Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: A post hoc analysis of the Da Qing Diabetes Prevention Outcome Study.

BACKGROUND: The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified. METHODS AND FINDINGS: In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population. CONCLUSIONS: In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction.

Premature death and risk of cardiovascular disease in young-onset diabetes: a 23-year follow-up of the Da Qing Diabetes Study.

OBJECTIVE: This study aimed to investigate premature mortality and the risk of cardiovascular disease (CVD) in Chinese adults with diabetes diagnosed before the age of 45 years. METHODS: A total of 519 participants with normal glucose tolerance (NGT) and 630 with newly diagnosed diabetes mellitus (DM) were recruited in 1986 in the Da Qing Diabetes Study. In 2009, the participants were followed up to assess mortality and CVD events. The subjects were stratified into four subgroups according to age and diabetes status: age <45 years with NGT (NGT<45y), age <45 years with DM (DM<45y), age ≥45 years with NGT (NGT≥45y), and age ≥45 years with DM (DM≥45y). The risk of death and CVD events in patients with young-onset DM and elder subjects with NGT were compared to show the extent of premature death and CVD in the DM participants. RESULTS: During the 23-year follow-up, 26 (10.40%) participants in NGT<45y, 72 (34.12%) in DM<45y, 74 (30.58%) in NGT≥45y, and 266 (68.73%) in DM≥45y died, including 13 (5.20%), 36 (17.06%), 24 (9.92%), and 128 (33.07%) death attributed to CVD. The corresponding rates of CVD events were 56 (22.40%), 90 (42.65%), 89 (36.78), and 213 (55.04%). It also showed that the risk of all-cause death (HR 1.23, 95% CI 0.88-1.71) or CVD events (HR 1.25, 95% CI 0.93-1.69) did not differ significantly between the DM<45y and NGT≥45y groups after adjusting for sex, smoking, body mass index, systolic blood pressure, total cholesterol and previous history of CVD. Of note, participants in the DM<45y group had an higher risk of CVD mortality compared with that in the NGT≥45y group (HR 1.76, 95% CI 1.04-2.98), although the mean age in the former group was 12 years lesser than that in the latter group (39.01 ± 5.00 vs 51.45 ± 5.14). CONCLUSIONS: Young-onset diabetes is a risk factor for the premature death and cardiovascular disease. Early prevention and intensive treatment are warrented in patients with young-onset diabetes.

Effects of variation in retinol binding protein 4 gene and adipose specific expression of gestational diabetes in Beijing, China.

OBJECTIVE: To investigate the clinical features of GDM in China and the effects of RBP4 genetic variants, and also to identify RBP4 expression changes in mRNA and protein levels. RESEARCH DESIGN AND METHODS: 1595 Chinese pregnant women were included in this study. Four known RBP4 single nucleotide polymorphisms (SNPs) were genotyped in 505 cases and 687 controls. Expression levels of adipose specific RBP4 mRNA and protein were detected in 41 samples of subcutaneous adipose tissue. RESULTS: The estimated indices of insulin resistance were gradually increased from NGT, GIGT to GDM. Two single SNPs were associated with GDM (rs3758539 G vs A, OR=1.446, P=0.009; rs3758539 GG vs AG+AA, OR=1.532, P=0.006; rs12265684C vs G, OR=1.296, P=0.038) and a haplotype of 3 common SNPs [G-G-T] was increased in subjects with GDM and GIGT (OR=1.322, 95% CI 1.054-1.659, P=0.016). RBP4 mRNA expression in adipose tissue of GDM patients was significantly increased in comparison to control subjects (1.438 ± 0.187 vs 1.034 ± 0.062, p=0.025). CONCLUSION: This finding suggests that impaired insulin sensitivity has an early onset in mild gestational intolerance. Two single SNPs were associated with GDM in the case-control study while a haplotype of 3 common SNPs [G-G-T] was increased in glucose intolerance subjects.