Excessive weight gain due to intensive type 1 therapy can lead to increased cardiovascular risk factors.
According to the Epidemiology of Diabetes Interventions and Complications (EDIC) study, intensive use of diabetes therapy that achieves near-normal glucose control helps reduce long term macrovascular complications in patients with type 1 diabetes compared with conventional therapy. However, patients receiving intensive therapy had greater weight gain leading to obesity than the conventional therapy group. This excessive weight gain has worsened cardiac risk factors compared with participants who did not have weight gain. This study definitely raises concerns that excessive weight gain due to intensive diabetes therapy might abrogate the benefits of the long-term macrovascular complication management. The overall goal of this study was to examine the association between changes in body mass index (BMI) and subsequent cardiovascular events with intensive diabetes therapy. The hypothesis of this study was that cardiovascular event rates would be higher in participants who gained excessive weight than participants who did not with intensive therapy.
Participants were randomly assigned to receive either intensive therapy or conventional therapy. The goal of intensive therapy was to maintain glycemic levels as close to the nondiabetes range and the goal of conventional therapy was to have freedom from symptoms of hypoglycemia and hyperglycemia. A total of 1,213 participants were included in this analysis and participants <18 years of age were excluded from enrollment. The primary outcome of this study was the time it takes to the first of any of the cardiovascular events, including nonfatal myocardial infraction (MI), stroke, death, silent MI, angina confirmed by ischemic changes with exercise, congestive heart failure with paroxysmal nocturnal dyspnea, orthopnea, or market limitation of physical activity caused by heart disease, or revascularization with angioplasty, and/or coronary artery bypass. Major adverse cardiovascular events (MACE) included nonfatal MI or stroke or CVD-related death.
Results of this study found that mostly female and slightly older participants experienced weight gain in intensive therapy group. Participants in the excess weight gain group had worse levels of cardiac risk factors, including higher systolic and diastolic blood pressure, higher LDL and non-HDL cholesterol, higher triglycerides, and lower HDL cholesterol levels than participants with minimal weight gain. It was also found that participants with excessive weight gain had larger waist circumference and higher HbA1c levels even after taking large doses of insulin. This indicates insulin resistance in that patient population. Moreover, at years 10 and 15 of the follow-up period, it was found that the excessive weight gain group used medications to treat high blood pressure and cholesterol at a higher frequency than the minimal weight gain group. Non-significant results were found in the frequency of use of aspirin and postmenopausal hormonal replacement therapy between the excessive weight gain group and the minimal weight gain group.
Although it was found that intensive therapy in patients with type 1 diabetes can worsen obesity-related cardiovascular risks, rates of cardiovascular events and MACE during the first 13 years were not significantly different from the participants in the minimal weight gain group. This may be due to the use of blood pressure and cholesterol-lowering medications by the excessive weight gain group.
After 14 years of follow up, it was found that there was a divergence of cardiovascular risk factor, frequency of aspirin, cholesterol-lowering and blood-pressure–lowering medication usage between the two weight gain groups. These findings are primarily due to more frequent revascularization procedures performed in the excessive weight gain group and additional nutritional counseling provided by dietitians to participants who were rapidly gaining weight.
This study had several limitations, including the fact that there was failure in the intensive therapy group to maintain target glucose control during the study. This limits the ability to determine the beneficial effects of persistent near normal glucose control despite how much weight was gained and its effect on cardiovascular events in patients with type 1 diabetes. Despite the findings mentioned above, more longer term follow-up studies need to be performed to determine trends of intensive treatment of type 1 diabetes and how it is associated with higher rates of macrovascular disease and mortality.
- Participants receiving intensive therapy for type 1 diabetes management who had excess weight gain showed higher cardiac risk factors.
- The excessive weight gain group used significantly more medications to treat high blood pressure and high cholesterol than the minimal weight gain group.
- Longer follow-up studies need to be performed to determine whether intensive therapy in type 1 diabetes is beneficial or not.
Purnell J, Braffett B, Zinman B et al. Impact of Excessive Weight Gain on Cardiovascular Outcomes in Type 1 Diabetes: Results From the Diabetes Control and Complications Trial/ Epidemiology of Diabetes Interventions and Complications Study. Diabetes Care. 2017; 40:1756-1762.
Vidhi Patel, Pharm. D. Candidate 2018, LECOM School of Pharmacy