scholarly journals Increased Plasma DPP4 Activity Is Predictive of Prediabetes and Type 2 Diabetes Onset in Chinese Over a Four-Year Period: Result From the China National Diabetes and Metabolic Disorders Study

2014 ◽  
Vol 99 (11) ◽  
pp. E2330-E2334 ◽  
Author(s):  
Tianpeng Zheng ◽  
Yun Gao ◽  
Attit Baskota ◽  
Tao Chen ◽  
Xingwu Ran ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Chinese Women ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Cox Proportional Hazards ◽  
Dipeptidyl Peptidase 4

Context: The significance of associations between prediabetes, type 2 diabetes, and dipeptidyl peptidase-4 (DPP4) activity in a Chinese population is not clear. Objective: The objective of the study was to determine whether DPP4 activity and active glucagon-like peptide-1 (GLP-1) were predictive of the onset of prediabetes and type 2 diabetes. Design, Setting, and Patients: This was a 4-year follow-up study conducted in Sichuan, China. A total of 474 Chinese women and men aged 18–70 years were studied. Main Outcome Measures: All subjects were divided into 3 groups (normal glucose tolerance, prediabetes, and type 2 diabetes) on the basis of their glucose metabolism status after 4 years. The DPP4 activity, active GLP-1, and glucagon were measured at baseline and 4 years later. Results: The baseline DPP4 activity was significantly higher in subjects who had progressed to prediabetes or type 2 diabetes compared with subjects who remained normoglycemic (P < .01). In a multiple linear regression analysis, baseline DPP4 activity and active GLP-1 were independent predictors of an increase in insulin resistance over a 4-year period (P < .05). Cox proportional hazards models revealed that DPP4 activity independently predicted the risk of developing prediabetes [relative risk 2.77 (95% confidence interval 1.38–5.55), P < .01] and type 2 diabetes [5.10 (95% confidence interval 1.48–17.61), P < .05] after adjustment for confounding risk factors. Conclusions: DPP4 activity is an important predictor of the onset of insulin resistance, prediabetes, and type 2 diabetes in apparently healthy Chinese individuals. This finding may have important implications for understanding the etiology of diabetes.

scholarly journals Serum Osteoprotegerin Is a Potential Biomarker of Insulin Resistance in Chinese Postmenopausal Women with Prediabetes and Type 2 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Peng Duan ◽  
Min Yang ◽  
Meilin Wei ◽  
Jia Liu ◽  
Ping Tu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Postmenopausal Women ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Glucose Regulation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Potential Biomarker ◽  
Chinese Postmenopausal Women

The aim of this study is to investigate the circulating OPG levels in postmenopausal women with diabetes and prediabetes and explore the relationships between serum OPG and insulin resistance. A total of 271 unrelated Chinese postmenopausal women were recruited in this study. The subjects were divided into type 2 diabetes mellitus (T2DM) group (n=93), impaired glucose regulation (IGR) (n=90), and normal glucose regulation group (NGR) (n=88), according to different glucose regulation categories. Serum OPG levels were measured by enzyme-linked immunosorbent assay. The serum OPG concentration in NGR group, 151.00 ± 45.72 pg/mL, was significantly lower than that in IGR group (169.28 ± 64.91 pg/mL) (p=0.031) and T2DM group (183.20 ± 56.53 pg/mL) (p<0.01), respectively. In multiple linear regression analysis, HOMA-IR, age, 2hPG, AST, ALP, and eGFR were found to be independent predictors of OPG. Increased serum OPG levels (OR = 1.009,p=0.006) may be a risk factor for insulin resistance. The present study suggests that OPG might be implicated in the pathogenesis of diabetes and is a potential biomarker of insulin resistance in subjects with diabetes and prediabetes.

scholarly journals Plasma Periostin Levels Are Increased in Chinese Subjects with Obesity and Type 2 Diabetes and Are Positively Correlated with Glucose and Lipid Parameters

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yuanyuan Luo ◽  
Hua Qu ◽  
Hang Wang ◽  
Huili Wei ◽  
Jing Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Linear Regression Analysis ◽  
Density Lipoprotein ◽  
Multiple Linear Regression Analysis ◽  
Chinese Patients ◽  
Model Assessment ◽  
Related Factors

