diabetes research and clinical practice 104 (2014) e26–e28
Contents available at ScienceDirect
Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
The relation between glycemic control and HDL-C in type 2 diabetes: a preliminary step forward? G. Barbarossa, A. Renzi, L. D’Erasmo, A. Gallo, E. Grieco, M. Rossetti, A. Carnovale, M. Santilli, E. Mandosi, P. Coletta, D. Pergolini, S. Morano, M. Maranghi * Dipartimento di Medicina Interna e Specialita` Mediche, Sapienza Universita` di Roma, Rome, Italy
article info
abstract
Article history:
Low high-density lipoprotein cholesterol (HDL-C) levels are associated with cardiovascular
Received 31 May 2013
(CV) disease in type 2 diabetes (T2D). Unfortunately available drugs to increase HDL-C have
Received in revised form
failed to demonstrate a reduction in CV risk. We assessed the effect of improving glycemic
14 November 2013
control on HDL-C levels. A 6-month intervention resulted in significant improvement in
Accepted 30 December 2013
HbA1c but not in HDL-C levels. However, when considering the subgroup of subjects with
Available online 8 January 2014
low levels of HDL-C at baseline, we found a significant and inverse relation between improvement in HbA1c and HDL-C levels. # 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: HDL-cholesterol Glycated haemoglobin Type 2 diabetes Glycemic control
1.
Background
Current standards of care targeting achieving very low levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy leave people with T2D at significant residual risk of vascular events [1]. In this context, recent evidence has emphasized the important association between low levels of HDL-C and increased CV risk [2]. In the general population a 0.02 mmol/l increment in HDL-C is estimated to result in a significant 2–3% reduction in CV mortality rates [3]. Thus, strategies to increase HDL-C remain a promising area of research to prevent CV disease particularly in high-risk individuals such as people with T2D [4]. Unfortunately, treatment that both raises HDL-C levels and enhances its atheroprotective function is still lacking. Furthermore available pharmacological options which specifically increase HDLC levels, have failed to demonstrate a significant reduction of
CV risk [5,6]. These results strengthen the need for finding other factors to modulate HDL-C levels and possibly optimize its protective effect on atherosclerosis. Previous studies have shown an inverse relationship between HDL-C levels and glycated haemoglobin (HbA1c), but data are not conclusive [7,8]. The aims of our pilot prospective study were to assess, in a population of subjects with T2D, if an improvement in glycemic control could result in an HDL-C increase and to examine the features of this relation.
2.
Materials and methods
A total of 47 people with T2D with poor glycemic control, defined as an HbA1c 7.0% (53 mmol/mol), were consecutively recruited at the Diabetes outpatient clinic of Policlinico Umberto I Hospital in Rome (Italy). The main inclusion criteria
* Corresponding author.Tel.: +39 6 49978391/39 3929091560; fax: +39 6 4463783. E-mail addresses: [email protected], [email protected] (M. Maranghi). 0168-8227/$ – see front matter # 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2013.12.061
e27
diabetes research and clinical practice 104 (2014) e26–e28
were age between 18 and 75 years and the presence of T2D diagnosed according to ADA criteria [9]. Exclusion criteria were hypothyroidism, history of CV disease, triglycerides (TG) levels >4.5 mmol/l and any therapy known to modify lipid metabolism (i.e. statins, fibrates and thiazolidinediones). A 6-month therapeutic intervention to improve glycemic control consisting of insulin metformin oral hypoglycemic agents was started. All subjects received diet and physical exercise counselling. Two telephone contacts and a 3-month visit were performed to assess compliance. Body mass index, blood pressure measurements and the fasting biochemical parameters were recorded at baseline and after 6 months. Fasting plasma glucose, total cholesterol (TC), TG and HDL-C were measured by commercially available enzymatic kits and HbA1c by ion-exchange HPLC. LDL-C was calculated with Friedewald formula. Immunoturbidimetric assay was used for quantifying apolipoprotein A1 (apoA1). Written informed consent was obtained from each participant. The protocol was approved by the Ethics Committee of the Policlinico Umberto I Hospital and carried out in accordance with the Helsinki Declaration.
3.
