Predictive value of insulin resistance surrogates for the development of diabetes in individuals with baseline normoglycemia: findings from two independent cohort studies in China and Japan.

BACKGROUND: Insulin resistance (IR) plays a crucial role in the occurrence and progression of diabetes. This study aimed to evaluate and compare the predictive value of four IR surrogates, including the triglycerides glucose (TyG) index, TyG and body mass index (TyG-BMI), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, and the metabolic score for IR (MetS-IR) for diabetes in two large cohorts. METHODS: A total of 116,661 adult participants from the China Rich Healthcare Group and 15,464 adult participants from the Japanese NAGALA cohort were included in the study. Multivariable Cox proportional hazards models were used to assess the standardized hazard ratio (HR) of the TyG index, TyG-BMI, TG/HDL-C ratio, and MetS-IR directly associated with diabetes. Receiver operating characteristic (ROC) curve and time-dependent ROC curve analysis were performed to evaluate and compare the predictive value of the four IR surrogates for diabetes. RESULTS: In the two independent cohorts, the average follow-up time was 3.1 years in the China cohort, with 2681(2.30%) incident cases of diabetes recorded, and 6.13 years in the Japan cohort, with 373 incident cases (2.41%) of diabetes recorded. After adjusting for potential confounding factors, we found that among the four IR surrogates, TyG-BMI and MetS-IR showed stronger associations with diabetes. The stronger associations persisted even after further stratification by age, sex, hypertension, and obese subgroups. In terms of diabetes prediction, based on ROC analysis, TyG-BMI demonstrated the highest predictive accuracy for diabetes in the Chinese population, while both TyG-BMI and MetS-IR showed the highest predictive accuracy in the Japanese population. The results of further subgroup ROC analysis confirmed the robustness of these findings. Furthermore, the time-dependent ROC results indicated that among the four IR surrogates, MetS-IR exhibited the highest accuracy in predicting future diabetes at various time intervals in the Japanese population. CONCLUSION: Our findings suggest that evaluating TyG-BMI and MetS-IR as IR surrogates may be the most useful for predicting diabetes events and assessing the risk of developing diabetes in East Asian populations.

Sex-specific associations between haemoglobin glycation index and the risk of cardiovascular and all-cause mortality in individuals with pre-diabetes and diabetes: A large prospective cohort study.

AIM: The aim of this study was to investigate the relationship between the haemoglobin glycation index (HGI), and cardiovascular disease (CVD) and all-cause mortality in adults with pre-diabetes and diabetes. METHODS: This study included 10 267 adults with pre-diabetes and diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Sex-differentiated relationships between HGI and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: During the median follow-up time of 103.5 months, a total of 535 CVD deaths and 1918 all-cause deaths were recorded. After multivariate adjustment, in males with pre-diabetes and diabetes, there was a U-shaped relationship between HGI and CVD mortality and all-cause mortality, with threshold points of -0.68 and -0.63, respectively. Before the threshold point, HGI was negatively associated with CVD mortality [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41, 0.89] and all-cause mortality (HR 0.56; 95% CI 0.43, 0.74), and after the threshold point, HGI was positively associated with CVD mortality (HR 1.46; 95% CI 1.23, 1.73) and all-cause mortality (HR 1.40; 95% CI 1.23, 1.59). In contrast, HGI had an L-shaped relationship with all-cause mortality and no significant association with CVD mortality in females. To the left of the threshold points, the risk of all-cause mortality decreased (HR 0.50; 95% CI 0.35, 0.71) progressively with increasing HGI. CONCLUSIONS: In the cohort study, HGI in pre-diabetic and diabetic populations was found to have a U-shaped association with CVD mortality and all-cause mortality in males and an L-shaped association with all-cause mortality only in females. Further prospective and mechanistic studies are warranted.

The predictive significance of lipid accumulation products for future diabetes in a non-diabetic population from a gender perspective: an analysis using time-dependent receiver operating characteristics.

