Independent association of atherogenic dyslipidaemia with all-cause mortality in individuals with type 2 diabetes and modifying effect of gender: A prospective cohort study

Abstract BackgroundIncreased LDL cholesterol is a major risk factor for morbidity and mortality from cardiovascular disease, though this association is attenuated by the widespread use of statins. Moreover, despite attainment of LDL cholesterol goals, a residual cardiovascular risk remains, partly attributed to atherogenic dyslipidaemia, the relationship of which with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of atherogenic dyslipidaemia with total mortality in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study.MethodsThis observational, prospective study enrolled 15,773 patients in 19 Diabetes Clinics throughout Italy in the years 2006–2008. Triglycerides and total and HDL cholesterol were measured by colorimetric enzymatic methods, whereas LDL cholesterol was estimated using the Friedewald formula. Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%). Participants were stratified by quartiles of triglycerides, HDL cholesterol, and triglyceride:HDL cholesterol ratio (TG:HDL).ResultsA total of 3,602 deaths occurred over a follow-up 7.42 ± 2.05 years (31.0 × 1,000 person-years). In the unadjusted analyses, the highest TG:HDL (but not triglyceride) and the lowest HDL cholesterol quartile were associated with increased death rate and mortality risk. When sequentially adjusting for confounders, including total or LDL cholesterol and lipid-lowering treatment, mortality risk was significantly higher in the highest triglyceride (hazard ratio 1.167 [95% confidence interval 1.055–1.291], p = 0.003) and TG:HDL (1.192 [1.082–1.314], p < 0.0001) and the lowest HDL cholesterol (1.232 [1.117–1.360], p < 0.0001) quartile, though the association of triglycerides and HDL cholesterol disappeared after further adjustment for each other. Interaction with gender was significant only for HDL cholesterol (p = 0.0009). The relationship with death was stronger for triglycerides in males and HDL cholesterol in females, with the latter remaining even after adjustment for triglycerides (1.366 [1.176–1.587], p < 0.0001, for the lowest vs the highest quartile).ConclusionsIn patients with type 2 diabetes, higher triglycerides and TG:HDL and lower HDL cholesterol were independently associated with increased all-cause mortality, with a modifying effect of gender for triglycerides and HDL cholesterol. These data suggest that atherogenic dyslipidaemia, especially TG:HDL, may serve as predictor of death in these individuals.Trial registrationClinicalTrials.gov, NCT00715481, 15 July, 2008.

Download Full-text

Independent association of atherogenic dyslipidaemia with all-cause mortality in individuals with type 2 diabetes and modifying effect of gender: A prospective cohort study

10.21203/rs.3.rs-123775/v2 ◽

2021 ◽

Author(s):

Emanuela Orsi ◽

Giuseppe Penno ◽

Anna Solini ◽

Enzo Bonora ◽

Cecilia Fondelli ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mortality Risk ◽

Hdl Cholesterol ◽

Lipid Lowering ◽

Cardiovascular Morbidity And Mortality ◽

All Cause Mortality ◽

Atherogenic Dyslipidaemia ◽

Modifying Effect ◽

Independent Association

Abstract Background. Atherogenic dyslipidaemia has been implicated in the residual risk for cardiovascular morbidity and mortality, which remains despite attainment of LDL cholesterol goals especially in individuals with type 2 diabetes. However, its relationship with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of increased triglycerides and triglyceride:HDL cholesterol ratio (TG:HDL) and decreased HDL cholesterol with total mortality and the possible modifying effect of gender in a large cohort of patients with type 2 diabetes.Methods. This observational, prospective study enrolled 15,773 patients in 19 Diabetes Clinics throughout Italy in the years 2006-2008. Triglycerides and total and HDL cholesterol were measured by colorimetric enzymatic methods. Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%). Participants were stratified by quartiles of triglycerides, HDL cholesterol, and TG:HDL.Results. There were 3,602 deaths over a follow-up 7.42±2.05 years (31.0 x 1,000 person-years). In the unadjusted analyses, the highest TG:HDL (but not triglyceride) and the lowest HDL cholesterol quartile were associated with increased death rate and mortality risk. When sequentially adjusting for confounders, including total, LDL, or non-HDL cholesterol and lipid-lowering treatment, mortality risk was significantly higher in the highest triglyceride (hazard ratio 1.167 [95% confidence interval 1.055-1.291], p=0.003) and TG:HDL (1.192 [1.082-1.314], p<0.0001) and the lowest HDL cholesterol (1.232 [1.117-1.360], p<0.0001) quartile, though the association of triglycerides and HDL cholesterol disappeared after further adjustment for each other. Interaction with gender was significant only for HDL cholesterol (p=0.0009). The relationship with death was stronger for triglycerides in males and HDL cholesterol in females, with these associations remaining significant even after adjustment for HDL cholesterol (1.161 [1.019-1.324], p=0.025, for the highest vs the lowest triglyceride quartile) and triglycerides (1.366 [1.176-1.587], p<0.0001, for the lowest vs the highest HDL cholesterol quartile).Conclusions. In patients with type 2 diabetes, higher triglycerides and TG:HDL and lower HDL cholesterol were independently associated with increased all-cause mortality, with a modifying effect of gender for triglycerides and HDL cholesterol. These data suggest that atherogenic dyslipidaemia, especially TG:HDL, may serve as predictor of all-cause death in these individuals.

