Development of a new risk score for incident type 2 diabetes using updated diagnostic criteria in middle-aged and older chinese.
ABSTRACT: Type 2 diabetes mellitus (T2DM) reaches an epidemic proportion among adults in China. However, no simple score has been created for the prediction of T2DM incidence diagnosed by updated criteria with hemoglobin A1c (HbA1c) ? 6.5% included in Chinese. In a 6-year follow-up cohort in Beijing and Shanghai, China, we recruited a total of 2529 adults aged 50-70 years in 2005 and followed them up in 2011. Fasting plasma glucose (FPG), HbA1c, and C-reactive protein (CRP) were measured and incident diabetes was identified by the recently updated criteria. Of the 1912 participants without T2DM at baseline, 924 were identified as having T2DM at follow-up, and most of them (72.4%) were diagnosed using the HbA1c criterion. Baseline body mass index, FPG, HbA1c, CRP, hypertension, and female gender were all significantly associated with incident T2DM. Based upon these risk factors, a simple score was developed with an estimated area under the receiver operating characteristic curve of 0.714 (95% confidence interval: 0.691, 0.737), which performed better than most of existing risk score models developed for eastern Asian populations. This simple, newly constructed score of six parameters may be useful in predicting T2DM in middle-aged and older Chinese.
Project description:BACKGROUND: Glycosylated hemoglobin A1c (HbA1c) has been applied to identify type 2 diabetes (T2DM) in the U.S. and European countries. It has not been used in China mainly due to lack of a standardized approach to measure HbA1c, short of knowledge about racial-specific standard and deficiency of an optimal cut-off point. METHODS: To evaluate combination of HbA1c and fasting plasma glucose (FPG) in diagnosing T2DM in Chinese adults, a multistage sampling cross-sectional study was conducted in Shanghai, China, in 2009. The FPG measurement, HbA1c assay, and oral glucose tolerance test (OGTT) were performed in 6,661 Chinese adults (3057 men, 3604 women) who had no prior history of diabetes to identify the unrecognized T2DM. RESULTS: A total of 454 participants were identified as T2DM based on the 1999 World Health Organization (WHO) diagnostic criteria. Of these patients, 239 were detected using an FPG???7.0 mmol/l and 141 were further identified using an HbA1c???43 mmol/mol (6.1%), achieving a sensitivity of 83.7% and a specificity of 89.3% for combining use of FPG and HbA1c. In subjects at high risk of diabetes, the combining use of FPG and HbA1c produced a higher sensitivity and an improved positive predictive value (PPV), and had a satisfactory specificity and negative predictive value (NPV). CONCLUSIONS: The combining use of FPG and HbA1c is a potential screening and diagnosis approach for T2DM in Chinese adults, especially among those at high risk of the disease.
Project description:A large proportion of patients with T2DM in China do not meet accepted HbA1c targets despite the availability of guidelines that describe a treatment pathway for achieving glycemic control. The aim of this study is to identify the fasting plasma glucose (FPG) target that will provide the highest control rate of HbA1c <7 % in Chinese patients with T2DM treated with an insulin glargine-based regimen as an adjunct to an established OAD regimen. This information will support improvements in diabetes care management in China.Approximately 934 men and women aged ?18 to ?65 years with poorly controlled T2DM will be enrolled and randomized to one of three FPG target groups; ?5.6 mmol/L, ?6.1 mmol/L, or ?7.0 mmol/L. They will be initiated on daily insulin glargine (Lantus®) in addition to their usual OAD regimen for 24 weeks. Patients will self-monitor fasting blood glucose (SM-FBG), and the study physician will titrate the basal insulin dose according to the SM-FBG results. In addition, HbA1c and safety will be recorded. We plan to statistically derive the optimal FPG target for an HbA1c of <7 %.In China, treatment strategies that would achieve an optimum balance between glycemic control (as per HbA1c) and hypoglycemia are imperative to ensure improvements in the management of T2DM. Furthermore, elucidating the contribution of FPG to HbA1c in Chinese patients with T2DM and identifying a predictable relationship between FPG and HbA1c would be a valuable tool for patient self-management of diabetes.NCT02545842 . Registered on 8 September 2015.
