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

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.

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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.

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Association between sleep duration and mortality risk among adults with type 2 diabetes: a prospective cohort study

Diabetologia ◽

10.1007/s00125-020-05214-4 ◽

2020 ◽

Vol 63 (11) ◽

pp. 2292-2304 ◽

Cited By ~ 1

Author(s):

Yafeng Wang ◽

Wentao Huang ◽

Adrienne O’Neil ◽

Yutao Lan ◽

Dagfinn Aune ◽

...

Keyword(s):

Type 2 Diabetes ◽

Sleep Duration ◽

Mortality Risk ◽

Oral Glucose ◽

Glucose Lowering ◽

Younger Age ◽

Increased Risk ◽

The Relationship ◽

Cvd Mortality

Abstract Aims/hypothesis This study aimed to investigate whether the effects of sleep duration interacted with the presence of diabetes. We specifically sought to examine the relationship between sleep duration and all-cause and cause-specific mortality in people with type 2 diabetes across sex, age at diagnosis, duration of diabetes and treatment type. Methods The sample consisted of 273,029 adults, including 248,817 without diabetes and 24,212 with type 2 diabetes, who participated in the National Health Interview Survey from 2004 to 2013 and whose data were linked to a mortality database up to 31 December 2015. Sleep duration was measured using self-report, whereby participants were asked ‘on average how long do you sleep each day (≤5, 6, 7, 8, 9 or ≥10 h/day)?’ The relationship between sleep duration and mortality risk was investigated using Cox proportional hazards regression model, with adjustments for demographics, BMI, lifestyle behaviours and clinical variables. Results Absolute mortality rate was higher in adults with diabetes and extremes of sleep duration (≤5 h/day, 215.0 per 10,000 person-years; ≥10 h/day, 363.5 per 10,000 person-years). There was a non-significant interaction between sleep duration and the presence of diabetes (p for interaction = 0.08). A J-shaped relationship existed between sleep duration and all-cause mortality risk in people with type 2 diabetes. Compared with the reference group (7 h/day), both shorter and longer sleep durations were associated with increased risk of all-cause mortality (≤5 h/day, HR 1.24 [95% CI 1.09, 1.40]; 6 h/day, HR 1.13 [1.01, 1.28]; 8 h/day, HR 1.17 [1.06, 1.30]; ≥10 h/day, HR 1.83 [1.61, 2.08]). Similar associations were also observed for mortality risk from CVD, cancer, kidney disease, Alzheimer’s disease and chronic lower respiratory diseases. Longer sleep duration in those with a younger age at diabetes onset was associated with greater risks of all-cause and CVD mortality. Shorter sleep duration in individuals treated with both insulin and oral glucose-lowering medication was also associated with higher risks of all-cause and CVD mortality. Conclusions/interpretation The associations between sleep duration and mortality risk may be different between diabetic and non-diabetic individuals. In people with type 2 diabetes, sleeping less or more than 7 h/day was associated with increased risk of all-cause and condition-specific mortality. The association was more prominent in those with a younger age at diabetes onset and receiving treatment with both oral glucose-lowering medication and insulin. This population may benefit from targeted sleep-related interventions to reduce the risks of adverse health outcomes.

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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

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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.

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Microalbuminuria in Type 2 diabetes indicates impaired microvascular vasomotion and perfusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00558.2007 ◽

2007 ◽

Vol 293 (6) ◽

pp. H3424-H3431 ◽

Cited By ~ 29

Author(s):

Ole Schmiedel ◽

Matthias L. Schroeter ◽

John N. Harvey

Keyword(s):

Type 2 Diabetes ◽

Sodium Nitroprusside ◽

Vascular Function ◽

Hdl Cholesterol ◽

Local Heat ◽

Diabetic Patients ◽

Low Frequencies ◽

Doppler Flowmetry ◽

The Relationship

Vascular oscillation (vasomotion) occurs in the microcirculation and is thought to be a significant contributor to tissue perfusion. Our aims were to assess the relationship of vasomotion to perfusion in the cutaneous microcirculation of diabetic patients, to determine the influence on it of endothelium-dependent and nonendothelium-dependent vasodilatory stimuli, and to assess the relationship to perfusion and vasomotion of various biochemical markers of vascular function (HbA1c, LDL- and HDL-cholesterol, triglycerides, insulin resistance, high sensitive C-reactive protein, L- and E-selectin, soluble ICAM, von Willebrand factor) and microalbuminuria. Perfusion and vasomotion (spectral density at low and very low frequencies) were measured by laser-Doppler flowmetry after local heat and iontophoresis of ACh and sodium nitroprusside. Perfusion responses to all stimuli were impaired in patients with Type 2 diabetes (heat: F = 28.0, P < 0.001; ACh: F = 7.11, P = 0.003; sodium nitroprusside: F = 4.0, P = 0.028). Responses to endothelium-dependent stimuli were further impaired in microalbuminuric patients (heat: P = 0.035; ACh: P = 0.034). Vasomotion responses at low frequencies after endothelium-dependent stimuli were impaired in diabetic patients compared with that shown in controls (heat: F = 5.62, P = 0.002; ACh: F = 4.32, P = 0.015). Multivariate modeling showed microalbuminuria to be the only consistent predictor of perfusion and vasomotion responses. The results suggest that microalbuminuria in Type 2 diabetes reflects a generalized disturbance of microvascular function related to endothelium-dependent mechanisms.

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