Download Full-text

Independent association of atherogenic dyslipidaemia with all‐cause mortality in individuals with type 2 diabetes and modifying effect of gender: a prospective cohort study

Cardiovascular Diabetology ◽

10.1186/s12933-021-01224-7 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Emanuela Orsi ◽

◽

Giuseppe Penno ◽

Anna Solini ◽

Enzo Bonora ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mortality Risk ◽

Hdl Cholesterol ◽

Lipid Lowering ◽

Cardiovascular Morbidity And Mortality ◽

All Cause Mortality ◽

Atherogenic Dyslipidaemia ◽

Modifying Effect ◽

Independent Association

Abstract Background Atherogenic dyslipidaemia has been implicated in the residual risk for cardiovascular morbidity and mortality, which remains despite attainment of LDL cholesterol goals especially in individuals with type 2 diabetes. However, its relationship with all-cause death has not been sufficiently explored. This analysis evaluated the independent association of increased triglycerides and triglyceride:HDL cholesterol ratio (TG:HDL) and decreased HDL cholesterol with total mortality and the possible modifying effect of gender in a large cohort of patients with type 2 diabetes. Methods This observational, prospective study enrolled 15,773 patients in 19 Diabetes Clinics throughout Italy in the years 2006–2008. Triglycerides and total and HDL cholesterol were measured by colorimetric enzymatic methods. Vital status was retrieved on 31 October 2015 for 15,656 patients (99.3%). Participants were stratified by quartiles of triglycerides, HDL cholesterol, and TG:HDL. Results There were 3,602 deaths over a follow-up 7.42 ± 2.05 years (31.0 × 1000 person-years). In the unadjusted analyses, the highest TG:HDL (but not triglyceride) and the lowest HDL cholesterol quartile were associated with increased death rate and mortality risk. When sequentially adjusting for confounders, including total, LDL, or non-HDL cholesterol and lipid-lowering treatment, mortality risk was significantly higher in the highest triglyceride (hazard ratio 1.167 [95% confidence interval 1.055–1.291], p = 0.003) and TG:HDL (1.192 [1.082–1.314], p < 0.0001) and the lowest HDL cholesterol (1.232 [1.117–1.360], p < 0.0001) quartile, though the association of triglycerides and HDL cholesterol disappeared after further adjustment for each other. Interaction with gender was significant only for HDL cholesterol (p = 0.0009). The relationship with death was stronger for triglycerides in males and HDL cholesterol in females, with these associations remaining significant even after adjustment for HDL cholesterol (1.161 [1.019–1.324], p = 0.025, for the highest vs the lowest triglyceride quartile) and triglycerides (1.366 [1.176–1.587], p < 0.0001, for the lowest vs the highest HDL cholesterol quartile). Conclusions In patients with type 2 diabetes, higher triglycerides and TG:HDL and lower HDL cholesterol were independently associated with increased all-cause mortality, with a modifying effect of gender for triglycerides and HDL cholesterol. These data suggest that atherogenic dyslipidaemia, especially TG:HDL, may serve as predictor of all-cause death in these individuals. Trial registration ClinicalTrials.gov, NCT00715481, 15 July, 2008