Project description:The aim of the study was to decipher the relationship between serum uric acid (SUA) and glycated hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) in both type 2 diabetes mellitus (T2DM) patients and normal subjects. A total of 2,250 unrelated T2DM patients and 4,420 Han Chinese subjects from a physical examination population were recruited for this study. In T2DM patients SUA levels were negatively correlated with HbA1c (rs = -0.109, P = 0.000) and 2 h plasma glucose levels (rs = -0.178, P = 0.000). In the physical examination population, SUA levels were inversely correlated with HbA1c (rs = -0.175, P = 0.000) and FPG (rs = -0.131, P = 0.009) in T2DM patients but positively correlated with HbA1c (rs = 0.040, P = 0.012) and FPG (rs = 0.084, P = 0.000) in normal-glucose subjects. Multivariate analyses showed that HbA1c was significantly negatively associated with HUA both in T2DM patients (OR = 0.872, 95% CI: 0.790~0.963) and in the physical examination T2DM patients (OR = 0.722, 95% CI: 0.539~0.968). Genetic association studies in T2DM patients showed that alleles of two glucose-uric acid transporter genes, ABCG2 and SLC2A9 were significantly associated with SUA levels (P < 0.05). SUA level is inversely correlated with HbA1c in T2DM patients but positively correlated with HbA1c in normal-glucose subjects. The reverse transporting of uric acid and glucose in renal tubules might be accounted for these associations.
Project description:To develop a new non-invasive risk score for predicting incident diabetes in a rural Chinese population.Data from the Handan Eye Study conducted from 2006-2013 were utilized as part of this analysis. The present study utilized data generated from 4132 participants who were ?30 years of age. A non-invasive risk model was derived using two-thirds of the sample cohort (selected randomly) using stepwise logistic regression. The model was subsequently validated using data from individuals from the final third of the sample cohort. In addition, a simple point system for incident diabetes was generated according to the procedures described in the Framingham Study. Incident diabetes was defined as follows: (1) fasting plasma glucose (FPG) ? 7.0 mmol/L; or (2) hemoglobin A1c (HbA1c) ? 6.5%; or (3) self-reported diagnosis of diabetes or use of anti-diabetic medications during the follow-up period.The simple non-invasive risk score included age (8 points), Body mass index (BMI) (3 points), waist circumference (WC) (7 points), and family history of diabetes (9 points). The score ranged from 0 to 27 and the area under the receiver operating curve (AUC) of the score was 0.686 in the validation sample. At the optimal cutoff value (which was 9), the sensitivity and specificity were 74.32% and 58.82%, respectively.Using information based upon age, BMI, WC, and family history of diabetes, we developed a simple new non-invasive risk score for predicting diabetes onset in a rural Chinese population, using information from individuals aged 30 years of age and older. The new risk score proved to be more optimal in the prediction of incident diabetes than most of the existing risk scores developed in Western and Asian countries. This score system will aid in the identification of individuals who are at risk of developing incident diabetes in rural China.
Project description:The PSMD6 variant rs831571 has been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of this variant with therapeutic effects of oral antidiabetic drugs in Chinese T2DM patients. 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs831571 showed significant associations with fasting plasma glucose (FPG), 2-h glucose and decrement of glycated haemoglobin (HbA1c) levels after 24 weeks of treatment (P = 0.0368, 0.0468 and 0.0247, respectively). The C allele was significantly associated with a better attainment of FPG at 24 and 32 weeks (P = 0.0172 and 0.0257, respectively). Survival analyses showed CC homozygotes were more likely to attain a standard FPG level (P = 0.0654). In the repaglinide cohort, rs831571 was significantly associated with decreased HbA1c levels after 24 weeks of treatment, the homeostatic model assessment of insulin resistance and fasting insulin level after 48 weeks of treatment with repaglinide (P = 0.0096, 0235 and 0.0212, respectively). In conclusion, we observed that the PSMD6 variant rs831571 might be associated with the therapeutic effects of rosiglitazone and repaglinide in Chinese T2DM patients. However, these findings need to be confirmed in the future.
