The Ca∗Cl/P Ratio: A Novel and More Appropriate Screening Tool for Normocalcaemic or Overt Primary Hyperparathyroidism.

OBJECTIVE: The main purpose of this study was to explore the diagnostic performance of the Ca∗Cl/P ratio for primary hyperparathyroidism (PHPT), especially normocalcaemic PHPT (NPHPT), to assist health care providers in making reliable and rapid clinical identifications. METHODS: From January 1, 2013, to March 31, 2023, 230 PHPT patients, including 65 with NPHPT and 230 sex- and age-matched controls, were enrolled in this retrospective study. Differences between hypercalcaemic PHPT (HPHPT) and NPHPT and between them and their respective controls were analyzed. The diagnostic accuracy of the Ca∗Cl/P ratio, Ca/P ratio, Cl/P ratio and albumin-corrected calcium was assessed by the area under the receiver operating characteristic curve. RESULTS: Compared with corresponding controls, NPHPT and HPHPT patients both had significantly higher Ca ∗ Cl/P ratios (271.64 ± 51.74 vs 192.71 ± 26; 419.91 ± 139.11 vs 199.14 ± 36.75, P < .001). In the overall cohort, the ROC-AUC of the Ca∗Cl/P ratio (0.964, 95% CI = 0.943-0.979) for diagnosis of PHPT patients was superior to albumin-corrected calcium (0.959, 95% CI = 0.934-0.973), the Ca/P ratio (0.956, 95% CI = 0.934-0.973), and the Cl/P ratio (0.923, 95% CI = 0.895-0.946). A Ca ∗ Cl/P ratio above 239.17 mmol/L, with sensitivity (0.952), specificity (0.922), PPV (0.924), NPV (0.951) and accuracy (0.937), can distinguish PHPT patients from healthy individuals. Furthermore, the Ca ∗ Cl/P ratio yielded a sensitivity of 0.831, specificity of 0.938, PPV of 0.931, NPV of 0.847 and accuracy of 0.885 for NPHPT. CONCLUSION: The Ca∗Cl/P ratio provides excellent diagnostic power for diagnosis of PHPT, especially NPHPT.

A simple fragility fracture risk score for type 2 diabetes patients: a derivation, validation, comparison, and risk stratification study.

OBJECTIVES: The aims of this study were to develop and validate 2 simple scores for stratification of the risks of (1) any fragility (AF) and (2) major osteoporotic fracture (MOF) in type 2 diabetes (T2D) patients; we also compared the performance of these scores with that of the Fracture Risk Assessment Tool (FRAX) and its adjustments. DESIGN AND METHODS: In this longitudinal cohort study, 1855 patients with T2D were enrolled from January 2015 to August 2019. Cox proportional hazard regression was used to model the 5-year risk of AF and MOF. These scores were internally validated using a bootstrap resampling method of 1000. RESULTS: During a median follow-up of 5 years, 119 (6.42%) cases of AF and 92 (4.96%) cases of MOFs were identified. Both the concordance index (C-index) and calibration plots indicated improved identification performance using the newly established scores. Furthermore, these scores also showed improved outcomes regarding the decision curve analysis (DCA) and area under the curve (AUC) compared to the widely used FRAX and its derivatives. More importantly, these scores successfully separated T2D patients into risk groups according to significant differences in fracture incidence. CONCLUSIONS: These novel scores enable simple and reliable fracture risk stratification in T2D patients. Future work is needed to validate these findings in external cohort(s).

Comparing the prognostic value of the old and new sarcopenia criteria from the Asian Working Group on Sarcopenia in older adults with type 2 diabetes: Which set is more appropriate?