The purpose of this study is to examine the relations among plasma periostin, glucose and lipid metabolism, insulin resistance and inflammation in Chinese patients with obesity (OB), and type 2 diabetes mellitus (T2DM). Plasma periostin levels in the T2DM group were significantly higher than the NGT group (P<0.01). Patients with both OB and T2DM had the highest periostin levels. Correlation analysis showed that plasma periostin levels were positively correlated with weight, waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), fasting plasma glucose (FPG), 2 h postchallenge plasma glucose (2 h PG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), TNF-α, and IL-6 (P<0.05or 0.001) and negatively correlated with high-density lipoprotein cholesterol (HDL-C) (P<0.001). Multiple linear regression analysis showed that TG, TNF-α, and HOMA-IR were independent related factors in influencing the levels of plasma periostin (P<0.001). These results suggested that Chinese patients with obesity and T2DM had significantly higher plasma periostin levels. Plasma periostin levels were strongly associated with plasma TG, chronic inflammation, and insulin resistance.

scholarly journals Higher-Dose Sitagliptin and the Risk of Congestive Heart Failure in Older Adults with CKD

2020 ◽  
Vol 15 (12) ◽  
pp. 1728-1739
Author(s):  
Flory T. Muanda ◽  
Matthew A. Weir ◽  
Lavanya Bathini ◽  
Kristin K. Clemens ◽  
Vlado Perkovic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Older Adults ◽  
Congestive Heart Failure ◽  
Confidence Interval ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Risk Of Death

Background and objectivesSitagliptin, a dipeptidyl peptidase-4 inhibitor, is commonly prescribed to patients with type 2 diabetes. As this drug is primarily eliminated by the kidney, a reduced dose is recommended for patients with CKD. Some evidence suggests that sitagliptin is associated with a higher risk of congestive heart failure, particularly at higher doses. We compare the 1-year risk of death or hospitalization with congestive heart failure in patients with CKD newly prescribed sitagliptin at >50 versus ≤50 mg/d.Design, setting, participants, & measurementsThis population-based cohort study included older adults (>66 years) with type 2 diabetes and an eGFR<45 ml/min per 1.73 m2 (but not receiving dialysis) who were newly prescribed sitagliptin between 2010 and 2017 in Ontario, Canada. We used inverse probability of treatment weighting on the basis of propensity scores to balance baseline characteristics. The primary composite outcome was death or hospitalization with congestive heart failure. Secondary outcomes included hospitalization with pancreatitis or hypoglycemia, all-cause hospitalization, and glycemic control. Weighted hazard ratios were obtained using Cox proportional hazards regression, and 95% confidence intervals were obtained using bootstrap variance estimators.ResultsOf 9215 patients, 6518 started sitagliptin at >50 mg/d, and 2697 started sitagliptin at ≤50 mg/d. The 1-year risk of death or hospitalization with congestive heart failure did not differ significantly between groups (79 versus 126 events per 1000 person-years; weighted hazard ratio, 0.88; 95% confidence interval, 0.67 to 1.14); hospitalization with pancreatitis (weighted hazard ratio, 0.98; 95% confidence interval, 0.32 to 3.03) and hypoglycemia (weighted hazard ratio, 1.10; 95% confidence interval, 0.64 to 1.90) also did not differ significantly between groups. Patients starting sitagliptin at >50 mg/d had lower mean glycated hemoglobin concentrations (weighted between-group difference, −0.12%; 95% confidence interval, −0.19 to −0.06) and a lower risk of all-cause hospitalization (weighted hazard ratio, 0.81; 95% confidence interval, 0.66 to 0.98).ConclusionsThe risk of death or congestive heart failure was not higher in older adults with CKD starting sitagliptin at >50 versus ≤50 mg/d.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_11_25_CJN08310520_final.mp3

scholarly journals Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study

2021 ◽  
Vol 9 (2) ◽  
pp. e002352
Author(s):  
Ingrid Hougen ◽  
Reid H Whitlock ◽  
Paul Komenda ◽  
Claudio Rigatto ◽  
Kristin K Clemens ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Real World ◽  
Cardiovascular Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Dipeptidyl Peptidase 4 ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
All Cause Mortality

