scholarly journals Diabetes status modifies the long-term effect of lipoprotein-associated phospholipase A2 on major coronary events

Diabetologia ◽  
2021 ◽  
Author(s):  
Moneeza K. Siddiqui ◽  
Gillian Smith ◽  
Pamela St Jean ◽  
Adem Y. Dawed ◽  
Samira Bell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Phospholipase A2 ◽  
Scientific Community ◽  
Risk Group ◽  
Diabetes Control ◽  
Pla2 Activity ◽  
Link Type ◽  
Diabetes Status ◽  
Coronary Events

Abstract Aims/hypothesis Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity has an independent prognostic association with major coronary events (MCE). However, no study has investigated whether type 2 diabetes status modifies the effect of Lp-PLA2 activity or inhibition on the risk of MCE. We investigate the interaction between diabetes status and Lp-PLA2 activity with risk of MCE. Subsequently, we test the resulting hypothesis that diabetes status will play a role in modifying the efficacy of an Lp-PLA2 inhibitor. Methods A retrospective cohort study design was utilised in two study populations. Discovery analyses were performed in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) cohort based in Scotland, UK. Participants were categorised by type 2 diabetes control status: poorly controlled (HbA1c ≥ 48 mmol/mol or ≥6.5%) and well-controlled (HbA1c < 48 mmol/mol or <6.5%) diabetes (n = 7420). In a secondary analysis of the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) trial of Lp-PLA2 inhibitor (darapladib) efficacy, 15,828 participants were stratified post hoc by type 2 diabetes diagnosis status (diabetes or no diabetes) at time of recruitment. Lp-PLA2 activity was then divided into population-specific quartiles. MCE were determined from linked medical records in GoDARTS and trial records in STABILITY. First, the interaction between diabetes control status and Lp-PLA2 activity on the outcome of MCE was explored in GoDARTS. The effect was replicated in the placebo arm of STABILITY. The effect of Lp-PLA2 on MCE was then examined in models stratified by diabetes status. This helped determine participants at higher risk. Finally, the effect of Lp-PLA2 inhibition was assessed in STABILITY in the higher risk group. Cox proportional hazards models adjusted for confounders were used to assess associations. Results In GoDARTS, a significant interaction between increased Lp-PLA2 activity (continuous and quartile divided) and diabetes control status was observed in the prediction of MCE (p < 0.0001). These effects were replicated in the placebo arm of STABILITY (p < 0.0001). In GoDARTS, stratified analyses showed that, among individuals with poorly controlled diabetes, the hazards of MCE for those with high (Q4) Lp-PLA2 activity was 1.19 compared with individuals with lower (Q1–3) Lp-PLA2 activity (95% CI 1.11, 1.38; p < 0.0001) and 1.35 (95% CI 1.16, 1.57; p < 0.0001) when compared with those with the lowest activity (Q1). Those in the higher risk group were identified as individuals with the highest Lp-PLA2 activity (Q4) and poorly controlled diabetes or diabetes. Based on these observations in untreated populations, we hypothesised that the Lp-PLA2 inhibitor would have more benefit in this higher risk group. In this risk group, Lp-PLA2 inhibitor use was associated with a 33% reduction in MCE compared with placebo (HR 0.67 [95% CI 0.50, 0.90]; p = 0.008). In contrast, Lp-PLA2 inhibitor showed no efficacy in individuals with low activity, regardless of diabetes status, or among those with no baseline diabetes and high Lp-PLA2 activity. Conclusions/interpretation These results support the hypothesis that diabetes status modifies the association between Lp-PLA2 activity and MCE. These results suggest that cardiovascular morbidity and mortality associated with Lp-PLA2 activity is especially important in patients with type 2 diabetes, particularly those with worse glycaemic control. Further investigation of the effects of Lp-PLA2 inhibition in diabetes appears warranted. Data availability STABILITY trial data are available from clinicaltrials.gov repository through the GlaxoSmithKline clinical study register https://clinicaltrials.gov/ct2/show/NCT00799903. GoDARTS datasets generated during and/or analysed during the current study are available following request to the GoDARTS Access Managements Group https://godarts.org/scientific-community/. Graphical abstract

scholarly journals Association between risk of type 2 diabetes and changes in energy intake at breakfast and dinner over 14 years: a latent class trajectory analysis from the China health and nutrition Survey, 1997–2011