BACKGROUND: This study aimed to compare the prevalence of sarcopenia according to the old and new Asian Working Group on Sarcopenia (AWGS) operational criteria and explore the effects of sarcopenia on adverse outcomes in older adults with type 2 diabetes (T2D). METHODS: A total of 386 patients with T2D aged ≥ 60 years were recruited in retrospective cohort study. Sarcopenia was assessed with different versions of the AWGS consensus, including the AWGS2014, AWGS2019H (muscle mass adjusted for height), and AWGS2019B (muscle mass adjusted for body mass index). The median follow-up period was 47 months. The composite primary endpoint was the first occurrence of cardiovascular disease (CVD), fragility fracture, and all-cause mortality and the secondary outcomes included the three separate components of the primary outcome. RESULTS: In this study, the prevalence of sarcopenia under different criteria was significantly different, with AWGS2019H having the highest prevalence of 31.3%. The agreement among sarcopenia criteria was unsatisfactory. By Cox regression analysis, all three AWGS definitions of sarcopenia were associated with the composite outcome of all-cause mortality, fracture and CVD (hazard ratio [HR], 2.69 vs. HR, 2.63; vs. HR, 2.23; model 3). Further exploratory analysis, sarcopenia defined by the AWGS2019H criteria was an independent risk factor for death, incident CVD, and fractures. While AWGS2014 criteria was an increased risk factor of death and CVD. The AWGS2019B criteria were only associated with incident fractures. CONCLUSION: All three AWGS definitions of sarcopenia were associated the composite primary endpoint. Additionally, the AWGS2019H criteria may be a better independent risk factor for negative health outcomes.

Sarcopenic obesity predicts negative health outcomes among older patients with type 2 diabetes: The Ageing and Body Composition of Diabetes (ABCD) cohort study.

BACKGROUND AND AIMS: The definition of and diagnostic criteria for sarcopenic obesity (SO) remain unclear, hindering the assessment of its prevalence as well as its clinical relevance to negative health outcomes, especially in diabetic patients, who are more prone to body composition changes. The aim of this study was to investigate the prevalence of SO and its impact on negative health outcomes among elderly patients with type 2 diabetes (T2DM) from the Ageing and Body Composition of Diabetes (ABCD) cohort. METHODS: This retrospective cohort study included 386 elderly patients with T2DM (177 males and 209 females, mean age of 67.91 ± 6.10 years). SO was defined as the coexistence of sarcopenia defined by the 2019 Asian Working Group for Sarcopenia up-to-date consensus and obesity identified by five alternative measurements as follows: body mass index (BMI)≥28 kg/m2 (BMI28), BMI≥25 kg/m2 (BMI25), body fat percentage (BF%)≥25% for men or 35% for women, visceral fat area (VFA)≥100 cm2, or android fat mass (AF) higher than the sex-specific median. The primary endpoint was all-cause death or fragility fracture, and the secondary endpoint was a composite of cardiovascular diseases (CVDs). Cox proportional hazards regression analysis was used to estimate the association between SO and negative health outcomes. RESULTS: The prevalence of SO was 0.2% (BMI28), 2.5% (BMI25), 9.8% (AF), and 18.7% (BF% or VFA) among elderly patients with T2DM, according to the different obesity surrogate markers. During a mean follow-up period of 3.46 ± 1.15 years, 50 patients reached the primary endpoint, and 33 patients had incident CVD. SO classified using BF% was significantly associated with the primary endpoint [hazard ratio (HR) = 2.94, 95% CI = 1.25-6.92] and incident CVD (HR = 6.02, 95% CI = 1.56-23.15), even after comprehensive adjustment for bone-, comorbidity-, and diabetes-specific confounding variables. When SO was classified using BMI25, VFA and AF, similar results were found for adverse outcomes. However, SO classified using BMI25 resulted in misclassification of SO for 61 participants, 19 of whom experienced adverse events during follow-up, and SO classified using VFA or AF was not significantly associated with incident CVD. CONCLUSIONS: SO is not uncommon in geriatric patients with T2DM, and its prevalence varies widely depending on the diverse surrogate indices of body fat excess. Furthermore, SO may be a better independent risk factor for negative health outcomes when classified using BF%.

Down-regulated TINAGL1 in fibroblasts impairs wound healing in diabetes.

