Parents play a critical role in the management of their children’s diabetes, and how they approach disease control can have long-lasting consequences.9 We hypothesized that parental type 1 diabetes may influence the metabolic control in offspring with the same condition, potentially affecting the risk of late complications. In the present study, we show that individuals with parental diabetes indeed are at an increased risk of renal failure and death. Pointing in the same direction, we also observed slightly higher HbA1c in young adulthood among those with parental diabetes compared with those with sporadic diabetes.

Few studies have previously investigated metabolic control or the risk of long-term complications, including nephropathy and death, in parental versus sporadic type 1 diabetes. In a 2007 nested case-control study by Monti et al, individuals with type 1 diabetes onset before 30 years of age were followed for 15 years. The study did not find significant effects of parental type 1 diabetes on the risk of developing diabetes-associated complications. However, parental type 2 diabetes was a significant risk factor for nephropathy (OR 1.9, 95% CI 1.2 to 1.9).26 This study had a smaller sample size compared with ours, and the presence of type 2 diabetes in the parent at the diagnosis of the index child was unclear. A retrospective comparative analysis by Lebenthal et al found significantly higher mean HbA1c in familial type 1 diabetes, but the occurrence of microvascular complications was similar in both familial and sporadic groups.27 Compared with the present study, the mean follow-up was shorter (11.2±8.7 years). Similarly, a retrospective chart review by Reddy et al from 2013, which included 27 patients, reported a trend toward higher HbA1c levels in familial type 1 diabetes, though the difference was not statistically significant between groups.28 Finally, a recent study by Karges et al compared HbA1c levels in familial and sporadic type 1 diabetes 10 years after onset, finding no significant differences.29 Consistent with prior studies, our findings suggest that metabolic control tends to be poorer in individuals with parental diabetes. However, most previous studies lacked a large, nationally representative sample, rigorous exposure and outcomes definitions, or sufficient follow-up time to detect severe but relatively uncommon complications.

The underlying causes of these elevated risks remain unclear. They may be due to social factors, genetic factors, or a combination of both. Social factors could include treatment strategies passed from parent to child, with parents potentially adhering to outdated diabetes management techniques. Children may also have experienced frightening acute or even late complications in the affected parent, which could affect their own disease management. Given the genetic basis of the condition, genetic predisposition to complications is another plausible explanation, though not necessarily modifiable by glycemic control. Genetic research on diabetic nephropathy, an archetypical long-term complication, has yet to fully delineate relevant genes, how they are inherited, and to what extent the increased risk is carried between generations.13 14 Further studies are needed to replicate the present findings and investigate the mechanisms underlying the observed risks. Nevertheless, implications from this study to health professionals suggest that tailored care of patients with parental type 1 diabetes, including enhanced education and support, is crucial.

Previous studies have shown that individuals with type 1 diabetes are at excessive risk of premature death.7 In the present cohort, individuals were young to middle-aged with a mean age of 33 years and a maximum age of 58 years at the end of the study. In this age span, Swedish men, irrespective of diabetes status, have 60% higher mortality compared with women.30 This, we believe, explains our finding of higher mortality in men compared with women, regardless of parental type 1 diabetes status.7

When adding parental diabetes, the risk of premature death in women increased by 79% compared with women with sporadic type 1 diabetes. However, the additional mortality risk due to parental diabetes was not seen in men. The reason for this sex difference is unclear, but one could be that parental diabetes conveys risks associated with cardiovascular or other factors that women are more sensitive to.31 Further analysis of this would require sufficient details on causes of death, which we at present lack due to few cases.

In our cohort, mortality risk was higher in individuals with diabetes onset age 10–15 compared with onset age 0–4 years. Other studies have seen vulnerability to complications when diagnosed in this age group,32 33 and our study confirms that diabetes onset during the pubertal years seems to be a disadvantage.

A strength of our study is the precise definition of type 1 diabetes and the nationwide collection of cases, with all diagnoses made in pediatric clinics according to national guidelines before the age of 15. This minimizes the risk of diagnostic misclassification. Data on parental diabetes were collected firsthand, and at the same time, as the child was diagnosed, reducing the likelihood of bias. The national registers used in the study are extensive and well validated.16 17 Another strength is the long follow-up period, with an average of 21.5 years for renal failure and 24 years for mortality.

However, our study has some limitations. Despite a follow-up of more than 20 years, the cohort is still relatively young, with the oldest individuals nearing 60 years of age, meaning that some clinically important complications have yet to become prevalent enough to allow in-depth analysis. Additionally, we categorized parents with type 2 diabetes (1.5%) in the group not having type 1 diabetes. This could underestimate the risk of death or renal failure, as type 2 diabetes incidence increases with age, and separating this group would not fully capture the associated risks. At the time of type 1 diabetes diagnosis, 2.8% had a mother with type 1 diabetes, and 5.7% had a father with the condition. However, we lack information on the child’s upbringing and whether both, one, or neither parent was actively involved in disease management, which limits our ability to analyze family influence on long-term complications. Finally, we have yet insufficient data to be able to explain the additional mortality risk of parental diabetes in women compared with men.

Interpreting HbA1c in young adulthood is another challenge, especially regarding missing data. Different individuals report HbA1c at different times, potentially introducing bias, as those individuals with poor metabolic control may avoid reporting their HbA1c levels or attending clinical visits. In the present study, we analyzed all HbA1c values between the ages of 20 and 30, calculating the mean over time. HbA1c may not yet be fully stabilized at this age, and while the differences were statistically significant, they were small and of limited clinical or public health relevance. Nevertheless, the results align with the more pronounced risks of renal disease and premature death.

Another limitation in our study is the diagnosis of nephropathy, based on the national patient register, which may include causes of renal failure unrelated to diabetes. However, our sensitivity analysis showed similar HRs when comparing the entire group to those diagnosed with nephropathy 15 or more years after their diagnosis of type 1 diabetes. Both the parental and sporadic groups have diabetes, and our findings indicate that, regardless of cause, the risk of nephropathy is higher in the parental group. Using a narrower definition, such as diabetes nephropathy, could introduce misclassification bias. Given the long latency between diabetes onset and renal failure development, we assume that nephropathy in a patient with type 1 diabetes is a late complication attributable to the primary condition. Finally, we lack information on potential confounders and effect modifiers such as smoking, body mass index, and blood pressure, which are associated with nephropathy and premature death.34–36 At present, we assume that the distribution of these factors is independent of parental diabetes status. However, the inclusion of these factors in future studies could modify the risk patterns.

In conclusion, our study demonstrates that children with parental type 1 diabetes have an increased risk of renal failure and premature death, possibly mediated by suboptimal glycemic control. We recommend that this patient group receive individualized care with increased recognition, with a focus on enhanced education, support, and recognition from healthcare providers.