Efficacy of 1-hour postload plasma glucose as a suitable measurement in predicting type 2 diabetes and diabetes-related complications: A post hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

AIM: To evaluate whether 1-hour plasma glucose (1hPG) can be a comparable measurement to 2-hour plasma glucose (2hPG) in identifying individuals at high risk of developing diabetes. METHODS: A total of 1026 non-diabetic subjects in the Da Qing IGT and Diabetes Study were included and classified according to baseline postload 1hPG. The participants were followed up and assessed at 6-, 20- and 30year follow-up for outcomes including diabetes, all-cause and cardiovascular mortality, cardiovascular disease (CVD) events, and microvascular disease. We then conducted a proportional hazards analysis in this post hoc study to determine the risks of developing type 2 diabetes and its complications in a '1hPG-normal' group (1hPG <8.6 mmol/L) and a '1hPG-high' group (≥8.6 mmol/L). The predictive values of 1hPG and 2hPG were evaluated using a time-dependent receiver-operating characteristic (ROC) curve. RESULTS: Compared with the 1hPG-normal group, the 1hPG-high group had increased risk of diabetes (hazard ratio [HR] 4.45, 95% CI 3.43-5.79), all-cause mortality (HR 1.46, 95% CI 1.07-2.01), CVD mortality (HR 1.84, 95% CI 1.16-2.95), CVD events (HR 1.39, 95% CI 1.03-1.86) and microvascular disease (HR 1.70, 95% CI: 1.03-2.79) after adjusting for confounders. 1hPG exhibited a higher area under the ROC curve (AUC) for predicting diabetes than 2hPG during the long-term follow-up (AUC [1hPG vs. 2hPG]: 10 years: 0.86 vs. 0.84, p = 0.08; 20 years: 0.88 vs. 0.87, p = 0.04; 30 years: 0.85 vs. 0.82, p = 0.009). CONCLUSIONS: Elevated 1hPG level (≥8.6 mmol/L) was associated with increased risk of developing type 2 diabetes and its long-term complications, and could be considered as a suitable measurement for identifying individuals at high risk of type 2 diabetes.

Influence of a diet and/or exercise intervention on long-term mortality and vascular complications in people with impaired glucose tolerance: Da Qing Diabetes Prevention Outcome study.

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.

Circulating palmitoyl sphingomyelin levels predict the 10-year increased risk of cardiovascular disease death in Chinese adults: findings from the Da Qing Diabetes Study.

BACKGROUND: Higher levels of palmitoyl sphingomyelin (PSM, synonymous with sphingomyelin 16:0) are associated with an increased risk of cardiovascular disease (CVD) in people with diabetes. Whether circulating PSM levels can practically predict the long-term risk of CVD and all-cause death remains unclear. This study aimed to investigate whether circulating PSM is a real predictor of CVD death in Chinese adults with or without diabetes. METHODS: A total of 286 and 219 individuals with and without diabetes, respectively, from the original Da Qing Diabetes Study were enrolled. Blood samples collected in 2009 were used as a baseline to assess circulating PSM levels. The outcomes of CVD and all-cause death were followed up from 2009 to 2020, and 178 participants died, including 87 deaths due to CVD. Cox proportional hazards regression was used to estimate HRs and their 95% CIs for the outcomes. RESULTS: Fractional polynomial regression analysis showed a linear association between baseline circulating PSM concentration (log-2 transformed) and the risk of all-cause and CVD death (p < 0.001), but not non-CVD death (p > 0.05), in all participants after adjustment for confounders. When the participants were stratified by PSM-tertile, the highest tertile, regardless of diabetes, had a higher incidence of CVD death (41.5 vs. 14.7 and 22.2 vs. 2.9 per 1000 person-years in patients with and without diabetes, respectively, all log-rank p < 0.01). Individuals with diabetes in the highest tertile group had a higher risk of CVD death than those in the lowest tertile (HR = 2.73; 95%CI, 1.20-6.22). CONCLUSIONS: Elevated PSM levels are significantly associated with a higher 10-year risk of CVD death, but not non-CVD death, in Chinese adults with diabetes. These findings suggest that PSM is a potentially useful long-term predictor of CVD death in individuals with diabetes.

Does high-normal blood pressure lead to excess cardiovascular disease events and deaths in Chinese people? A post-hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