IntroductionMetformin is the initial oral antihyperglycemic agent (OHA) of choice for most patients with type 2 diabetes (T2D). However, more than one agent is often required for optimal glucose control. As the choice of preferred second OHAs is less well defined, we sought to compare the real-world safety of sulfonylureas to other OHAs as add-on therapy to metformin in patients with T2D.Research design and methodsThis retrospective cohort study included adults in Manitoba, Canada with T2D from 2006 to 2017. Using a new-user design, we divided patients who started on metformin into two groups: add-on therapy with a sulfonylurea and add-on therapy with a different OHA. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. We calculated propensity scores and applied inverse probability of treatment weights to each individual. We compared groups using Cox proportional hazards regression and explored differences in HRs between pre-2008 (acarbose, meglitinides, and thiazolidinediones) and post-2008 (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose linked transporter-2 inhibitors) OHAs.ResultsOur cohort included 32 576 individuals (28 077 metformin plus sulfonylurea and 4499 metformin plus ‘other’). Patients newly prescribed a sulfonylurea in the setting of metformin had a higher risk of all-cause mortality (HR 1.44, 95% CI 1.12 to 1.84, p=0.005) and major hypoglycemic episodes (HR 2.78, 95% CI 1.66 to 4.66, p<0.001) than those prescribed an ‘other’ OHA. No differences in cardiovascular events were observed (HR 0.99, 95% CI 0.81 to 1.22, p=0.92). In subgroup analyses, mortality and cardiovascular event risk was higher in patients prescribed sulfonylureas versus post-2008 OHAs.ConclusionsSulfonylureas as add-on therapy to metformin are associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with ‘other’ OHAs. Post hoc analysis suggests newer OHAs may be preferred to sulfonylureas as second-line therapy for glycemic control.

scholarly journals Association of Plasma Myeloperoxidase Level with Risk of Coronary Artery Disease in Patients with Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Ping Song ◽  
Jin Xu ◽  
Yongfeng Song ◽  
Shiliang Jiang ◽  
Haitao Yuan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Logistic Analysis ◽  
Artery Disease

Aims. This study aimed to investigate whether the change of plasma myeloperoxidase (MPO) level would be associated with the incidence of coronary artery disease (CAD) among diabetic patients.Methods. 339 patients with type 2 diabetes mellitus (DM) underwent coronary angiography. Of them, 204 cases had CAD and were assigned to CAD group and 135 cases without CAD were assigned to non-CAD group.Results. Compared to non-CAD group, CAD group had higher level of plasma MPO (p<0.01). Multiple linear regression analysis showed that plasma MPO level was correlated with Gensini score. Multiple logistic analysis showed that the odds ratios for CAD across increasing tertiles of MPO level were 1.191 (0.971–1.547) and 1.488 (1.115–2.228) (p=0.048,p=0.009versus 1st tertile of MPO level, resp.) by adjusting for age, sex, and other conventional risk factors for CAD. The subjects were stratified into nine groups according to tertiles of MPO and HbA1c. The odds ratio for CAD was significantly higher in group with highest levels of MPO and HbA1c (OR = 4.08,p<0.01).Conclusion. Plasma MPO level was positively correlated with the degree of coronary artery stenosis in type 2 diabetic patients, and increasing blood glucose might amplify the association between MPO and CAD.

scholarly journals Association Between Change in Accelerometer-Measured and Self-Reported Physical Activity and Cardiovascular Disease in the Look AHEAD Trial

2022 ◽  
Author(s):  
John M. Jakicic ◽  
Robert I. Berkowitz ◽  
Paula Bolin ◽  
George A. Bray ◽  
Jeanne M. Clark ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Self Report ◽  
Look Ahead ◽  
The Look

