI) ≥24, hypertension, and with or without anemia (all P < 0.05). Kaplan-Meier survival analysis identified that the lower-level GNRI group had a higher cumulative incidence of fragility fractures (log-rank, all P < 0.001). CONCLUSION: This study confirms for the first time that GNRI is negatively related to a fragility fracture and the 10-year probability of osteoporotic fragility fractures assessed by FRAX in an inverse S-shaped and Z-shaped dose-dependent pattern in elderly with T2DM, respectively. GNRI may serve as a valuable predictor for fragility fracture risk in elderly with T2DM. Therefore, in routine clinical practice, paying attention to the nutritional status of the elderly with T2DM and giving appropriate dietary guidance may help prevent a fragility fracture event.

Triglyceride-glucose index is strongly associated with all-cause mortality in elderly females with diabetic foot ulcers: A 9-year follow-up study.

This study aims to explore the association between the triglyceride-glucose (TyG) index and all-cause mortality in patients with diabetic foot ulcers (DFUs) through an ambispective cohort study. A total of 555 inpatients with DFUs were qualified to participate in the trial study from 2013 to 2022. Throughout a median 63-month period, all subjects were followed up every 6 months. According to the three quantiles of the TyG index, participants were divided into three groups: low-level (≤8.75, n = 185), moderate-level (8.76-9.33, n = 185) and high-level (≥9.34, n = 185). The association between the TyG index and all-cause mortality in patients with DFUs was then assessed. During the follow-up period, out of 555 patients with DFUs, 116 died (20.9%). After adjusting for confounding factors, the TyG index was positively associated with all-cause mortality in patients with DFUs (HR = 1.733; 95% CI = 1.341-2.241; p < 0.001). Compared with the low-level TyG index, the moderate-level TyG index (HR = 1.685; 95% CI = 1.011-2.810; p = 0.045) and the high-level TyG index (HR = 2.769; 95% CI = 1.678-4.568; p < 0.001) were positively correlated with all-cause mortality in patients with DFUs. Additionally, in subgroup analysis, both females (HR = 1.905; 95% CI = 1.250-2.904; p = 0.003), males (HR = 1.729; 95% CI = 1.240-2.409; p = 0.001), younger (<65 years old) (HR = 1.467; 95% CI = 1.008-2.135; p = 0.046) and elderly (≥ 65) (HR = 1.933; 95% CI = 1.339-2.791; p < 0.001) showed a positive correlation between TyG index and all-cause mortality rate in patients with DFUs. Furthermore, in the high-level TyG index group compared, males (HR = 2.699; 95% CI = 1.457-4.998) and participants aged <65 years (HR = 2.031; 95% CI = 0.972-4.242), with the TyG index level increase by 1.0, the risk for all-cause mortality increased 3.277-fold in females (HR = 4.277; 95% CI = 1.645-11.124) and 1.909-fold in elderly aged ≥65 years (HR = 2.909; 95% CI = 1.486-5.695), respectively. Kaplan-Meier survival curve analysis showed that the higher the TyG index level, the higher risk of all-cause mortality in patients with DFUs (log-rank, all p < 0.001). Briefly, this study implies a strong positive correlation between the TyG index and all-cause mortality in patients with DFUs, especially in older women. Therefore, special attention should be paid to elderly females with DFUs because they have a higher TyG index level and risk of all-cause mortality than other populations in daily clinical practice.

A Novel Wound Therapy Modality: Autologous Wound Edge Dotted Full-Thickness Skin Grafting Improving Diabetic Foot Ulcer Healing.

