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Aim: We aimed to investigate the long‐term influence of a diet and/or exercise intervention on long‐term mortality and cardiovascular disease (CVD) events. Methods: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet‐only, exercise‐only and diet‐plus‐exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow‐up the participants for up to 24 years after the end of 6‐year intervention. In total, 540 participants completed the follow‐up, while 36 subjects lost in follow‐up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. Results: Compared with controls, the diet‐only intervention in people with IGT was significantly associated with a reduced risk of all‐cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61‐0.97)], CVD death [HR 0.67, 95% CI (0.46‐0.97)] and CVD events [HR 0.72, 95% CI (0.54‐0.96)]. The diet‐plus‐exercise intervention was significantly associated with a decreased risk of all‐cause death [HR 0.64, 95% CI (0.48‐0.84)], CVD death [HR 0.54, 95% CI (0.30‐0.97)] and CVD events [HR 0.68, 95% CI (0.52‐0.90)]. Unexpectedly, the exercise‐only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. Conclusions: A diet‐only intervention and a diet‐plus‐exercise intervention in people with IGT were significantly associated with a reduced risk of all‐cause death, CVD death and CVD events, while an exercise‐only intervention was not. It suggests that diet‐related interventions may have a potentially more reliable influence on long‐term vascular complications and mortality. [ABSTRACT FROM AUTHOR]

Background. The purpose of this research was to assess the relationship between the severity of diabetic retinopathy (DR) and indexes of left ventricle (LV) structure and function in type 2 diabetes mellitus (T2DM). Methods. Retrospective analysis of 790 patients with T2DM and preserved LV ejection fraction. Retinopathy stages were classified as no DR, early nonproliferative DR, moderate to severe nonproliferative DR, or proliferative DR. The electrocardiogram was used to assess myocardial conduction function. Echocardiography was used to evaluate myocardial structure and function. Results. Patients were divided into three groups based on the DR status: no DR group (NDR, n = 475), nonproliferative DR group (NPDR, n = 247), and proliferative DR group (PDR, n = 68). LV interventricular septal thickness (IVST) increased significantly with more severe retinopathy (NDR: 10.00 ± 1.09 ; NPDR: 10.42 ± 1.21 ; and PDR: 10.66 ± 1.58 ; P < 0.001). Multivariate logistic regression analysis showed that the significant correlation of IVST persisted between subjects with no retinopathy and proliferative DR (odds ratio = 1.35 , P = 0.026). Indices of myocardial conduction function were assessed by electrocardiogram differences among groups of retinopathy (all P < 0.001). In multiple-adjusted linear regression analyses, the increasing degree of retinopathy was closely correlated with heart rate (β = 1.593 , P = 0.027), PR interval (β = 4.666 , P = 0.001), and QTc interval (β = 8.807 , P = 0.005). Conclusion. The proliferative DR was independently associated with worse cardiac structure and function by echocardiography. Furthermore, the severity of retinopathy significantly correlated with abnormalities of the electrocardiogram in patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: The triglyceride glucose (TyG) index has been considered a new biomarker for the diagnosis of angiocardiopathy and insulin resistance. However, the association of the TyG index with subclinical left ventricular (LV) systolic dysfunction still lacks comprehensive exploration. This study was carried out to examine this relationship in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 150 T2DM patients with preserved LV ejection fraction (LVEF ≥ 50%) from June 2021 to December 2021 were included in this study. The subclinical LV function was evaluated through global longitudinal strain (GLS), with the predefined GLS < 18% as the cutoff for subclinical LV systolic dysfunction. The TyG index calculation was obtained according to ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2), which was then stratified into quartiles (TyG index—Q). Results: Analyses of clinical characteristics in the four TyG indexes-Q (Q1 (TyG index ≤ 8.89) n = 38, Q2 (8.89 < TyG index ≤ 9.44) n = 37, Q3 (9.44 < TyG index ≤ 9.83) n = 38, and Q4 (TyG index > 9.83) n = 37) were conducted. A negative correlation of the TyG index with GLS (r = -0.307, P < 0.001) was revealed according to correlation analysis. After gender and age were adjusted in multimodel logistic regression analysis, the higher TyG index (OR 6.86; 95% CI 2.44 to 19.30; P < 0.001, Q4 vs Q1) showed a significant association with GLS < 18%, which was still maintained after further adjustment for related clinical confounding factors (OR 5.23, 95% CI 1.12 to 24.51, p = 0.036, Q4 vs Q1). Receiver operator characteristic analysis indicated a diagnostic capacity of the TyG index for GLS < 18% (area under curve: 0.678; P < 0.001). Conclusions: A higher TyG index had a significant association with subclinical LV systolic dysfunction in T2DM patients with preserved ejection fraction, and the TyG index may have the potential to exert predictive value for myocardial damage. [ABSTRACT FROM AUTHOR]

