Our data suggest that obesity predicts the presence as well the progression of CAC, and overweight was associated with the presence of atherosclerosis. Excess weight is not considered a typical feature of T1D, but we observed that it is frequent among patients with T1D (56.7% were above normal weight).
Several studies have shown that the aggregation of cardiovascular risk factors in T1D subjects predicts the development of micro- and macrovascular complications,2,3,15
and these studies showed that higher BMI is associated with more clustering of risk factors, but they did not evaluate if the presence of excess weight is an independent factor of the presence of MA in association with vascular complications. In this study, we observed higher prevalence of MA among the subjects with overweight and obesity in adults with T1D. Recently, in a study that evaluated 5,440 participants of the National Health and Nutrition Examination Surveys 1999–2004, the authors reported that among U.S. adults there is a high prevalence of clustering of MA among normal weight individuals and a high prevalence of overweight and obese individuals who are metabolically healthy,10
reinforcing the role of obesity as heterogeneous and nonuniform in different individuals. However, we have shown obese individuals who appear to be metabolically healthy are nevertheless at increased risk for subclinical atherosclerosis.
Of note is that we observed the same prevalence of overweight and obesity in our sample as in the general U.S. adult population of the same age (20–39 years) (56.7% of excess weight in T1D vs. 57.5% in general population).16
When the general population is stratified by different ages, it is observed that the presence of MA among normal weight individuals is associated with older age and that the prevalence of the metabolically healthy phenotype among obese individuals decreased with increasing age.10
T1D subjects with normal weight and MA were older than normal weight T1D subjects without MA, in concordance with the results of the general population.10
As expected, the insulin dose was higher in excess weight T1D subjects with MA compared with individuals with an excess of weight and without MA. The association between insulin resistance and excess weight in T1D and its effects on the metabolic profile of these patients have been documented.1
Although higher doses of insulin have been used in obese patients, they had no better glycemic control than the patients with lower doses. Worse insulin resistance (lower eGDR) was associated with the presence of obesity.
There is some evidence that obesity is not associated with an increased risk of future cardiovascular events among individuals without metabolic syndrome, but only in those participants with MA.9,17,18
In T1D, that appears to be different. Although we did not evaluate cardiovascular events, we observed that overweight and obesity were associated with the presence of atherosclerosis, assessed by CAC, and obesity was associated with progression of CAC. These finding were independent of the presence of MA or other factors, including AER, a known hard-risk factor associated with CVD in T1D. Overweight was associated with CAC progression, but it was not independent of the presence of the MA. These differences between the effect of overweight and obesity on the progression of atherosclerosis could be explained by data from the Diabetes Control and Complications Trial, which showed that weight gain had no homogeneous effect in all intensively treated group: patients with excessive weight gain (fourth quartile of weight gain) had an adverse lipid profile, higher blood pressure levels, greater insulin requirements, and increased waist–hip ratio, suggesting increased insulin resistance.1
Our data show the effect of obesity on the atherosclerosis process in a prospective analysis. Although overweight was associated with the presence of CAC, it may have a limited burden on the evolution of atherosclerosis and may not be independent of MA. Furthermore, subjects with higher weight gain in the intensive treatment group during the Diabetes Control and Complications Trial study had increased CRP,19
a marker associated with early atherosclerosis lesions.20
Higher BMI is associated with elevated levels of CRP;21
in our sample CRP levels were higher in the entire group of obese, independently of the presence of MA.
Our data agree with the findings from the Pittsburgh Epidemiology of Diabetes Complications study cohort, which showed that at baseline BMI (as a continuous variable) was associated with the progression of CAC in T1D subjects.22
We evaluated excess weight as a categorical variable and believe that this way it allows a better visualization of the impact of obesity on the outcome and makes the interpretation of the data easier for clinical practice. However, even when BMI was evaluated as a continuous variable, it still had the same association with the outcomes (data not shown).
A possible limitation of our study is the very small group with obesity but without MA (n=26), which did not allow for observing the burden of obesity on CAC progression because we had just 15 obese individuals with CAC progression.
In summary, T1D patients with excess weight and obesity had higher odds for presence of subclinical atherosclerosis, but only obesity was strongly associated with the progression of CAC, independent of the presence of MA. Although obesity is known to increase CVD risk through inducing metabolic abnormalities such as dyslipidemia, hypertension, and inflammation, it is also a strong predictor of subclinical atherosclerosis progression in adults with T1D independent of these factors. One possible explanation is the insulin resistance associated with excess weight. Weight control should be pursued as one of the target treatments in T1D subjects, and further studies with reduction or prevention of gain of weight should be conducted to examine reduction/prevention of macrovascular complication in T1D individuals.