In Youth-Onset Diabetes, Type 2 Is Deadlier Than Type 1

Miriam E. Tucker

July 19, 2013

Type 2 diabetes is associated with twice the death rate of type 1 diabetes among people diagnosed in adolescence or early adulthood, and this is primarily driven by cardiovascular mortality, a new retrospective 20-year follow-up study has found.

The findings were published online July 11 in Diabetes Care by Maria I. Constantino, data manager at the Diabetes Centre, Royal Prince Alfred Hospital, Sydney, Australia, and colleagues.

The findings were surprising, Constantino, a diabetes educator, told Medscape Medical News. "Type 1 diabetes is generally considered a more severe type of diabetes, mainly because of the need for insulin and risk of hypoglycemia. In fact, a diagnosis of type 2 diabetes rather than type 1 diabetes in a young person is often met with relief by both clinicians and patients alike."

"However, our results...highlight that young people with type 2 diabetes have double the risk of dying compared with type 1 diabetes and after a much shorter duration. We hope this work will alert practicing clinicians to the risks for this group of young people," she said in an email.

Philip S. Zeitler, MD, told Medscape Medical News that the results are not unexpected; rather, they are in line with those of other trials, including the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, which he chaired. In TODAY and in studies of Native American and Canadian First Nation populations, complications and comorbidities in youth-onset type 2 patients were found to be worse than for youths with type 1 and also appear to be more aggressive than in adults with type 2 diabetes.

"These findings fit well in line with expectations, though this is the largest report that I am aware of to date," Dr. Zeitler, professor and head of endocrinology in the department of pediatrics, University of Colorado School of Medicine, Aurora, told Medscape Medical News.

Type 2 Patients Fare Worse on Many Measures

The study population was derived from the Royal Prince Alfred Hospital Diabetes Database and focused on individuals diagnosed with diabetes between the ages of 15 and 30 years. Records were matched with the Australian National Death Index to establish mortality outcomes for all subjects until June 2011. Clinical and mortality outcomes in 354 patients with type 2 diabetes (mean age at diagnosis, 25.6 years) were compared primarily with 470 patients with type 1 diabetes with a similar age of onset (mean age at diagnosis, 22.0 years) to minimize the confounding effect of age on outcome; disease duration was 11.6 vs 14.7 years, respectively (P = .001).

The type 1 patients were primarily Anglo Celtic in background (77.8%), while the type 2 group was more ethnically diverse, with only 28.1% of Anglo Celtic origin.

Within 5 years of diagnosis, most of the type 2 patients were treated with diet and/or oral agents and only 7% were being treated with insulin alone. The type 2 group had a significantly higher mean body mass index (BMI), 32.2 vs 25.6 kg/m2 (< .0001).

HbA1c levels were the same, 8.1%, for both groups.

At the last clinic visit, the type 2 group had higher serum triglycerides (1.9 vs 1.0 mmol/L), lower HDL cholesterol (1.2 vs 1.5 mmol/L) and higher diastolic blood pressure readings (78 vs 74 mm Hg) (< .0001 for all), compared with those for type 1 diabetes patients. Use of antihypertensives (49.3% vs 24.6%) and statins (38.3% vs 21.0%) was also significantly greater among the type 2 patients (< .0001 for both).

And despite their shorter diabetes duration, the type 2 group had significantly higher albumin-creatinine ratios (2.2 vs 0.7 mg/mmol, < .0001) and a higher prevalence of albuminuria (47.4% vs 15.3%, < .0001) compared with those with type 1 diabetes. However, there was no significant difference in renal function as assessed by estimated glomerular filtration rate.

The type 2 diabetes cohort also had less favorable neuropathy scores than the type 1 diabetes cohort (higher Bio-Thesiometer Z scores, < .0001 for all indices); this is "a novel finding," the researchers say. They hypothesize that as dyslipidemia has been implicated in the pathogenesis of diabetic neuropathy, it is possible that the less favorable lipid profiles in the type 2 diabetes patients are contributory. There was no increased risk for retinopathy in the type 2 diabetes patients, however.

The prevalence of macrovascular disease complications was markedly increased in the type 2 group, including ischemic heart disease (12.6% vs 2.5%, < .0001), stroke (4.3% vs 0.7%, = .002) and the composite end point of any macrovascular disease (14.4% vs 5.7%, < .0001).

Risk for Early Death Twice as Likely in Type 2 as in Type 1

After a similar follow-up period of more than 20 years in both groups, there was a significantly greater fatality rate for the type 2 diabetes patients compared with the type 1 group (11% vs 6.8%, = .03). Deaths among the type 2 patients occurred significantly sooner in the course of diabetes, at an average 26.9 vs 36.5 years (P = .01). Deaths in both groups occurred at relatively young ages, at a mean of52.9 years for type 2 and 57.4 years for type 1.

The hazard ratio for death in the type 2 vs the type 1 group was 2.0, the authors report.

The excess risk for death in the type 2 group persisted after analyses by ethnic group and when compared with a larger group of 870 unmatched type 1 diabetes patients, thereby accounting for the potential for increased duration of undiagnosed type 2 diabetes.

Cardiovascular causes accounted for 50% of the type 2 deaths, compared with just 30.3% among the type 1 patients.

"This analysis of systematically collected data provides a unique opportunity to examine the future burden of a disease that, until recently, has been a relatively rare phenomenon," say Ms. Constantino and colleagues. "With the results of the present study, we now have confirmatory evidence of more concrete outcomes of clinically apparent vascular disease and death."

Redouble Efforts to Prevent Type 2 Diabetes in Young

Given that type 1 diabetes carries an approximately 4-fold higher mortality risk by age compared with the general population, "the present findings give a disquieting perspective on the long-term mortality risk of type 2 diabetes mellitus and a sobering glimpse of the future for patients," Constantino and colleagues add.

Dr. Zeitler noted that insulin resistance is likely the main driving force in the excess morbidity and mortality seen among the type 2 population.

He told Medscape Medical News, "Youth-onset type 2 diabetes is an aggressive disorder associated with significant health risks and must be taken seriously, with attention to treatment of associated abnormalities."

Prevention of type 2 diabetes should be a goal as well, Constantino told Medscape Medical News. "'If today we are going to protect against tomorrow's outcomes as predicted by this study, there is an urgent need for efforts to be redoubled toward diabetes prevention targeted to youth."

The authors and Dr. Zeitler have reported no relevant financial relationships.

Diabetes Care . Published online July 11, 2013. Abstract

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