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e046183
Author(s):  
Xiyun Ren ◽  
Jian Gao ◽  
Tianshu Han ◽  
Changhao Sun
Keyword(s):  
Type 2 Diabetes ◽  
Energy Consumption ◽  
Energy Intake ◽  
Latent Class ◽  
Early Stage ◽  
Harmful Effect ◽  
Nutrition Survey ◽  
Health And Nutrition ◽  
Diabetes Status

ObjectiveThis study aimed to investigate the association between the trajectories of energy consumption at dinner versus breakfast and the risk of type 2 diabetes (T2D).DesignCohort study.SettingThe study was conducted in China.ParticipantsA total of 10 727 adults, including 5239 men and 5488 women, with a mean age of 42.7±11.2 years and a mean follow-up time of 9.1 years, met the study criteria and completed a questionnaire about energy intake and diabetes status from the China Health and Nutrition Survey in 1997–2011.Primary outcome measuresParticipants were divided into subgroups based on the trajectories of the ratio of energy consumption at dinner versus breakfast. Cox multivariate regression models were used to explore the associations between different trajectories and the risk of T2D after adjustment for confounders and their risk factors. Mediation analysis was performed to explore the intermediary effect of triacylglycerol (TG), total cholesterol (TC), uric acid (UA) and apolipoprotein B (ApoB) between the trajectories and the risk of T2D.ResultsFor energy consumption at dinner versus breakfast, compared with a low-stable trajectory, the adjusted HR of T2D in low-increasing from early-stage trajectory was 1.29 (95% CI 1.04 to 1.60). TG, TC, UA and ApoB were significantly higher in low-increasing from early-stage trajectory than other trajectories and play partial regulation roles between trajectories and T2D.ConclusionsThis study emphasised the harmful effect of a gradual increase in the ratio of energy consumption at dinner versus breakfast from early stage on the development of T2D and partially mediated by TG, TC, UA and ApoB, highlighting that it is necessary to intake more energy at breakfast compared with dinner to prevent T2D in adults.

scholarly journals Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control

Diabetologia ◽  
2021 ◽  
Author(s):  
Johanne Tremblay ◽  
Mounsif Haloui ◽  
Redha Attaoua ◽  
Ramzan Tahir ◽  
Camil Hishmih ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
High Risk ◽  
Glucose Control ◽  
Risk Group ◽  
Cardiovascular Death ◽  
Polygenic Risk ◽  
Renal Complications ◽  
Intensive Blood Pressure

Abstract Aims/hypothesis Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. Methods We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. Results The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10−21 and p = 9.6 × 10−31, respectively) and a 4.4-fold (p = 6.8 × 10−33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. Conclusions/interpretation This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy. Graphical abstract

Efficacy of a pedometer-based physical activity program on parameters of diabetes control in type 2 diabetes mellitus

Metabolism ◽  
2006 ◽  
Vol 55 (10) ◽  
pp. 1382-1387 ◽  
Author(s):  
Paul Araiza ◽  
Hilary Hewes ◽  
Carrie Gashetewa ◽  
Chantal A. Vella ◽  
Mark R. Burge
Keyword(s):  
Physical Activity ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetes Control ◽  
Physical Activity Program ◽  
Activity Program

Effect of RU486 on Hepatic and Adipocyte Gene Expression Improves Diabetes Control in Obesity-type 2 Diabetes

2009 ◽  
Vol 41 (12) ◽  
pp. 899-904 ◽  
Author(s):  
A. I. Taylor ◽  
N. Frizzell ◽  
A. M. McKillop ◽  
P. R. Flatt ◽  
V. A. Gault
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Diabetes Control

scholarly journals Effects of efpeglenatide versus liraglutide on gastric emptying, glucose metabolism and beta-cell function in people with type 2 diabetes: an exploratory, randomized phase Ib study

2021 ◽  
Vol 9 (1) ◽  
pp. e002208
Author(s):  
Marcus Hompesch ◽  
Jahoon Kang ◽  
OakPil Han ◽  
Michael E Trautmann ◽  
Christopher H Sorli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Phase Ib ◽  
Link Type ◽  
Drug Concentrations

