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The purpose of this study was to examine whether a 9-month intensive lifestyle intervention could lead to weight loss and improve cardiovascular risk factors among young women with both gestational diabetes mellitus (GDM) and newly diagnosed diabetes. A total of 83 young women, who had GDM and were subsequently diagnosed as type 2 diabetes at an average of 2.6 years after delivery, participated in a 9-month intensive lifestyle intervention and a follow-up survey at 6–9 years postintervention. After the 9-month intervention, these women had a weight loss of 2.90 kg (−4.02% of initial weight), decreased waist circumference (−3.12 cm), body fat (−1.75%), diastolic blood pressure (−3.49 mmHg), fasting glucose (−0.98 mmol/L) and HbA1c (−0.72%). During the 6–9 years postintervention period, they still had lower weight (−3.71 kg; −4.62% of initial weight), decreased waist circumference (−4.56 cm) and body fat (−2.10%), but showed a slight increase in HbA1c (0.22%). The prevalence of using glucose-lowering agents increased from 2.4% at baseline to 34.6% after the 9-month lifestyle intervention, and to 48.4% at 6–9 years postintervention. A 9-month intensive lifestyle intervention can produce beneficial effects on body weight, HbA1c and other cardiovascular risk factors among young women with previous GDM who subsequently developed new diabetes. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to explore additive interactions of CDKAL1 rs7747752 and GUDCA/DCA for GDM risk and whether the interactive effects on the risk of GDM was mediated via increasing lysophosphatidylcholines (LPC) 18:0 and/or saturated fatty acid (SFA) 16:0. Methods: A 1:1 age-matched study nested in a prospective cohort of pregnant women (207 pairs) was organized in Tianjin, China. Additive interactions were used to test interaction effects while mediation analyses and Sobel tests were used to test mediation effects of LPC18:0 and SFA16:0 between copresence of rs7747752 and low GUDCA/DCA, and GDM risk. Results: The CDKAL1 rs7747752 was associated with GDM (P<0.05). The rs7747752 C polymorphism markedly enhanced ORs of low GUDCA from 4.04 (0.72-22.8) to 9.02 (1.63-49.7) and low DCA from 1.67 (0.68-4.11) to 4.24 (1.84-9.76), both with significant additive interactions. Further adjustment for LPC18:0 attenuated the interactive effects of rs7747752 and low DCA, with a significant mediation effect (P=0.003). High SFA16:0 did not mediate the interactive effects of rs7747752 and low DCA/GUDCA on GDM risk. Conclusions: The CDKAL1 rs7747752 C carrier status and low GUDCA/DCA had significant additive interactions on the risk of GDM with the effect from interaction with DCA being partially mediated via increasing LPC18:0. [ABSTRACT FROM AUTHOR]

Summary: We performed two meta‐analyses to estimate the effects of lifestyle intervention during pregnancy and after delivery on the risk of postpartum diabetes among women with gestational diabetes mellitus (GDM). We searched the major databases to retrieve articles published in English or Chinese before 15 December 2019. The inclusion criteria were randomized controlled trials (RCTs) of diet, physical activity or both, conducted during or after pregnancy among women with GDM. The exclusion criteria were (1) having type 1 or type 2 diabetes before the intervention and (2) without postpartum diabetes documented. Fixed‐effects model analysis was used to obtain the pooled relative risks (RRs) and 95% confidence intervals (CIs) of lifestyle intervention for diabetes in women with GDM. Four RCTs were identified to have implemented the intervention during pregnancy (n = 2883) and 10 to have conducted it within 3 years after delivery (n = 1733). Lifestyle intervention during pregnancy was not effective at reducing the risk of postpartum diabetes (RR: 0.91, 95%CI: 0.66–1.25). However, lifestyle intervention initiated within 3 years after delivery was highly effective in reducing the risk of postpartum diabetes (pooled RR: 0.57, 95% CI: 0.42–0.78). In conclusion, our findings support the early initiation of lifestyle intervention in women with GDM for the prevention of diabetes. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Women with gestational diabetes mellitus are at increased risk for type 2 diabetes. We characterized the association between maternal glycemia during pregnancy with long‐term outcomes. Methods and Methods: In this prospective nested case–cohort study, participants were recalled for follow up with detailed evaluation including oral glucose tolerance test at 8, 15 and 22 years. Logistic regression was used to estimate the risk of developing impaired glucose tolerance/type 2 diabetes and metabolic syndrome at follow up. The association between maternal glycemia at pregnancy and follow up was evaluated by linear regression. We also charted trajectory of β‐cell function during follow up. Results: The analysis included 121 women with a mean follow‐up period of 22.5 years, and a mean age of 50.3 years. Gestational diabetes was associated with an adjusted odds ratio of 2.48 (95% confidence interval 1.03–5.99) for combined diabetes/impaired glucose tolerance at follow up (P = 0.04). Women with a pre‐pregnancy body mass index ≥23 had an odds ratio of 5.43 (95% confidence interval 1.87–15.72) for metabolic syndrome at follow up, compared with those with body mass index <23 (P = 0.002). Both fasting and 2‐h glucose during pregnancy were strongly associated with glycemic indices at follow up (P‐value <0.001–0.016). Gestational diabetes was associated with impaired β‐cell function that remained relatively stable after the index pregnancy. Conclusions: Chinese women with a history of gestational diabetes have a high prevalence of impaired glucose tolerance/type 2 diabetes at 22‐year follow up. Glucose levels during mid‐pregnancy are strongly associated with those of middle age. [ABSTRACT FROM AUTHOR]

Objective: The association between acylcarnitine metabolites and cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to investigate associations between acylcarnitines and CVD in Chinese patients with T2DM. Methods: A cross-sectional study was conducted from May 2015 to August 2016. Medical records of 741 patients with T2DM were retrieved from the main electronic database of Liaoning Medical University First Affiliated Hospital. CVD was defined as having either coronary artery disease (CAD) or heart failure (HF) or stroke. Mass Spectrometry was utilized to measure levels of 25 acylcarnitine metabolites in fasting plasma. Factor analysis was used to reduce the dimensions and extracted factors of the 25 acylcarnitine metabolites. Multivariable binary logistic regression was used to obtain odds ratios (OR) of the factors extracted from the 25 acylcarnitine metabolites and their 95% confidence intervals (CI) for CVD. Results: Of the 741 patients with T2DM, 288 had CVD. Five factors were extracted from the 25 acylcarnitines and they accounted for 65.9% of the total variance. Factor 1 consisted of acetylcarnitine, butyrylcarnitine, hydroxylbutyrylcarnitine, glutarylcarnitine, hexanoylcarnitine, octanoylcarnitine, and tetradecanoyldiacylcarnitine. Factor 2 consisted of decanoylcarnitine, lauroylcarnitine, myristoylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, tetradecenoylcarnitine, and 3-hydroxypalmitoylcarnitine. After adjusting for potential confounders, increased factor 1 and 2 were associated with increased risks of CVD in T2DM (OR of factor 1: 1.45, 95% CI: 1.03–2.03; OR of factor 2: 1.23, 95% CI: 1.02–1.50). Conclusions: Elevated plasma levels of some acylcarnitine metabolites, i.e., those extracted into factor 1 and 2, were associated with CVD risk in T2DM. [ABSTRACT FROM AUTHOR]

