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An Overview of Double Diabetes (DD)

Oct 8, 2019
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Nour Salhab, Pharm.D. Candidate, USF College of Pharmacy

What do we know today about patients who have double diabetes? 

Double diabetes or double disease (DD) is a way to define a disease that involves having type 1 diabetes (T1D) along with insulin resistance, a characteristic of type 2 diabetes (T2D). Clear criteria to define this group of patients is lacking. Existing criteria include family history, obesity/metabolic syndrome, and insulin resistance. There is also a lack of implementing alternative and targeted management strategies in these individuals. This review provided few updates regarding the best and most pragmatic measure to identify patients with DD, if there is a difference in the rate or severity of diabetes complications and the mechanisms involved, and the extent of difference in management strategies.

A genetic predisposition to type 1 diabetes exists. However, there is a large population of patients with type 1 diabetes that reported no genetic association with the disease. As we know, T2D is largely associated with a genetic predisposition. Those genetic factors play a role in pancreatic beta-cell function and insulin resistance/metabolic syndrome. Additionally, there are genes that are associated with increased fat mass and preferential visceral fat distribution leading to the risk of having T2D. A family history with T2D was found to be associated with higher BMI, insulin doses, HbA1c, triglycerides, LDL cholesterol, and apolipoprotein B in patients with T1D. There are conflicting data regarding linking family history of T2D with diabetes-related complications in patients with T1D. Having a family history of T2D does not appear to be a strong independent predictor of complications that are associated with diabetes in patients with T1D. 

As we know, continued subcutaneous injections of insulin can lead to peripheral resistance. Additionally, increased administration of insulin, as a result of resistance, can lead to weight gain resulting in increased complications. However, it’s been found that initial moderate weight gain in patients with T1D correlates with improved HbA1c and reduction in mortality. Nevertheless, having a BMI of ≥ 30 kg/m2 has been associated with an increased risk of mortality. Obesity might be a marker for DD. However, it might not be as accurate because it might miss a significant number of individuals with DD. 

Metabolic syndrome is one of the markers of DD. Some components of metabolic syndrome in patients with T1D were associated with increased cardiovascular and all-cause mortality. Additionally, it has been associated with an increased risk of micro- and macrovascular disease. However, metabolic syndrome has too many flaws to be a marker of DD because it has many definitions. Additionally, the effects of managing metabolic syndrome would not be apparent until the patient drops into the non-metabolic syndrome range; this can be challenging for patients and can cause them to be disengaged in their health maintenance. Metabolic syndrome can be used to identify individuals at risk but is not a useful marker because of its binary nature.

Insulin resistance can be associated with asymptomatic atherosclerosis and coronary artery disease. When having T1D on board, this risk increases. Insulin resistance can be measured by the estimated glucose disposal rate (eGDR). eGDR is a continuous variable that contains weight and blood pressure. The lower the eGDR the higher the risk of nephropathy, peripheral vascular disease, coronary artery disease, and death. Results from the Diabetes Control and Complications Trial show the superiority of eGDR over metabolic syndrome to define DD. eGDR of <8 was found to identify DD in patients with T1D. Regarding complications, the risk of vascular pathology should be considered because of the increased use of insulin, leading to hypoglycemia and glucose variations. Additionally, insulin resistance is associated with an inflammatory environment leading to endothelial dysfunction and atherosclerotic process, increased lipolysis, increased blood pressure due to decreased vasodilation efficiency, increased hyperinsulinemia, and a thrombotic environment.

In conclusion, there is a lack of reliable criteria to identify individuals with DD. Relying on genetics or presence of metabolic syndrome is inadequate. eGDR can be a credible measure of DD when used with HbA1c. Different effects of glycemic markers such as hypoglycemia and glucose variability still need to be studied. Future studies should include the assessment of using an insulin pump vs. daily injections of insulin and their effect on DD. Additionally, glycemic markers and vascular complications should be studied more extensively in DD along with preventative measures to protect against the risks with DD. A more intensive weight loss should be considered in patients with DD because of the burden of the disease. Future studies should incorporate long-term assessments to understand the effects of having a family history of T2D on complications in individuals with T1D. 

Practice Pearls:

  • Double disease / diabetes (DD) in individuals with type 1 diabetes still lacks clear criteria to define and manage.
  • DD should not be exclusively defined by obesity, metabolic syndrome, or family history of type 2 diabetes.
  • Estimated Glucose Disposal Rate (eGDR) can be used as one of the measures to detect DD in addition to monitoring responses to interventions.

Kietsiriroje, Noppadol, et al. “Double Diabetes: A Distinct HighRisk Group?” Diabetes, Obesity and Metabolism, 2019

Nour Salhab, Pharm.D. Candidate, USF College of Pharmacy