Download Full-text

The relationship between high levels of HDL cholesterol and mortality risk in patients with well-regulated type 2 diabetes

Atherosclerosis ◽

10.1016/j.atherosclerosis.2018.06.507 ◽

2018 ◽

Vol 275 ◽

pp. e168

Author(s):

T. Athanasopoulou ◽

I.L. Matsoukis ◽

K. Kanellopoulou ◽

A. Ganotopoulou ◽

N. Zimpounoumi ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mortality Risk ◽

Hdl Cholesterol ◽

The Relationship

Download Full-text

Mortality risk in people with type 2 diabetes: a large prospective population-based cohort study (The Ayrshire Diabetes fOllow-up Cohort (ADOC) study)

10.21203/rs.3.rs-35929/v1 ◽

2020 ◽

Author(s):

Andrew Collier ◽

Mario Hair ◽

Lyall Cameron ◽

Sujoy Ghosh ◽

James Boyle ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mortality Risk ◽

Smoking Status ◽

Economic Status ◽

Hdl Cholesterol ◽

Population Based ◽

Risk Difference ◽

All Cause Mortality ◽

Low Hdl

Abstract BackgroundThe aims of this study were to investigate the effects of age, gender, body mass index (BMI), glycaemic control, socio-economic status, dyslipidaemia, hypertension, ischaemic heart disease (IHD) and smoking status in type 2 diabetes in a population-based analysis. MethodsData were collected from 46 General Practice databases in 2009 and 2014. Cox regressions were run in the non-diabetes population plus type 2 diabetes patients. ResultsPeople with type 2 diabetes (n=16,643) had higher mortality rates than non-diabetes subjects. Ranked in order of Hazard Ratio (HR), increasing age (HR 2.31), smoking (HR 1.79), IHD (HR 1.65), deprivation (HR 1.36), hypertension (HR 1.23) and male gender (HR 1.20) all increased mortality risk (p<0.01). Statin therapy was associated with better outcome (HR 0.65, p<0.01). Abnormal lipid levels whilst not on a statin significantly increased mortality risk for raised total-cholesterol (HR 1.74) and low HDL-cholesterol (HR 1.48) but not for triglycerides (HR 0.67) (all p<0.01). ConclusionsThis large study confirmed that the all-cause mortality risk in people with type 2 diabetes remains elevated. In the study we demonstrated that a man with type 2 diabetes of 5-10 years duration who smoked, had hypertension and IHD plus lived in the most deprived area had a HR of 6.2 compared with a non-smoking, normotensive, non-diabetes subject without IHD living in the least deprived area. . Further research is required to understand the gender risk difference in all-cause mortality in type 1 compared with type 2 diabetes and why obesity plus raised triglycerides appear to be protective.

Download Full-text

Response to Comment on Sharif et al. HDL Cholesterol as a Residual Risk Factor for Vascular Events and All-Cause Mortality in Patients With Type 2 Diabetes. Diabetes Care 2016;39:1424–1430

Diabetes Care ◽

10.2337/dci16-0023 ◽

2016 ◽

Vol 39 (10) ◽

pp. e190-e191

Author(s):

Shahnam Sharif ◽

Yolanda van der Graaf ◽

Hendrik M. Nathoe ◽

Harold W. de Valk ◽

Frank L.J. Visseren ◽

...

Keyword(s):

Type 2 Diabetes ◽

Risk Factor ◽

Diabetes Care ◽

Hdl Cholesterol ◽

Residual Risk ◽

Vascular Events ◽

All Cause Mortality

Download Full-text

MON-LB029 The Influence of SGLT-2 Inhibitors and Other Glucose-Lowering Therapies on All-Cause Mortality Risk and Cardiovascular Outcomes in Older Patients with Newly Treated Type 2 Diabetes: A Population-Based Cohort Study

Journal of the Endocrine Society ◽

10.1210/js.2019-mon-lb029 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Mary-Anne Doyle ◽

Amel Arnaout ◽

Janine Malcolm ◽

Heather Lochnan ◽

Erin Keely ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cohort Study ◽

Mortality Risk ◽

Older Patients ◽

Population Based ◽

Cardiovascular Outcomes ◽

Glucose Lowering ◽

All Cause Mortality

Download Full-text

Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all‐cause mortality: Findings from the SMART cohort