Project description:OBJECTIVES:About 11%-30% of individuals with impaired fasting plasma glucose (IFG) have type 2 diabetes mellitus (T2DM), diagnosed by the 75 g oral glucose tolerance test (75 g OGTT). This study investigated (1) the prevalence and cut-off levels for fasting plasma glucose (FPG) and glycated haemoglobin A1c (HbA1c) in IFG individuals that most effectively predict the presence of T2DM diagnosed by a 75 g OGTT; (2) the predictors associated with T2DM; and (3) the pathophysiological characteristics of patients with IFG. MATERIALS AND METHODS:A single-centre, cross-sectional study was conducted in a primary care setting. A standard 75 g OGTT was performed on 123 subjects with IFG. Their beta-cell function and insulin resistance were calculated through plasma glucose and insulin levels monitored during the 75 g OGTT. RESULTS:In the IFG subjects, the prevalence of T2DM using the 2-hour postload plasma glucose (2hPG) criterion was 28.5%. Pre-diabetes and normal glucose metabolism were found in 48.7% and 22.8%, respectively, by 75 g OGTT. An HbA1c level ?6.0%?or FPG ?5.9?mmol/L were the optimal cut-off thresholds for the prediction of the presence of T2DM. HbA1c had a sensitivity of 76.7% and specificity of 55.7% (95% CI 57.7% to 90.1% and 95% CI 43.3% to 67.6%, respectively), while FPG had a sensitivity of 85.7% and specificity of 23.9% (95% CI 69.7% to 95.2% and 95% CI 15.4% to 34.1%, respectively). The presence of metabolic syndrome, a higher HbA1c and higher FPG levels were associated with the risk of T2DM in the Thai IFG population. CONCLUSIONS:Almost one-third of the people with IFG had T2DM diagnosed by the 2hPG criterion. HbA1c was more effective than FPG in predicting the presence of T2DM in the IFG subjects. IFG individuals with HbA1c?6.0%?or FPG?5.9?mmol/L should be advised to undergo a 75 g OGTT to detect T2DM earlier than otherwise.
Project description:Previous pharmacogenomic studies of oral anti-diabetic drugs have primarily focused on the effect of a single site. This study aimed to examine the joint effects of multiple loci on repaglinide or rosiglitazone efficacy in newly diagnosed type 2 diabetes mellitus (T2DM) patients. A total of 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks. The reductions in fasting glucose (?FPG), 2h glucose (?2hPG) and glycated hemoglobin (?HbA1c) levels were significantly associated with genetic score that was constructed using the sum of the effect alleles both in the repaglinide (P?=?0.0011, 0.0002 and 0.0067, respectively) and rosiglitazone cohorts (P?=?0.0002, 0.0014 and 0.0164, respectively) after adjusting for age, gender, body mass index and dosage. Survival analyses showed a trend towards a greater attainment rate of target HbA1c level in individuals with a high genetic score in the repaglinide cohort and rosiglitazone cohort (Plog-rank?=?0.0815 and 0.0867, respectively) when the attainment of treatment targets were defined as more than 20% decrease of FPG, 2hPG, and HbA1c levels after treatment. In conclusion, we identified the joint effects of several T2DM-related loci on the efficacy of oral anti-diabetic drugs; moreover, we built a model to predict the drug efficacy.
Project description:OBJECTIVE:Antidepressant medication use (ADM) has been shown to predict diabetes. This article assessed the role of inflammatory markers in this relationship within the Diabetes Prevention Program (DPP). METHODS:DPP participants randomized to metformin (MET), life-style intervention (ILS), or placebo (PLB) were assessed for depression (Beck Depression Inventory [BDI]) annually, ADM use semiannually, serum inflammatory markers (C-reactive protein [CRP], interleukin 6 [IL-6]) at baseline and year 1, and diagnosis of type 2 diabetes mellitus (T2DM) semiannually (for 3.2 years). RESULTS:At baseline (N = 3187), M (SD) body mass index was 34 (6) kg/m and the median (interquartile range) BDI score was 3 (1-7). One hundred eighty-one (5.7%) reported ADM use and 328 (10%) had BDI scores of 11 or higher. CRP and IL-6 levels did not differ by treatment group. Baseline ADM, but not BDI score, was associated with higher levels of baseline CRP adjusted for demographic, anthropometric variables, and other medications (20% higher, p = .01). Year 1 CRP decreased for non-ADM users in the MET (-13.2%) and ILS (-34%) groups and ADM users in the ILS group (-29%). No associations were found with IL-6. CRP and continuous use of ADM predicted incident T2DM in the PLB group. In the ILS group, continuous and intermittent ADM, but not CRP, predicted T2DM. In the MET group, CRP predicted incident T2DM. CRP did not mediate the risk of T2DM with ADM use in any group. CONCLUSIONS:ADM was significantly associated with elevated CRP and incident T2DM. In the PLB group, ADM and CRP independently predicted onset of T2DM; however, CRP did not significantly mediate the effect of ADM.
