Increased insulin secretion and decreased glucose concentrations, but not allostatic load, are associated with stress-related exhaustion in a clinical patient population

Figures & data

Table I.  Demographic factors for patients with stress-related exhaustion and controls.

	Patients (n = 90)	Controls (n = 90)	p value
Age (years)
Mean (SD)	44 (8)	41 (7)	0.002^*
Range	31–61	25–56
Sex, n (%)			0.655^†
Female	47 (52)	44 (49)
Male	43 (48)	46 (51)
Antidepressant use, n (%)	29 (32)	0 (0)
Exercise, n (%)			0.007^†
Sedentary	20 (23)	4 (6)
Light physical activity	45 (51)	27 (44)
Regular physical activity and training	21 (24)	28 (45)
Hard training or competitive sports	2 (2)	3 (5)
Burnout scores (SMBQ quartiles), n (%)			< 0.001^†
< 2.2	1 (1)	42 (48)
≥ 2.2 and < 4.0	3 (3)	38 (44)
≥ 4.0 and < 5.4	39 (45)	7 (8)
≥ 5.4	43 (50)	0 (0)
HAD depression, n (%)			< 0.001^†
< 7	30 (34)	80 (93)
7–10	31 (35)	6 (7)
>10	28 (31)	0 (0)
HAD anxiety, n (%)			< 0.001^†
< 7	10 (11)	71 (83)
7–10	25 (28)	9 (10)
>10	54 (61)	6 (7)

Notes: SMBQ, Shirom–Melamed Burnout Questionnaire; HAD, Hospital Anxiety and Depression scale; ^* t-test; ^†χ² test.

Table II.  Quartile distributions of all biomarkers and AL scores in patients with stress-related exhaustion and controls.

		Patients in each quartile				Controls in each quartile
Biomarkers	High risk cut-off	Q1 n (%)	Q2 n (%)	Q3 n (%)	Q4 n (%)	Q1 n (%)	Q2 n (%)	Q3 n (%)	Q4 n (%)
BMI (kg/m^2)	>25.9	26 (29)	16 (18)	20 (22)	28 (31)	22 (24)	29 (32)	22 (24)	17 (19)
WHR	>0.93	23 (26)	24 (27)	24 (27)	19 (21)	23 (26)	22 (24)	24 (27)	21 (23)
SBP (mmHg)	>130	25 (28)	24 (27)	24 (27)	17 (19)	21 (23)	25 (28)	27 (30)	17 (19)
DBP (mmHg)	>80	23 (26)	24 (27)	20 (22)	23 (26)	25 (28)	28 (31)	19 (21)	18 (20)
HDL (mmol/l)	≤ 1.4	33 (37)	20 (22)	20 (22)	16 (18)	33 (37)	10 (11)	22 (24)	25 (28)
TC/HDL	>3.7	19 (21)	20(22)	24 (27)	26 (29)	25 (28)	27 (30)	21 (23)	17 (19)
LDL (mmol/l)	>3.5	24 (28)	16 (18)	27 (31)	20 (23)	21 (23)	28 (31)	22 (24)	19 (21)
Triglycerides (mmol/l)	>1.2	18 (20)	19 (21)	29 (33)	23 (26)	29 (32)	26 (29)	20 (22)	15 (17)
CRP (mg/l)	>1.28	17 (19)	24 (27)	20 (22)	29 (32)	28 (31)	24 (27)	22 (24)	16 (18)
Insulin (mU/l)	>7.5	16 (18)	17 (19)	30 (33)	27 (30)	29 (33)	31 (35)	12 (13)	17 (19)
Glucose (mmol/l)	>5.3	34 (38)	27 (30)	20 (22)	8 (9)	12 (13)	19 (21)	29 (32)	30 (33)
HbA1c (%)	>4.3	34 (38)	24 (27)	23 (26)	8 (9)	25 (28)	23 (26)	24 (27)	18 (20)
Cortisol (nmol/l)	≤ 10.8 or >20.0	23 (26)	25 (28)	23 (26)	19 (21)	20 (24)	19 (23)	21 (25)	24 (29)
		Patients		Controls		Student's t-test		ANCOVA adjusted for age and antidepressants
Allostatic load index		Mean (SD)	Median (range)	Mean (SD)	Median (range)	t value	p value	F value	p value
AL1		3.1 (2.5)	2 (0–9)	2.9 (2.6)	2 (0–12)	0.4	0.698	1.1	0.286
	Men	4.6 (2.5)	4 (1–9)	4.0 (2.7)	4 (0–12)	0.9	0.351	2.6	0.109
	Women	1.8 (1.7)	1.5 (0–8)	1.8 (1.9)	1 (0–7)	− 0.1	0.910	0.0	0.983
AL2		3.1 (2.6)	2 (0–9)	2.9 (2.5)	2 (0–11)	0.5	0.589	1.0	0.311
	Men	4.7 (2.5)	4 (1–9)	4.0 (2.7)	3 (0–11)	1.3	0.205	3.5	0.065
	Women	1.7 (1.7)	1.5 (0–8)	1.8 (1.8)	1 (0–7)	− 0.3	0.771	0.1	0.765

