scholarly journals Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study

Diabetologia ◽  
2021 ◽  
Author(s):  
Geert Jan Biessels ◽  
Chloë Verhagen ◽  
Jolien Janssen ◽  
Esther van den Berg ◽  
Gudrun Wallenstein ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Cognitive Performance ◽  
Mmse Score ◽  
Cognitive Outcome ◽  
Cognitive Changes ◽  
Double Blind ◽  
Treatment Assignment ◽  
Increased Risk

Abstract Aims/hypothesis Type 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes. Methods The CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA1c 48–69 mmol/mol (6.5–8.5%) receiving standard care, excluding insulin therapy. Participants were randomised 1:1 using an interactive telephone- and web-based system and treatment assignment was determined by a computer-generated random sequence with stratification by center. The primary cognitive outcome was occurrence of ACD at end of follow-up, defined as a regression-based index score ≤16th percentile on either the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning, in participants with a baseline MMSE score ≥24. Prespecified additional analyses included effects on ACD at week 160, in subgroups (sex, age, race, ethnicity, depressive symptoms, cardiovascular risk, duration of type 2 diabetes, albuminuria), and absolute changes in cognitive performance. Participants, caregivers, and people involved in measurements, examinations or adjudication, were all masked to treatment assignment. Results Of 6033 participants recruited from hospital and primary care sites, 3163 (38.0% female, mean age/diabetes duration 64/7.6 years, MMSE score 28.5, HbA1c 54 mmol/mol [7.1%]) represent the CAROLINA-COGNITION cohort. Over median 6.1 years, ACD occurred in 27.8% (449/1618, linagliptin) vs 27.6% (426/1545, glimepiride), OR 1.01 (95% CI 0.86, 1.18). Also, no differences in ACD were observed at week 160 (OR 1.07 [0.91, 1.25]), between treatments across subgroups, or for absolute cognitive changes. Conclusions/interpretation In a large, international outcome trial in people with relatively early type 2 diabetes at elevated cardiovascular risk, no difference in risk for ACD was observed between linagliptin and glimepiride over 6.1 years. Funding This study was sponsored by Boehringer Ingelheim. Trial registration ClinicalTrials.gov NCT01243424. Graphical abstract

scholarly journals Cardiovascular Benefit of Empagliflozin Across the Spectrum of Cardiovascular Risk Factor Control in the EMPA-REG OUTCOME Trial

2020 ◽  
Vol 105 (9) ◽  
pp. 3025-3035
Author(s):  
Silvio E Inzucchi ◽  
Kamlesh Khunti ◽  
David H Fitchett ◽  
Christoph Wanner ◽  
Michaela Mattheus ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Density Lipoprotein ◽  
Baseline Risk ◽  
Risk Factor Control ◽  
Increased Risk ◽  
Outcome Trial

Abstract Context Control of multiple cardiovascular (CV) risk factors reduces CV events in individuals with type 2 diabetes. Objective To investigate this association in a contemporary clinical trial population, including how CV risk factor control affects the CV benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor. Design Post hoc analysis. Setting Randomized CV outcome trial (EMPA-REG OUTCOME). Participants Type 2 diabetes patients with established CV disease. Intervention Empagliflozin or placebo. Main Outcome Measures Risk of CV outcomes—including the treatment effect of empagliflozin—by achieving 7 goals for CV risk factor control at baseline: (1) glycated hemoglobin <7.5%, (2) low-density lipoprotein cholesterol <100 mg/dL or statin use, (3) systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg, (4) pharmacological renin-angiotensin-aldosterone system blockade, (5) normoalbuminuria, (6) aspirin use, (7) nonsmoking. Results In the placebo group, the hazard ratio (HR) for CV death was 4.00 (95% CI, 2.26–7.11) and 2.48 (95% CI, 1.52–4.06) for patients achieving only 0–3 or 4–5 risk factor goals at baseline, respectively, compared with those achieving 6–7 goals. Participants achieving 0–3 or 4–5 goals also had increased risk for the composite outcome of hospitalization for heart failure or CV death (excluding fatal stroke) (HR 2.89 [1.82–4.57] and 1.90 [1.31–2.78], respectively) and 3-point major adverse CV events (HR 2.21 [1.53–3.19] and 1.42 [1.06–1.89]). Empagliflozin significantly reduced these outcomes across all risk factor control categories (P > 0.05 for treatment-by-subgroup interactions). Conclusions Cardiovascular risk in EMPA-REG OUTCOME was inversely associated with baseline CV risk factor control. Empagliflozin’s cardioprotective effect was consistent regardless of multiple baseline risk factor control.

Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Hypertension ◽  
2022 ◽  
Author(s):  
Maddalena Ardissino ◽  
Eric A.W. Slob ◽  
Ophelia Millar ◽  
Rohin K. Reddy ◽  
Laura Lazzari ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Increased Risk

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

scholarly journals Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: a post hoc analysis

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Gilles R. Dagenais ◽  
Lars Rydén ◽  
Lawrence A. Leiter ◽  
Mark Lakshmanan ◽  
Leanne Dyal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Double Blind ◽  
Absolute Reduction ◽  
Total Incidence ◽  
Conditional Time ◽  
Time Gap

Abstract Background The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants Methods We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models. Results Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82–0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80–0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87–0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82–0.99) p = 0.028]. Conclusions These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk. Clinical Trial Registration:https://www.clinicaltrials.gouv. Unique Identifier NCT01394952).

scholarly journals FINDRISK and occupation: need of prevention of diabetes type 2 at the workplace

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
K Lyubomirova ◽  
M Tabanska ◽  
L Hristova ◽  
M Samuneva ◽  
M Yancheva ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Risk ◽  
Older Workers ◽  
Significant Proportion ◽  
Diabetes Type 2 ◽  
Diabetes Type ◽  
Increased Risk

Abstract Background Diabetes mellitus is a risk factor for atherosclerosis, cardiovascular morbidity and increased mortality. Identifying people at a high risk of developing diabetes determine the prognosis and quality of life of the patients and prevent the development of macrovascular complications of diabetes. Within the framework of an international project, the ten-year risk of developing type 2 diabetes mellitus in two age groups workers (up to 25 and over 55) of four economic sectors (construction, clothing, hairdressing and cosmetics, and healthcare) has been estimated. Methods The survey included 150 workers from four economic activities. The FINDRISK questionnaire was distributed among them. Plasma glucose and serum lipids (HDL, LDL, triglycerides) were analyzed. The statistical analysis of the results was done using SPSS 16. Results The mean FINDRISK score for the age group up to 25 years is 3.6 ± 3.8, and for respondents above 55 years - 10.1 ± 5.0. The analysis highlights the higher risk of developing diabetes among healthcare workers, where the score of older workers is 11.63 ± 6.61, as well as in the textile and clothing industry (11.17 ± 4.3). These results call attention to a potential link between the occupation and the risk of developing type 2 diabetes in these sectors of the economy and the need for additional measures to search for causes and prevention. Conclusions A significant proportion of the participants over 55 years old in the healthcare and textile and clothing sectors are at an increased risk of developing type 2 diabetes, which requires a change in lifestyle, as well as the identification of workplace hazards that lead to these results. The FINDRISK questionnaire can serve as an indirect assessment of the cardiovascular risk of older workers. Additional preventive measures are needed to limit the risk of developing type 2 diabetes mellitus as well as cardiovascular risk in the identified risky occupations. Key messages Occupation could contribute to the life style risk factors for developing diabetes type 2. Occupational risk reduction measures and health promotion are needed to protects workers.