Aim: To explore the therapeutic efficacy of autologous wound edge-dotted full-thickness skin grafting in improving diabetic foot ulcer healing. Methods: Sixty-three patients were divided into three groups: conventional wound therapy (CWT) (n = 23), platelet-rich plasma (PRP) (n = 20), and graft (n = 20). All participants were followed up for 12 weeks. The therapeutic efficacy of the three different wound treatment modalities was analyzed. Results: After follow-up, 37 (58.7%) patients showed complete wound re-epithelialization, of which 10 (43.5%) occurred in the CWT group, 14 (70.0%) in the PRP group, and 13 (65.0%) in the graft group. Multivariate Cox analysis showed that the independent predictive factors for ulcer healing were different treatment modalities (graft: HR = 3.214, 95% CI=1.300-7.945, P < 0.05; platelet-rich plasma: HR = 3.075, 95% CI=1.320-7.161, P < 0.01), ABI (HR = 9.917, 95% CI=2.675-36.760, P < 0.01), and TcPO2 (HR = 1.040; 95% CI=1.005-1.076; P < 0.05). Stratified analysis showed that higher ABI in graft group or PRP group had higher wound healing rate (graft group: HR = 3.748, 95% CI=1.210-11.607, P < 0.05; PRP group: HR = 5.029, 95% CI=1.743-14.509, P < 0.05); higher TcPO2 in the graft group had higher wound healing rate (HR = 15.805, 95% CI=4.414-56.594, P < 0.01). Additionally, the wound healing time (P < 0.0167) and cumulative healing rate (P < 0.05) in both the PRP group and graft group were more advantageous. The graft group promotes wound re-epithelialization earlier and faster than in the CWT group and PRP group (P < 0.05). Meanwhile, the graft group had lower medical costs (P < 0.0167). Conclusion: Autologous wound edge dotted full-thickness skin grafting has a higher cost-performance ratio than traditional diabetic foot ulcer wound care and is worthy of further clinical application.

The Ratio of Serum Uric Acid to Glycosylated Haemoglobin as a Predictor of All-Mortality in Elderly Patients with Diabetic Foot Ulcers: A Longitudinal Cohort Study.

Aim: To clarify the relationship between serum uric acid (UA) and glycosylated hemoglobin (UA/HbA1c) ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). Methods: A total of 172 inpatients with DFUs (PEDIS grades 2-4) were eligible for inclusion in this study from 2018 to 2023. This was a retrospective, longitudinal cohort study. All subjects were followed up every 6 months for a median of 60 months. According to the cutoff value of the UA/HbA1c ratio of 39.07 obtained from ROC analysis, the participants were divided into two groups: low-level (≤ 39.07, n = 107) and high-level (> 39.07, n = 65) groups. The correlation between UA/HbA1c ratio and all-cause mortality was also evaluated by Cox regression analysis TheKaplan-Meier survival curve analysis and Log rank tests were used to assess the incidence rates of all-cause mortality. The contribution rate of risk factors was estimated by the population-attributable risk percentage (PAR%) analysis. Results: ROC analysis showed that the optimal cutoff values for UA and the UA/HbA1c ratio were 372 µmol/L and 39.07, respectively. Multivariate Cox regression analysis indicated that a high UA/HbA1c ratio (HR =4.63; 95% CI = 2.004-10.7, P < 0.001) was independently associated with a high risk of all-cause mortality in patients with DFUs. Stratified analysis indicated that subjects aged ≥ 60 years had a greater risk of all-cause mortality associated with a high UA/HbA1c ratio (HR = 4.450; 95% CI = 1.711-11.574, P = 0.002). Kaplan-Meier survival analysis showed that all-cause mortality had a significant positive association with a high UA/HbA1c ratio (log-rank, P < 0.001) and a significant negative correlation with the lowered HbA1c level (< 6.5%) after a follow-up of 32 months (log-rank, P < 0.001). The population attributable risk percentage (PAR%) analysis suggested that the contribution rate of the high-level UA/HbA1c ratio to all-cause mortality was 33.7%, which was much greater than the 19.69% of UA. Conclusion: In brief, our study showed that for every 1.0% increase in the UA/HbA1c ratio, the all-cause mortality rate in elderly patients with DFUs aged ≥ 60 years increased by 3.45-fold. For elderly patients with DFUs, a safe and effective strategy to reduce all-cause mortality is to strictly control serum UA levels to < 372 µmol/L and appropriately loosen the control goal of HbA1c to ≥ 6.5%.

Risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis and diabetic nephropathy: A 3-year follow-up study.

This study aimed to explore the risk factors for foot ulcer recurrence in patients with comorbid diabetic foot osteomyelitis (DFO) and diabetic nephropathy (DN). This is a prospective cohort study. Between May 2018 and May 2021, we selected 120 inpatients with comorbid severe diabetic foot infection (PEDIS Grade 3 or above) and DN for inclusion in our study. All cases were followed up for 36 months. The study outcomes were whether foot ulcer recurred and the time to recurrence. The risk factors of ulcer recurrence were analysed by comparing the data of the three groups. According to the recurrence of foot ulcer, the participants were divided into three groups: Group A (no foot ulcer recurrence, n = 89), Group B (foot ulcer recurrence within 12-36 months, n = 19) and Group C (foot ulcer recurrence within 6-12 months, n = 12). The multivariate Cox regression analysis showed that urine albumin-creatinine ratio (UACR) (HR: 1.008, 95% CI: 1.005-1.011, P < .001) and vibration perception threshold (VPT) (HR: 1.064, 95% CI: 1.032-1.096, P < .001) were identified as independent risk factors. Kaplan-Meier curves showed a significant positive association between UACR or VPT and the risk of foot ulcer recurrence (log rank, all P < .05). Areas under the ROC curves for UACR, VPT and the combination of UACR and VPT were 0.802, 0.799 and 0.842, respectively. The best cut-off values of UACR and VPT were 281.51 mg/g and 25.12 V, respectively. In summary, elevated UACR and VPT were independent risk factors. The best clinical cut-off values of UACR and VPT for prediction of foot ulcer recurrence were 281.51 mg/g and 25.12 V, respectively. Besides, our results suggested that microcirculation disorders rather than macrovascular complications play a major role in the recurrence of foot ulcer in patients with comorbid DFO and DN.

Autologous wound margin point columnar full-thickness skin grafting combined with negative pressure wound therapy improves wound healing in refractory diabetic foot ulcers.

Diabetic lower extremity ulcers (DLEUs) are a severe complication of diabetes mellitus (DM) and are difficult to heal. This study aimed to explore the efficacy of autologous point columnar full-thickness skin graft taken from the ulcer wound margin combined with negative pressure wound therapy (NPWT) in refractory DLEUs. This is a prospective cohort study. A total of 40 inpatients with refractory DLEUs were recruited in the Diabetes Foot Center of Guangxi Zhuang Autonomous Region People's Hospital from October 2019 to November 2021. According to the doctors' professional suggestions and the patients' personal wishes, these enrolled patients were divided into two groups based on different topical wound management: the graft group (n = 18) and the conventional wound therapeutic (CWT) group (n = 22). The efficacy evaluations included the time to complete re-epithelialization of the wound and healing speed within 14 days of graft treatment or after 14 days of graft treatment in the two groups. Before the treatment, the graft group had a significantly larger ulcer area than the CWT group [27.22 (15.28, 46.59) versus 10.92 (7.00, 24.93) cm2 , P < .01]. However, the time to complete wound re-epithelialization in the graft group was shorter than in the CWT group [58.22 ± 30.60 versus 86.09 ± 49.54 d, P < .05]. Meanwhile, the healing speed in graft group was markedly faster than in CWT group, whether within 14 days [0.60 (0.40, 0.92) versus 0.16 (0.07, 0.34) cm2 /d, P < .01] or after 14 days of graft treatment [0.57 (0.45, 0.91) versus 0.13 (0.08, 0.27) cm2 /d, P < .01]. However, the total treatment cost in the graft group was lower than in the CWT group [419.59 ± 137.20 versus 663.97 ± 497.02 $, P < .05]. The novel treatment modality of autologous full-thickness skin graft taken from the ulcer wound margin combined with NPWT has hereby proposed for the first time, and is a safe, effective, and reliable method with a good performance-to-cost ratio to promote wound healing and shorten the healing time for DLEUs.