Aim: The study aimed to investigate the prevalence of metabolic syndrome (MetS) and its determinants in newly-diagnosed adult-onset diabetes in China. Methods: From April 2015 to October 2017, 15,492 consecutive patients with diabetes diagnosed within 1 year and aged ≥30 years were recruited from 46 tertiary care hospitals in 24 cities across China. Glutamic acid decarboxylase autoantibody was assayed centrally and clinical data were collected locally. Classic type 1 diabetes mellitus (T1DM), latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM) were defined using the criteria of American Diabetes Association, Immunology of Diabetes Society and World Health Organization. MetS was defined using Chinese Diabetes Society's criteria. Logistic regression analysis was used to obtain odds ratios (OR) of determinants of MetS. Results: The overall prevalence of MetS was 66.5%, with the highest prevalence in T2DM (68.1%), followed by those in LADA (44.3%) and T1DM (34.2%) (P < 0.05 for all comparisons). After adjustment for traditional risk factors, T2DM had a 2.8-fold [95% confidence interval (CI): 2.36–3.37] MetS risk compared with LADA, whereas T1DM had significantly lower OR than LADA (OR: 0.68, 95% CI: 0.50–0.92). After further adjustment for insulin resistance, the OR of T2DM vs. LADA was slightly reduced but the OR of T1DM vs. LADA was greatly attenuated to non-significance (OR: 0.96, 95% CI: 0.70–1.33). In addition to types of diabetes, age, gender, geographical residence, education attainment, alcohol consumption and HOMA2-IR were independent determinants of MetS. Conclusions: MetS was highly prevalent, not only in T2DM but also in T1DM and LADA in Chinese newly diagnosed patients; higher risk of MetS in LADA than in T1DM was partially attributable to higher insulin resistance in LADA. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Metabolomic markers have the potential to improve the predicting accuracy of existing risk scores for type 2 diabetes mellitus. The present study aimed to test the associations between plasma tyrosine and type 2 diabetes mellitus with special attention to identifying possible cut‐off points for type 2 diabetes mellitus, and its interactive effects with low high‐density lipoprotein cholesterol (HDL‐C) and/or high triglyceride for type 2 diabetes mellitus. Methods: From 27 May 2015 to 3 August 2016, we retrieved the medical notes of 1,898 inpatients with type 2 diabetes mellitus as the cases, and 1,522 individuals without diabetes as the controls who attended annual medical checkups from the same tertiary care center in Jinzhou, China. Logistic regression analyses were carried out to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline analysis nested in the logistic regression analysis was used to identify possible cut‐off points of tyrosine for type 2 diabetes mellitus. The additive interaction was used to estimate interactions between high tyrosine and low HDL‐C in type 2 diabetes mellitus patients. Results: The OR of tyrosine for type 2 diabetes mellitus did not increase until 46 μmol/L and after that point, the OR rapidly rose with increasing tyrosine in a nearly linear manner. If 46 μmol/L was used to define high tyrosine, high tyrosine was associated with an increased OR of type 2 diabetes mellitus (adjusted OR 1.88, 95% CI 1.44–2.45). The presence of low HDL‐C greatly enhanced the ORs of tyrosine for type 2 diabetes mellitus from 1.11 (95% CI 0.82–1.51) to 54.11 (95% CI 33.96–86.22) with significant additive interaction. Conclusions: In Chinese adults, tyrosine >46 μmol/L was associated with increased odds of type 2 diabetes mellitus, which was contingent on low HDL‐C. This study aimed to test associations between plasma tyrosine and T2DM with special attention to identifying possible cutoff points for T2DM; and its interactive effects with low high‐density lipoprotein cholesterol (HDL‐C) or/and high triglyceride for T2DM. We found that 1) tyrosine was associated with type 2 diabetes in a V‐shaped manner; 2) high tyrosine> 46 ?mol/L was associated with increased OR of type 2 diabetes; 3) high tyrosine had an additive effect with low HDL‐C for the increased OR of type 2 diabetes. Our novel observation is likely to suggest that the association between tyrosine and the risk of type 2 diabetes is mediated via the AMPK pathway. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to test associations between type 2 diabetes mellitus (T2DM) and metabolites in urea cycle including arginine, citrulline and ornithine. Methods: This study used a hospital-based cross-sectional study design. We retrieved medical notes of 401 in-patients with onset of T2DM within 2 years and 1,522 healthy subjects who attended annual physical examination. All cases were admitted to a tertiary care center in Jinzhou, China from May 2015 to August 2016. Binary logistic regression analyses were performed to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Results: Patients with T2DM had higher arginine, and lower ornithine than control subjects. Levels of citrulline were similar in two groups. Arginine was positively associated with T2DM (ORs: 1.20, 1.17–1.23) while ornithine was negatively associated with T2DM (OR: 0.89, 0.88–0.91). After adjustment for other amino acids and traditional risk factors, these associations were still significant and persistent for arginine and ornithine. The association between citrulline and T2DM was not significant. Their ratios of pairs of two amino acids were associated with increased risk of T2DM. After adjustment for other ratios of amino acids, effect size for T2DM remained significant. Further adjustment for traditional risk factors did not lead to large changes (ORs: 1.78, 1.20–2.65 for the ratio of arginine to ornithine; ORs: 1.59, 1.37–1.86 for the ratio of citrulline to ornithine, respectively) except the ratio of arginine to citrulline. Conclusions: Plasma levels of amino acids related to urea cycle and their ratios of these amino-acids were associated with T2DM in Chinese adults. [ABSTRACT FROM AUTHOR]

Background: There are inconsistent findings regarding associations between triglyceride levels and cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). This study aimed to test whether the association between triglycerides and CVD depends upon duration of diabetes.Methods: From April 1, 2012, to June 30, 2012, we conducted a cross-sectional survey of 223 612 patients with T2DM from 630 hospitals in China. Cardiovascular disease was defined as having either prior coronary heart disease or stroke, or diabetic foot. Binary logistic regression was used to estimate odds ratios of triglyceride for CVD. Relative excess risk due to interaction, attributable proportion due to interaction, and synergy index were used to estimate effect size of additive interaction between low triglyceride, ie, <1.7 mmol/L, and duration of diabetes, ie, ≥15 years.Results: Among 223 612 T2DM patients, 31 898 (14.27%) suffered from CVD. A low level of triglyceride was associated with decreased risk of CVD (univariable OR, 0.91, 95% CI, 0.88-0.93; multivariable OR, 0.94, 95% CI, 0.92-0.97) among patients with <15 years of duration of diabetes but increased risk of CVD (univariable OR, 1.12, 95% CI, 1.04-1.21; multivariable OR, 1.18, 95% CI, 1.09-1.27) among those patients with 15 and more years of duration of diabetes with significant additive interactions (relative excess risk due to interaction, 0.39, 95% CI, 0.25-0.52; attributable proportion due to interaction, 0.20, 95% CI, 0.14-0.27; and synergy index, 1.80, 95% CI, 1.43-2.28).Conclusions: Whereas a high triglyceride level was associated with increased risk of CVD in short-term T2DM, low triglyceride was associated with increased CVD risk in long-term T2DM. Low triglyceride may be a marker of CVD risk in Chinese patients with long-term T2DM. [ABSTRACT FROM AUTHOR]

