Acute Increase in Creatinine after Starting ACE Inhibitor and Vascular Events and Premature Death in Patients with Type 2 Diabetes—The ADVANCE Trial

In patients with type 2 diabetes (T2D) hypertension is accompanied by an increase in CV risk which can be substantially attenuated if BP is lowered by drug treatment. Empagliflozin (EMPA) is a new glucose-lowering agent of the sodium glucose co-transporter 2 inhibitor (SGLT2i) class, which has been shown to reduce body weight and also lower BP. It is not known, however, whether the EMPA-related BP lowering effect is preserved in patients under background antihypertensive treatment. We investigated the effect of 12 weeks with EMPA on 24 hour (h) mean BP in 823 T2D patients (age 60.2 ± 9.0 years, HbA1c 7.9 ± 0.7%, office systolic (S)/diastolic (D) BP 142.1 ± 12.3/83.9 ± 7.0 mmHg, mean ± SD) in a study with a randomized design. EMPA was given at 10mg (n=276) or 25mg (n=276) daily; 271 patients were randomized to placebo. Patients were under no, 1 or ≥ 2 antihypertensive drugs (n= 62, 353 and 408, respectively) such as an ACE inhibitor (ACEI), an angiotensin receptor antagonist (ARB) or a diuretic (D). HbA1c and weight were significantly reduced with EMPA 10 mg (mean [SE] -0.62% [0.05], -1.5 kg [0.2]) and EMPA 25 mg (-0.65 [0.05], -2.0 [0.2]) relative to placebo (all p < 0.001). As shown in the Table, compared to placebo, EMPA at the lower or higher dose reduced 24h mean SBP and DBP in all groups. With the lower dose the BP reduction was somewhat less pronounced in patients with ≥ 2 antihypertensive drugs whereas with the higher dose the BP effect was similar irrespective of the presence and intensity of background antihypertensive treatment. The antihypertensive effect of EMPA was preserved also irrespective of the type of treatment (D and ACEIs or ARBs), especially at the higher dose. Thus, EMPA reduces BP in patients with T2D regardless of whether they are untreated or more or less intensively treated for hypertension.

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Effect of Fixed‐Dose ACE‐Inhibitor/Calcium Channel Blocker Combination Therapy vs. ACE‐Inhibitor Monotherapy on Arterial Compliance in Hypertensive Patients With Type 2 Diabetes

Preventive Cardiology ◽

10.1111/j.1520-037x.2005.3535.x ◽

2005 ◽

Vol 8 (2) ◽

pp. 87-92 ◽

Cited By ~ 13

Author(s):

Nathaniel Winer ◽

Amy Folker ◽

Julie A. Murphy ◽

Elena Hung ◽

Mara Bard ◽

...

Keyword(s):

Type 2 Diabetes ◽

Combination Therapy ◽

Calcium Channel ◽

Calcium Channel Blocker ◽

Ace Inhibitor ◽

Channel Blocker ◽

Arterial Compliance ◽

Fixed Dose ◽

Hypertensive Patients

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Risk factors for the development of micro-vascular complications of type 2 diabetes in a single-centre cohort of patients

Diabetes and Vascular Disease Research ◽

10.1177/1479164118780808 ◽

2018 ◽

Vol 15 (5) ◽

pp. 424-432 ◽

Cited By ~ 12

Author(s):

Marsida Teliti ◽

Giulia Cogni ◽

Lucia Sacchi ◽

Arianna Dagliati ◽

Simone Marini ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Risk Factor ◽

Peripheral Neuropathy ◽

Vascular Complications ◽

Glycated Haemoglobin ◽

Vascular Complication ◽

Single Centre ◽

Vascular Events

Aims: In type 2 diabetes, we aimed at clarifying the role of glycated haemoglobin variability and other risk factors in the development of the main micro-vascular complications: peripheral neuropathy, nephropathy and retinopathy. Methods: In a single-centre cohort of 900 patients, glycated haemoglobin variability was evaluated as intra-individual standard deviation, adjusted standard deviation and coefficient of variation of serially measured glycated haemoglobin in the 2-year period before a randomly selected index visit. We devised four models considering different aspects of glycated haemoglobin evolution. Multivariate stepwise logistic regression analysis was performed including the following covariates at the index visit: age, disease duration, body mass index, total cholesterol, high-density lipoprotein cholesterol, triglycerides, sex, smoking habit, hypertension, dyslipidemia, treatment with anti-diabetic drugs, occurrence of macro-vascular events and the presence of another micro-vascular complication. Results: Males with high mean glycated haemoglobin, long duration of diabetes, presence of macro-vascular events and retinopathy emerged at higher risk for peripheral neuropathy. Development of nephropathy was independently associated with higher glycated haemoglobin variability, older age, male sex, current smoking status, presence of retinopathy, of peripheral neuropathy and of hypertension. Higher mean glycated haemoglobin, younger age, longer duration of diabetes, reduced estimated glomerular filtration rate and the presence of peripheral neuropathy were significantly associated with increased incidence of retinopathy. Conclusion: Glycated haemoglobin variability was associated with increased incidence of nephropathy, while mean glycated haemoglobin emerged as independent risk factor for the development of retinopathy and peripheral neuropathy. The presence of macro-vascular events was positively correlated with peripheral neuropathy. Finally, the occurrence of another micro-vascular complication was found to be a stronger risk factor for developing another micro-vascular complication than the mean or variability of glycated haemoglobin.