Background: We aimed to examine the association between glycated hemoglobin (HbA1c), microvascular complications, and subclinical left ventricular (LV) systolic dysfunction, and to determine the strength of the correlation in asymptomatic patients with type 2 diabetes mellitus (T2DM). Methods: Global longitudinal strain (GLS) was employed to assess the subclinical LV function of 152 enrolled T2DM patients with preserved LV ejection fraction, with the cutoff for subclinical LV systolic dysfunction predefined as GLS < 18%. Results: According to univariate analysis, the reduced GLS exhibited association with the clinical features including HbA1c, triglyceride, systolic blood pressure, fasting glucose, heart rate, diabetic retinopathy, and urinary albumin creatinine ratio (UACR) (all p <.05). After the factors of gender, age, and related clinical covariables adjusted, multiple logistic regression analysis revealed the HbA1c (odds ratio [OR] 1.66; 95% confidence interval [CI] 1.30–2.13; p <.001), UACR (OR 2.48; 95% CI 1.12–5.47; p =.025) and triglyceride (OR 1.84; 95% CI 1.12–3.03; p =.017) as the independent risk factors for the reduced GLS. Receiver operating characteristic curve showed a predictive value of the HbA1c for the subclinical LV systolic dysfunction (area under curve: 0.74; p <.001). Conclusions: In asymptomatic T2DM patients, subclinical LV systolic dysfunction was associated with HbA1c, diabetic complications, and triglyceride. More prominently, HbA1c may exert a prognostic significance for the progression of myocardial damage. [ABSTRACT FROM AUTHOR]