IntroductionTo evaluate the effects of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA), on gastric emptying, glucose metabolism, and islet beta-cell function versus liraglutide and placebo in people with type 2 diabetes.Research design and methodsThis phase Ib study (ClinicalTrials.gov identifier: NCT02059564) randomized participants (n=47) to three cohorts. Within the first two cohorts, participants were randomized to placebo, efpeglenatide 6 mg weekly (QW; first cohort), or efpeglenatide 16 mg monthly (QM; second cohort). The third cohort received liraglutide 1.8 mg daily (QD). Gastric emptying was assessed through the pharmacokinetic (PK) profile of acetaminophen at baseline and steady state. Glucose metabolism and beta-cell function were assessed based on mixed-meal tolerance testing and a graded glucose infusion procedure.ResultsTreatment duration was approximately 3 months for efpeglenatide 16 mg QM and 1 month for efpeglenatide 6 mg QW and liraglutide. At peak drug concentrations, efpeglenatide 6 mg QW was non-inferior to liraglutide 1.8 mg QD in delaying gastric emptying, as assessed by acetaminophen PK (lower bound of 90% CI for the efpeglenatide:liraglutide ratio >0.8 for area under the curve (AUC)0–120, AUC0–180, AUC0–360 and maximum concentration (Cmax)). Efpeglenatide 16 mg QM did not decrease the rate of gastric emptying to as great an extent as liraglutide (ie, non-inferiority was not shown). Compared with liraglutide, both efpeglenatide dosing regimens demonstrated comparable or more favorable glucometabolic effects and improved beta-cell function. All gastrointestinal adverse events reported with efpeglenatide were mild or moderate in severity and transient over treatment and follow-up.ConclusionsThe glucometabolic effects of efpeglenatide 6 mg QW and 16 mg QM were comparable to liraglutide. Additional studies are necessary to further examine these benefits of efpeglenatide.Trial registration numberNCT02059564.

Abstract P162: Comparison Of The Clinical Effect Of Empagliflozin On Glycemic And Non-glycemic Parameters In Japanese Patients With Type 2 Diabetes And Cardiovascular Disease Treated With Or Without Baseline Metformin

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Koichi Node
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Troponin I ◽  
Treatment Guidelines ◽  
Geometric Mean ◽  
Sglt2 Inhibitors ◽  
Hypoglycemic Agents ◽  
Clinical Parameters ◽  
Diabetes Status

Introduction: Recent treatment guidelines for type 2 diabetes (T2D) recommend sodium-glucose cotransporter 2 (SGLT2) inhibitors to be considered preferentially in patients with T2D at high cardiovascular risk or with cardiovascular disease (CVD), regardless of their diabetes status and prior use of metformin. Hypothesis: We assessed the hypothesis that the therapeutic impact of SGLT2 inhibitors on clinical parameters differs according to the use of metformin. Methods: This was a post hoc analysis of the Effect of Empagliflozin on Endothelial Function in Cardiovascular High Risk Diabetes Mellitus: Multi-Center Placebo-Controlled Double-Blind Randomized (EMBLEM) trial. All participants (n=105; women 31.4%; mean age 64.8 years) had both T2D and DVD and were randomized to either 24 weeks of empagliflozin 10mg daily or placebo. We assessed the effect of empagliflozin on changes from baseline to 24 weeks in glycemic and non-glycemic clinical parameters, according to the baseline use of metformin. Results: Overall, 53 (50.5%) patients received baseline metformin. In the 52 patients treated with empagliflozin (48.1% with baseline metformin), the change from baseline systolic blood pressure was greater in patients receiving metformin, compared to metformin-naïve patients (group difference -8.5 [95%CI -17.7 to 0.6 mmHg], p=0.066). Reduction in body mass index was significantly greater in patients receiving baseline metformin, relative to nonusers (-0.54 [95%CI -1.07 to -0.01] kg/m 2 , p=0.047). The group ratio (baseline metformin users vs. nonusers) of proportional changes in the geometric mean of high-sensitivity Troponin-I was 0.74 (95%CI 0.59 to 0.92, p=0.009). No obvious difference was observed in glycemic parameters, such as fasting plasma glucose and HbA1c, between the baseline metformin users and nonusers. Conclusions: Our findings suggest empagliflozin has a partially different impact on clinical parameters according to whether or not metformin has been used at baseline. As clinical opportunities for prescribing SGLT2 inhibitors are likely to increase, further research is needed to investigate the effect of SGLT2 inhibitors on clinical parameters taking into account the background situation of hypoglycemic agents, such as metformin.