scholarly journals Aggregation and combination of cardiovascular risk factors and their association with 10-year all-cause mortality: the PERU MIGRANT Study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Janina Bazalar-Palacios ◽  
J. Jaime Miranda ◽  
Rodrigo M. Carrillo-Larco ◽  
Robert H. Gilman ◽  
Liam Smeeth ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Cox Regression ◽  
Secondary Data ◽  
National Registry ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Objective To estimate the association between the aggregation and pair-wise combination of selected cardiovascular risk factors (CVRF) and 10-year all-cause mortality. Methods Secondary data analysis of the PERU MIGRANT study, a prospective population-based cohort. Ten-year all-cause mortality was determined for participants originally enrolled in the PERU MIGRANT Study (baseline in 2007) through the National Registry of Identification and Civil Status. The CVRF included hypertension, type 2 diabetes mellitus, hypercholesterolemia, and overweight/obesity. Exposures were composed of both the aggregation of the selected CVRF (one, two, and three or more CVRF) and pair-wise combinations of CVRF. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI). Findings Of the 989 participants evaluated at baseline, 976 (98.8%) had information about vital status at 10 years of follow-up (9992.63 person-years), and 63 deaths were recorded. In the multivariable model, adjusting for sociodemographic and lifestyle variables, participants with two CVRF (HR: 2.48, 95% CI: 1.03–5.99), and those with three or more CVRF (HR: 3.93, 95% CI: 1.21–12.74) had higher all-cause mortality risk, compared to those without any CVRF. The pair-wise combinations associated with the highest risk of all-cause mortality, compared to those without such comorbidities, were hypertension with type 2 diabetes (HR: 11.67, 95% CI: 3.67–37.10), and hypertension with overweight/obesity (HR: 2.76, 95% CI: 1.18–6.71). Conclusions The aggregation of two or more CVRF and the combination of hypertension with type 2 diabetes or overweight/obesity were associated with an increased risk of 10-year all-cause mortality. These risk profiles will inform primary and secondary prevention strategies to delay mortality from cardiovascular risk factors.

scholarly journals High cardiovascular risk of patients with type 2 diabetes is only partially attributed to angiographic burden of atherosclerosis

2020 ◽  
Vol 17 (5) ◽  
pp. 147916412095361
Author(s):  
Simone Battermann ◽  
Andrea Milzi ◽  
Rosalia Dettori ◽  
Kathrin Burgmaier ◽  
Nikolaus Marx ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Quantitative Coronary Angiography ◽  
High Cardiovascular Risk ◽  
Coronary Syndrome ◽  
Increased Risk ◽  
Angiographic Data ◽  
Artery Disease ◽  
Stable Cad

Background: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events and present more severe coronary artery disease (CAD). The Gensini and COURAGE scores are established angiographic instruments to assess CAD severity, which may also predict future cardiovascular risk. However, it is unclear if these scores are able to depict the increased risk of patients with T2DM and stable CAD (T2DM-SAP). Methods: We performed quantitative coronary angiography and assessed the Gensini and COURAGE scores in 124 patients with T2DM-SAP. Angiographic data were compared to patients with stable angina without T2DM (Non-DM-SAP, n = 74), and to patients with acute coronary syndrome and T2DM (T2DM-ACS, n = 53). Results: T2DM-SAP patients had similar Gensini and COURAGE-scores compared to Non-DM-SAP-patients (Gensini: 14.44 ± 27.34 vs 11.49 ± 26.99, p = 0.465; COURAGE: 3.48 ± 4.49 vs 3.60 ± 4.72, p = 0.854). In contrast, T2DM-SAP patients had significantly lower Gensini (14.44 ± 27.34 vs 30.94 ± 48.74, p = 0.003) and lower COURAGE (3.48 ± 4.49 vs 5.30 ± 4.63, p = 0.016) scores compared to T2DM-ACS-patients. Conclusion: Both the Gensini and the COURAGE score fail to predict the high cardiovascular risk of patients with T2DM-SAP. Therefore, these scores should be used with caution in the assessment of future risk of patients with T2DM. However, among T2DM-ACS patients, both scores are increased, reflecting the high cardiovascular risk in this patient population.

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