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Improved Lipid Profiles are Associated with Reduced Incidence of Coronary Vascular Events in Asymptomatic Patients with Type 2 Diabetes and Impaired Myocardial Perfusion

Journal of Atherosclerosis and Thrombosis ◽

10.5551/jat.13474 ◽

2013 ◽

Vol 20 (4) ◽

pp. 330-335 ◽

Cited By ~ 1

Author(s):

Yoshimitsu Yamasaki ◽

Naoto Katakami ◽

Hideaki Kaneto ◽

Kenichi Nakajima ◽

Hideo Kusuoka ◽

...

Keyword(s):

Type 2 Diabetes ◽

Myocardial Perfusion ◽

Lipid Profiles ◽

Vascular Events ◽

Asymptomatic Patients

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Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Severe Hypoglycemia Complicating Type 2 Diabetes: The Fremantle Diabetes Study

Endocrinology ◽

10.1210/endo.152.3.zee1195a ◽

2011 ◽

Vol 152 (3) ◽

pp. 1195-1195

Author(s):

Wendy A. Davis ◽

Simon G. A. Brown ◽

Ian G. Jacobs ◽

Max Bulsara ◽

John Beilby ◽

...

Keyword(s):

Type 2 Diabetes ◽

Confidence Interval ◽

Angiotensin Converting Enzyme ◽

Ace Inhibitor ◽

Severe Hypoglycemia ◽

Community Dwelling ◽

Inhibitor Therapy ◽

First Episode ◽

Converting Enzyme

Abstract Aims/Hypotheses: The aims of this study were to determine whether the angiotensin-converting enzyme (ACE) gene I/D polymorphisms independently predict severe hypoglycemia in community-dwelling type 2 patients. Methods: Six hundred two patients who were ACE genotyped at baseline and assessed in 1998 were followed up to the end of June 2006. Severe hypoglycemia was defined as that requiring documented health service use as the primary diagnosis. Cox proportional hazards modeling was used to determine the predictors of first episode and zero-inflated negative binomial regression modeling identified predictors of frequency. Results: Forty-nine patients (8.1%) experienced 63 episodes of severe hypoglycemia. After adjusting for previously identified significant independent predictors of time to first episode, both ACE DD genotype and ACE inhibitor therapy, but not their interaction, added to the model [hazard ratio (95% confidence interval): 2.34 (1.29–4.26), P = 0.006, and 1.77 (0.99–3.13), P = 0.052, respectively]. Similarly, after adjusting for previously identified risk factors for multiple episodes of severe hypoglycemia, ACE DD genotype was independently associated with increased risk [incidence relative risk (95% confidence interval): 1.80 (1.00–3.24), P = 0.050]. Conclusions/Interpretation: ACE DD genotype is associated with an increased the risk of the first episode of severe hypoglycemia and its subsequent frequency approximately 2-fold in well-characterized patients with type 2 diabetes. Consistent with previous case-control studies, ACE inhibitor therapy was a weak predictor of severe hypoglycemia. ACE I/D genotyping might provide useful adjunctive prognostic information when intensive glycemic control measures are contemplated.

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Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa394 ◽

2020 ◽

Vol 105 (9) ◽

pp. 3005-3014

Author(s):

Brittany R Lapin ◽

Kevin M Pantalone ◽

Alex Milinovich ◽

Shannon Morrison ◽

Andrew Schuster ◽

...

Keyword(s):

Type 2 Diabetes ◽

Proportional Hazards ◽

Negative Binomial ◽

Cox Proportional Hazards ◽

Vascular Events ◽

Proportional Hazards Regression ◽

Increased Risk ◽

History Of ◽

Mortality Hazard Ratio

Abstract Purpose Type 2 diabetes–related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). Methods A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. Results Of 43 945 patients with type 2 diabetes (age 64.6 ± 14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). Conclusions Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.

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