Carotid Intima-Media Thickness in Patients With T1DM
Carotid Intima-Media Thickness in Patients With T1DM
Our study showed that in our sample, patients with type 1 diabetes had a higher IMT compared with the control subjects. Despite having type 1 diabetes for a relatively long time, our patients with type 1 diabetes had a lower IMT than expected, similar to the findings of another study. In our study, in patients with type 1 diabetes, having a family history of type 2 diabetes was associated with a 4.4% increase in carotid IMT and unlike the control group, women with type 1 diabetes had a IMT as high as men.
In the control group, the female gender was associated with a thinner IMT, but this association was not found in our patients with type 1 diabetes. A study that evaluated the distribution of IMT according to age in the general population showed that men had a higher IMT compared with women. These findings could reflect a loss of gender protection for CVD risk in women with type 1 diabetes as suggested by The Diabetes UK Cohort Study and another study. In fact, in patients with type 1 diabetes, women may have a higher increase in CVD risk compared with men. In a cohort of 23,000 patients with type 1 diabetes the CVD risk in women with diabetes was not only greater than that for women without diabetes but was also considerably higher than that for men without diabetes. Another study demonstrated that women had a higher arterial stiffness measured at the carotid and radial arteries compared to men. The EURODIAB PCS found that in patients with type 1 diabetes, the CVD risk may be increased approximately 9–29 times in women and 4–9 times in men compared to individuals without diabetes.
The higher IMT found in our patients with type 1 diabetes was not associated with current parameters of glycemic control. This findings are similar to the findings in the DCCT/EDIC study, in which carotid IMT was only associated with the HbA1c six years before the IMT measurement. This delayed effect suggests a glycemic memory that favors an early and intensive metabolic control.
Among all of the factors associated with IMT, age may be a major one and in our study it was associated with a higher IMT in both groups, which is in accordance with another study. In fact, age is the most important characteristic in IMT normality tables. Furthermore, our findings suggest that there was a higher impact of age in the IMT of patients with type 1 diabetes than in the IMT of the control subjects. This higher impact may be partly due to the duration of the disease. It is important to note that in one study, it was found that CVD was the main cause of death in patients with type 1 diabetes, primarily in those who had had diabetes for more than 20 years.
A family history of type 2 diabetes was an important factor that influenced the IMT in both groups. The DCCT/EDIC study found that patients with type 1 diabetes and family histoy of type 2 diabetes in the intensive treatment group had a greater increase in the carotid IMT in both EDIC year 1 and 6. It is important to emphasize that in the general population, a family history of type 2 diabetes was a major determinant of endothelial dysfunction and this was able to predict the progression of carotid IMT. Unfortunately, such an association was not evaluated in our study. However, one author failed to find any association between type 1 diabetes and endothelial dysfunction. In patients with Type 1 diabetes, a family history of type 2 diabetes is associated with a metabolic profile of insulin resistance, increased carotid IMT and increased CVD risk. One study showed that in non-obese patients with type 1 diabetes the insulin resistance was associated with a higher IMT. In our study the association of IMT with family history of type 2 diabetes may reflect the insulin resistance. Another study showed an increased prevalence of a family history of type 2 diabetes in patients with type 1 diabetes and a history of coronary artery disease compared with patients with type 1 diabetes without a history of coronary artery disease. Therefore, patients with type 1 diabetes and a family history of type 2 diabetes should be under an even more aggressive treatment in regards to not only glucose control but also other CVD risk factors such as blood pressure and lipid profile.
Another important CVD risk factor is the presence of renal dysfunction. The presence of renal dysfunction in type 1 diabetes patients is associated with a 10- fold increase in CVD risk compared with those patients with type 1 diabetes without renal dysfunction. In our study, the association of IMT with creatinine clearance in patients with type 1 diabetes may reflect the association of CVD risk and some renal dysfunction.
The DCCT/EDIC study demonstrated that in patients with type 1 diabetes the excess weight gain was associated with higher carotid IMT, independently of treatment group. In our study, the association of BMI with IMT in both patients with type 1 diabetes and in control group may reflect role of role of visceral adipose tissue on endothelial dysfunction and CVD risk as recently demonstrated.
