Association of glycated hemoglobin levels with 3-year mortality in hospitalized older adults with diabetes: The role of frailty

Table 1 Baseline demographics, comorbidities, and laboratory findings stratified by glycated hemoglobin levels in older patients with diabetes mellitus, n (%)

Variables	Total population (n = 430)	HbA1c < 6.5% (n = 246)	HbA1c 6.5%-8.0% (n = 137)	HbA1c > 8.0% (n = 47)	P value
Demographics
Female sex	240 (55.8)	145 (58.9)	72 (52.6)	23 (48.9)	0.291
Age, years	81.5 ± 7.3	82.5 [76.8-87.0]	82.0 [75.5-87.5]	82.0 [78.0-86.0]	0.870
BMI, kg/m2	25.6 [23.4-28.0]	25.7 [23.5-28.0]	25.5 [23.4-28.0]	25.7 [23.5-28.7]	0.929
Functional status
Median Katz index					0.05
Katz Index - no limitation	156 (36.4)	87 (35.5)	59 (43.1)	10 (21.3)
Katz Index - mild limitation	78 (18.2)	50 (20.4)	20 (14.6)	8 (17.0)
Katz Index - severe limitation	196 (45.5)	109 (44.1)	58 (42.3)	29 (61.7)
CFS
Median CFS					0.003
CFS 1-3 (fit-managing well)	145 (33.7)	76 (30.9)	60 (43.8)	9 (19.1)
CFS 4-5 (vulnerable-mildly frail)	84 (19.5)	57 (23.2)	20 (14.6)	7 (14.9)
CFS ≥ 6 (moderate-severe frailty)	201 (46.7)	113 (45.9)	57 (41.6)	31 (66.0)
CCI
Median CCI					0.193
CCI 1-3	7 (1.6)	4 (1.6)	3 (2.2)	0 (0.0)
CCI 4-5	132 (30.7)	80 (32.5)	44 (32.1)	8 (17.0)
CCI ≥ 6	291 (67.7)	162 (65.9)	90 (65.7)	39 (83.0)
Diabetes-related variables
Diabetes duration, years	13 [11-16]	13 [11-16]	13 [10-16.5]	12 [10-16]	0.735
HbA1c, % [IQR]	6.1 [5.5-7.1]	5.5 [5.1-6.0]	7.1 [6.9-7.45]	9.0 [8.8-9.8]	< 0.001
Number of drugs	8.4 ± 3.2	8.0 [6.0-10.0]	8.0 [6.0-10.0]	9.0 [7.0-11.0]	0.314
Living status/care needs
Nursing home resident	33 (7.7)	19 (7.7)	9 (6.6)	5 (10.6)	0.664
Urinary catheter	49 (11.4)	31 (12.6)	13 (9.5)	5 (10.6)	0.646
Bed-ridden patient	186 (43.3)	104 (42.3)	53 (38.7)	29 (61.7)	0.020
Outcomes
In-hospital mortality	62 (14.4)	34 (13.8)	17 (12.4)	11 (23.4)	0.166
Readmission within 3 years	228 (62.0)	137 (64.6)	64 (53.3)	27 (75.0)	0.029
3-year mortality	202 (54.9)	128 (63.4)	54 (26.7)	20 (55.6)	0.026
3-year mortality by sex
Male	85 (23.1)	53 (58.2)	22 (39.3)	10 (55.6)	0.249
Female	117 (31.8)	75 (62.0)	32 (50.0)	10 ( 55.6)

BMI: Body mass index; CFS: Clinical Frailty Scale; CCI: Charslon Comorbidity Index; HbA1c: Glycated hemoglobin; IQR: Interquartile range.

Table 2 Distribution of antidiabetic treatment according to glycated hemoglobin categories in the total study sample, n (%)

Variable	Total population, n = 430	HbA1c < 6.5%, n = 246	HbA1c 6.5%-8.0%, n = 137	HbA1c > 8.0%, n = 47	P value
Metformin	258 (60.0)	144 (58.5)	86 (62.8)	28 (59.6)	0.718
Sulfonylureas	81 (18.8)	45 (18.3)	25 (18.2)	11 (23.4)	0.698
DPP4-i	188 (43.7)	105 (42.7)	54 (39.4)	29 (61.7)	0.026
SGLT2i	25 (5.8)	13 (5.3)	11 (8.0)	1 (2.1)	0.284
GLP-1 agonists	10 (2.3)	5 (2.0)	5 (3.6)	0 (0.0)	0.322
Basal insulin	129 (30.0)	81 (32.9)	38 (27.7)	10 (21.3)	0.219
Rapid insulin	54 (12.6)	33 (13.4)	15 (10.9)	6 (12.8)	0.783

DPP4-i: Dipeptidyl peptidase-4 inhibitor; SGLT2i: Sodium glucose co-transporter 2 inhibitors; GLP-1: Glucagon like peptide; HbA1c: Glycated hemoglobin.

Table 3 Multivariate logistic regression analysis for 3-year post discharge mortality

Variable	OR	95%CI	P value
Age (per year)	1.02	0.98-1.06	0.294
Male sex	0.88	0.60-1.62	0.959
HbA1c (per 1% decrease)	1.24	1.05-1.46	0.010
CFS categories
CFS 1-3	Reference	-	-
CFS 4-5	2.10	1.12-3.91	0.021
CFS 6	7.57	3.65-15.70	< 0.001
HF	1.00	0.61-1.62	0.992
CKD	1.07	0.57-1.91	0.823
Dementia	0.84	0.46-1.54	0.778
Stroke	1.09	0.55-2.16	0.604
Cancer	7.69	2.14-27.65	0.002

Adjusted for age, sex. HbA1c: Glycated hemoglobin; CFS: Clinical Frailty Score; HF: Heart failure; CKD: Chronic kidney disease; OR: Odds ratio.

Table 4 Multivariate logistic regression model including the association between glycated hemoglobin categories and 3-year post discharge mortality

Variable	OR	95%CI	P value
Age (per year)	1.02	0.99-1.06	0.268
Male sex	1.00	0.61-1.63	0.989
HF	0.97	0.60-1.58	0.915
CKD	1.09	0.59-2.02	0.778
Dementia	0.93	0.49-1.74	0.811
Stroke	1.12	0.55-2.29	0.757
CFS categories
CFS 1-3	Reference	-	-
CFS 4-5	1.98	1.06-3.73	0.034
CFS ≥ 6	7.02	3.38-14.57	< 0.001
Cancer	8.08	2.24-29.18	0.001
HbA1c categories
HbA1c 6.5%-8%	Reference	-	-
HbA1c < 6.5%	1.73	1.03-2.91	0.039
HbA1c > 8.0%	0.81	0.34-1.94	0.639

Adjusted for age, sex. HbA1c: Glycated hemoglobin; CFS: Clinical Frailty Score; HF: Heart failure; CKD: Chronic kidney disease; OR: Odds ratio.