Young-onset Diabetes, Prediabetes and Early Glycaemic Recovery-Establishing their Link with All-cause and CVD Mortality

6 Oct, 20

Introduction

The increasing incidence of diabetes in young adults (age; 20-39 years) contributes largely to additional disease burden. Early-onset diabetes has been associated with similar or worse metabolic risk factors when compared with late-onset diabetes. Nevertheless, the impact of early onset diabetes, prediabetes and glycaemic recovery on cardiovascular disease (CVD) or mortality remains to be established. In case this association is established, early detection of these disorders may have a crucial role in diabetes management.

Aim

To determine the association of early-onset diabetes, prediabetes and early glycaemic recovery on 10 year all-cause mortality, CVD mortality and CVD incidence.

Study Population

Young adults without diabetes and CVD at baseline (aged; 20-39 years, n= 2,502,375)

Methods

Study Design

Retrospective, longitudinal cohort study based on the Korean National Health Insurance Service-National Health Information Database

Assessments

Glycaemic status of the study participants was measured twice, first in 2002–2003 and again in 2004–2005. Based on baseline fasting blood glucose (FBG) levels, the study participants were categorized as follows:
Normal fasting glucose (NFG) group: Baseline FBG <100.0 mg/dl (n=2,101,599)
Impaired fasting glucose (IFG) group: Baseline FBG 100.0-125.9 mg/dl (n=365,663)
Diabetic fasting glucose (DFG) group: Baseline FBG ≥126.0 mg/dl (n=35,113)
Participants with NFG at first visit but IFG or DFG at second visit were considered as having newly diagnosed diabetes
Participants with IFG/DFG at first visit and NFG at second visit were considered as exhibiting early glycaemic recovery.

Outcomes

Primary Outcomes

All-cause mortality and CVD mortality

Secondary Outcome

Incidence of CVD, including acute myocardial infarction (AMI) and stroke

Follow-up

Mean follow-up period: 9.9 years (24,933,615 person years of follow-up)

Results

The incidence of all-cause and CVD mortality during follow-up was 21,076 (0.84%) and 1627 (0.07%), respectively.
Individuals with NFG at baseline, who were subsequently newly diagnosed with diabetes and prediabetes (IFG), had significantly increased risk of all-cause mortality [adjusted hazard ratio (aHR); 1.60 and 1.13, respectively) and of CVD incidence (aHR 1.13 and 1.04, respectively) (Tables 1, 2).
On the other hand, in those individuals with DFG at baseline, early recovery to NFG and IFG was significantly associated with decreased all-cause mortality (HR 0.57 and 0.65, respectively) and CVD incidence (HR 0.70 and 0.78, respectively) (Tables 1, 2).

Table 1: Association between change in FBG and all-cause mortality and CVD mortality

Change from baseline in FBG	aHR (95% CI): All-cause mortality	aHR (95% CI): CVD Mortality
NFG →NFG	1.00 (ref)	1.00 (ref)
NFG→IFG	1.13 (1.09, 1.18)	1.05 (0.91, 1.21)
NFG→DFG	1.60(1.44, 1.78)	1.26 (0.86, 1.85)
IFG→NFG	0.96 (0.90, 1.03)	0.74 (0.59, 0.93)
IFG→IFG	1.00 (ref)	1.00 (ref)
IFG→DFG	1.35 (1.17, 1.56)	0.97 (0.61, 1.56)
DFG→NFG	0.57 (0.46, 0.70)	0.53 (0.27, 1.05)
DFG→IFG	0.65 (0.53, 0.81)	0.60 (0.30, 1.24)
DFG→DFG	1.00 (ref)	1.00 (ref)

aHR: Adjusted hazard ratio

95% CI: 95% confidence interval

The changes in FBG were associated with similar pattern of risk for all CVD outcomes (AMI and stroke). Thus, individuals with NFG at baseline who were subsequently diagnosed with diabetes and prediabetes had increased CVD risk vs. those in whom NFG persisted. Individuals with IFG at baseline who subsequently developed increased DFG range had increased CVD risk vs. those in whom IFG persisted. On the contrary, individuals with DFG and IFG at baseline who exhibited early glycaemic recovery had decreased risk of CVD risk (Table 2).

Table 2: Association between change in FBG and incident CVD

Change from baseline in FBG	aHR (95% CI): CVD	aHR (95% CI): AMI	aHR (95% CI): Stroke
NFG →NFG	1.00 (ref)	1.00 (ref)	1.00 (ref)
NFG→IFG	1.04 (1.01, 1.07)	1.00 (0.93, 1.08)	1.07 (1.02, 1.13)
NFG→DFG	1.13 (1.05, 1.23)	1.32 (1.08, 1.60)	1.11 (0.95, 1.30)
IFG→NFG	0.97 (0.92, 1.01)	0.88 (0.78, 0.99)	0.91 (0.83, 0.99)
IFG→IFG	1.00 (ref)	1.00 (ref)	1.00 (reference)
IFG→DFG	1.12 (1.01, 1.24)	1.24 (0.98, 1.57)	1.21 (1.01, 1.45)
DFG→NFG	0.70 (0.60, 0.81)	0.60 (0.42, 0.86)	0.58 (0.45, 0.77)
DFG→IFG	0.78 (0.66, 0.91)	0.87 (0.61–1.24)	0.81 (0.62, 1.06)
DFG→DFG	1.00 (ref)	1.00 (ref)	1.00 (ref)

aHR: Adjusted hazard ratio

95% CI: 95% confidence interval

As per a subgroup analysis, individuals who were males, aged ≥30 years, with body mass index (BMI) ≥23 kg/m², and those who were ever smokers had increased risk of all-cause mortality when FBG increased from NFG to IFG or DFG. These individuals had decreased risk of all-cause mortality when FBG decreased from DFG to NFG or IFG. The same association was true for CVD risk as well.

Conclusions

Young-onset diabetes or prediabetes was associated with an increased CVD risks and all-cause mortality during a long-term follow-up of 10 years.
The subsequent 10-year risk for CVD incidence and all-cause mortality could be reduced with recovery of hyperglycaemia.

Diabetologia. Aug 21, 2020 (Published Online); DOI: 10.1007/s00125-020-05252-y.