AIM: Whether systolic/diastolic blood pressure (SBP/DBP) values of 130-139/80-89 mmHg should be defined as hypertension has been debated for decades. We aimed to characterize the effect of high-normal BP on cardiovascular disease (CVD) events and deaths. METHODS: In total, 1726 individuals from the original Da Qing IGT and Diabetes Study were enrolled, and divided into the normal BP group (SBP <130 mmHg and DBP <80 mmHg), high-normal BP group (SBP 130-139 mmHg and/or DBP 80-89 mmHg) and hypertension group (SBP ≥140 mmHg and/or DBP ≥90 mmHg). CVD events and their components were assessed from 1986 to 2016. RESULTS: During the 30-year follow-up, the high-normal BP group was not at higher risk for CVD events [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.84-1.30, p = .68], coronary heart disease (HR 1.12, 95% CI 0.77-1.63, p = .57), stroke (HR 1.05, 95% CI 0.82-1.34, p = .71), or CVD deaths (HR 1.15, 95% CI 0.82-1.60, p = .41) compared with the normal BP group, after adjusting for covariates. However, the hypertension group exhibited significantly increased cardiovascular risk (CVD events, HR 1.91, 95% CI 1.48-2.46, p < .0001; coronary heart disease, HR 1.73, 95% CI 1.12-2.67, p = .01; stroke, HR 1.90, 95% CI 1.43-2.52, p < .0001; CVD deaths, HR 2.07, 95% CI 1.43-3.01, p = .0001) than the normal BP group. Subgroup analyses showed that, regardless of the presence of diabetes, high-normal BP did not increase CVD events compared with normal BP. CONCLUSIONS: This post-hoc study provided no evidence that the high-normal BP increased cardiovascular risk in the Da Qing study population, suggesting that it was reasonable to continue to define hypertension at 140/90 mmHg in China.

Hyperinsulinemia and plasma glucose level independently associated with all-cause and cardiovascular mortality in Chinese people without diabetes-A post-hoc analysis of the 30-year follow-up of Da Qing diabetes and IGT study.

AIMS: We aimed to characterize the effect of insulin resistance and plasma glucose on all-cause and cardiovascular disease (CVD) death. METHODS: A total of 462 individuals without diabetes in the original Da Qing Diabetes and IGT Study were enrolled in the present analysis, and further divided into G1 (low insulin low glucose), G2 (high insulin low glucose), G3 (low insulin high glucose) and G4 (high insulin high glucose) groups according to medians of glucose and insulin level at baseline. The all-cause and CVD death were assessed from 1986 to 2016. RESULTS: During the 30-year follow-up, compared with G1, G2, G3, and G4 groups were all at increased death risk after adjusting covariates. G2 and G3 were associated with similar risks in both all-cause (G2: HR 1.65, 95%CI 1.02-2.67; G3: HR 1.76, 95%CI 1.11-2.81) and CVD death (G2: HR 2.03, 95%CI 1.01-4.05; G3: HR 1.85, 95%CI 0.93-3.68). The highest risk was observed in G4 (all-cause death: HR 2.32, 95%CI 1.45-3.69; CVD death: HR 2.68, 95%CI 1.35-5.29). CONCLUSIONS: In this post-hoc study, participants with either high glucose or high insulin were related to increased risk of mortality, implying that strategies targeting eliminating both hyperglycemia and hyperinsulinemia may favor the long-term outcomes.

Long-term influence of type 2 diabetes and metabolic syndrome on all-cause and cardiovascular death, and microvascular and macrovascular complications in Chinese adults - A 30-year follow-up of the Da Qing diabetes study.

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.

Circulating levels of GDF-15 for predicting cardiovascular and cancer morbidity and mortality in type 2 diabetes: Findings from Da Qing IGT and Diabetes Study.

AIM: To investigate the relationship between circulating growth differentiation factor (GDF-15) levels and the risk of cardiovascular disease and cancer in people with diabetes. METHODS: 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. RESULTS: 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 loge 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). CONCLUSIONS: 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.

Cancer and its predictors in Chinese adults with newly diagnosed diabetes and impaired glucose tolerance (IGT): a 30-year follow-up of the Da Qing IGT and Diabetes Study.

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.

Phenotype of higher post-load insulin response as a predictor of all-cause mortality and cardiovascular mortality in the Chinese non-diabetic population.

AIM: This study aimed to assess whether a higher insulin response increased the long-term risk of mortality in a non-diabetic population. METHODS: A total of 446 people with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) who participated in the Da Qing Diabetes Study, were stratified into quartiles subgroups according to their baseline insulin area under the curve (AUC) during oral glucose tolerance test, defined as Q1, Q2, Q3 and Q4. The participants were followed from 1986 to 2016 to assess the risk of death in association with the magnitude of post-load insulin response. RESULTS: Over 30 years, the rates of all cause death were 9.94, 14.81, 15.02, and 17.58 per 1000 person-years across the four groups respectively. The rate for cardiovascular disease (CVD) death was 5.14, 6.50, 6.80 and 10.47 per 1000 person-years. Compared with Q1, the risk of all-cause death was significantly higher in participants in Q4 (HR = 2.14, 95% CI 1.34-3.42), Q3 (HR = 1.94, 95% CI 1.20-3.14), and Q2 group (HR = 1.70, 95% CI 1.06-2.74). In the Fine-Gray model with non-CVD death as competing risk, the increased insulin AUC were also significantly associated with the CVD death (Q4 vs Q1, HR = 2.04, 95% CI 1.10-3.79). In the fractional polynomial regression analysis, a nonlinear association between insulin AUC and all-cause and CVD death was demonstrated. In addition, insulin AUC was associated with a progressively higher risk of all-cause death and CVD death (fractional power 3, P < 0.001). CONCLUSION: A higher post-load insulin response was significantly associated with a long-term increased risk of all-cause and CVD deaths in the Chinese non-diabetic population. It suggests that people featured by this phenotype is a potential important target for further intervention.