The effect of the Lenten fast on diabetes control in patients with type 2 diabetes mellitus

2019 ◽  
Vol 13 (1) ◽  
pp. 848-852
Author(s):  
Dina Ali Ahmed ◽  
Lobna Farag El-Toony ◽  
Omer Mohammed Herdan ◽  
Amal Mohammed Abd El-All
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetes Control

scholarly journals Detection of Diabetes Status and Type in Youth using Electronic Health Records (EHRs): The SEARCH for Diabetes in Youth Study

2020 ◽  
Author(s):  
Brian J. Wells ◽  
Kristin M. Lenoir ◽  
Lynne E. Wagenknecht ◽  
Elizabeth J. Mayer-Davis ◽  
Jean M. Lawrence ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Multinomial Regression ◽  
Rule Based ◽  
Diabetes Status ◽  
Icd 10 ◽  
Youth Study ◽  
Diabetes In Youth

<u>Objective:</u> Diabetes surveillance often requires manual medical chart reviews to confirm status and type. This project aimed to create an electronic health record (EHR)-based procedure for improving surveillance efficiency through automation of case identification. <p><u> </u></p> <p><u>Research Design and Methods:</u> Youth (< 20 years) with potential evidence of diabetes (N=8,682) were identified from EHRs at three children’s hospitals participating in the SEARCH for Diabetes in Youth Study. True diabetes status/type was determined by manual chart reviews. Multinomial regression was compared with an ICD-10 rule-based algorithm in the ability to correctly identify diabetes status and type. Subsequently, the investigators evaluated a scenario of combining the rule based algorithm with targeted chart reviews where the algorithm performed poorly.</p> <p> </p> <p><u>Results:</u> The sample included 5308 true cases (89.2% type 1 diabetes). The rule-based algorithm outperformed regression for overall accuracy (0.955 vs 0.936). Type 1 diabetes was classified well by both methods: sensitivity (<i>Se</i>) (>0.95), specificity (<i>Sp</i>) (>0.96), and positive predictive value (PPV) (>0.97). In contrast, the PPVs for type 2 diabetes were 0.642 and 0.778 for the rule-based algorithm and the multinomial regression, respectively. Combining the rule-based method with chart reviews (n=695, 7.9%) of persons predicted to have non type 1 diabetes resulted in perfect PPV for the cases reviewed, while increasing overall accuracy (0.983). The sensitivity, specificity, and PPV for type 2 diabetes using the combined method were >=0.91. </p> <p> </p> <p><u>Conclusions</u>: An ICD-10 algorithm combined with targeted chart reviews accurately identified diabetes status/type and could be an attractive option for diabetes surveillance in youth. </p> <br>

scholarly journals Impact of Prediabetes and Type-2 Diabetes on Outcomes in Patients with COVID-19

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jasbir Makker ◽  
Haozhe Sun ◽  
Harish Patel ◽  
Nikhitha Mantri ◽  
Maleeha Zahid ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mechanical Ventilation ◽  
Older Patients ◽  
Control Group ◽  
Newly Diagnosed ◽  
Conflicting Evidence ◽  
Diabetes Status ◽  
Binomial Regression ◽  
Diabetes Patients

Introduction. The true impact of prediabetes and type-2 diabetes in patients with COVID-19 remains unknown, with studies thus far providing conflicting evidence. Methods. This is a single-center retrospective observational study involving 843 hospitalized patients with SARS-CoV-2 infection. Primary outcomes, mortality, and mechanical ventilation use were compared among the three groups: control, prediabetes, and type-2 diabetes. Binomial regression analysis was used to determine predictors of mortality and mechanical ventilation requirement. Results. Age was a significant predictor of mortality. On stratifying our patients based on their age, older patients aged 55 years and above had no difference in mortality or mechanical ventilation requirement among the three groups of control, prediabetes, and type-2 diabetes. However, among the younger population aged less than 55 years, patients with type-2 diabetes had significantly higher mortality as compared with patients in control and prediabetes groups (27% vs 12.5% vs 9%, p   0.025 ). Additionally, newly diagnosed type-2 diabetes patients demonstrated lower mortality rate in comparison to previously known type-2 diabetes patients (18% vs 40%, p   0.005 ). Outcomes in the prediabetes group were similar to that in the control group. Admission hyperglycemia was associated with higher mortality regardless of diabetes status. Conclusion. In older patients aged 55 years and above, status of type-2 diabetes does not influence their mortality. However, in younger patients aged less than 55 years, the presence of type-2 diabetes is an important driver of mortality. Newly diagnosed type-2 diabetes, in comparison with previously diagnosed type-2 diabetes, may have better survival. Presence of prediabetes did not affect outcomes in patients with COVID-19 infection.

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