Objective: The increasing prevalence of diabetes is strongly associated with visceral adipose tissue (VAT), and gender differences in VAT remarkably affect the risk of developing diabetes. This study aimed to assess the predictive significance of lipid accumulation products (LAP) for the future onset of diabetes from a gender perspective. Methods: A total of 8,430 male and 7,034 female non-diabetic participants in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) program were included. The ability of LAP to assess the risk of future new-onset diabetes in both genders was analyzed using multivariate Cox regression. Subgroup analysis was conducted to explore the impact of potential modifiers on the association between LAP and diabetes. Additionally, time-dependent receiver operator characteristics (ROC) curves were used to assess the predictive power of LAP in both genders for new-onset diabetes over the next 2-12 years. Results: Over an average follow-up of 6.13 years (maximum 13.14 years), 373 participants developed diabetes. Multivariate Cox regression analysis showed a significant gender difference in the association between LAP and future diabetes risk (P-interaction<0.05): the risk of diabetes associated with LAP was greater in females than males [hazard ratios (HRs) per standard deviation (SD) increase: male 1.20 (1.10, 1.30) vs female 1.35 (1.11, 1.64)]. Subgroup analysis revealed no significant modifying effect of factors such as age, body mass index (BMI), smoking history, drinking history, exercise habits, and fatty liver on the risk of diabetes associated with LAP (All P-interaction <0.05). Time-dependent ROC analysis showed that LAP had greater accuracy in predicting diabetes events occurring within the next 2-12 years in females than males with more consistent predictive thresholds in females. Conclusions: This study highlighted a significant gender difference in the association between LAP and future diabetes risk. The risk of diabetes associated with LAP was greater in females than in males. Furthermore, LAP showed superior predictive ability for diabetes at different time points in the future in females and had more consistent and stable predictive thresholds in females, particularly in the medium and long term.

M6A regulator methylation patterns and characteristics of immunity in acute ST-segment elevation myocardial infarction.

M6A methylation is the most prevalent and abundant RNA modification in mammals. Although there are many studies on the regulatory role of m6A methylation in the immune response, the m6A regulators in the pathogenesis of acute ST-segment elevation myocardial infarction (STEMI) remain unclear. We comprehensively analysed the role of m6A regulators in STEMI and built a predictive model, revealing the relationship between m6A methylations and the immune microenvironment. Differential analysis revealed that 18 of 24 m6A regulators were significantly differentially expressed, and there were substantial interactions between the m6A regulator. Then, we established a classifier and nomogram model based on 6 m6A regulators, which can easily distinguish the STEMI and control samples. Finally, two distinct m6A subtypes were obtained and significantly differentially expressed in terms of infiltrating immunocyte abundance, immune reaction activity and human leukocyte antigen genes. Three hub m6A phenotype related genes (RAC2, RELA, and WAS) in the midnightblue module were identified by weighted gene coexpression network analysis, and were associated with immunity. These findings suggest that m6A modification and the immune microenvironment play a key role in the pathogenesis of STEMI.

The impact of arm circumference on noninvasive oscillometric blood pressure referenced with intra-aortic blood pressure.

OBJECTIVE: To investigate the influence of arm circumference (AC) on the brachial blood pressure (BP) measured with an adult cuff. PARTICIPANTS AND METHODS: This study included 208 patients (150 men, 61.0±8.0 years) for coronary angiography. Intra-aortic BP and noninvasive right brachial oscillometric BP (noninvasive BP) were measured simultaneously before coronary angiography. The noninvasive BP was measured using an electronic oscillometric device with an adult cuff (12×22 cm). The mid-ACs were measured. Thus, proper cuff-arm (≤26 cm) and small cuff (>26 cm) groups were created. The difference in intra-aortic and noninvasive BP was calculated as BPi-n. RESULTS: The correlation coefficients (r) between noninvasive and invasive systolic blood pressure (SBP), mean artery pressure, and diastolic blood pressure (DBP) were 0.88, 0.76, and 0.58, respectively. The SBPi-n was higher (7.9±1.6 vs. 5.2±1.1 mmHg), but the DBPi-n (3.9±1.4 vs. 6.1±1.0 mmHg, P<0.05) was lower in the group ≤26 cm than in the group >26 cm. Among the four subgroups divided by 20-23, 24-26, 27-30, and 31-37 cm of AC, as the AC increased, the SBPi-n increased, but DBP decreased, resulting in noninvasive SBP 4.6 mmHg higher and noninvasive DBP 4.6 mmHg lower in the 31-37 cm group in comparison with the 20-23 cm group. CONCLUSION: When an adult cuff was used, the noninvasive oscillometric SBP was overestimated, but DBP was underestimated in the individuals with large arms against the intra-aortic BP.

Modified shock index is a predictor for 7-day outcomes in patients with STEMI.

SUBJECT: The aim of this study was to compare the predictive values of modified shock index (MSI) and shock index (SI) for 7-day outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This retrospective study included 160 consecutive patients with STEMI and emergency percutaneous coronary intervention. The blood pressure (BP) and heart rate (HR) measured at emergency department were used to calculate SI (HR/systolic BP) and MSI (HR/mean artery pressure). The major adverse cardiac events (MACE) included all-cause mortality, life-threatening arrhythmias, cardiogenic shock, and Killip class within 7 days. RESULTS: Forty-nine patients had increased MSI (≥1.4), whereas 72 had increased SI (≥0.7). Except the parameters on BP and HR, other parameters were similar between the normal and increased SI groups. However, the increased MSI group had significantly higher age (69.0 ± 13.0 years vs 63.9 ± 12.9 years, P = .025) than the normal MSI group. The 7-day all-cause mortality was 8.8%, and MACE rate was 24.4% in this study. Both increased SI and increased MSI predicted higher MACE rates. However, the odds ratios of increased MSI for all-cause mortality (6.8 vs 3.4), cardiogenic shock (3.0 vs 1.6), life-threatening arrhythmias (9.1 vs 4.6), and MACE (6.8 vs 3.4) were higher than those of increased SI. Modified shock index and SI were independent factor for MACE, but the odds ratio of MSI was higher than of SI (3.05 vs 1.07). CONCLUSIONS: Both SI and MSI in emergency department could predict the all-cause mortality and MACE rates within 7 days in patients with STEMI, but MSI may be more accurate than SI.

Association of an inter-arm systolic blood pressure difference with all-cause and cardiovascular mortality: An updated meta-analysis of cohort studies.

OBJECTIVE: To evaluate whether an association exists between an inter-arm systolic blood pressure difference (sIAD) and all-cause and cardiovascular mortality. METHODS: We searched for cohort studies that evaluated the association of a sIAD and all-cause or cardiovascular mortality in the electronic databases Medline/PubMed and Embase (August 2014). Random effects models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Nine cohort studies (4 prospective and 5 retrospective) enrolling 15,617 participants were included. The pooled HR of all-cause mortality for a sIAD of ≥ 10 mm Hg was 1.53 (95% CI 1.14-2.06), and that for a sIAD of ≥ 15 mm Hg was 1.46 (1.13-1.88). Pooled HRs of cardiovascular mortality were 2.21 (95% CI 1.52-3.21) for a sIAD of ≥ 10mm Hg, and 1.89 (1.32-2.69) for a sIAD of ≥ 15 mm Hg. In the patient-based cohorts including hospital- and diabetes-based cohorts, both sIADs of ≥ 10 and ≥ 15 mm Hg were associated with increased all-cause (pooled HR 1.95, 95% CI 1.01-3.78 and 1.59, 1.06-2.38, respectively) and cardiovascular mortality (pooled HR 2.98, 95% CI 1.88-4.72 and 2.10, 1.07-4.13, respectively). In the community-based cohorts, however, only a sIAD of ≥ 15 mm Hg was associated with increased cardiovascular mortality (pooled HR 1.94, 95 % CI 1.12-3.35). CONCLUSIONS: In the patient populations, a sIAD of ≥ 10 or of ≥ 15 mm Hg could be a useful indictor for increased all-cause and cardiovascular mortality, and a sIAD of ≥ 15 mm Hg might help to predict increased cardiovascular mortality in the community populations.

[Review of the initiation and development of the conception of clinical pathway].

Dupont, an American company, used the concept of "pathway" in industry to improve the quality of their products in 1957. In the 1970s, under the pressure of a rise in medical costs, some people realized the concept of the "key pathway" could be used in medicine too. In 1985, the Boston New England Medical Center Hospital (NEMC) succeeded in using the concept of the clinical pathway in medical practice, and afterwards the concept gradually found worldwide application. In 1996, the Fourth Military Medical University in China reported the application of clinical pathway in America. The West China Hospital began to try out the clinical pathway in 1998 and the concept gradually found application in China.