A new systematic review has found that girls with type 1 diabetes have it much tougher than boys. The work, which reviewed many previous studies with data from tens of thousands of patients, showed that young girls with the condition tend to have poorer metabolic control and experience more diabetic complications. The differences are stunningly comprehensive, and will hopefully spur the development of targeted treatment efforts to erase sex-based inequities.
The study was published on February 14 in Diabetologia. Previously, the lead author shared the results in a presentation at the 2022 European Association for the Study of Diabetes (EASD) Annual Meeting in Stockholm, Sweden.
Multiple studies of type 1 diabetes and life expectancy have found that women experience premature death earlier than men. And a 2015 review referenced in the EASD presentation found that women with T1D had a 40 percent higher risk of all-cause mortality, most notably a nearly doubled risk of fatal cardiovascular disease.
But we didn’t know if the difference in metabolic health reached all the way back to childhood. Silvia de Vries of Amsterdam University Medical Centers partnered with colleagues to find out. They combed through the medical literature, identifying 90 studies with data that could help illuminate the answer.
The results are jaw-dropping:
Girls with T1D had higher average blood sugar (6.4 mmol/mol, about 0.5 percent on the A1C scale more familiar to Americans), both at diagnosis and later, during treatment.
Girls were more likely to experience diabetic ketoacidosis (DKA), both during and after diagnosis. DKA incidents were also more severe, on average.
Girls used more insulin.
Girls experienced a higher rate of vascular complications, such as nephropathy.
Most studies showed that girls with T1D had a higher body mass index (BMI) than boys.
Most studies showed that adolescent girls were more likely to have unhealthy cholesterol levels.
Girls experienced a higher rate of co-morbidities, including thyroid disease and celiac, two autoimmune disorders common in people with T1D.
Girls reported a lower quality of life, and greater rates of diabetes distress.
The analysis also showed that boys were more likely to experience hypoglycemia than girls, a likely consequence of their lower overall blood sugars.
What is the possible explanation for these disparities? Is it genetic, behavioral, or cultural? Do girls receive lesser care?
Unfortunately, the new study was not designed to answer the question of why girls have it so much tougher — its intent is merely to highlight the existence of these disparities, and assess their scope. Future study will be required to explain the differences. “We strongly believe that identification of these differences is a very important first step and to also be aware of risks in young females,” de Vries stated.
In her presentation at the EASD conference, De Vries offered some light speculation as to the reasons behind these inequities:
Girls and boys exhibit differences “in body composition and fat distribution,” which might lead diabetes to behave differently in each sex. The fact that girls have higher glycemic levels and higher rates of DKA at diagnosis suggests that these metabolic differences might be present from the very first days of the disease, before puberty in many cases.
Parents and caregivers may be slower to seek treatment for girls than for boys. There could be something about the physiology of boys that just makes the early symptoms of acute hyperglycemia more noticeable. Or the same symptoms might be interpreted differently by adults — a “treatment bias” that might lead to parents or doctors (or both) giving less effective care to girls.
Physiological differences are magnified during puberty, a period of intense hormonal changes that bring significant glucose management difficulties to adolescents. But we do know that girls experience more insulin resistance during puberty, perhaps because testosterone is associated with improved insulin sensitivity. Puberty, of course, also inaugurates the menstrual cycle, a monthly blood sugar management challenge.
Behavioral and cultural differences could play a role in diverging outcomes. Girls are far more likely than boys to experience mental health issues during puberty, which is likely to affect glycemic management. For one example, girls are overwhelmingly more likely to suffer from “diabulimia,” an eating disorder exclusive to type 1 diabetes. (Transgender or non-binary children with diabetes may face an even greater struggle with some of the same issues.)
“We also think that psychological causes are very important,” de Vries explained. “Boys and girls differ in disease-related attitudes and behaviors. We already know, for example, that quality of life scores are lower in girls without diabetes, as well. But this may very well interfere with treatment of type 1 diabetes.”
The bottom line is that type 1 diabetes is simply more difficult and more dangerous in girls than it is in boys, likely for a variety of reasons. De Vries urged authorities and clinicians to do everything they could to improve outcomes for girls:
“Our findings of troubling inequities call for urgent and targeted efforts, such as increased surveillance for sex disparities in daily clinical practice and cardiovascular risk prevention, sex-appropriate diabetic ketoacidosis awareness campaigns and screening of quality of life tailored to adolescent girls.”
“Improving disease-related coping mechanisms and quality of life during this vulnerable period may be an important strategy to improve glycemic control and reduce the risk of complications … All young people with type 1 diabetes should be offered care that is tailored to their individual needs so they are able to manage their condition effectively. With the right care and support in place, there is no reason why both girls and boys with type 1 diabetes can’t live equally long and healthy lives.”