Diabetes Obesity and Metabolism ◽

10.1111/dom.13759 ◽

2019 ◽

Vol 21 (8) ◽

pp. 1935-1943 ◽

Cited By ~ 3

Author(s):

Shahnam Sharif ◽

Rolf H. H. Groenwold ◽

Yolanda Graaf ◽

Gijs F. N. Berkelmans ◽

Maarten J. Cramer ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mediation Analysis ◽

Cardiovascular Events ◽

All Cause Mortality ◽

The Relationship

Download Full-text

Comments on Li et al. HbA1c and all-cause mortality risk among patients with type 2 diabetes. International Journal of Cardiology. 2015; 202:490–496

International Journal of Cardiology ◽

10.1016/j.ijcard.2015.10.202 ◽

2016 ◽

Vol 203 ◽

pp. 445-446

Author(s):

Fang-Yang Huang ◽

Mao Chen

Keyword(s):

Type 2 Diabetes ◽

Mortality Risk ◽

All Cause Mortality

Download Full-text

Oxidized LDL and lipids as risk factors for ischemic heart disease in type 2 diabetes

Vojnosanitetski pregled ◽

10.2298/vsp0508529z ◽

2005 ◽

Vol 62 (7-8) ◽

pp. 529-536 ◽

Cited By ~ 5

Author(s):

Miroslava Zamaklar ◽

Katarina Lalic ◽

Natasa Rajkovic ◽

Danijela Trifunovic ◽

Mirjana Dragasevic ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Lipid Profile ◽

Total Cholesterol ◽

Ldl Cholesterol ◽

Oxidized Ldl ◽

Hdl Cholesterol ◽

Apo B ◽

Significant Difference

Background. Abnormal lipid profile is an important risk factor in the development of macrovascular atherosclerotic complications in patients with type 2 diabetes mellitus (T2D). Factors that contribute to endothelial cell dysfunction associated with the initiation of atherosclerosis include oxidative stress. The aim of this study was to investigate the relationship between lipid profile and oxidative stress in type 2 diabetics with and without ischemic heart disease (IHD). Methods. We studied 80 patients with T2D, 40 with IHD (group A1) and 40 without IHD (group A2). We also studied 51 non-diabetics, 31 with IHD (group B1), and 20 without IHD (group B2 - control group). Lipid profile was estimated by the total cholesterol, HDL cholesterol, LDL cholesterol, the level of triglyceride (Tg), lipoproteina a (Lp a), Apo A I, A II, B 100 and E. To evaluate the oxidative status we measured circulating oxidized LDL (ox LDL), erythrocyte antioxidative enzyme activity: superoxide dismutase (E-SOD), glutathione peroxidase (E-GPX), as well as the total antioxidative serum activity (TAS). Inflammatory reaction was estimated by C-reactive protein (CRP) and fibrinogen. Results. No significant difference was found in the lipid profile in groups A1, A2 and B1, but the group B2 had the lowest one. Lp a level was significantly higher in group B1 comparing to other groups (p < 0.05). There was no significant difference in the level of ox LDL between the groups. In diabetics, ox LDL positively correlated with the total cholesterol, LDL cholesterol, non HDL cholesterol, Apo B 100 and the relations between LDL/HDL and Tg/HDL (p < 0.001), as well as with Tg and fibrinogen (p < 0.05). In group B1, ox LDL positively correlated with total cholesterol, Tg (p < 0.01), LDL, and non HDL cholesterol (p < 0.05) and significantly with Apo B 100 (p < 0.001). There was no significant difference in the antioxidant enzyme activities between the groups of diabetics (A1 and A2), but fibrinogen was higher in the group with IHD (group A1, p < 0.05). Group B1 had lower ESOD activity than the groups A1 and A2 (p < 0.05), but CRP was higher (p < 0.05). There were no significant correlations between oxLDL and CRP in groups A1 and A2, but it was statistically significant in the group B1 (p < 0.05). Conclusion. In this study we demonstrated the increased oxidative stress in diabetics compared to non-diabetics regardless of the presence of IHD. Fibrinogen, but not CRP, was higher in diabetics with IHD, compared to diabetics without IHD. The increased oxidative stress, the reduced antioxidative activity E-SOD, and the higher level of CRP were found in non-diabetics with IHD compared to non-diabetics without IHD.

Download Full-text