The risk of developing nonfatal cardiovascular disease (CVD) is almost twice as high in patients who develop type 2 diabetes before the age of 40 compared with those who develop later-onset disease, although the risk is attenuated when adjusted for disease duration, a large cross-sectional survey from China indicates.

The study was published online December 15 in The Lancet Diabetes Endocrinology.

"The age of diagnosis for type 2 diabetes is falling globally, predominantly driven by the rising obesity rates," Soon Song, MD, Northern General Hospital, Sheffield, UK, who wrote an accompanying editorial, told Medscape Medical News in an email.

"Given the onset of type 2 diabetes at a young age, it is not surprising that CV complications occur at an earlier stage due to [the patients'] ... long exposure to an adverse atherogenic environment," she added.

"So once type 2 diabetes is diagnosed, adverse CV risk factors ... must be intensively treated to reduce CV complication risk." This includes lipid-lowering therapy and ensuring good glucose control, she noted.

Study Used China's Largest Diabetes Database

Under lead author Xiaoxu Huo, PhD, Tianjin Medical University, China, investigators used China's largest diabetes database to compare the risk of developing nonfatal CVD in early vs late-onset type 2 diabetes among residents of mainland China. The database is derived from the China National HbA1c Surveillance System (CNHSS).

A total of 630 hospitals participated in the study, including 12 primary care hospitals, 132 secondary care hospitals, and 486 tertiary care hospitals.

Overall, 222,773 patients were included in the analysis. The mean age of the cohort was 58.3 years and the mean duration of diabetes was 5.6 years. The mean age of patients who had early onset diabetes was 34 years compared with 55 years for those who developed diabetes later in life.

After adjustment for age and sex, early onset type 2 diabetes was associated with a 1.91 times greater risk of nonfatal CVD events (coronary heart disease and stroke) compared with late-onset disease.

 

The risk was attenuated at an odds ratio (OR) of 1.13 when adjusted for duration of disease, the authors add, but additional adjustment for other factors only slightly attenuated effect sizes.

"Patients with early onset type 2 diabetes had a significantly higher prevalence of nonfatal CVD at each age group at all levels of hospital," Dr Huo and colleagues observe.

And the authors point out that women with early onset type 2 diabetes were more susceptible to CV complications than men, an observation that has been made in other studies of non-Chinese populations.

Prevalence of Nonfatal CVD Events by Age Group in Early vs Late Onset Patients (all P < .001)

Age, years CHD, early onset, % CHD, late onset, % Stroke, early onset, % Stroke, late onset, % CVD, early onset, % CVD, late-onset, %
40–44 4.6 2.6 1.5 0.6 5.8 2.9
55–59 21.3 9.0 9.4 2.6 26.7 10.9
60–64 29.6 11.3 13.2 4.2 35.7 14.2
65–69 28.4 13.3 10.1 4.9 37.6 16.5
≥ 70 42.7 22.1 14.6 9.4 50.0 27.5

Investigators further tested the findings in a validation study — the 3B study —a cross-sectional, multicenter study of 25,454 outpatients with established type 2 diabetes recruited from at least 100 hospitals.

"Of 25,454 patients with type 2 diabetes, 5760 (23%) had nonfatal CVD," the authors note.

In total, 11% of the validation cohort was diagnosed with early onset diabetes, and among this group the risk of nonfatal CVD was 34% higher compared with late-onset diabetes. Again, however, after adjusting for diabetes duration the risk of nonfatal CVD was also attenuated in the validation cohort (OR, 0.94).

Implications for Clinical Practice: Prevention of CVD, Early Treatment

Overall, poorer glycemic control and higher burden of atherogenic risk factors were reported in the early onset cohort compared with the late-onset cohort.

 

And the association of CV burden with early onset disease was consistent irrespective of the hospital setting, confirming that this adverse lifetime risk also applies to patients with early onset diabetes who receive care in the community, a lower-risk group than patients treated in secondary and tertiary hospitals, observes Dr Song.

Intriguingly, the association between early onset type 2 diabetes and risk of CVD was mainly driven by patients with a body mass index (BMI) of less than 24 kg/m2 in this study population, but as Dr Song explained, BMI does not reliably measure central obesity and it is the latter that is an important risk factor for type 2 diabetes. Additionally, overweight and obesity are defined at lower BMIs for Asians than whites.