Project description:This study applied a pharmacodynamic model-based approach to evaluate the long-term durability and glycemic control of pioglitazone in comparison with other oral glucose-lowering drugs in Japanese type 2 diabetes mellitus (T2DM) patients.Japanese T2DM patients were enrolled in a prospective, randomized, open-label, blinded-end point study and received pioglitazone with or without other oral glucose-lowering drugs (excluding another thiazolidinedione [TZD]) (n=293) or oral glucose-lowering drugs excluding TZD (n=294). Treatment was adjusted to achieve glycosylated hemoglobin (HbA1c) <6.9%, and samples for fasting plasma glucose (FPG) and HbA1c were collected over 2.5-4 years. A simultaneous cascading indirect response model structure was applied to describe the time course of FPG and HbA1c. HbA1c levels were described using both an FPG-dependent and an FPG-independent function. To account for titration, drug effects for both treatment groups were implemented using a time-dependent Emax model.Pioglitazone was superior in both time to maximum effect and the magnitude of reduction achieved in FPG and HbA1c. A greater reduction in median FPG (-21?mg/dL vs. -9?mg/dL) was observed with pioglitazone (P<0.05). Maximum drug effect for FPG was predicted to occur earlier (11 months) for pioglitazone than for the control group (14 months). The simulated additional reduction in FPG and HbA1c achieved with pioglitazone was predicted to be maintained beyond the currently observed study duration.Pioglitazone was found to result in improved glycemic control and durability compared with control treatment. This model-based approach enabled the quantification of differences in FPG and HbA1c for both treatment groups and simulation to evaluate longer-term durability on FPG and HbA1c.
Project description:BACKGROUND:Glycemic variability (GV) confers a risk of cardiovascular events. In this study, we aimed to investigate whether long-term GV has an impact on coronary atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM). METHODS:A total of 396 patients with T2DM who had coronary computed tomography angiography and laboratory data available at baseline and for follow-up evaluations [median 2.3 (1.8-3.1) years] were included. Fasting plasma glucose (FPG) was measured every 1-3 months, and HbA1c was measured quarterly. The coefficient of variation (CV) of HbA1c and FPG were calculated as measures of GV. Quantitative assessment of coronary plaques was performed by measuring the annual change and progression rate of total plaque volume (TPV). Significant progression was defined as annual TPV progression???15%. Multivariable regression analyses were used to assess the effects of GV on atherosclerosis progression. RESULTS:In the 396 patients, the annual change in TPV was 12.35?±?14.23 mm3, and annual progression rate was 13.36?±?12.69%. There were 143 (36.11%) patients with significant progression, and they had a significantly higher CV-HbA1c (P?<?0.001) and CV-FPG (P?<?0.001) than those without significant progression. In multivariable regression analyses, both CV-HbA1c and CV-FPG were independent predictors of annual change in TPV [CV-HbA1c: ??=?0.241 (0.019-0.462), P?=?0.034; CV-FPG: ??=?0.265 (0.060-0.465), P?=?0.012], annual TPV progression [CV-HbA1c: ??=?0.214 (0.023-0.405), P?=?0.029; CV-FPG: ??=?0.218 (0.037-0.399), P?=?0.019], and significant atherosclerosis progression [CV-HbA1c: odds ratio [OR]?=?1.367 (1.149-1.650), P?=?0.010; CV-FPG: OR?=?1.321 (1.127-1.634), P?=?0.013]. CONCLUSIONS:Long-term GV is associated with accelerated progression of coronary atherosclerosis independent of conventional risk factors in patients with T2DM. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015; retrospectively registered.