posted on 2019-09-09, 15:04authored byM Kosiborod, MB Gomes, A Nicolucci, S Pocock, W Rathmann, MV Shestakova, H Watada, I Shimomura, H Chen, J Cid-Ruzafa, P Fenici, N Hammar, F Surmont, F Tang, K Khunti, DISCOVER investigators
BACKGROUND: The global prevalence of type 2 diabetes-related complications is not well described. We assessed prevalence of vascular complications at baseline in DISCOVER (NCT02322762; NCT02226822), a global, prospective, observational study program of 15,992 patients with type 2 diabetes initiating second-line therapy, conducted across 38 countries. METHODS: Patients were recruited from primary and specialist healthcare settings. Data were collected using a standardized case report form. Prevalence estimates of microvascular and macrovascular complications at baseline were assessed overall and by country and region, and were standardized for age and sex. Modified Poisson regression was used to assess factors associated with the prevalence of complications. RESULTS: The median duration of type 2 diabetes was 4.1 years (interquartile range [IQR]: 1.9-7.9 years), and the median glycated hemoglobin (HbA1c) level was 8.0% (IQR: 7.2-9.1%). The crude prevalences of microvascular and macrovascular complications were 18.8% and 12.7%, respectively. Common microvascular complications were peripheral neuropathy (7.7%), chronic kidney disease (5.0%), and albuminuria (4.3%). Common macrovascular complications were coronary artery disease (8.2%), heart failure (3.3%) and stroke (2.2%). The age- and sex-standardized prevalence of microvascular complications was 17.9% (95% confidence interval [CI] 17.3-18.6%), ranging from 14.2% in the Americas to 20.4% in Europe. The age- and sex-standardized prevalence of macrovascular complications was 9.2% (95% CI 8.7-9.7%), ranging from 4.1% in South-East Asia to 18.8% in Europe. Factors positively associated with vascular complications included age (per 10-year increment), male sex, diabetes duration (per 1-year increment), and history of hypoglycemia, with rate ratios (95% CIs) for microvascular complications of 1.14 (1.09-1.19), 1.30 (1.20-1.42), 1.03 (1.02-1.04) and 1.45 (1.25-1.69), respectively, and for macrovascular complications of 1.41 (1.34-1.48), 1.29 (1.16-1.45), 1.02 (1.01-1.02) and 1.24 (1.04-1.48), respectively. HbA1c levels (per 1.0% increment) were positively associated with microvascular (1.05 [1.02-1.08]) but not macrovascular (1.00 [0.97-1.04]) complications. CONCLUSIONS: The global burden of microvascular and macrovascular complications is substantial in these patients with type 2 diabetes who are relatively early in the disease process. These findings highlight an opportunity for aggressive early risk factor modification, particularly in regions with a high prevalence of complications. Trial registration ClinicalTrials.gov; NCT02322762. Registered 23 December 2014. https://clinicaltrials.gov/ct2/show/NCT02322762 . ClinicalTrials.gov; NCT02226822. Registered 27 August 2014. https://clinicaltrials.gov/ct2/show/NCT02226822.
Funding
The DISCOVER study program is funded by AstraZeneca. DISCOVER is a noninterventional study, and no drugs are supplied or funded.
Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Additional fle 1: Table S1. Inclusion and exclusion criteria. DDP-4
dipeptidyl peptidase-4. a
≥20 years in Japan. b
In Japan, only patients using
an oral monotherapy as frst-line treatment were included. Table S2.
Comparisons between patients for whom either HbA1c or total cholesterol
data are unreported, and those with complete HbA1c and total cholesterol
data. ACEi angiotensin-converting-enzyme inhibitor, ARB angiotensin
receptor blocker, ASA acetylsalicylic acid, BMI body mass index, HbA1c
glycated hemoglobin, SBP systolic blood pressure, SD standard deviation,
TC total cholesterol. a
Patients with reported data for all variables included
in the hierarchical logistic model. b
P values calculated for continuous
variables using Student’s t-test, and for categorical variables using the
χ2
or Fisher’s exact test, as appropriate. c
Minor hypoglycemic event in
the previous month or major hypoglycemic event in the previous year. Table S3. Number and proportion of patients with microvascular and
macrovascular complications according to country (unadjusted). Percent‑
ages were calculated for all patients with data available; unreported data
were excluded. UAE United Arab Emirates. Figure S1. Sensitivity analysis
including only patients with complete data to assess factors associated
with (A) microvascular and (B) macrovascular complications. a
RRs adjusted
for all variables in the fgure with the addition of SBP, total, cholesterol
levels and comedication use, using a modifed Poisson model with clusterbased sandwich variance estimator as described in “Methods”. RRs for the
associations between complication prevalence and SBP, total cholesterol
levels, and comedication use are not reported due to reverse-causality. b
Minor hypoglycemic event in the previous month or major hypogly‑
cemic event in the previous year. BMI body mass index, CI confdence
interval, HbA1c glycated hemoglobin, RR rate ratio. Figure S2. Sensitivity
analysis with additional variables for site specialty and patient-reported
ethnicity to assess factors associated with (A) microvascular and (B) mac‑
rovascular complications. a
RRs adjusted for all variables in the fgure with
the addition of SBP, total, cholesterol levels and comedication use, using a
modifed Poisson model with cluster-based sandwich variance estimator
as described in “Methods”. RRs for the associations between complication
prevalence and SBP, total cholesterol levels, and comedication use are
not reported due to reverse-causality. b
Minor hypoglycemic event in the
previous month or major hypoglycemic event in the previous year. BMI
body mass index, CI confdence interval, HbA1c glycated hemoglobin, RR
rate ratio.