In her editorial, Dr Song says these new results have several implications for clinical practice.

The findings "reinforce the importance of primary prevention of CVD in early onset type 2 diabetes. This patient population is a clinical priority in view of their substantially increased mortality after the first vascular event and the inadequate use of cardioprotective drugs in this population, especially in women."

 

Therefore, once type 2 diabetes has been diagnosed, aggressive risk-factor modification, notably lipid-lowering therapy, is mandatory.

The results also suggest that it would be more appropriate to assess lifetime rather than short-term (10-year) risk for future CV events in young patients with type 2 diabetes because "the life expectancies of these individuals will probably exceed the duration" of short-term risk assessment tools, she notes.

As she told Medscape Medical News, the best way to gauge lifetime risk in young patients with type 2 diabetes is to count how many adverse CV risk factors they have. "A very high proportion — about 80% — of young people with type 2 diabetes have at least two CV risk factors," she explained.

 

And in view of the increased lifetime CVD risk of type 2 diabetes across all care settings, awareness should be raised among primary care doctors in countries where such physicians manage the majority of patients with early onset type 2 diabetes, such as the United Kingdom, she stressed.

Finally, the service provision for the care of young people with diabetes, which has traditionally focused on type 1 diabetes, should place more emphasis on type 2 diabetes.

"This point is pertinent, with recent evidence showing higher risk of CV death in patients with early onset type 2 diabetes compared with those with type 1 diabetes with similar age of onset," she concludes.

 

The CNHSS study was funded by Novo Nordisk China and the 3B study by Merck Sharp & Dohme China. Dr Song had no competing interests to declare.

Lancet Diabetes Endocrinol. Published online December 15, 2015. 

ABSTRACT

http://www.thelancet.com/pdfs/journals/landia/PIIS2213-8587%2815%2900508-2.pdf

Background

The age of onset of type 2 diabetes is decreasing. Because non-Chinese patients with early-onset type 2 diabetes (defined here as diagnosis at <40 years) have increased risk of vascular complications, we investigated effects of early-onset versus late-onset type 2 diabetes on risk of non-fatal cardiovascular diseases in China.

Methods

We did a cross-sectional survey using data from the China National HbA1c Surveillance System (CNHSS), including 222 773 Chinese patients with type 2 diabetes in 630 hospitals from 106 cities in 30 provinces of China in 2012. We documented demographic information and clinical profiles. Non-fatal cardiovascular disease was defined as non-fatal coronary heart disease or non-fatal stroke. Prevalence of non-fatal cardiovascular diseases was standardised to the Chinese population in 2011. We did logistic regression analysis to obtain odds ratios (ORs) for the risk of cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Because the CNHSS did not contain patients on diet or lifestyle treatment alone, and did not capture information on smoking or lipid or antihypertensive treatment, we validated our findings in another dataset from a cross-sectional, multicentre observational study (the 3B study) of outpatients with type 2 diabetes to confirm that exclusion of patients with diet treatment only and non-adjustment for lipid-lowering and antihypertensive drugs did not introduce major biases in the main analysis.

Findings

Of 222 773 patients recruited from April 1, 2012, to June 30, 2012, 24 316 (11%) had non-fatal cardiovascular disease. Patients with early-onset diabetes had a higher age-adjusted prevalence of non-fatal cardiovascular disease than did patients with late-onset diabetes (11·1% vs 4·9%; p<0·0001). After adjustment for age and sex, patients with early-onset type 2 diabetes had higher risk of non-fatal cardiovascular disease than did those with late-onset type 2 diabetes (OR 1·91, 95% CI 1·81–2·02). Adjustment for duration of diabetes greatly attenuated the effect size for risk of non-fatal cardiovascular disease (1·13, 1·06–1·20). Results of the validation study showed that exclusion of patients with diet only and non-adjustment for lipid-lowering and antihypertensive drugs resulted in marginal changes in ORs for risk of non-fatal cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Early-onset type 2 diabetes remained associated with increased risk of cardiovascular disease, attributable to longer duration of diabetes.

Interpretation

Chinese patients with early-onset type 2 diabetes are at increased risk of non-fatal cardiovascular disease, mostly attributable to longer duration of diabetes.

EDITORIAL

http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2815%2900390-3/abstract

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