Family History of T2D May Increase MACE Risk in Those With T1D

Patients with type 1 diabetes (T1D) and a family history of type 2 diabetes (T2D) had more diabetes complications than those without a family history of T2D, according to results of a cohort study carried out in Taiwan. Findings were published in JAMA Network Open.

“T1D and T2D differ in pathophysiologic characteristics and risk factors for cardiovascular disease,” authors explained. “The major adverse cardiovascular events (MACEs) seen in T2D are associated with insulin resistance, whereas those in T1D are associated with the presence of renal disease,” they said.

Because T1D and T2D have different mechanisms, it may be possible both diseases could develop in certain individuals, researchers hypothesized. In addition, the potential coexistence of spontaneous insulin deficiency and inherited insulin resistance could serve as a risk factor for cardiovascular disease, thus leading to an increased risk of MACEs.

To better elucidate the association between a positive family history of presumed T2D and the microvascular and macrovascular complications of T1D, authors assessed data from the Taiwan National Health Insurance Research Database (NHIRD).

The NHIRD contains demographic and clinical information of those enrolled dating back to 1995, and the NHI coverage rate was greater than 99.9% of the Taiwan population in 2005. “In the present study, familial transmission was defined as the function of the difference in normal variance of the threshold from the mean liability between individuals with affected relatives and the healthy population,” researchers wrote.

Of the individuals included in the analysis, 11,237 had a diagnosis of T1D and had a mean (SD) age of 22.7 (14.4) years; 54% were female. Data recorded between March 1995 and December 2017 were used to create HRs. In 2017, 1302 individuals had T1D and at least 1 first-degree relative with T2D.

Overall, the crude prevalence of T1D was 0.04%, with a female to male ratio of 1.22:1, authors explained. Furthermore, “the adjusted HRs in individuals who had a first-degree relative with T2D were 2.61 (95% CI, 1.32-5.16) for MACEs at an age at diagnosis of less than 20 years.”

Specifically, the incidence of hypertension and hyperlipidemia was significantly higher in this population. “Adjusted HRs were 1.44 (95% CI, 1.27-1.64) for diabetic neuropathy, 1.28 (95% CI, 1.12-1.47) for retinopathy, and 1.24 (95% CI, 1.06-1.47) for neuropathy at all ages of diagnosis,” they said.

Results indicate that those with T1D and a family history of T2D may have more complications and thus could require closer management. Shared environmental factors in the family could play a role in the increased risk. However, the family incidence of T2D “does not account for the associations between the genetic and environmental factors of insulin resistance,” and further studies are warranted to clarify the association between insulin resistance and MACEs among those with T1D.

The relatively small sample size of those with T1D in the Taiwanese population marks a limitation to the study, and researchers were unable to include information on family history of T1D, cardiovascular disease, or kidney disease.

“Having T1D as well as a family history of T2D was associated with increases in individual risks of hypertension, hyperlipidemia, microvascular complications, and MACEs,” they concluded. “An increased focus on this patient population in the prevention of these diabetes complications is warranted in further clinical investigations.”

Reference

Lin C, Lo F, Huang Y, et al. Evaluation of disease complications among adults with type 1 diabetes and a family history of type 2 diabetes in Taiwan. JAMA Netw Open. Published online December 14, 2021. doi:10.1001/jamanetworkopen.2021.38775