Background: This study aimed to test whether early-onset (defined as <40 years of age) type 2 diabetes mellitus (T2DM) imparted different risks of microvascular disease to Chinese men and women. Methods: 222,537 Chinese patients with T2DM were recruited in 630 hospitals from 106 cities in 30 provinces of China in 2012 using a cross-sectional design. Logistic regression analysis was performed to obtain odds ratios (ORs) of male vs. female for diabetic retinopathy (DR) and diabetic nephropathy (DN). Additive interaction was used to test whether male gender and early-onset T2DM had interactive effects for DR and DN. Results: More men than women with T2DM had DN (4.5 vs. 3.0%, P < 0.0001), DR (5.3 vs. 5.1%, P < 0.0001), and microvascular disease (either DN or DR) (8.4 vs. 7.1%, P < 0.0001). After adjustment for age and levels of hospitals, the effect sizes of early- onset T2DM for microvascular disease were higher in men than in women, with a 2.67 [95% confidence intervals (CI): 2.51-2.85] fold risk in men and a 2.53 (95% CI: 2.35-2.72) fold risk in women. The risk effect sizes were greatly attenuated by further adjusting for diabetes durations and other traditional risk factors, with a 1.28 (95% CI: 1.19-1.37) fold risk in men and a 1.07 (95% CI: 0.99-1.16) fold risk in women. After adjustment for diabetes durations and other traditional risk factors, using women with late-onset T2DM as the reference, co-presence of early-onset and male gender significantly enhanced the ORs of either early-onset alone (1.10, 95% CI: 1.03-1.19) or male gender alone (0.96, 95% CI: 0.93-0.99) to 1.32 (95% CI: 1.24-1.41), with significant additive interaction. Kaplan-Meier analysis showed that in early-onset T2DM, DN developed 5 years earlier in men than in women. Conclusion: Early-onset T2DM increased more risk of microvascular complications in Chinese men than in women, most of increased risks being attributable to longer diabetes durations. [ABSTRACT FROM AUTHOR]

Background: Passive smoking increased type 2 diabetes mellitus risk, but it is uncertain whether it also increased gestational diabetes mellitus (GDM) risk. We aimed to examine the association of passive smoking during pregnancy and its interaction with maternal obesity for GDM.Methods: From 2010 to 2012, 12 786 Chinese women underwent a 50-g 1-hour glucose challenge test at 24 to 28 weeks of gestation and further underwent a 75-g 2-hour oral glucose tolerance test if the glucose challenge test result was ≥7.8 mmol/L. GDM was defined by the International Association of Diabetes and Pregnancy Study Group's cut points. Self-reported passive smoking during pregnancy was collected by a questionnaire. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction between maternal obesity and passive smoking was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). Significant RERI > 0, AP > 0, or S > 1 indicated additive interaction.Results: A total of 8331 women (65.2%) were exposed to passive smoking during pregnancy. More women exposed to passive smoking developed GDM than nonexposed women (7.8% versus 6.3%, P = 0.002) with an adjusted OR of 1.29 (95%CI, 1.11 to 1.50). Compared with nonobesity and nonpassive smoking, prepregnancy obesity and passive smoking was associated with GDM risk with an adjusted OR of 3.09 (95%CI, 2.38-4.02) with significant additive interaction (P < .05 for RERI and AP).Conclusions: Passive smoking during pregnancy increased GDM risk in Chinese women independently and synergistically with prepregnancy obesity. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore independent associations between serum uric acid and hypoglycaemia, and whether mildly increased serum uric acid exacerbated the association between mild decline in estimated glomerular filtration rate (eGFR) and hypoglycaemia.Methods: A cross-sectional survey of 6713 inpatients with type 2 diabetes and eGFR ≥60 mL/min/1.73 m2 and admitted to 81 tertiary care hospitals in China was conducted. Self-reported asymptotic hypoglycaemia with plasma glucose ≤3.9 mmol/L, hypoglycaemia episodes with symptoms in 1 month or hypoglycaemia that needed assistance from other people in 3 months before hospitalization was used to define hypoglycaemia. Binary logistic regression was used to estimate odds ratios of serum uric acid for hypoglycaemia. Three measures, that is, relative excess risk due to interaction (RERI), attributable proportion due to interaction and synergy index (S) were used to estimate the effect of mildly decreased eGFR on the association of serum uric acid with hypoglycaemia.Results: Serum uric acid was associated with hypoglycaemia in an ordinal manner (P for trend <0.01) with an odds ratio of top quartile versus the lowest quartile up to 3.03 (95% confidence interval: 2.13-4.32). The odds ratio of serum uric acid levels ≥ versus <283 µmol/L (i.e. the median) was 1.98 (95% confidence interval:1.58-2.48). Serum uric acid levels ≥ versus <283 µmol/L greatly enhanced the association between mild decline in eGFR (eGFR < 90 mL/min/1.73 m2 ) and hypoglycaemia from 0.94 (0.36-2.43) to 3.90 (2.55-5.95), with a significant additive interaction (P < 0.05 for RERI, AP and S).Conclusions: Mildly increased serum uric acid was associated with increased risk of hypoglycaemia and enhanced the association between mildly decreased eGFR and hypoglycaemia in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We recruited a group of 6713 consecutive Chinese patients with T2D but normal renal and liver function who were admitted to one of 81 top tertiary care hospitals in China. Mild hypoglycaemia was defined as having symptomatic hypoglycaemia in one month before hospitalization. Severe hypoglycaemia was defined as having hypoglycaemia that needed assistance from other people in three months before hospitalization. Prior cardiovascular disease (CVD) was defined as having coronary heart disease, stroke, or peripheral arterial disease. Of 6713 patients, 80 and 304 had severe and mild hypoglycaemia episodes, respectively, and 561 had CVD. Patients with severe and mild hypoglycaemia episodes were more likely to have prior CVD (32.5% versus 16.5% versus 7.7%, P < 0.0001). Both mild and severe hypoglycaemia were associated with increased risk of CVD (adjusted odds ratios (ORs): 2.64, 95% CI: 1.85-3.76 for mild hypoglycaemia; 6.59, 95% CI: 3.79-11.45 for sever hypoglycaemia) than those patients free of hypoglycaemia. Further adjustment for lipid profile did not change these two ORs. In the same way, the ORs of lipid profile for CVD were similar before and after adjustment for hypoglycaemia. We concluded that hypoglycaemia and lipid profile were independently associated with increased risk of CVD. [ABSTRACT FROM AUTHOR]

Background In type 2 diabetes (T2D), copresence of low-density lipoprotein cholesterol (LDL-C) <2.8 mmol/L with triglyceride <1.7 mmol/L or with albuminuria synergistically increased cancer risk. We tested whether use of renin angiotensin system inhibitors attenuated the increased cancer risk associated with these two risk subphenotypes. Methods A prospective cohort of 4307 patients with T2D enrolled from December 1996 to January 2005 was analysed using a new user cohort design. Cox model analysis was used to obtain hazard ratios and 95% confidence intervals. The study measured additive interactions between nonuse of renin angiotensin system inhibitors and low LDL-C plus low triglyceride or albuminuria for the risk of cancer. A positive interaction suggests a specific drug effect on the low LDL-C-related cancer risk. Results During 18 769 person years of follow-up (median follow-up years: 4.44), 4.48% ( n = 193) of patients developed cancer. Use of renin angiotensin system inhibitors was associated with reduced cancer risk among patients with copresence of low LDL-C plus low triglyceride or low LDL-C plus albuminuria but not in patients without these subphenotypes. In multivariable analysis, renin angiotensin system inhibitor usage attenuated the hazard ratio of copresence of low LDL-C plus low triglyceride versus lack of this subphenotype for cancer from 2.08 (95% CI: 1.25-3.47) to 1.13 (0.61-2.11) with significant additive interaction ( p = 0.0225). Similarly, RAS inhibitor usage attenuated the hazard ratio of copresence of low LDL-C plus albuminuria versus lack of this subphenotype for cancer from 1.99 (95% CI: 1.12-3.56) to 0.82 (0.43-1.54) with significant additive interaction ( p = 0.0009). Conclusion In T2D, renin angiotensin system inhibitor usage may specifically attenuate the low LDL-C-related cancer risk. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background In type 2 diabetes, tight glycaemic control lowers the risk of diabetic complications, but it remains uncertain whether variability of glycaemia influences outcomes. We examined the association of glycated haemoglobin (HbA1c) variability with incident chronic kidney disease and cardiovascular disease in a prospective cohort of 8439 Chinese patients with type 2 diabetes recruited from 1994 to 2007. Methods Intrapersonal mean and SD of serially measured HbA1c were calculated. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min per 1.73 m2. Cardiovascular disease was defined as events of ischemic heart disease, heart failure, ischemic stroke or peripheral vascular disease. Results Over a median follow-up period of 7.2 years, 19.7 and 10.0% of patients developed chronic kidney disease and cardiovascular disease, respectively. Patients who progressed to chronic kidney disease had higher mean HbA1c (7.8 ± 1.3% vs 7.4 ± 1.2%, p < 0.001) and SD (1.0 ± 0.8% vs 0.8 ± 0.6%, p < 0.001) than nonprogressors. Similarly, patients who developed cardiovascular disease had higher mean HbA1c (7.7 ± 1.3% vs 7.4 ± 1.2%, p < 0.001) and SD (1.4 ± 1.1% vs 1.1 ± 0.8%, p < 0.001) than patients who did not develop cardiovascular disease. By using multivariate-adjusted Cox regression analysis, adjusted SD was associated with incident chronic kidney disease and cardiovascular disease with corresponding hazard ratios of 1.16 (95% CI 1.11-1.22), p < 0.001) and 1.27 (95% CI 1.15-1.40, p < 0.001), independent of mean HbA1c and other confounding variables. Conclusions Long-term glycaemic variability expressed by SD of HbA1c predicted development of renal and cardiovascular complications. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We have reported associations of cancer with low triglyceride and high high-density lipoprotein cholesterol (HDL-C) as well as co-presence of low low-density lipoprotein cholesterol (LDL-C) and albuminuria in type 2 diabetes (T2D). This analysis aims to test (1) whether low LDL-C and low triglyceride have synergistic effects to increase cancer risk in T2D and (2) whether high HDL-C enhances the effect of co-presence of low LDL-C and albuminuria on cancer risk. A prospective cohort of patients with T2D, established within the Prince of Wales Hospital, was used in the analysis. A total of 3,476 T2D patients in Hong Kong enrolled between 1996 and 2005, free of cancer at enrolment and not using statins or fibrates within 2.5 years before enrolment and during follow-up, were followed until 2005. The study measured additive interactions of low LDL-C with other factors for cancer using relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). A statistically significant RERI > 0 or AP > 0 indicates additive interaction. During 5.11 years of follow-up, 199 patients developed cancer. Co-presence of triglyceride <1.70 mmol/L and LDL-C < 2.80 mmol/L was associated with increased cancer risk (multivariable hazard ratio [HR]:2.13, P = 0.0008) with significant interaction. Co-presence of HDL-C ≥ 1.30 mmol/L and LDL-C < 2.80 mmol/L plus albuminuria was also associated with increased cancer risk (HR: 3.84, P < 0.0001) with significant interaction. In T2D, low triglyceride may potentiate cancer risk associated with low LDL-C while high HDL-C enhances the synergistic effect of low LDL-C with albuminuria towards increased cancer risk. [ABSTRACT FROM AUTHOR]

Aims: The progression to type 2 diabetes mellitus (DM) and other long-term cardiometabolic risks in Chinese women with prior history of gestational diabetes (GD) was studied at 15 years postpartum. Methods: 139 Chinese women (45 with GD and 94 with normal glucose tolerance (NGT) at the index pregnancy) who had their insulin sensitivity and β-cell functions examined at 8 years postpartum were again followed up at 15 years for the investigation of the rate of type 2 DM, hypertension and metabolic syndrome. Results: Women with prior history of GD had a significantly higher rate of hypertension (35.6% vs. 16.0%, p = 0.01), type 2 DM (24.4% vs. 5.3%, p < 0.001) and impaired glucose regulation (26.6% vs. 14.9%, p < 0.001) than women with NGT during the index pregnancy. The Matsuda insulin sensitivity index and the quantitative insulin sensitivity check index at 8 years postpartum were independent predictors of both DM and metabolic syndrome at 15 years postpartum. Conclusions: The conversion rate of type 2 DM increased at an average rate of 1.6% per year after a pregnancy affected by GD. Insulin resistance at 8 years postpartum could refine a future diabetic risk in women with prior history of GD. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Chinese diabetic patients are at greater risk of developing chronic kidney disease (CKD) than Caucasian counterparts. In this hypothesis-generating study, we examined the independent and joint effects of multiple genetic variants on CKD in a prospective Chinese cohort of Type 2 diabetic patients. Methods. Seventy-seven single-nucleotide polymorphisms (SNPs) of 54 candidate genes for cardiorenal diseases and inflammation were genotyped in 1163 patients with no past history of CKD at baseline. CKD was defined as the first estimated glomerular filtration rate <60mL/min/1.73m2 or the first hospitalization with a diagnosis of renal disease. Results. In Cox-regression analysis, 15 SNPs of 13 genes were associated with incident CKD. After correction for multiple comparisons, 6 SNPs including PON1 55Met, PON2 311Cys CETP-629C, ITGA2 873A, LTA 26Asn and LTA 252Gly remained independently associated with CKD, with respective hazard ratios (95% confidence interval):2.6 (1.4–4.8, P = 0.002), 1.5 (1.2–1.9, P = 0.003), 1.4 (1.1–1.7, P = 0.001), 2.2 (1.3–3.7, P = 0.002), 1.6 (1.1–2.2, P = 0.008) and 1.5 (1.1–2.1, P = 0.019). Analysis of joint effect of the six SNPs showed stepwise increase in risk of CKD with the accumulation of risk alleles and weighted genetic risk score (Ptrend = 8.9 × 10−7 and 4.0 × 10−5, respectively). Conclusions. In Type 2 diabetes, there are independent and joint effects of multiple genetic variants on risk of CKD. Risk associations with PON1, PON2, CETP, ITGA2 and LTA genetic polymorphisms underline the importance of lipid metabolism, haemostasis and inflammation in the development of CKD in patients with Type 2 diabetes. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Hyperglycaemia is a risk factor for cancer and some sulphonylureas have anti-oxidant properties. This study examined associations between use of sulphonylureas and cancer. Methods: A consecutive cohort of 6103 Hong Kong Chinese patients with T2DM, free of cancer, was analysed using Cox models. Sulphonylurea usage was defined as use of the drugs at or within 2.5 years before enrolment and/or during follow-up periods. We adjusted for identified risk factors of cancer, use of other drugs, non-linear associations of lipids with cancer and probabilities of use of these drugs at different times and doses where appropriate. Results: During a median of 4.91 years of follow-up, 271 developed cancer. Glibenclamide, gliclazide and glipizide were ever used in 32.5% (n =1983), 47.8% (n =2920) and 13.5% (n =823). After adjustment for covariates, use of gliclazide and glibenclamide was associated with reduced cancer risk in a dose-dependent manner. In addition, there were interactions between metformin and glibenclamide/glipizide use towards lower adjusted cancer risks. Conclusions: In T2DM, use of glibenclamide and gliclazide may be associated with reduced cancer risk. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the risk association of protein kinase C-Β (PKC-Β) polymorphisms and end-stage renal disease (ESRD) in an 8-year prospective cohort with Chinese patients with type 2 diabetes. There has been an association between the cell-signaling intermediate PKC-Β and the development of diabetic complications. Eighteen common tag single-nucleotide polymorphisms (SNPs) were genotyped by the authors. It was concluded that genetic variants in the PRKCB1 gene were independently associated with development of ESRD.

Abstract: Aim: Dyslipidaemia may be a risk factor for diabetic kidney disease. We examined prospectively association between the use of statins and development of renal dysfunction in type 2 diabetes. Methods: A consecutive cohort of 5264 diabetic patient recruited between 1996 and 2005 underwent detailed assessments. Renal dysfunction was defined as first estimated glomerular filtration rate <60ml/min/1.73m2, or, the first hospitalisation with a diagnosis of renal disease as coded by the International Classification of Disease, Ninth Revision. Drug use was quantified using the proportion of exposure time from baseline to event/death/censored time, as appropriate. Results: In this cohort (male: 47.3%, median age: 55 years, median duration of diabetes: 6.0 years), none had renal dysfunction at baseline. During a median follow-up period of 4.9 (quartiles: 2.77, 7.04) years, 703 patients (13.4%) developed renal dysfunction, 1275 patients (22.2%) were exposed to statins. After controlling for baseline risk factors, multivariable adjusted hazard ratio of statin use for development of renal dysfunction was 0.32 (95% CI 0.21–0.50, p <0.0001). Conclusion: Use of statins was associated with reduced risk of developing renal dysfunction in type 2 diabetes and this association was independent of baseline risk factors. [Copyright &y& Elsevier]

Abstract: Background: High white blood cell (WBC) predicted cancer-associated mortality and renin–angiotensin system (RAS) inhibitors have immunomodulating effects. We hypothesize that RAS inhibitors may reduce cancer risk associated with high WBC in type 2 diabetes mellitus (T2DM). Methods: A prospective cohort of 4570 Chinese T2DM patients, free of cancer at enrolment, were analyzed. Biological interaction between WBC groups and use of RAS inhibitors was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). RERI>0, AP>0 or S>1 indicates biological interaction. Results: During 4.89 years of follow-up, 205 (4.49%) patients developed cancer. WBC≥8.2×109 counts/L plus non-use of RAS inhibitors was associated with elevated cancer risks in multivariable models. The RERI and AP for interaction between WBC≥8.2×109 counts/L and non-use of RAS inhibitors were, respectively, 1.26 (95% CI: 0.22–2.31) and 0.50 (0.23–0.78). In patients with WBC≥8.2×109 counts/L, use of RAS inhibitors was associated with 64% (31–81%) cancer risk reduction in multivariable analysis. Conclusions: In T2DM, increased WBC predicts cancer while use of RAS inhibitors may reduce cancer risks associated with high WBC count. [Copyright &y& Elsevier]

OBJECTIVE -- LDL cholesterol <2.80 mmol/l was associated with increased cancer risk in type 2 diabetes. We explored the 1) interaction between low LDL cholesterol and albuminuria and 2) interaction between copresence of these two risk factors and statin use for cancer in type 2 diabetes. RESEARCH DESIGN AND METHODS-- We analyzed prospective data for 3,793 Chinese type 2 diabetic patients who remained naive for statin treatment and 1,483 patients in whom statin treatment was initiated during a median follow-up period of 5.24 years. All patients were free of cancer at baseline. Biological interactions were estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates biological interaction. RESULTS -- In 3,793 statin-naive type 2 diabetic patients, copresence of low LDL cholesterol and albuminuria increased cancer risk by 2.8-fold (hazard ratio 2.77 [95% CI 1.78-4.31]) with significant biological interactions (RERI 1.05 [0.04-2.06]; AP 0.38 [0.09-0.66]). In the whole cohort of 5,276 type 2 diabetic patients, there was interaction between nonuse of statins and copresence of low LDL cholesterol and albuminuria with increased cancer risk (RERI 2.87 [0.64-5.09] and AP 0.60 [0.29-0.90]). Statin nonusers with LDL cholesterol <2.80 mmol/l and albumunuria had a 4.9-fold risk of cancer compared with statin users with or without both risk factors. CONCLUSIONS-- In type 2 diabetes, there was interaction between low LDL cholesterol and albuminuria with increased cancer risks. The latter was attenuated in the presence of statin treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Clinical and experimental studies suggest cross-talk between lipid metabolism and the renin-angiotensin system (RAS) in atherogenesis. The aim of this study was to explore interactions between these two systems in mediating cancer risk in type 2 diabetes. RESEARCH DESIGN AND METHODS--A prospective cohort of 4,160 Chinese patients with type 2 diabetes, free of cancer at enrollment, were analyzed using Cox models. Interaction of RAS inhibitors (angiotensin I-converting enzyme inhibitors or angiotensin II receptor blockers) and statins was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates additive interaction between the two classes of drugs. Molecular mechanisms underlying these interactions were explored using a uninephrectomy (UNX) rat model with renal carcinogenesis. RESULTS--During 21,992 person-years of follow-up, 190 patients developed cancer. Use of RAS inhibitors and statins in isolation or combination during follow-up was associated with reduced risk of cancer after adjustment for covariates. The multivariable RERI and AP for the additive interaction between these drug classes for cancer were significant (0.53 [95% CI 0.20-0.87] and 2.65 [0.38-4.91], respectively). In the UNX rat model, inhibition of the RAS prevented renal cell carcinoma by normalizing hydroxymethylglutaryl-CoA reductase (HMGCR) expression and the insulin-like growth factor-1 (IGF-1) signaling pathway. CONCLUSIONS--Combined use of RAS inhibitors and statins may act synergistically to reduce cancer risk, possibly via HMGCR and IGF-1 signaling pathways in high-risk conditions such as type 2 diabetes. Diabetes 58:1518-1525, 2009 [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Multiple risk factors in type 2 diabetes may explain their high risk for ischemic stroke (IS). However, it remains unknown whether these risk factors exhibit threshold characteristics and whether these relationships are influenced by albuminuria. The study aims to investigate whether risk factors exhibit any albuminuria specific threshold for IS. Patients and methods: This is a prospective cohort study with 6969 Chinese type 2 diabetic patients without history of stroke after a median follow-up of 5.36 years. We identified thresholds of risk factors for IS using hazard ratio plots followed by confirmation using traditional Cox regression analysis. Results: In the non-albuminuric group (n =4008), IS risk started to increase rapidly at a body mass index threshold of 24kg/m2. The risk of IS declined with increasing blood hemoglobin reaching a threshold value of 14g/dl. Using these threshold values as cutoff point, body mass index ≥24kg/m2 and hemoglobin <14g/dl were associated with 2-fold increased risk of IS in these subjects. In the albuminuric group (n =2961). IS risk started to increase rapidly from a systolic blood pressure threshold of 135mmHg and declined with increasing estimated glomerular filtration rate (eGFR) reaching a trough of 115ml/min per 1.73m2. Using these values as cutoff points, patients with systolic blood pressure ≥135mmHg and eGFR <115ml/min per 1.73m2 had 2-fold increased risk of IS. Conclusion: In type 2 diabetic patients, body mass index, hemoglobin, systolic blood pressure and eGFR exhibit different risk relationships and thresholds for IS contingent upon presence or absence of albuminuria. [Copyright &y& Elsevier]

There are no validated risk scores for predicting coronary heart disease (CHD) in Chinese patients with type 2 diabetes mellitus. This study aimed to validate the UKPDS risk engine and, if indicated, develop CHD risk scores. A total of 7,067 patients without CHD at baseline were analyzed. Data were randomly assigned to a training data set and a test data set. Cox models were used to develop risk scores to predict total CHD in the training data set. Calibration was assessed using the Hosmer-Lemeshow test, and discrimination was examined using the area under the receiver-operating characteristic curve in the test data set. During a median follow-up of 5.40 years, 4.97% of patients (n = 351) developed incident CHD. The UKPDS CHD risk engine overestimated the risk of CHD with suboptimal discrimination, and a new total CHD risk score was developed. The developed total CHD risk score was 0.0267 × age (years) − 0.3536 × sex (1 if female) + 0.4373 × current smoking status (1 if yes) + 0.0403 × duration of diabetes (years) − 0.4808 × Log10 (estimated glomerular filtration rate [ml/min/1.73 m2]) + 0.1232 × Log10 (1 + spot urinary albumin-creatinine ratio [mg/mmol]) + 0.2644 × non–high-density lipoprotein cholesterol (mmol/L). The 5-year probability of CHD = 1 − 0.9616EXP(0.9440 × [RISK SCORE − 0.7082]). Predicted CHD probability was not significantly different from observed total CHD probability, and the adjusted area under the receiver-operating characteristic curve was 0.74 during 5 years of follow-up. In conclusion, the UKPDS CHD risk engine overestimated the risk of Chinese patients with type 2 diabetes mellitus and the newly developed total CHD risk score performed well in the test data set. External validations are required in other Chinese populations. [Copyright &y& Elsevier]

OBJECTIVE -- The purpose of this study was to compare the predictive value for coronary heart disease (CHD) of the International Diabetes Federation (IDF) definition (with Asian criteria for central obesity) of the metabolic syndrome with existing criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) in Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS -- Subjects with type 2 diabetes and without macrovascular diseases or end-stage renal disease were categorized by the criteria of the IDF and the NCEP ATP III. CHD was defined as myocardial infarction, ischemic heart disease, coronary revascularization, heart failure, and death related to CHD. RESULTS -- Of 4,350 patients (aged 54.4 ± 13.4 years; median follow-up period 7.1 [interquartile range 5.2-8.5] years), 65.9% had metabolic syndrome according to either IDF or NCEP ATP III criteria. The NCEP ATP III definition identified metabolic syndrome in 786 subjects (18.1%) who did not fulfill the criteria of the IDF. HDL cholesterol and systolic blood pressure were predictors of CHD after adjustment for other confounding factors. Compared with subjects without metabolic syndrome, the IDF criteria failed to predict CHD (hazard ratio 1.13 [95% CI 0.86-1.48], P = 0.374). In contrast, the NCEP ATP III definition (2.51 [1.80-3.50], P ,< 0.001) predicted an increased risk of CHD with the NCEP-only group having the highest risk (2.49 [1.66-3.73], P < 0.001). CONCLUSIONS -- With established type 2 diabetes, the IDF definition of the metabolic syndrome failed to identify a subgroup of patients who had the highest risk for CHD. Practitioners must recognize the appropriate setting for its application. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- International guidelines recommend optimal control of risk factors in diabetes to prevent cardiovascular events. We examined risk associations between achieving treatment targets for glycemia, blood pressure and lipid control, and other risk factors on subsequent cardiovascular events in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS-- Between 1995 and 2005, 6,386 Chinese type 2 diabetic patients without a history of coronary heart disease (CHD) or stroke were recruited. They were classified according to the number of treatment targets attained at baseline, and their cardiovascular outcomes were compared. Treatment targets were defined as A1C <7.0%, blood pressure <130/80 mmHg, and LDL cholesterol <2.6 mmol/l. RESULTS -- After a median follow-up of 5.7 years, cumulative incidence of CHD or stroke (n = 749) increased with decreasing numbers of treatment targets attained at baseline. Attainment of two or more targets at baseline was associated with reduced risk of CHD compared with those with no target achieved (hazard ratio 0.69 [95% C10.50-0.94], P = 0.020). However, the association lost its significance after adjustment for urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and hemoglobin. CONCLUSIONS-- Reaching more treatment targets was associated with reduced risk of new onset of CHD in Chinese patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The authors discuss biases in studies on drug effects in non-clinical trial settings in type 2 diabetes mellitus (T2DM). The authors state that failure to consider the biases including indications to use the drug under study, prevalent user bias and immortal time bias can lead to erroneous conclusions on the studies' effects on clinical outcomes. They mention the study by Currie and colleagues on the effects of oral antidiabetes drugs (OADs) and insulin on cardiovascular disease and cancer.

Abstract: We examined possible anticancer effects of thiazolidinediones (TZDs) in 6074 Chinese with Type 2 diabetes free of cancer at enrolment. During a median follow-up of 4.93years, 270 patients developed cancer. Use of TZDs was associated with reduced risk of cancer in a dose–response manner in multivariable analysis. [Copyright &y& Elsevier]

Aims: To assess the development of treatment failure in Chinese patients with type 2 diabetes mellitus (T2DM) initiated on metformin or sulphonylurea (SU) monotherapy, with consideration of various potential sources of biases.Methods: A 1:1-matched new metformin and SU user cohort on immortal time and mean propensity score after multiple imputation was selected from a cohort of 5889 Chinese patients with T2DM. Treatment failure was defined as progression to (i) combination oral anti-hyperglycemia drug therapy, (ii) insulin use, or (iii) a treatment haemoglobin A1c (HbA1c) >7.5% (58 mmol/mol). Stratified Cox regression analysis on the matched pairs was employed to examine the associations between initial monotherapy and onset of treatment failure.Results: Of 554 new metformin and 840 new SU users, 380 were matched. During a median follow-up duration of 3 years, 173 (45.6%) metformin users and 220 (57.9%) SU users experienced treatment failure (annual failure rates of 15% and 19%, respectively). The median time from monotherapy starting to treatment failure was 3.0 [inter-quartile range (IQR): 1.8-5.4] years for metformin users, versus 1.8 (IQR: 0.9-4.1) years for SU users (p<0.001). Stratified Cox regression analysis showed significantly lower risk of treatment failure for metformin users (HR [95% CI], 0.62[0.47-0.81]; p<0.001). Consistent results were found in analyses based on traditional adjustment schemes with or without imputation.Conclusions: By systematically incorporating new-user design, multiple imputation and matching methods, we found that Chinese patients with T2DM initiated on metformin monotherapy were associated with a significant delay in the onset of treatment failure compared to SU monotherapy. [ABSTRACT FROM AUTHOR]

Aims: Serum uric acid (SUA) and bilirubin at high levels had both pro-oxidant and anti-oxidant properties. The present study aimed to examine additive interactions between SUA and total bilirubin (TBIL) for the risk of micro-vascular disease (MVD) in type 2 diabetes mellitus (T2DM).Methods: A cross-sectional survey of 6713 inpatients with T2DM was conducted in 81 tertiary care hospitals in China. MVD was defined as having either prior diabetic retinopathy (DR) or diabetic nephropathy (DN). Binary logistic regression was used to estimate odds ratios of SUA and TBIL for MVD. Additive interaction was measured by three indices, i.e., relative excess risk due to interaction, attributable proportion due to interaction and synergy index.Results: Among 6713 inpatients, 408 (6.08%) suffered from MVD. SUA ≥ 283 μmol/l (i.e., its media) was defined as high SUA, and TBIL <11.5 μmol/l (n = 2290 or 34.11%) was defined as low TBIL. Overall, 621 patients were exposed to co-presence of high SUA and low TBIL. The co-presence of both factors greatly increased the effect sizes from 1.03(95%CI: 0.72-1.46) (high SUA alone) or 0.70(95%CI: 0.48-1.05) (low TBIL alone) to 1.90 (95%CI: 1.26-2.87) for MVD in multivariable analysis. The additive interaction of both factors was significant for MVD in both univariable analysis and multivariable analysis.Conclusions: Co-presence of both high SUA and low TBIL indentified a group of patients at a markedly increased risk of MVD in high-risk Chinese patients with T2DM. [ABSTRACT FROM AUTHOR]

Aims: To investigate the risk of Chinese females versus males for non-fatal coronary heart disease (CHD) due to long exposure to type 2 diabetes mellitus (T2DM).Methods: 223,612 Chinese patients with T2DM were recruited from China in 2012. Binary logistic regression analysis was performed to obtain odds ratios (OR) of females versus males for non-fatal CHD. Additive interaction was used to test whether female gender and long exposure to T2DM (≥15 years) had a synergistic effect for non-fatal CHD. Significant relative excess risk due to interaction (RERI > 0), attributable proportion due to interaction (AP > 0) or synergy index (SI > 1) suggest a significant additive interaction.Results: More females than males with T2DM had non-fatal CHD (11.3% versus 10.6%, P < .0001). Females had slightly higher risk of non-fatal CHD since 5-10 years of diabetic duration and the effect size became larger since 15 years and onwards. Overall effect of females versus males for non-fatal CHD was 1.04 (95% CI: 1.01-1.08) among patients with <15 years of duration while the effect size increased to 1.17 (95% CI: 1.07-1.28) among patients with ≥15 years of duration. Using males with <15 years of duration as the reference, females with ≥15 years of duration were at 1.82-fold (95% CI: 1.70-1.95) non-fatal CHD risk while males with ≥15 years of duration were only at 1.56 (95% CI: 1.45-1.68) fold non-fatal CHD risk, with significant additive interaction (all three measures < 0.05).Conclusions: Long exposure to T2DM imparted a larger risk of non-fatal CHD to Chinese females than to Chinese males. [ABSTRACT FROM AUTHOR]

Aims: To assess the association of uric acid (UA) with the risks of postpartum type 2 diabetes and prediabetes among women with prior gestational diabetes mellitus (GDM).Methods: We performed a cross-sectional study of 1262 GDM women at 1-5 years after delivery using the baseline data from the Tianjin Gestational Diabetes Mellitus Prevention Program. Logistic regression models were used to estimate the association of different levels of serum UA with the risks of type 2 diabetes and prediabetes.Results: The multivariable-adjusted odds ratios (ORs) across quartiles of serum UA were 1.00, 1.23 (95% confidence interval [CI] 0.55-2.78), 2.05 (95% CI 0.96-4.39), and 3.17 (95% CI 1.54-6.55) (Ptrend < 0.001) for type 2 diabetes, and 1.00, 1.50 (95% CI 1.03-2.19), 2.28 (95% CI 1.58-3.30), and 2.88 (95% CI 1.99-4.17) (Ptrend < 0.001) for prediabetes, respectively. Restricted cubic splines models showed positive linear associations of serum UA as a continuous variable with the risks of type 2 diabetes and prediabetes. This positive association was significant when stratified by healthy weight and overweight participants.Conclusions: Serum UA levels have a graded positive association with the risks of type 2 diabetes and prediabetes among Chinese with a history of GDM. [ABSTRACT FROM AUTHOR]

Aims: To examine the association of connecting peptide (C-peptide) and the risks of postpartum diabetes and pre-diabetes among women with prior gestational diabetes.Methods: A cross-sectional study of 1263 women with prior gestational diabetes was carried out at 1-5years after delivery in Tianjin, China. Logistic regression was used to assess the associations of C-peptide and the risks of diabetes and pre-diabetes.Results: The multivariable-adjusted odds ratios based on different levels of C-peptide (0-33%, 34-66%, 67-90%, and >90% as C-peptide cutpoints) were 1.00, 1.93 (95% confidence interval [CI] 0.85-4.39), 2.49 (95% CI 1.06-5.87), and 3.88 (95% CI 1.35-11.1) for diabetes (P for trend <0.0001), and 1.00, 1.66 (95% CI 1.18-2.36), 2.38 (95% CI 1.56-3.62) and 2.35 (95% CI 1.27-4.37) for pre-diabetes (P for trend <0.0001), respectively. Restricted cubic splines models showed a positive linear association of C-peptide as a continuous variable with the risks of type 2 diabetes and pre-diabetes. The positive association was significant when stratified by healthy weight and overweight participants.Conclusions: We found a positive association between serum C-peptide levels and the risks of diabetes and pre-diabetes among Chinese women with prior gestational diabetes. Our finding suggested that elevated C-peptide levels may be a predictor of diabetes and pre-diabetes. [ABSTRACT FROM AUTHOR]

Aims The present study aimed to examine the nonlinear associations between risk factors and mild hypoglycemia in Chinese patients with type 2 diabetes mellitus (T2DM). Methods From May 2013 to August 2013, we conducted a cross sectional survey of 6633 inpatients with T2DM and without severe hypoglycemia, aged 21–77 years, from 81 top tertiary hospitals in China. Mild hypoglycemia was defined as having hypoglycemia with symptoms in one month. Binary logistic regression analysis with restricted cubic splines was used to estimate odds ratio curves of non-linear risk factors for mild hypoglycemia. Results Increasing body mass index was associated with decreasing risk of mild hypoglycemia in a linear manner while age, duration of diabetes, glycated hemoglobin (HbA1 c ), mean artery pressure and lipids were associated with mild hypoglycemia in non-linear manners. Age ≥ 40 years, duration ≥ 2 years, HbA1 c ≥ 7.0–<11.5% (≥ 53–<102 mmol/mol), triglyceride ≥ 1.7–<3.6 mmol/L, low-density lipoprotein cholesterol (LDL-C) ≥ 2.6–<4.8 mmol/L, and high-density lipoprotein cholesterol (HDL-C) ≥ 1.2–<4.8 mmol/L were associated with increased risks of mild hypoglycemia. Conclusions Chinese T2DM patients with age ≥ 40 years, duration of diabetes ≥ 2–<6 years, HbA1 c ≥ 7.0–<11.5% (≥ 53–<102 mmol/mol), LDL-C ≥ 2.6–<4.8 mmol/L, HDL-C ≥ 1.2–<4.8 mmol/L or triglyceride ≥ 1.7–<3.6 mmol/L were at particularly high risk for mild hypoglycemia. [ABSTRACT FROM AUTHOR]

Aims: To explore associations between adverse pregnancy outcomes and risk of postpartum diabetes and prediabetes among Chinese women with gestational diabetes mellitus (GDM).Methods: A total of 507 women with GDM who participated in a randomized controlled trial were successfully followed up at a median of 9.1  (interquartile range: 7.7-11.3) weeks after delivery and underwent a 75 g 2-h oral glucose tolerance test. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Group's criteria. Postpartum diabetes and prediabetes were defined by the World Health Organization's. Generalized logit model was used to obtain odds ratios (OR) and 95% confidence interval (CI) of adverse pregnancy outcomes for postpartum diabetes, prediabetes and abnormal glucose regulation (AGR).Results: Of 507 women with GDM, 3.7% (19) women developed postpartum diabetes, 35.1% (178) women developed postpartum prediabetes. Preterm birth was associated with increased risk of postpartum prediabetes and AGR (adjusted OR: 3.24, 95%CI: 1.48-7.07 & 3.16, 1.46-6.85). Low birth weight was associated with the risk of postpartum prediabetes, diabetes and AGR (adjusted OR: 2.78, 95%CI: 1.13-6.86; 5.21, 1.13-24.02 & 2.99, 1.24-7.21).Conclusions: Preterm birth and low birth weight were predictive of postpartum prediabetes, diabetes or AGR in Chinese women with GDM. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the prevalence of pre-existing diabetes in pregnancy from studies published during 2010-2020.Methods: We searched PubMed, CINAHL, Scopus and other sources for relevant data sources. The prevalence of overall pre-existing, type 1 and type 2 diabetes, by country, region and period of study was synthesised from included studies using the inverse-variance heterogeneity model and the Freeman-Tukey transformation. Heterogeneity was assessed using the I2 statistic and publication bias using funnel plots.Results: We identified 2479 records, of which 42 data sources with a total of 78 943 376 women, met the eligibility criteria. The included studies were from 17 countries in North America, Europe, the Middle East and North Africa, Australasia, Asia and Africa. The lowest prevalence was in Europe (0.5%, 95 %CI 0.4-0.7) and the highest in the Middle East and North Africa (2.4%, 95 %CI 1.5-3.1). The prevalence of pre-existing diabetes doubled from 0.5% (95 %CI 0.1-1.0) to 1.0% (95 %CI 0.6-1.5) during the period 1990-2020. The pooled prevalences of pre-existing type 1 and type 2 diabetes were 0.3% (95 %CI 0.2-0.4) and 0.2% (95 %CI 0.0-0.9) respectively.Conclusion: While the prevalence of pre-existing diabetes in pregnancy is low, it has doubled from 1990 to 2020. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess whether lifestyle intervention can reduce type 2 diabetes risk in women with prior GDM in the Tianjin Gestational Diabetes Mellitus (GDM) Prevention Program. Methods: 1180 women who were diagnosed with GDM from 2005 to 2009 were randomly assigned to either a lifestyle intervention (n =586) or a control group (n =594). Major elements of the intervention include six face-to-face meetings with study dietitians in the first year, and two additional sessions and two telephone calls in second year. Results: During the first year, average body weight loss in the first 404 subjects was 1.40kg (2.1%) in the intervention group vs 0.21kg (0.3%) in the control group (P =0.001), and the decrease was more significant among baseline overweight women (body bass index [BMI]≥24kg/m2) in the intervention (2.91kg/4.2%) compared with that in the control group (0.51kg/0.7%) (P <0.001). In addition, women in the intervention group, compared with those in the control group, have decreased BMI, body fat, waist circumference, and plasma insulin levels, and have improved behaviors including increased leisure time activity and dietary fiber intake and decreased sedentary time and fat consumptions. Conclusion: The interim results support the efficacy and feasibility of the lifestyle intervention program. [Copyright &y& Elsevier]

Abstract: Objective: Ischemic stroke is prevalent in type 2 diabetes and may be due to metabolic, vascular and inflammatory factors. Genetic variants implicated in these pathways may have joint effects on stroke risk. In this proof-of-concept study, we examined gene–gene interactions on risk of incident ischemic stroke in an 8-year prospective cohort of Chinese type 2 diabetic patients. Methods: Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for cardiovascular disease and inflammation were genotyped in 1327 patients with no past history of ischemic stroke. The association of SNPs with stroke was tested using Cox proportional hazard regression analysis. Permutation procedure was performed to control for multiple statistical comparisons. Results: Genetic variants including A/A of IL5RA (interleukin-5 alpha subunit) -5091G>A, X/X of LPL (lipoprotein lipase) S447X, A/A of ITGA2 (integrin A2) G873A and T/T or G/T of NOS3 (endothelial nitric oxide synthase) G894T showed significant correlations with incident ischemic stroke. The hazard ratios (HR) increased with number of genetic risk factors reaching an adjusted HR (confidence interval) of 3.68 (1.78–7.62, P =4.4×10−4) in those with ≥2 genetic risk factors compared to those without. Conclusion: Polymorphisms in IL5RA, LPL, ITGA2 and NOS3 genes were independently associated with ischemic stroke in Chinese diabetic population. [Copyright &y& Elsevier]

Abstract: In this report, we examined the usage of anti-diabetic treatments including oral anti-diabetic drug (OAD) and/or insulin and their combination from baseline data of a consecutive cohort of 7549 Chinese type 2 diabetic subjects in the Hong Kong Diabetes Registry. Pattern of usage of anti-diabetic treatment and corresponding glycemic control was analyzed. OAD failure was defined as the need to add insulin to maintain glycemic target (glycated hemoglobin, HbA1c level<7%) with or without continuation of OAD. There were 4109 [54.4%] women and 3440 [45.6%] men (age: median 57.0 years; range 13–92 years). The mean HbA1c level was 7.7±1.8% with 39.7% attaining glycemic target. Long disease duration was associated with more complex regimens and the respective rates of OAD failure requiring insulin use were 23.7%, 39.3%, 57.1% and 75.9% in those with disease duration <5 years, 5–9.9 years, 10–19.9 years and ≥20 years (p <0.001). In conclusion, in a clinic-based type 2 diabetic population, 39.7% attained glycemic target with HbA1c <7%. Long disease duration and complexity of treatment regimens were associated with suboptimal glycemic control. Early intensification of therapy and system improvement are needed to enhance the effectiveness of these drugs in clinical practice. [Copyright &y& Elsevier]