OBJECTIVE: To conduct <i>post-hoc</i> secondary analysis examining the association between change in physical activity (PA), measured with self-report and accelerometry, from baseline to 1 and 4 years and cardiovascular disease (CVD) outcomes in the Look AHEAD Trial. <p>RESEARCH DESIGN AND METHODS: Participants were adults with overweight/obesity and type 2 diabetes with PA data at baseline and year 1 or 4 (n = 1,978). Participants were randomized to diabetes support and education or intensive lifestyle intervention. Measures included accelerometry-measured moderate-to-vigorous PA (MVPA), self-reported PA, and composite (morbidity and mortality) CVD outcomes.</p> <p>RESULTS: In pooled analyses of all participants, using Cox proportional hazards models, each 100 MET-min/wk increase in accelerometry-measured MVPA from baseline to 4 years was associated with decreased risk of the subsequent primary composite outcome of CVD. Results were consistent for changes in total MVPA [HR=0.97 (95% CI: 0.95, 0.99)] and MVPA accumulated in <u>></u>10-minute bouts [HR=0.95 (95% CI: 0.91, 0.98)], with a similar pattern for secondary CVD outcomes. Change in accelerometry-measured MVPA at 1 year and self-reported change in PA at 1 and 4 years were not associated with CVD outcomes.</p> <p>CONCLUSIONS: Increased accelerometry-measured MVPA from baseline to year 4 is associated with decreased risk of CVD outcomes. This suggests the need for long-term engagement in MVPA to reduce the risk of CVD in adults with overweight/obesity and type 2 diabetes.</p>

scholarly journals Associations of Diet Quality and All-Cause Mortality Across Levels of Cardiometabolic Health and Disease: A 7.6-Year Prospective Analysis From the Dutch Lifelines Cohort

2021 ◽  
Author(s):  
Petra C Vinke ◽  
Gerjan Navis ◽  
Daan Kromhout ◽  
Eva Corpeleijn
Keyword(s):  
Type 2 Diabetes ◽  
Diet Quality ◽  
Total Population ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Dietary Guidelines ◽  
Cardiometabolic Health ◽  
Ageing Population ◽  
All Cause Mortality

<b>Objective: </b>To simultaneously investigate the association of diet quality and all-cause mortality in groups with varying cardiometabolic diseases (CMDs) at baseline.<br><p> <b>Design:</b> From the population-based Lifelines cohort, 40,892 non-underweight participants aged ≥50 years with data on diet quality and confounding factors were included (enrollment 2006-2013). From food frequency questionnaire data, tertiles of the Lifelines diet score were calculated (T1 = poorest, T3 = best diet quality). Four CMD categories were defined: 1) CMD-free, 2) type 2 diabetes, 3) one cardiovascular disease (CVD), 4) two or more CMDs. Months when deaths occurred were obtained from municipal registries up until November 2019. Multivariable Cox proportional hazards models were applied for the total population and stratified by CMD categories.<br> <b>Results</b>: After a median follow-up of 7.6 years, 1,438 participants died. Diet quality and CMD categories were independently associated with all-cause mortality in crude and adjusted models (p < 0.001). A dose-response relationship of diet quality with all-cause mortality was observed in the total population (P for trend < 0.001, T2 vs. T3 = 1.22 (1.07-1.41), T1 vs. T3 = 1.57 (1.37-1.80)). In stratified analyses, the association was significant for CMD-free individuals (T1 vs. T3 = 1.63 (1.38-1.93)) and for type 2 diabetes patients (1.87 (1.17-3.00)), but not for patients with one CVD (1.39 (0.93-2.08)) or multiple CMDs (1.19 (0.80-1.76)).<br> <b>Conclusions</b>: A high-quality diet can potentially lower all-cause mortality risk in the majority of the ageing population. Its effect may be greatest for CMD-free individuals and patients with type 2 diabetes. Tailored dietary guidelines may be required for patients with extensive histories of CMDs. </p>

scholarly journals Pioglitazone and cause-specific risk of mortality in patients with type 2 diabetes: extended analysis from a European multidatabase cohort study

2018 ◽  
Vol 6 (1) ◽  
pp. e000481 ◽  
Author(s):  
Helen Strongman ◽  
Solomon Christopher ◽  
Maila Majak ◽  
Rachael Williams ◽  
Shahram Bahmanyar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Propensity Score ◽  
Cardiovascular Mortality ◽  
Proportional Hazards ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Exposed Group ◽  
Mortality Data ◽  
Exact Matching