Risk of Death and Heart Failure among Patients with Type 2 Diabetes Treated by Metformin and Nonmetformin Monotherapy: A Real-World Study.

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.

Prediction of 10-year mortality using hs-CRP in Chinese people with hyperglycemia: Findings from the Da Qing diabetes prevention outcomes study.

AIMS: To examine whether high-sensitivity C-reactive protein (hs-CRP) can predict all-cause death in Chinese adults with hyperglycemia. METHODS: All the 237 diabetes and 49 prediabetes recruited in the study were evolved from the participants with impaired glucose tolerance in the original Da Qing Diabetes Study. Blood hs-CRP level was measured at 2006. Ten-year outcome of death was traced from 2006 to 2016. Cox model was used to analyse the association between hs-CRP level and the risk of all-cause death occurred over the subsequent 10 years. RESULTS: During the follow-up, death occurred in 36 (37.9%) subjects in the highest hs-CRP tertile group (hs-CRP > 2.16 mg/L) and 19 (20.0%) in the lowest hs-CRP tertile group (hs-CRP < 0.82 mg/L, p < 0.05). The corresponding incidence of all-cause death (per 1,000 person-years) was 44.7 (95% CI 30.1-59.3) and 21.6 (95% CI 11.9-31.3) in the two groups respectively (p < 0.0001). The highest hs-CRP tertile was associated with the increased risk of all-cause death significantly (hazard ratio 1.88, 95% CI 1.07-3.32) after controlling for traditional risk factors. CONCLUSIONS: Serum hs-CRP was predictive of 10-year all-cause death in Chinese adults with hyperglycemia, suggesting the impact of low-grade inflammation on mortality deserves more attention.

Patient decisional needs when considering treatment intensification for type 2 diabetes: A qualitative study in China.

AIMS: This study explored decisional needs of patients with type 2 diabetes in China when considering treatment intensification to achieve good glycemic control, from both the patient's and practitioners' perspectives. METHODS: Interviews were conducted with 35 patients, and individual interviews and focus groups with 28 practitioners in Beijing, China. Topic guides based on the Ottawa Decisional Support Framework were modified for the Chinese context. Two interviewers independently extracted and coded transcripts of their notes into-overarching themes. Content analysis was performed to analyze participants' responses. RESULTS: Patients (34/35) reported having tried different medications and some (15/35) visited multiple hospitals and consulted different doctors. Patients' knowledge of medications was suboptimal (26/35), and most patients were not aware of their glucose levels (23/35). Although most were receptive to add-on medications, both patients and practitioners reported a range of uncertainty about the decision, and patients wanted more reliable information. Patients (15/35) and practitioners (19/28) recognized the importance of a trusting relationship when adding medications. Both reported similar values and preferences, but these were rarely discussed when adding medications. Although most patients (32/35) reported that they were capable of making a decision on adding medications, few practitioners (6/28) perceived their patients were capable. CONCLUSIONS: Findings suggest a need for reliable information, more discussion about values and preferences and decision support to help engage patients and practitioners in a shared decision-making process. Decision support tools may facilitate the process for patients with type 2 diabetes in China considering add-on medications.

Hypertriglyceridaemia predicts subsequent long-term risk of cardiovascular events in Chinese adults: 23-year follow-up of the Daqing Diabetes Study.

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.

Ionic Liquids as Electrolytes for Electrochemical Double-Layer Capacitors: Structures that Optimize Specific Energy.

Key parameters that influence the specific energy of electrochemical double-layer capacitors (EDLCs) are the double-layer capacitance and the operating potential of the cell. The operating potential of the cell is generally limited by the electrochemical window of the electrolyte solution, that is, the range of applied voltages within which the electrolyte or solvent is not reduced or oxidized. Ionic liquids are of interest as electrolytes for EDLCs because they offer relatively wide potential windows. Here, we provide a systematic study of the influence of the physical properties of ionic liquid electrolytes on the electrochemical stability and electrochemical performance (double-layer capacitance, specific energy) of EDLCs that employ a mesoporous carbon model electrode with uniform, highly interconnected mesopores (3DOm carbon). Several ionic liquids with structurally diverse anions (tetrafluoroborate, trifluoromethanesulfonate, trifluoromethanesulfonimide) and cations (imidazolium, ammonium, pyridinium, piperidinium, and pyrrolidinium) were investigated. We show that the cation size has a significant effect on the electrolyte viscosity and conductivity, as well as the capacitance of EDLCs. Imidazolium- and pyridinium-based ionic liquids provide the highest cell capacitance, and ammonium-based ionic liquids offer potential windows much larger than imidazolium and pyridinium ionic liquids. Increasing the chain length of the alkyl substituents in 1-alkyl-3-methylimidazolium trifluoromethanesulfonimide does not widen the potential window of the ionic liquid. We identified the ionic liquids that maximize the specific energies of EDLCs through the combined effects of their potential windows and the double-layer capacitance. The highest specific energies are obtained with ionic liquid electrolytes that possess moderate electrochemical stability, small ionic volumes, low viscosity, and hence high conductivity, the best performing ionic liquid tested being 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide.