Multimorbidity, mortality, and HbA1c in type 2 diabetes: A cohort study with UK and Taiwanese cohorts

Abstract

Background

There is emerging interest in multimorbidity in type 2 diabetes (T2D), which can be either concordant (T2D related) or discordant (unrelated), as a way of understanding the burden of disease in T2D. Current diabetes guidelines acknowledge the complex nature of multimorbidity, the management of which should be based on the patient’s individual clinical needs and comorbidities. However, although associations between multimorbidity, glycated haemoglobin (HbA1c), and mortality in people with T2D have been studied to some extent, significant gaps remain, particularly regarding different patterns of multimorbidity, including concordant and discordant conditions. This study explores associations between multimorbidity (total condition counts/concordant/discordant/different combinations of conditions), baseline HbA1c, and all-cause mortality in T2D.

Methods and findings

We studied two longitudinal cohorts of people with T2D using the UK Biobank ( n = 20,569) and the Taiwan National Diabetes Care Management Program (NDCMP) ( n = 59,657). The number of conditions in addition to T2D was used to quantify total multimorbidity, concordant, and discordant counts, and the effects of different combinations of conditions were also studied. Outcomes of interest were baseline HbA1c and all-cause mortality. For the UK Biobank and Taiwan NDCMP, mean (SD) ages were 60.2 (6.8) years and 60.8 (11.3) years; 7,579 (36.8%) and 31,339 (52.5%) were female; body mass index (BMI) medians (IQR) were 30.8 (27.7, 34.8) kg/m ² and 25.6 (23.5, 28.7) kg/m ²; and 2,197 (10.8%) and 9,423 (15.8) were current smokers, respectively. Increasing total and discordant multimorbidity counts were associated with lower HbA1c and increased mortality in both datasets. In Taiwan NDCMP, for those with four or more additional conditions compared with T2D only, the mean difference (95% CI) in HbA1c was −0.82% (−0.88, −0.76) p < 0.001. In UK Biobank, hazard ratios (HRs) (95% CI) for all-cause mortality in people with T2D and one, two, three, and four or more additional conditions compared with those without comorbidity were 1.20 (0.91–1.56) p < 0.001, 1.75 (1.35–2.27) p < 0.001, 2.17 (1.67–2.81) p < 0.001, and 3.14 (2.43–4.03) p < 0.001, respectively. Both concordant/discordant conditions were significantly associated with mortality; however, HRs were largest for concordant conditions. Those with four or more concordant conditions had >5 times the mortality (5.83 [4.28–7.93] p <0.001). HRs for NDCMP were similar to those from UK Biobank for all multimorbidity counts. For those with two conditions in addition to T2D, cardiovascular diseases featured in 18 of the top 20 combinations most highly associated with mortality in UK Biobank and 12 of the top combinations in the Taiwan NDCMP. In UK Biobank, a combination of coronary heart disease and heart failure in addition to T2D had the largest effect size on mortality, with a HR (95% CI) of 4.37 (3.59–5.32) p < 0.001, whereas in the Taiwan NDCMP, a combination of painful conditions and alcohol problems had the largest effect size on mortality, with an HR (95% CI) of 4.02 (3.08–5.23) p < 0.001. One limitation to note is that we were unable to model for changes in multimorbidity during our study period.

Conclusions

Multimorbidity patterns associated with the highest mortality differed between UK Biobank (a population predominantly comprising people of European descent) and the Taiwan NDCMP, a predominantly ethnic Chinese population. Future research should explore the mechanisms underpinning the observed relationship between increasing multimorbidity count and reduced HbA1c alongside increased mortality in people with T2D and further examine the implications of different patterns of multimorbidity across different ethnic groups. Better understanding of these issues, especially effects of condition type, will enable more effective personalisation of care.

Abstract

Jason Chiang and colleagues reveal the relationship between multimorbidity, HbA1c and all-cause mortality in 2 large cohorts.

Author summary

Why was this study done?

• People with type 2 diabetes (T2D) commonly have other coexisting chronic medical conditions (‘multimorbidity’). These conditions can be either concordant (T2D related) or discordant (T2D unrelated).

• Multimorbidity is associated with higher mortality and hypoglycaemia; however, the effect of multimorbidity on glycaemia (measured by glycated haemoglobin [HbA1c]) is mixed.

• Significant knowledge gaps remain, particularly regarding the prevalence and impacts of different patterns of multimorbidity, including concordant and discordant conditions, and their associations with HbA1c and mortality.

What did the researchers do and find?

• We assessed the associations between different counts of multimorbidity, including concordant and discordant conditions, and HbA1c and the effects of different combinations of conditions on all-cause mortality in people with T2D.

• In two large community cohorts of people with T2D (UK Biobank and Taiwan National Diabetes Care Management Program [NDCMP]), we found that increasing multimorbidity is significantly associated with increased mortality and with lower HbA1c.

• The combinations of conditions with the greatest association with mortality differed between UK Biobank, a population predominantly comprising people of European descent, and the Taiwan NDCMP, a predominantly ethnic Chinese population.

What do these findings mean?

• To our knowledge, this is the first study to assess and compare the relationship between total, concordant, and discordant multimorbidity counts; HbA1c; and all-cause mortality in people with T2D or to look at the effects of such a range of combinations of comorbid conditions.

• Our findings suggest the need for further research to explore the effects of different combinations of conditions on outcomes in those with T2D across different ethnic groups.

• Our findings suggest that poor glycaemic control is unlikely to explain the increased mortality seen in those with increasing multimorbidity count.