Risk associations of long-term HbA1c variability and obesity on cancer events and cancer-specific death in 15,286 patients with diabetes - A prospective cohort study

Dandan Mao; Eric S H Lau; Hongjiang Wu; Aimin Yang; Mai Shi; Baoqi Fan; Claudia H T Tam; Elaine Chow; Alice P S Kong; Ronald C W Ma; Andrea Luk; Juliana C N Chan

doi:10.1016/j.lanwpc.2021.100315

Risk associations of long-term HbA1c variability and obesity on cancer events and cancer-specific death in 15,286 patients with diabetes - A prospective cohort study

Lancet Reg Health West Pac. 2021 Nov 12:18:100315. doi: 10.1016/j.lanwpc.2021.100315. eCollection 2022 Jan.

Authors

Dandan Mao¹, Eric S H Lau¹, Hongjiang Wu¹, Aimin Yang^{1

2}, Mai Shi¹, Baoqi Fan¹, Claudia H T Tam¹, Elaine Chow^{1

2

3}, Alice P S Kong^{1

2

4}, Ronald C W Ma^{1

2

4}, Andrea Luk^{1

2

3

4}, Juliana C N Chan^{1

2

4}

Affiliations

¹ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR China.
² Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong.
³ Phase 1 Clinical Trial Centre, The Chinese University of Hong Kong.
⁴ Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China.

Abstract

Background: Obesity, cancer and diabetes frequently coexist. The association of glycaemic variability (GV) and obesity with cancer events had not been explored in diabetes.

Methods: In the prospective Hong Kong Diabetes Register cohort (1995-2019), we used cox proportional hazards models to examine the risk associations of GV with all-site cancer (primary outcome) and cause-specific death (secondary outcome). We also explored the joint association of obesity and GV with these outcomes and site-specific cancer. We expressed GV using HbA1c variability score (HVS) defined as percentage of HbA1c values varying by 0.5% compared with values in preceding visit.

Findings: We included 15,286 patients (type 2 diabetes: n=15,054, type 1 diabetes: n=232) with ≥10 years of diabetes and ≥3 years of observation (51.7% men, age (mean±SD): 61.04±10.73 years, HbA1c: 7.54±1.63%, body mass index [BMI]: 25.65±3.92 kg/m², all-site cancer events: n=928, cancer death events: n=404). There were non-linear relationships between HVS and outcomes but there was linearity within the high and low HVS groups stratified by the median (IQR) value of HVS (42.31 [27.27, 56.28]). In the high HVS group, the adjusted hazard ratios (aHR) of each SD of HVS was 1.15 (95% CI: 1.04, 1.26) for all-site cancer (n=874). The respective aHRs for breast (n=77), liver (n=117) and colorectal (n=184) cancer were 1.44 (1.07, 1.94), 1.37 (1.08, 1.74), and 1.09 (0.90, 1.32). In the high GV group, the respective aHRs were 1.21 (1.06, 1.39), 1.27 (1.15, 1.40), and 1.15 (1.09, 1.22) for cancer, vascular, and noncancer nonvascular death. When stratified by obesity (BMI ≥25 kg/m²), the high HVS & obese group had the highest aHRs of 1.42 (1.16, 1.73), 2.44 (1.24, 4.82), and 2.63 (1.45, 4.74) respectively for all-site, breast, and liver cancer versus the low GV & non-obese group. The respective aHRs were 1.45 (1.07, 1.96), 1.47 (1.12, 1.93), and 1.35 (1.16, 1.57) for cancer, vascular, and noncancer nonvascular death.

Interpretation: Obesity and high GV were associated with increased risk of all-site, breast, liver cancer, and cancer-specific death in T2D.

Funding: The Chinese University of Hong Kong Diabetes Research Fund.

Keywords: ALT, alanine aminotransferase; BMI, body mass index; BP, blood pressure; CI, confidence interval; CVD, cardiovascular disease; EMR, electronic medical record; GV, glycaemic variability; HA, Hospital Authority; HDLC, high-density lipoprotein cholesterol; HKDR, Hong Kong Diabetes Register; HR, hazard ratio; HVS, HbA1c variability score; IQR, inter‐quartile range; LDLC, low-density lipoprotein cholesterol; LLD, lipid lowering drug; MD, median; Mn, mean; OGLDs, oral glucose lowering drugs; RAS, renin angiotensin system; SD, standard deviation; SDIM, SD independent of mean; T2D, type 2 diabetes; TC, total cholesterol; TG, triglyceride; aHR, adjusted hazard ratio; cancer and all cause death; diabetes; glycaemic variability; obesity.