The positive association of IMT and total cholesterol in patients with type 1 diabetes was an unexpected finding.
Carotid IMT is an established surrogate end point for CVD risk in the general population and has a strong correlation with CVD risk factors. However, there are no longitudinal studies in type 1 diabetes showing a causal relationship between a higher carotid IMT and cardiovascular events, as demonstrated in the DCCT/EDIC study. In this study, after 12 years of follow up, only 75 patients experienced cardiovascular events, and the authors could not demonstrate a causal effect between the increase in carotid IMT and CVD events. Despite the high CVD mortality in patients with type 1 diabetes, there is no specific method for CVD screening and no method to stratify CVD risk in these patients. Additionally, there is difficulty in identifying factors associated with impaired cardiac function and cardiac remodeling as suggested by the DCCT/EDIC study. In this study, there was an association between the mean glycated hemoglobin over the entire follow-up period and parameters of cardiac function and structures evaluated by cardiac magnetic resonance. However, this study failed to find any difference between previously intensive versus conventionally treated patients. In a review of CVD in type 1 diabetes the authors state that in the past 40 years, there was a 70% reduction in CVD mortality in type 1 diabetes presumably because of the progress in CVD risk management. However, CVD mortality may increase approximately 50% for each 1% increase in HbA1c between the ages of 45 and 64 years. The difficulty in identifying those patients with high CVD risk was illustrated by a recent case report of a 48- years-old woman with a long duration of type 1 diabetes but without evidence of microvascular complication, traditional CVD risk factors and a family history of diabetes. She had a rapidly progressive severe coronary atherosclerosis and experienced a myocardial infarction by the age of 42.
The primary strength of our study resides in the fact that all IMT data were measured using a semi-automated edge-detection software and confirmed by a second independent echocardiographist. Both were blinded to the subject condition, and there was a high agreement between them. This high agreement convince us that this is a reliable and reproducible procedure that can improve the detection of patients with type 1 diabetes and increased CVD risk. Some limitations must be addressed. We studied the patients with type 1 diabetes in a single center with only internal validation. Furthermore, considering that our study was a cross-sectional one, the inference of cause-effect was not possible.
Discussion
Our study showed that in our sample, patients with type 1 diabetes had a higher IMT compared with the control subjects. Despite having type 1 diabetes for a relatively long time, our patients with type 1 diabetes had a lower IMT than expected, similar to the findings of another study. In our study, in patients with type 1 diabetes, having a family history of type 2 diabetes was associated with a 4.4% increase in carotid IMT and unlike the control group, women with type 1 diabetes had a IMT as high as men.
In the control group, the female gender was associated with a thinner IMT, but this association was not found in our patients with type 1 diabetes. A study that evaluated the distribution of IMT according to age in the general population showed that men had a higher IMT compared with women. These findings could reflect a loss of gender protection for CVD risk in women with type 1 diabetes as suggested by The Diabetes UK Cohort Study and another study. In fact, in patients with type 1 diabetes, women may have a higher increase in CVD risk compared with men. In a cohort of 23,000 patients with type 1 diabetes the CVD risk in women with diabetes was not only greater than that for women without diabetes but was also considerably higher than that for men without diabetes. Another study demonstrated that women had a higher arterial stiffness measured at the carotid and radial arteries compared to men. The EURODIAB PCS found that in patients with type 1 diabetes, the CVD risk may be increased approximately 9–29 times in women and 4–9 times in men compared to individuals without diabetes.
The higher IMT found in our patients with type 1 diabetes was not associated with current parameters of glycemic control. This findings are similar to the findings in the DCCT/EDIC study, in which carotid IMT was only associated with the HbA1c six years before the IMT measurement. This delayed effect suggests a glycemic memory that favors an early and intensive metabolic control.
Among all of the factors associated with IMT, age may be a major one and in our study it was associated with a higher IMT in both groups, which is in accordance with another study. In fact, age is the most important characteristic in IMT normality tables. Furthermore, our findings suggest that there was a higher impact of age in the IMT of patients with type 1 diabetes than in the IMT of the control subjects. This higher impact may be partly due to the duration of the disease. It is important to note that in one study, it was found that CVD was the main cause of death in patients with type 1 diabetes, primarily in those who had had diabetes for more than 20 years.
