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

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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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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