Focus on Risk Factors Instead of AIC for Type 1 Diabetes

Despite extensive glycemic control, macrovascular complications remain significant in type 1 diabetes, indicating other factors like HDL dysfunction and hypertension may be to blame.

A recent article published in the Journal of Diabetes and its Complications showed that those with type 1 diabetes and hypertension are at an increased risk of macrovascular disease. This study observed that the addition of comorbidities such as hypertriglyceridemia, low HDL, or obesity increased this risk exponentially.

It is documented that 2.2 million deaths were the result of diabetes related cardiovascular risk. According to previous studies, even when patients with type 1 diabetes present with a less atherogenic lipid profile, they are still at a significantly higher risk of complications compared to their counterparts who do not have diabetes. Recent data indicates that HDL may impact glucose metabolism; this is because HDL promotes insulin secretion and modifies glucose uptake.

It is known that HDL levels are inversely related to cardiovascular risk. In a perfect world, normal HDL has numerous antiatherogenic properties, but research shows these properties are compromised in some patients with diabetes due to oxidative modification and other factors. More research is needed to understand this mechanism, but HDL dysfunction seems present in a subset of patients with diabetes. Numerous studies have suggested that HDL in this population has a reduced ability to suppress inflammation. Once we understand this mechanism in vivo, targeted therapies will significantly reduce macrovascular complications.

To reduce micro and macrovascular complications, guidelines have placed an emphasis on intensive glycemic control. Even with strict adherence to glycemic guidelines, risk of complications remains high. This data suggests that other factors play a larger role than previously thought in macrovascular risk.

This study evaluated medical records of 920 patients with type 1 diabetes from a clinical database in London. Researchers then established risk factors based on comorbidities such as hypertension, obesity, hypertriglyceridemia, or low HDL. Hypertension was defined as blood pressure greater than 130/85 mmHg, obesity as a BMI greater than 30 kg/m2, hypertriglyceridemia as a triglyceride level of 1.7 mmol/L or higher, and low HDL was considered < 1.03 mmol/L. Cohort participant risk factor breakdown was as follows: 74% hypertension, 17% obesity, 16% hypertriglyceridemia, and 11% low HDL. It was also documented that 39% of participants had retinopathy, 17% had nephropathy, and 10% had neuropathy.

Results show the odds of developing macrovascular disease, OR = 2.82; 95% CI, 1.05-7.56, are significantly higher in patients with type 1 who have hypertension. Additionally, low HDL also increases the chance of macrovascular disease, OR = 2.71; 95% CI, 1.44-5.1. The more risk factors a patient has, the more likely they are to develop complications. Patients who presented with all the discussed risk factors were 5.7 times more likely to have retinopathy, 43.7 times more likely to have nephropathy, 13.9 times more likely to have neuropathy, and 11.9 times more likely to develop macrovascular disease.

Future studies should investigate the mechanisms of HDL dysfunction in patients with diabetes to reduce the risk of micro and macrovascular complications. Remarkably, glycemic levels, determined from patient A1C, did not have any association with complications. This study indicates a lack of association between A1C level and complications. Instead, the data indicates a greater focus is needed on the management of hypertension, obesity, hypertriglyceridemia, and low HDL to reduce complications.

Practice Pearls:

• Providers should place more emphasis on treating risk factors to reduce diabetic complications.
• This study found no correlation between A1C level and complication risk.
• Research is needed to understand HDL dysfunction in patients with diabetes, and how this relates to micro and macrovascular risk.
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References

S, Bhattarai. “Hypertension, Low HDL Amplify Macrovascular Risk in Type 1 Diabetes.” Healio, www.healio.com/endocrinology/diabetes/news/online/{047011fc-2de5-4871-9951-d02b935aba39}/hypertension-low-hdl-amplify-macrovascular-risk-in-type-1-diabetes?M_BT=2469436429117.

Femlak, Marek, et al. “The Role and Function of HDL in Patients with Diabetes Mellitus and the Related Cardiovascular Risk.” Lipids in Health and Disease, vol. 16, no. 1, 2017, doi:10.1186/s12944-017-0594-3.

Kassey James, Pharm.D.Candidate, LECOM School of Pharmacy