What is the relationship between multimorbidity, all-cause mortality and glycaemic outcomes in people with type 2 diabetes? A systematic review

Problem

Type 2 diabetes (T2D) is a major health priority, with a heavy burden of complications and mortality and cost to the community. Most people with diabetes live with multimorbidity (MM) (the co-occurrence of two or more chronic conditions) yet the relationship between MM and mortality and measures of blood glucose (glycaemia) in T2D is unclear. The aim of this systematic review is to examine the association between MM condition count and all-cause mortality and glycaemic outcomes in people with T2D.

Approach

The search strategy centred on: T2D, MM, comorbidity, mortality and glycaemia. We searched: MEDLINE, EMBASE, CINAHL Complete, The Cochrane Library, and SCOPUS. We included English language papers and quantitative empirical studies, with no restrictions on publication date. Two reviewers independently carried out abstract and full-text screening, data extraction, and quality appraisal using a modified Newcastle-Ottawa quality assessment scale. All disagreements were adjudicated by a third reviewer.

Findings

4882 papers were identified; 41 met inclusion criteria. 24 studies had glycaemia as an outcome, 16 studies had all-cause mortality as an outcome and one study included both. Only 11 studies had primary objectives of exploring the relationship between MM and our outcomes of interest, however, all included studies provided data about the association between MM and mortality or glycaemia. 28 studies were longitudinal cohort studies and the remaining 13 studies were cross-sectional studies. The number of participants ranged from 96 to 892,223. All included studies were conducted in high-income countries or upper-middle-income countries according to the UN country classifications. The included studies were of a reasonable quality based on the assessment scale, however an aspect of quality that was most poorly demonstrated was the representativeness of the study participants, where study cohorts were not always truly representative of people with T2D in the community.

15/17 studies showed a statistically significant association between increasing MM and increased mortality. 10/14 studies showed no associations between MM and HbA1c, while 4 found higher levels of MM were associated with higher HbA1c. An increase in MM was significantly associated with hypoglycaemia in 9/10 studies. The one study that looked at fasting glucose showed no association between MM and fasting glucose. No studies explored the association of MM with glycaemic variability.

Consequences

Our systematic review demonstrates that MM in T2D is associated with increased mortality and hypoglycaemia but the evidence of effects on other measures of glycaemic control is mixed. The current approach to management for T2D that is focused on a single condition with glycaemia as a key target seems inappropriate. Our findings highlight the need for clinical guidelines to support a holistic approach to the complex care needs of those with T2D and MM, accounting for the various conditions that people with T2D may be living with.