A family history of type 2 diabetes was an important factor that influenced the IMT in both groups. The DCCT/EDIC study found that patients with type 1 diabetes and family histoy of type 2 diabetes in the intensive treatment group had a greater increase in the carotid IMT in both EDIC year 1 and 6. It is important to emphasize that in the general population, a family history of type 2 diabetes was a major determinant of endothelial dysfunction and this was able to predict the progression of carotid IMT. Unfortunately, such an association was not evaluated in our study. However, one author failed to find any association between type 1 diabetes and endothelial dysfunction. In patients with Type 1 diabetes, a family history of type 2 diabetes is associated with a metabolic profile of insulin resistance, increased carotid IMT and increased CVD risk. One study showed that in non-obese patients with type 1 diabetes the insulin resistance was associated with a higher IMT. In our study the association of IMT with family history of type 2 diabetes may reflect the insulin resistance. Another study showed an increased prevalence of a family history of type 2 diabetes in patients with type 1 diabetes and a history of coronary artery disease compared with patients with type 1 diabetes without a history of coronary artery disease. Therefore, patients with type 1 diabetes and a family history of type 2 diabetes should be under an even more aggressive treatment in regards to not only glucose control but also other CVD risk factors such as blood pressure and lipid profile.
Another important CVD risk factor is the presence of renal dysfunction. The presence of renal dysfunction in type 1 diabetes patients is associated with a 10- fold increase in CVD risk compared with those patients with type 1 diabetes without renal dysfunction. In our study, the association of IMT with creatinine clearance in patients with type 1 diabetes may reflect the association of CVD risk and some renal dysfunction.
The DCCT/EDIC study demonstrated that in patients with type 1 diabetes the excess weight gain was associated with higher carotid IMT, independently of treatment group. In our study, the association of BMI with IMT in both patients with type 1 diabetes and in control group may reflect role of role of visceral adipose tissue on endothelial dysfunction and CVD risk as recently demonstrated.
The positive association of IMT and total cholesterol in patients with type 1 diabetes was an unexpected finding.
Carotid IMT is an established surrogate end point for CVD risk in the general population and has a strong correlation with CVD risk factors. However, there are no longitudinal studies in type 1 diabetes showing a causal relationship between a higher carotid IMT and cardiovascular events, as demonstrated in the DCCT/EDIC study. In this study, after 12 years of follow up, only 75 patients experienced cardiovascular events, and the authors could not demonstrate a causal effect between the increase in carotid IMT and CVD events. Despite the high CVD mortality in patients with type 1 diabetes, there is no specific method for CVD screening and no method to stratify CVD risk in these patients. Additionally, there is difficulty in identifying factors associated with impaired cardiac function and cardiac remodeling as suggested by the DCCT/EDIC study. In this study, there was an association between the mean glycated hemoglobin over the entire follow-up period and parameters of cardiac function and structures evaluated by cardiac magnetic resonance. However, this study failed to find any difference between previously intensive versus conventionally treated patients. In a review of CVD in type 1 diabetes the authors state that in the past 40 years, there was a 70% reduction in CVD mortality in type 1 diabetes presumably because of the progress in CVD risk management. However, CVD mortality may increase approximately 50% for each 1% increase in HbA1c between the ages of 45 and 64 years. The difficulty in identifying those patients with high CVD risk was illustrated by a recent case report of a 48- years-old woman with a long duration of type 1 diabetes but without evidence of microvascular complication, traditional CVD risk factors and a family history of diabetes. She had a rapidly progressive severe coronary atherosclerosis and experienced a myocardial infarction by the age of 42.
The primary strength of our study resides in the fact that all IMT data were measured using a semi-automated edge-detection software and confirmed by a second independent echocardiographist. Both were blinded to the subject condition, and there was a high agreement between them. This high agreement convince us that this is a reliable and reproducible procedure that can improve the detection of patients with type 1 diabetes and increased CVD risk. Some limitations must be addressed. We studied the patients with type 1 diabetes in a single center with only internal validation. Furthermore, considering that our study was a cross-sectional one, the inference of cause-effect was not possible.