Statistical analysis
For all variables changes after the intervention were calculated as the difference between 6 months and baseline values. Paired sample t-test was used for pre-post comparisons. A stepwise linear regression model was used to identify
predictors of HDL-C and apoA1 changes. TC change predicted HDL changes, while HDL-C change and smoking status predicted apoA1 changes. Linear regression analysis was used to assess the relation between HbA1c and HDL-C and HbA1c and apoA1 changes. The analysis was repeated after stratifying the cohort in two groups according to HDL-C levels at baseline: the ‘‘low HDL’’ subgroup (HDL-C
Contents available at ScienceDirect
Diabetes Research and Clinical Practice jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es
The relation between glycemic control and HDL-C in type 2 diabetes: a preliminary step forward? G. Barbarossa, A. Renzi, L. D’Erasmo, A. Gallo, E. Grieco, M. Rossetti, A. Carnovale, M. Santilli, E. Mandosi, P. Coletta, D. Pergolini, S. Morano, M. Maranghi * Dipartimento di Medicina Interna e Specialita` Mediche, Sapienza Universita` di Roma, Rome, Italy
article info
abstract
Article history:
Low high-density lipoprotein cholesterol (HDL-C) levels are associated with cardiovascular
Received 31 May 2013
(CV) disease in type 2 diabetes (T2D). Unfortunately available drugs to increase HDL-C have
Received in revised form
failed to demonstrate a reduction in CV risk. We assessed the effect of improving glycemic
14 November 2013
control on HDL-C levels. A 6-month intervention resulted in significant improvement in
Accepted 30 December 2013
HbA1c but not in HDL-C levels. However, when considering the subgroup of subjects with
Available online 8 January 2014
low levels of HDL-C at baseline, we found a significant and inverse relation between improvement in HbA1c and HDL-C levels. # 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: HDL-cholesterol Glycated haemoglobin Type 2 diabetes Glycemic control
1.
Background
Current standards of care targeting achieving very low levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy leave people with T2D at significant residual risk of vascular events [1]. In this context, recent evidence has emphasized the important association between low levels of HDL-C and increased CV risk [2]. In the general population a 0.02 mmol/l increment in HDL-C is estimated to result in a significant 2–3% reduction in CV mortality rates [3]. Thus, strategies to increase HDL-C remain a promising area of research to prevent CV disease particularly in high-risk individuals such as people with T2D [4]. Unfortunately, treatment that both raises HDL-C levels and enhances its atheroprotective function is still lacking. Furthermore available pharmacological options which specifically increase HDLC levels, have failed to demonstrate a significant reduction of
CV risk [5,6]. These results strengthen the need for finding other factors to modulate HDL-C levels and possibly optimize its protective effect on atherosclerosis. Previous studies have shown an inverse relationship between HDL-C levels and glycated haemoglobin (HbA1c), but data are not conclusive [7,8]. The aims of our pilot prospective study were to assess, in a population of subjects with T2D, if an improvement in glycemic control could result in an HDL-C increase and to examine the features of this relation.
2.
Materials and methods
A total of 47 people with T2D with poor glycemic control, defined as an HbA1c 7.0% (53 mmol/mol), were consecutively recruited at the Diabetes outpatient clinic of Policlinico Umberto I Hospital in Rome (Italy). The main inclusion criteria
* Corresponding author.Tel.: +39 6 49978391/39 3929091560; fax: +39 6 4463783. E-mail addresses: [email protected], [email protected] (M. Maranghi). 0168-8227/$ – see front matter # 2014 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.diabres.2013.12.061
e27
diabetes research and clinical practice 104 (2014) e26–e28
were age between 18 and 75 years and the presence of T2D diagnosed according to ADA criteria [9]. Exclusion criteria were hypothyroidism, history of CV disease, triglycerides (TG) levels >4.5 mmol/l and any therapy known to modify lipid metabolism (i.e. statins, fibrates and thiazolidinediones). A 6-month therapeutic intervention to improve glycemic control consisting of insulin metformin oral hypoglycemic agents was started. All subjects received diet and physical exercise counselling. Two telephone contacts and a 3-month visit were performed to assess compliance. Body mass index, blood pressure measurements and the fasting biochemical parameters were recorded at baseline and after 6 months. Fasting plasma glucose, total cholesterol (TC), TG and HDL-C were measured by commercially available enzymatic kits and HbA1c by ion-exchange HPLC. LDL-C was calculated with Friedewald formula. Immunoturbidimetric assay was used for quantifying apolipoprotein A1 (apoA1). Written informed consent was obtained from each participant. The protocol was approved by the Ethics Committee of the Policlinico Umberto I Hospital and carried out in accordance with the Helsinki Declaration.
3.
Statistical analysis
For all variables changes after the intervention were calculated as the difference between 6 months and baseline values. Paired sample t-test was used for pre-post comparisons. A stepwise linear regression model was used to identify
predictors of HDL-C and apoA1 changes. TC change predicted HDL changes, while HDL-C change and smoking status predicted apoA1 changes. Linear regression analysis was used to assess the relation between HbA1c and HDL-C and HbA1c and apoA1 changes. The analysis was repeated after stratifying the cohort in two groups according to HDL-C levels at baseline: the ‘‘low HDL’’ subgroup (HDL-C
