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.

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.

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.

Development of models to predict 10-30-year cardiovascular disease risk using the Da Qing IGT and diabetes study.

BACKGROUND:This study aimed to develop cardiovascular disease (CVD) risk equations for Chinese patients with newly diagnosed type 2 diabetes (T2D) to predict 10-, 20-, and 30-year of risk.METHODS:Risk equations for forecasting the occurrence of CVD were developed using data from 601 patients with newly diagnosed T2D from the Da Qing IGT and Diabetes Study with a 30-year follow-up. The data were randomly assigned to a training and test data set. In the training data set, Cox proportional hazard regression was used to develop risk equations to predict CVD. Calibration was assessed by the slope and intercept of the line between predicted and observed probabilities of outcomes by quintile of risk, and discrimination was examined using Harrell's C statistic in the test data set. Using the Sankey flow diagram to describe the change of CVD risk over time.RESULTS:Over the 30-year follow-up, corresponding to a 10,395 person-year follow-up time, 355 of 601 (59%) patients developed incident CVD; the incidence of CVD in the participants was 34.2 per 1,000 person-years. Age, sex, smoking status, 2-h plasma glucose level of oral glucose tolerance test, and systolic blood pressure were independent predictors. The C statistics of discrimination for the risk equations were 0.748 (95%CI, 0.710-0.782), 0.696 (95%CI, 0.655-0.704), and 0.687 (95%CI, 0.651-0.694) for 10-, 20-, and 30- year CVDs, respectively. The calibration statistics for the CVD risk equations of slope were 0.88 (P = 0.002), 0.89 (P = 0.027), and 0.94 (P = 0.039) for 10-, 20-, and 30-year CVDs, respectively.CONCLUSIONS:The risk equations forecast the long-term risk of CVD in patients with newly diagnosed T2D using variables readily available in routine clinical practice. By identifying patients at high risk for long-term CVD, clinicians were able to take the required primary prevention measures.

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.

Correction to: Development of models to predict 10-30-year cardiovascular disease risk using the Da Qing IGT and diabetes study.

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.

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.

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 Palmitoyl Sphingomyelin Is Associated With Cardiovascular Disease in Individuals With Type 2 Diabetes: Findings From the China Da Qing Diabetes Study.

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.

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.

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.

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.

Development of models to predict 10-30-year cardiovascular disease risk using the Da Qing IGT and diabetes study.

BACKGROUND:This study aimed to develop cardiovascular disease (CVD) risk equations for Chinese patients with newly diagnosed type 2 diabetes (T2D) to predict 10-, 20-, and 30-year of risk.METHODS:Risk equations for forecasting the occurrence of CVD were developed using data from 601 patients with newly diagnosed T2D from the Da Qing IGT and Diabetes Study with a 30-year follow-up. The data were randomly assigned to a training and test data set. In the training data set, Cox proportional hazard regression was used to develop risk equations to predict CVD. Calibration was assessed by the slope and intercept of the line between predicted and observed probabilities of outcomes by quintile of risk, and discrimination was examined using Harrell's C statistic in the test data set. Using the Sankey flow diagram to describe the change of CVD risk over time.RESULTS:Over the 30-year follow-up, corresponding to a 10,395 person-year follow-up time, 355 of 601 (59%) patients developed incident CVD; the incidence of CVD in the participants was 34.2 per 1,000 person-years. Age, sex, smoking status, 2-h plasma glucose level of oral glucose tolerance test, and systolic blood pressure were independent predictors. The C statistics of discrimination for the risk equations were 0.748 (95%CI, 0.710-0.782), 0.696 (95%CI, 0.655-0.704), and 0.687 (95%CI, 0.651-0.694) for 10-, 20-, and 30- year CVDs, respectively. The calibration statistics for the CVD risk equations of slope were 0.88 (P = 0.002), 0.89 (P = 0.027), and 0.94 (P = 0.039) for 10-, 20-, and 30-year CVDs, respectively.CONCLUSIONS:The risk equations forecast the long-term risk of CVD in patients with newly diagnosed T2D using variables readily available in routine clinical practice. By identifying patients at high risk for long-term CVD, clinicians were able to take the required primary prevention measures.

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.

Correction to: Development of models to predict 10-30-year cardiovascular disease risk using the Da Qing IGT and diabetes study.

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.

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.

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 Palmitoyl Sphingomyelin Is Associated With Cardiovascular Disease in Individuals With Type 2 Diabetes: Findings From the China Da Qing Diabetes Study.

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.