Background: We aimed to explore if hyperglycaemia and hyperinsulinemia in the diabetes and prediabetes population were associated with increased risk of cancer occurence.Methods: Overall, 1700 participants with different glycaemic statuses were screened from the 110,660 residents of Da-Qing, China, in 1985. They were followed up to 30 years to access cancer outcomes.Results: Cancer was identified in 15.2% (259/1700) of the participants. The incidence of cancer in the normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes groups was 6.06, 6.77, and 7.18 per 1000 person-years, respectively (P = 0.02). In the Fine-Gray model with all cause death as competing risk, compared with the NGT controls, both IGT and diabetes groups demonstrated significantly higher risk of cancer (for the IGT group, adjusted hazard ratio (aHR) = 1.77, 95% CI 1.38-2.27, P < 0.0001; for the diabetes, aHR = 3.34, 95% CI 2.64-4.22, P < 0.0001). Among the IGT participants, progress to diabetes (aHR = 2.28, 95%CI 1.24-4.20, P = 0.008) and insulin-area under the curve at baseline (for 1 SD increase, aHR = 1.39, P = 0.02) were also associated with the risk of cancer after adjustment of covariables.Conclusions: Hyperglycaemia in patients with diabetes, hyperinsulinemia, and progression to diabetes in people with IGT is significantly associated with the long-term increased risk of cancer occurrence. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association of potential cardiovascular disease (CVD) biomarkers in patients with type 2 diabetes.Research Design and Methods: We enrolled 120 participants (aged 61.5-69.5 years) with type 2 diabetes and 60 (aged 62.5-73.5 years) with normal glucose tolerance in the discovery group from the original Da Qing Diabetes Study. Their diabetes status was confirmed in 1986; then, the participants were followed over 23 years to collect CVD outcome data. Untargeted and targeted metabolomics analyses based on ultra-high-performance liquid chromatography-tandem mass spectrometry were used to identify potential markers. Multivariable regression analysis was used to evaluate the association between metabolites and CVD outcomes. An independent group of 335 patients (aged 67.0-77.0 years) with diabetes was used for biomarker validation.Results: In the discovery group, untargeted metabolomics analysis found 16 lipids and fatty acids metabolites associated with CVD risk in patients with diabetes, with palmitoyl sphingomyelin (PSM) having the strongest association. Plasma PSM concentrations were significantly higher in cases of diabetes with CVD than without (41.68 ± 10.47 vs. 9.69 ± 1.47 μg/mL; P < 0.0001). The odds ratio (OR) of CVD for 1 µg/mL PSM change was 1.19 (95% CI 1.13-1.25) after adjustment of clinical confounders. The validation study confirmed that PSM was significantly associated with increased CVD risk in diabetes (OR 1.22 [95% CI 1.16-1.30]).Conclusions: Changes in lipid and fatty acid content were significantly associated with CVD risk in the Chinese population with diabetes. PSM is a potential biomarker of increased CVD risk in diabetes. [ABSTRACT FROM AUTHOR]

Background. To assess the association of metformin monotherapy with the risk of all-cause deaths and cardiovascular deaths and events in type 2 diabetes patients in real clinical practice. Methods. This retrospective, observational study comprised patients with type 2 diabetes initially treated with metformin or nonmetformin monotherapy over 2011-2016. Data were extracted from the National Healthcare Big Data database in Fuzhou, China. Propensity score matching (PSM) was performed, matching each patient on metformin to one on nonmetformin in terms of a set of covariates. The primary endpoint was all-cause death, and secondary endpoints were cardiovascular death, heart failure, and heart failure hospitalization. Covariate-adjusted associations of metformin use with all the endpoints were assessed by Cox proportional hazards models. Results. Among 24,099 patients, 5491 were initially treated with metformin and 18,608 with nonmetformin. PSM yielded 5482 patients in each cohort. During a median follow-up of 2.02 years, we observed 110 and 211 deaths in the metformin and nonmetformin groups, respectively. Metformin was significantly associated with reduced risk of all-cause death (adjusted hazard ratio (aHR) 0.52, 95% confidence interval (CI) 0.39-0.69), cardiovascular death (aHR 0.63, 95% CI 0.43-0.91), and heart failure (aHR 0.61, 95% CI 0.52-0.73), whereas the reduced risk in heart failure hospitalization was not statistically significant (aHR 0.70, 95% CI 0.47-1.02). Conclusions. In this analysis of electronic health record data from a large database in China, metformin as first-line monotherapy greatly reduced the risk of all-cause death, cardiovascular death, and heart failure in diabetes patients as compared with nonmetformin medications. [ABSTRACT FROM AUTHOR]

