Twelve studies investigated the association of multimorbidity and diabetes outcomes (Table 12). Heikkala et al., reported that multimorbidity was associated with achievement of glycaemic and LDL treatment targets. However, this was a cross-sectional study which did not reflect a cause-and effect relationship and the findings were just an indication that clinicians focused on patients with multimorbidity to achieve targets more than on patients with diabetes as a single disease ^[1][64]. Umeh et al., have shown that multimorbidity is associated with poor self-rated health in a proportionate manner and this association was unconnected to glycaemic control ^[2][65]. Certain multimorbidity combinations especially those that include depression, hypertension and arthritis increased the risk of disability in older people with diabetes as demonstrated by McClellan et al., while Coles B et al., in their large retrospective analysis found that, in addition to the level of multimorbidity, cardiovascular multimorbidity increased the risk of subsequent cardiovascular events, mortality and cardiovascular mortality ^[3][4][66,67]. However, the effect of multimorbidity on mortality may be affected by the ethnicity of the population studied. For example, data from the UK Biobank (a population predominantly of European origin), showed that a combination of coronary heart disease and heart failure, while the Taiwan National Diabetes Care Management Program (a population predominantly of Chinese ethnicity), showed that a combination of painful conditions and alcohol problems to be associated with the largest effect size on mortality, respectively. Although the UK cohort tended to have higher body weight than that of the Taiwanese cohort, which may increase their cardiovascular risk, {median (IQR) body mass index 30.8 (27.7, 34.8) kg/m² vs. 25.6 (23.5, 28.7) kg/m², there is still a need for further exploration of the effects of different patterns of multimorbidity on outcomes across different ethnic groups as suggested by Chiang et al. ^[5][68]. Increased risk of emergency department visits and hypoglycaemia-related hospitalisation are another multimorbidity-related outcomes which increases in proportion with the number of morbidities as demonstrated by McCoy et al. ^[6][69]. Another retrospective report by McCoy et al., demonstrated that HbA1c levels declined as the number of comorbidities increased reflecting clinical practice of tighter glycaemic control in multimorbid patients, rather than a direct relationship between multimorbidity and glycaemic control ^[7][70]. Similarly, Chiang et al., have demonstrated no association between multimorbidity and glycaemic control in their large cross-sectional general practice study ^[8][71]. Wong et al., found that health-related quality of life was impaired with increasing number of morbidities ^[9][72]. Mental health conditions such as depression, schizophrenia, substance use disorder and anxiety, which was present in 1 in 5 of older people with diabetes, was also associated with increased risk of mortality and hospital services use as reported by Guerrero Fernández de Alba et al. in their retrospective analysis ^[10][73]. Chiang el al, found no association between multimorbidity-related adverse outcomes and glycaemia markers such as HbA1c, glycaemic variability or time blood glucose in normal range suggesting that other factors, rather than dysglycaemia, contribute to the adverse outcomes associated with multimorbidity in older people with diabetes ^[11][74]. Among comorbidities, Quiñones et al., found that the presence of depressive symptoms or stroke, in particular, pose a substantial functional burden and contributed more to disabilities in ADL and IADL in older people with diabetes than other conditions ^[12][75].

Twelve studies investigated the association of frailty and diabetes outcomes (Table 23). Hanlon et al., analysed a large UK Biobank data (20,566 participants) using two frailty and two multimorbidity measures and found that each measure was associated with mortality, major adverse cardiovascular events (MACE), hypoglycaemia and fall or fracture ^[13][76]. Data from the Look AHEAD clinical trial showed that, after 8 years, the increases in frailty and multimorbidity were associated with poor cognitive function, physical function and increased mortality as reported by Espeland et al. ^[14][77]. Results From the ADVANCE trial showed that frailty predicted macro and microvascular events, all-cause mortality, cardiovascular mortality and hypoglycaemia as demonstrated by Nguyen et al., who concluded that frailty attenuated the benefits from blood pressure lowering and intensive glycaemic control ^[15][78]. In a retrospective analysis by Sable-Morita et al., frailty was a predictor of hospitalisations, institutional admissions, emergency outpatient visits, fractures, and mortality in older people with diabetes ^[16][79]. Ferri-Guerra et al., prospectively demonstrated association of frailty with all-cause hospitalisation and mortality independent of comorbidity ^[17][80]. Gual et al., investigated the impact of frailty on the outcome of a very old (≥80 years) cohort with diabetes and acute coronary syndrome. The association between diabetes and outcomes (incidence of death or readmission after 6 months) was not significant in robust patients, but it was significant in frail patients ^[18][81]. Among patients with diabetic kidney disease, frailty increased the risk of progression to end stage renal disease on a dose–response relationship and mortality, compared to those without frailty as reported by Chao et al. ^[19][82]. The prospective study by Kitamura et al., showed that all-cause mortality and disability in older people with mild diabetes were strongly affected by the presence of frailty ^[20][83]. Frailty was associated with low health related quality of life, depression, lean body mass and higher numbers of health-care visits in people with diabetes and chronic kidney disease as demonstrated in a cross-sectional analysis by Adame Perez et al. ^[21][84]. Chao et al., showed that both pre-frailty and frailty were associated with increased mortality, cardiovascular events, hospitalisation and health care utilisation ^[22][85]. In the community prospective study by Thein et al., frailty was associated with disability, which was potentiated by the presence of cognitive impairment. In addition, frailty, cognitive impairment or both were strong predictors of mortality ^[23][86]. In another community study by Li et al., frailty was associated with increased hospitalisation while both pre-frailty and frailty were associated with increased emergency department visits ^[24][87].