Urine Albumin-Creatinine ratio is associated with prognosis in patients with diabetic foot osteomyelitis.

AIMS: We aimed to explore the association between albuminuria and clinical outcomes in patients with diabetic foot osteomyelitis (DFO). METHODS: This is an observational retrospective study and a total of 202 inpatients with DFO were eligible for inclusion in our study. Based on urine albumin-creatinine ratio (UACR), the patients were divided into three groups: normoalbuminuria group, microalbuminuria group and macroalbuminuria group. The data collected include demographics data, laboratory data, clinical diagnostic data, diabetic foot examination and clinical visit data. The association was then evaluated between albuminuria and all-cause mortality, major cardiovascular adverse events (MACE) and mixed endpoint events. RESULTS: The mean age was 60.3 years, 62.9% were male and 45.05% were urinary protein-positive. The incidence rates of all-cause mortality, MACE and mixed endpoint events related to elevated UACR were significantly increased in patients with DFO (all P for trend < 0.01). After adjusting for confounders, compared with normoalbuminuria group, the risk of all-cause mortality, MACE and mixed endpoint events in the microalbuminuria group increased by 81.8%, 135.4% and 136.4%, respectively. The risk of all-cause mortality, MACE and mixed endpoint events in the macroalbuminuria group increased by 246.2%, 145.1% and 252.3%, respectively. The population attributable risk percentage (PAR%) suggested that 50.16% of all-cause mortality, 47.85% of MACE and 59.11% of mixed endpoint events could be attributed to the elevated UACR. Meanwhile, compared with normoalbuminuria, those with microalbuminuria or macroalbuminuria have lower apoA1 and ABI, higher SCr and higher incidence rate of CHD, hindfoot infection and severe infection (all P < 0.05). CONCLUSIONS: In patients with DFO, the UACR level is associated with all-cause mortality, MACE and mixed endpoint events and elevated UACR levels increase the risk of all-cause mortality, MACE and mixed endpoint events.

Associations of Estimated Glomerular Filtration Rate with All-Cause Mortality and Cardiovascular Mortality in Patients with Diabetic Foot Osteomyelitis.

AIM: The purpose of this study was to explore the association between estimated glomerular filtration rate (eGFR) and clinical outcomes in patients with diabetic foot osteomyelitis (DFO). METHODS: This was a retrospective observational study. A total of 199 patients with DFO were recruited and divided into three groups by eGFR: normal kidney function group (eGFR ≥ 90), mildly decreased kidney function group (eGFR 60-89) and moderately to severely decreased kidney function group (eGFR < 60). The patients were followed-up for a median of 36 months, and the study outcomes were all-cause mortality and major cardiovascular adverse events (MACE). Cox proportional hazard models were used to assess the association between eGFR and the outcomes, and a stratified analysis by sex was conducted. RESULTS: During follow-up, all-cause mortality occurred in 51 (25.63%) patients among 199 participants, 54 (28.72%) had MACE in 188 participants and 26 (48.15%) of them died. After fully adjusting for potential confounders, compared to eGFR < 90 mL/min/1.73 m2, eGFR ≥ 90 mL/min/1.73 m2 had lower incidence of all-cause mortality (HR = 0.43, 95% CI: 0.22-0.85; P = 0.015) and MACE (HR = 0.51, 95% CI: 0.27-0.96; P = 0.038). Additionally, compared to eGFR < 90 mL/min/1.73 m2, eGFR ≥ 90 mL/min/1.73 m2 was independently associated with decreased risk of all-cause mortality (HR = 0.33; 95% CI 0.14-0.76, P = 0.010) and MACE (HR = 0.27; 95% CI 0.11-0.65, P = 0.004) in male, but not in female. CONCLUSION: In conclusion, decreased eGFR is a risk factor for all-cause mortality and MACE in individuals with DFO. Additionally, male with decreased eGFR had a higher risk of all-cause mortality and MACE, but female did not.