Type 2 diabetes [T2D] and thyroid dysfunction [TD] often co-occur, have overlapping pathologies, and their risk increases with age. Since 1995, universal salt iodization has been implemented in China to prevent disorders caused by iodine deficiency. However, after two decades of implementation of universal salt iodization, the prevalence of TD in elderly Chinese patients with T2D is not well described and may have been underestimated. We conducted a questionnaire-based survey across 24 endocrinology centers in China between December 2015 and July 2016. Demographic and clinical data from 1677 patients with T2D were obtained and analyzed to examine the prevalence of TD along with T2D in these patients. We assessed TD prevalence according to the four TD subtypes [subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism], TD history, gender, and age. The diagnosis rates were calculated for TD and also for the TD subtype. The number of patients reaching treatment goals for T2D [hemoglobin A1c <7%] and TD [normal free thyroxine and thyroid-stimulating hormone [TSH]] and the incidences of complications and comorbidities were recorded. Among the enrolled patients with T2D [N = 1677], TD was diagnosed in 23.79% [399/1677] out of which 61% (245/399) were previously diagnosed and 38.59% (154/399) were newly diagnosed cases. Subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and clinical hyperthyroidism were reported in 4.89%, 9.3%, 1.13%, and 3.16% of the total population, respectively. Among patients previously diagnosed with TD, the incidence in women [166/795; 20.88%] was higher than in men [79/882; 8.96%]. The treatment goals for TD and T2D were attained in 39.6% [97/245] and 34.41% [577/1677] of the cases, respectively. Diabetic complications and comorbidities were reported in 99.7% of patients, with peripheral neuropathy being the most common [43.46%] followed by cataract [24.73%]. We had found that the incidences of dyslipidemia, elevated LDL levels, and osteoporosis were significantly higher in patients with TD than those without TD. TD is underdiagnosed in elderly Chinese patients with T2D. [ABSTRACT FROM AUTHOR]

Background and aim We sought to determine the effect of regression to normal glucose tolerance (NGT) or progression to diabetes in early years of impaired glucose tolerance (IGT) on subsequent risk of stroke. Methods In 1986, 576 adults aged 25 years and older with impaired glucose tolerance in Da Qing, China, were randomly assigned by clinic to control, diet, exercise, or diet plus exercise intervention groups for a six-year period. Subsequently participants received medical care in their local clinics. We tracked participants for additional 17 years to ascertain stroke events and other outcomes. Results At the end of 6-year intervention trial follow-up, 272 (50.2%) had progressed to diabetes, 169 (31.2%) regressed to normal glucose tolerance, and 101 (18.6%) remained impaired glucose tolerance. During the subsequent 17-year follow-up, 173 (31.9%) developed a stroke, 26.7% of normal glucose tolerances, 30.7% of impaired glucose tolerances, and 36.1% of those with diabetes. After controlling for age, sex, baseline blood pressure, smoking, total cholesterol, previous cardiovascular disease and intervention group, those who developed diabetes in the first six years had a higher incidence of stroke than those who reverted to normal glucose tolerance (HR = 1.49, 95% CI 1.01–2.19, p = 0.04), whereas for those who remained impaired glucose tolerance compared to those who regressed to normal glucose tolerance the HR was 1.25 (95% CI 0.80–1.93; p = 0.30). A 1-mmol/L increase in both fasting and 2-h post-load plasma glucose from entry to end of the six-year trial was significantly associated with a higher risk of development of stroke in the subsequent 17 years, respectively (HR = 1.07, 95% CI 1.03–1.11, p < 0.0001 for fasting glucose, HR = 1.05, 95% CI 1.02–1.09, p = 0.007 for 2-h post-load plasma glucose). Conclusions Among Chinese adults with impaired glucose tolerance, early progression to diabetes predicted a higher risk of stroke, compared those who regressed to normal glucose tolerance. [ABSTRACT FROM AUTHOR]

• People with type 2 diabetes have metabolic disorders. • If GDF-15 related to the risk of CVD and cancer in people with diabetes remains unclear. • GDF-15 levels were related to increased risk of CVD and cancer morbidity and mortality. • GDF-15 is a marker for the dual risk of CVD and cancer in people with diabetes. To investigate the relationship between circulating growth differentiation factor (GDF-15) levels and the risk of cardiovascular disease and cancer in people with diabetes. Totally, 510 participants with type 2 diabetes were enrolled from the long-term follow-up of the Da Qing Impaired Glucose Tolerance (IGT) and Diabetes Study (2006–2009). Plasma GDF-15 levels were assessed. Outcomes of cardiovascular events, cancer, and related death were followed up until 2016. Over a 7.5-year follow-up period, 143 (28.0%) of the participants died, and 155 and 56 experienced cardiovascular events and cancer respectively. Multivariable Cox analysis showed that higher circulating GDF-15 levels were significantly associated with the increased risk of cardiovascular and cancer death. The HRs after adjustment of traditional confounders were 1.90 (95%CI 1.31–2.74) and 2.50 (95%CI 1.34–4.67) respectively for an increase in one unit of log e transformed GDF-15 (pg/ml). The cause-specific hazard model analysis further confirmed the results after adjusting the same confounders. In addition, the higher GDF-15 levels were also significantly associated with the increased risk of cardiovascular events (HR=1.35, 95%CI: 1.04–1.76) and cancer (HR=1.62, 95%CI 1.06–2.47). Elevated circulating levels of GDF-15 predicted a significant increase in the dual risk of cancer and cardiovascular diseases in Chinese people with type 2 diabetes. Thus, it may be a potential predictor of these outcomes in people with diabetes. [ABSTRACT FROM AUTHOR]

Background: Limited information is available on the long-term risk of cardiovascular disease (CVD) associated with hypertriglyceridaemia (HTG) in the Chinese population. We estimated this risk over a 23-year period in participants recruited from among those included in the Da Qing Diabetes Study.Methods: A total of 833 Chinese adults including 379 with normal glucose levels and 454 with hyperglycaemia were identified by their oral glucose tolerance in 1986 in Da Qing, China. CVD outcomes were monitored until 2009. Thirty-four percent (280/833) of the participants had HTG, which was defined as a fasting plasma triglyceride (TG) level ≥ 1.7 mmol/L, at the baseline time point.Results: Over the 23-yearfollow-up period, 149 subjects in the HTG group and 190 subjects in the non-HTG group (NTG group) experienced their first CVD event, including fatal or nonfatal myocardial infarction (MI) and stroke. The age and sex-adjusted annual incidence of the first CVD event per 1000 person-years was 30.23 for the HTG group vs 18.68 for the NTG group. The corresponding rates for MI and stroke were 7.71 vs 3.89 and 19.55 vs 13.98, respectively. After adjusting for confounders, the HTG group had a 28% higher risk of the first CVD event than the NTG group. This association was significant among only the subjects with a serum cholesterol level > 5.7 mmol/L and those with diabetes or impaired glucose tolerance (IGT).Conclusion: HGT predicted a substantially higher subsequent long-term risk of the first CVD event in Chinese adults, especially in those with hypercholesterolaemia and hyperglycaemia. [ABSTRACT FROM AUTHOR]

Aims: To examine the long-term influence of metabolic syndrome (MetS) on death and vascular complications.Methods: Altogether, 1419 individuals with different levels of glycemia and MetS were recruited for this study. The participants were followed up for 30 years to assess outcomes.Results: Compared with the non_MetS, individuals with impaired glucose tolerance (IGT) plus MetS had a higher incidence (per 1000 person-years) of all-cause death (20.98 vs 11.70, hazard ratio [HR] = 1.84), macrovascular events (29.25 vs 15.94, HR = 1.36), and microvascular complications (10.66 vs 3.57, HR = 1.96). The incidence of these outcomes was even higher in participants with type 2 diabetes mellitus (T2DM) plus MetS. The T2DM without MetS shared a comparable risk profile of the outcomes with the T2DM plus MetS group (HRs were 3.45 vs 3.15, 2.21 vs 2.65, and 6.91 vs 7.41, respectively).Conclusions: The degree of hyperglycemia in MetS is associated with the severity of death and both micro- and macrovascular complications. T2DM was associated with a comparable risk for all outcomes as T2DM plus MetS. The findings highlight the need of early prevention of diabetes in individuals with IGT plus MetS, while the justification to redefine a subgroup of patients with T2DM as having MetS remains to be clarified. [ABSTRACT FROM AUTHOR]