Youth-Onset Type 2 Diabetes Ups Risk of Serious Mental Illness

People who develop type 2 diabetes before the age of 40 are at increased risk for hospitalizations compared with those who develop it later in life, with a notably increased risk for mental illness-related hospitalizations, new research indicates.

Findings from a large population-based study in Hong Kong were published online January 14 in Annals of Internal Medicine by Calvin Ke, MD, of The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, and colleagues.

By age 60, those who had developed type 2 diabetes at ages 10 to 39 years had twice the rate of hospitalizations for all causes compared with those with a diabetes onset that occurred at age 40 years or older.

And among hospitalizations prior to age 40 in the younger-onset group, more than a third were for mental illness-related reasons.

"The burden of hospitalization in patients with [young-onset type 2 diabetes] showed a striking evolution across the lifespan. We found a previously unknown burden of serious mental illness before age 40 years, and understanding its causes is imperative to improving mental healthcare in young adults," Ke and colleagues write.

And, they say, the overall increased hospitalization rates for all causes, including cardiovascular events, renal complications, diabetes itself, and infections, "reveal the disproportionate effects of increased disease duration and glycemic burden in [young-onset type 2 diabetes] and challenge the perception that youth protects against hospitalization."

Because at least some of the excess risk is because of modifiable risk factors, the results point to "the importance of early intervention to reduce the adverse effects of cumulative exposure to cardiometabolic risk factors," Ke and coauthors say.

Recognizing Unique Aspects of Young-Onset Type 2 Diabetes

Neither the mental illness nor the overall hospitalization findings surprise Philip S. Zeitler, MD, PhD, head of endocrinology, Department of Pediatrics, University of Colorado School of Medicine, and chair, Department of Endocrinology, Children's Hospital Colorado, Aurora.

"Obviously, our system in the United States is different and individuals are less likely to have insurance coverage for mental health admissions, so I wouldn't be surprised if our stats in the United States are a bit different."

"But the concept of increased mental health problems in early onset type 2 diabetes is not surprising at all. We see this in our kids — not necessarily hospitalizations, but chronic mental health problems like depression, anxiety, and suicidal ideation or attempts. This is a complicated relationship and there is a well-known, probably bidirectional, relationship between depression and anxiety and type 2 diabetes in adults."

Regarding the hospitalizations for other causes, Zeitler, who was coprincipal investigator of the TODAY study of treatments for youth with type 2 diabetes, noted, "the population is heavily burdened with chronic medical problems and complications of their diabetes and obesity and of the environment in which they live."

"I suspect that, other than cultural issues related to Hong Kong versus the United States, the findings wouldn't be much different. There may be some differences in specific rates of various causes of hospitalization, as there are ethnic risks for various things, but the overall picture would be similar."

Zeitler advises that clinicians who care for adults with early onset type 2 diabetes "recognize that it is different from type 2 diabetes arising in older individuals."

"It is more aggressive, with more complications and often complicated by mental illness, stress, stressful environments, etcetera."

"Previously Unknown Burden of Serious Mental Illness Before 40"

The prospective cohort study included 422,908 adults aged 20 to 75 years during 2002-2014 from a population-based registry and 20,886 individuals with type 2 diabetes during 2000-2014 from a nationwide diabetes registry.

Among those with diabetes, 17% (3566) were diagnosed between ages 10 and 39 years ("young onset"), 63% were diagnosed at ages 40 to 59 years, and 20% at age 60 or older.

At the time of assessment, the three groups had mean ages of 45, 58, and 70 years, respectively.

The young-onset group had the highest hospitalization rates by attained age. For example, the number of bed-days per 1000 patient-years at age 45-49 among those diagnosed prior to age 40 was 1245.6, compared with 953.8 for those diagnosed after age 40.

And the overall hospitalization rate for the young-onset group "far exceed[ed]" the age-specific rates for the general population in 2006 and 2012, Ke and colleagues say.

Among those younger than 40 at the time of assessment, 37% of bed-days were because of mental illness, primarily psychotic (55%) and mood disorders (31%).

Although some antipsychotics can lead to weight gain and type 2 diabetes, very few of the participants (1%) had received any atypical antipsychotic prescriptions prior to their diabetes diagnoses, and excluding those who had received them didn't change the values significantly, the authors note.

Risks From Early Onset Type 2 Diabetes Continue Throughout Life

After age 60 years, cardiovascular disease was the most common cause of hospitalization among patients regardless of age of diabetes onset (26% of bed-days for young-onset and 20% for older onset).

But for the young-onset group, rates of hospitalizations for all causes by age 60 years were double those of older-onset patients, with a significant rate ratio of 1.8 after multivariate analysis, and the risk was greater for younger attained ages (P for interaction < .001).

Compared to those with older-onset type 2 diabetes, the younger-onset group had a 6.7 times greater rate of hospitalizations for renal causes, 3.7 times greater for diabetes-specific reasons, and 2.1 times greater for cardiovascular causes. All were significantly higher.

And although the younger-onset group had worse modifiable risk factors such as HbA_1c, LDL-cholesterol, and body mass index, even after adjustment for those, the results remained significant for hospitalizations for all causes except for infection-related reasons.

Based on the observed hospitalization rates, the authors calculated that a patient diagnosed with type 2 diabetes prior to age 40 would spend nearly 100 days in the hospital by his or her 75th birthday, compared with 59 and 29 days, respectively, for those with type 2 diabetes onset at ages 50 and 65 years.

But intensification of treatment of modifiable risk factors in the young-onset group would decrease that risk to about 65 days, they say.

The findings, Ke and colleagues write, represent "an urgent call for policymakers, payers, patients, and healthcare providers to take action and address this unmet need."

"An integrated system is needed to identify patients with [young-onset type 2 diabetes] for comprehensive assessment of physical and psychological health, followed by optimization of cardiometabolic risk factors and individualized care to improve quality of life and reduce the effects of long-term complications on patients, their families, employers, and the healthcare system."

The study was funded by the Asia Diabetes Foundation. Ke is supported by the Canadian Institutes of Health Research Canada Graduate Scholarship and Michael Smith Foreign Study Supplements, University of Toronto Clinician Investigator Program, Canadian Society of Endocrinology and Metabolism, Dr Fernand Labrie Fellowship Research Grant, and Royal College of Physicians and Surgeons of Canada Detweiler Travelling Fellowship. Zeitler is a consultant for Daiichi-Sankyo, Merck, Boehringer-Ingelheim, and Eli Lilly.

Ann Intern Med. Published online January 14, 2019. Abstract

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