Matricellular proteins, a group of extracellular matrix (ECM) proteins, are key regulators of skin repair and their dysregulation impairs wound healing in diabetes. Tubulointerstitial nephritis antigen like 1 (TINAGL1) is a new member of matricellular protein family, and the understanding of its functional role is still relatively limited. In the current study, we detected the expression of TINAGL1 in diabetic skin wound tissues through RT-PCR, ELISA and Western blot analysis, investigated the contribution of TINAGL1 to wound healing through cutaneous administration of recombinant TINAGL1 protein, and characterized its regulation by hyperglycemia through RNA-seq and signal pathway inhibition assay. We showed that TINAGL1 expression has dynamic change and reaching a peak on day-9 after wound during the wound healing process in wild-type (WT) mice. Interestingly, decreased TINAGL1 expression is detected in skin tissues of diabetic patients and mice after wound. Then, we found that high glucose (HG), an important factor that impairs wound healing, reduces the expression of TINAGL1 in fibroblasts through JNK pathway. Notably, the histology analysis, Masson trichrome assay and IHC assay showed that exogenous TINAGL1 promotes wound healing in diabetic mice by accelerating the formation of granulation tissues. Our study provides evidence that TINAGL1 has an essential role in diabetic wound healing, and meanwhile, indicates that manipulation of TINAGL1 might be a possible therapeutic approach.

Anemia in Patients With Diabetic Foot Ulcer: Prevalence, Clinical Characteristics, and Outcome.

The aim of this study was to describe the characteristics of diabetic foot ulcer (DFU) patients with anemia and assess the relationship between anemia and DFU outcome. A retrospective cohort study was conducted on patients with DFU who attended our hospital from May 2007 to September 2014. All of the variables in the DFU patients with and without anemia were compared. In this study, 353 subjects were included, anemia was present in 236 patients (66.9%). These patients were significantly male, more likely to be a smoker, had a lower level of serum albumin and worse kidney function, more likely to use at least 2 types of antibiotics and had a worse perfusion of the lower limb, a larger and deeper ulcer and a more severe infection. A multivariate analysis showed that male sex, lower serum albumin, and worse kidney function were independent predictors of anemia in DFU patients. Additionally, in multivariate models, anemia was one of the variables that was most significantly associated with adverse outcomes and with similar findings for secondary outcomes. Receiver operating characteristic analysis determined a hemoglobin cutoff of 12.3 g/dL (females) and 12.1 g/dL (males) to identify a high-risk population of DFU patients who would have adverse outcomes. So anemia is common in patients with DFU. Although typically mild or moderate, anemia has been associated with substantial morbidity and mortality in patients with DFU.

Reliability and validity of the perfusion, extent, depth, infection and sensation (PEDIS) classification system and score in patients with diabetic foot ulcer.

AIMS: To validate the perfusion, extent, depth, infection and sensation (PEDIS) classification system and to make the clinical practice easier, we created a score system and compared this system with two previously published common score systems. METHODS: A retrospective cohort study was conducted on patients with diabetic foot ulcer (DFU) attending our hospital (n=364) from May 2007 to September 2013. Participants' characteristics and all variables composing the PEDIS classification system were assessed. RESULTS: During a median follow-up of 25 months (range 6-82), ulcers healed in 217 of the 364 patients (59.6%), remained unhealed in 37 patients (10.2%), and were resolved by amputation in 62 patients (17.0%); 48 patients (13.2%) died. When measured using the PEDIS classification system, the outcome of DFU deteriorated with increasing severity of each subcategory. Additionally, longer ulcer history, worse perfusion of lower limb, a larger extent of the ulcer, a deeper wound, more severe infection, and loss of protective sensation were independent predictors of adverse outcome. More importantly, the new PEDIS score system showed good diagnostic accuracy, especially when compared with the SINBAD and Wagner score systems. CONCLUSIONS: The PEDIS classification system, which encompasses relevant variables that contribute to the outcome of DFU and has excellent capacity for predicting the ulcer outcome, demonstrated acceptable accuracy. The PEDIS classification system might be useful in clinical practice and research both for the anticipation of health care costs and for comparing patient subgroups.