ObjectivesDescribe and compare the risk of cardiovascular and non-cardiovascular mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression.Research design and methodsThis exploratory linked database cohort analysis used pooled health and mortality data from three European countries: Finland, Sweden and the UK. Propensity score together with exact matching was used to match 31 133 patients with type 2 diabetes first prescribed pioglitazone from 2000 to 2011, to 31 133 patients never prescribed pioglitazone. Exact matching variables were treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry. Mean follow-up time was 2.60 (SD 2.00) and 2.69 (SD 2.31) years in the pioglitazone and non-pioglitazone-exposed groups, respectively. Crude cause-specific mortality rates were ascertained. Association with pioglitazone use was estimated using Cox proportional hazards models adjusted a priori for country, age, sex, the propensity score quintile and time-dependent variables representing use of antidiabetic drugs. Stepwise testing identified no additional confounders to include in adjusted models.ResultsThe crude mortality rate was lower in the pioglitazone-exposed group than the non-exposed group for both cardiovascular and non-cardiovascular mortality. Adjusted HRs comparing pioglitazone to alternative antidiabetic exposure were 0.58 (95% CI 0.52 to 0.63) and 0.63 (95% CI 0.58 to 0.68) for cardiovascular and non-cardiovascular mortality, respectively. A protective effect associated with pioglitazone was also found for all specific cardiovascular causes.ConclusionsThis analysis suggests that pioglitazone is associated with a decrease in both cardiovascular and non-cardiovascular mortality. Results should be interpreted with caution due to the potential for residual confounding in this exploratory analysis. Further studies, specifically designed to test the association between pioglitazone use and patient-focused outcomes, are suggested.Study registration numberEuropean Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP; EUPAS3626).

scholarly journals High Betaine, a Trimethylamine N-Oxide Related Metabolite, Is Prospectively Associated with Low Future Risk of Type 2 Diabetes Mellitus in the PREVEND Study

2019 ◽  
Vol 8 (11) ◽  
pp. 1813 ◽  
Author(s):  
Erwin Garcia ◽  
Maryse C. J. Osté ◽  
Dennis W. Bennett ◽  
Elias J. Jeyarajah ◽  
Irina Shalaurova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Regression ◽  
Proportional Hazards Regression ◽  
Study Results ◽  
Future Risk

Background: Gut microbiota-related metabolites, trimethylamine-N-oxide (TMAO), choline, and betaine, have been shown to be associated with cardiovascular disease (CVD) risk. Moreover, lower plasma betaine concentrations have been reported in subjects with type 2 diabetes mellitus (T2DM). However, few studies have explored the association of betaine with incident T2DM, especially in the general population. The goals of this study were to evaluate the performance of a newly developed betaine assay and to prospectively explore the potential clinical associations of betaine and future risk of T2DM in a large population-based cohort. Methods: We developed a high-throughput, nuclear magnetic resonance (NMR) spectroscopy procedure for acquiring spectra that allow for the accurate quantification of plasma/serum betaine and TMAO. Assay performance for betaine quantification was assessed and Cox proportional hazards regression was employed to evaluate the association of betaine with incident T2DM in 4336 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study. Results: Betaine assay results were linear (y = 1.02X − 3.75) over a wide range of concentrations (26.0–1135 µM). The limit of blank (LOB), limit of detection (LOD) and limit of quantitation (LOQ) were 6.4, 8.9, and 13.2 µM, respectively. Coefficients of variation for intra- and inter-assay precision ranged from 1.5–4.3% and 2.5–5.5%, respectively. Deming regression analysis of results produced by NMR and liquid chromatography coupled to tandem mass spectrometry(LC-MS/MS) revealed an R2 value of 0.94 (Y = 1.08x – 1.89) and a small bias for higher values by NMR. The reference interval, in a cohort of apparently healthy adult participants (n = 501), was determined to be 23.8 to 74.7 µM (mean of 42.9 ± 12.6 µM). In the PREVEND study (n = 4336, excluding subjects with T2DM at baseline), higher betaine was associated with older age and lower body mass index, total cholesterol, triglycerides, and hsCRP. During a median follow-up of 7.3 (interquartile range (IQR), 5.9–7.7) years, 224 new T2DM cases were ascertained. Cox proportional hazards regression models revealed that the highest tertile of betaine was associated with a lower incidence of T2DM. Hazard ratio (HR) for the crude model was 0.61 (95% CI: 0.44–0.85, p = 0.004). The association remained significant even after adjusting for multiple clinical covariates and T2DM risk factors, including fasting glucose. HR for the fully-adjusted model was 0.50 (95% CI: 0.32–0.80, p = 0.003). Conclusions: The newly developed NMR-based betaine assay exhibits performance characteristics that are consistent with usage in the clinical laboratory. Betaine levels may be useful for assessing the risk of future T2DM.

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