Notes: The number of patients and controls in high-risk quartiles are indicated in bold. AL scores were calculated as individual counts of biomarkers in the high-risk quartile, with either the highest quartile (AL1) or the lowest quartile (AL2) for cortisol regarded as high risk; BMI, body mass index; WHR, waist–hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, serum high-density lipoprotein; TC, serum total cholesterol; LDL, serum low-density lipoprotein; triglycerides, serum concentration; CRP, serum C-reactive protein; Insulin, serum concentration; glucose, plasma concentration; HbA1c, blood glycated haemoglobin; cortisol, mean morning salivary concentration; for AL index, patients: n = 87; controls = 83, as there was a missing biomarker value for 10 of the original 180 participants.

Table III.  Results from the MANOVA performed to test differences between patients with stress-related exhaustion and controls for each of the 13 biomarkers.

	Patients (n = 87)		Controls (n = 83)		MANOVA		MANOVA adjusted for age, sex and antidepressants		Cut-off
Biomarkers	Mean	SD	Mean	SD	p value	η^2	p value	η^2	High-risk quartile
BMI (kg/m^2)	24.2	3.0	23.7	2.4	0.126		0.081		>25.9
WHR	0.88	0.07	0.88	0.07	0.546		0.079		>0.93
SBP (mmHg)	121	13.9	121	13.5	0.941		0.737		>130
DBP (mmHg)	75	9.8	74	8.0	0.264		0.169		>80
HDL (mmol/l)	1.6	0.4	1.7	0.4	0.290		0.086		< 1.4
TC/HDL	3.4	1.1	3.1	0.9	0.293		0.023	0.031	>3.7
LDL (mmol/l)	3.0	0.9	2.9	0.8	0.600		0.113		>3.5
Triglycerides (mmol/l)	1.1	0.8	0.9	0.5	0.051		0.015	0.035	>1.2
CRP (mg/l)	1.8	3.2	1.1	1.7	0.016	0.034	0.053		>1.28
Insulin (mU/l)	7.4	4.2	5.6	3.1	0.001	0.059	0.003	0.053	>7.5
Glucose (mmol/l)	4.7	0.4	5.1	0.5	< 0.001	0.176	< 0.001	0.132	>5.3
HbA1c (%)	4.0	0.3	4.1	0.3	0.026	0.029	0.184		>4.3
Cortisol (nmol/l)	15.8	7.4	16.3	7.8	0.848		0.639		>20.0 or < 10.8

Notes: BMI, body mass index; WHR, waist–hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, serum high-density lipoprotein; TC, serum total cholesterol; LDL, serum low-density lipoprotein; triglycerides, serum concentration; CRP, serum C-reactive protein; Insulin, serum concentration; glucose, plasma concentration; HbA1c, blood glycated haemoglobin; cortisol, mean morning salivary concentration; significant differences are indicated in bold; total n = 170 participants as there was a missing biomarker value for 10 of the original 180 participants.

Table IV.  Separate analyses for men and women showing the results from the MANOVA performed to test differences between patients with stress-related exhaustion and controls for each of the 13 biomarkers.

	Men						Women
	Patients (n = 41)		Controls (n = 42)		MANOVA adjusted for age and antidepressants		Patients (n = 46)		Controls (n = 41)		MANOVA adjusted for age and antidepressants
Biomarkers	Mean	SD	Mean	SD	p value	η^2	Mean	SD	Mean	SD	p value	η^2
BMI (kg/m^2)	25.9	2.4	24.4	2.1	0.001	0.128	22.7	2.5	23.0	2.6	0.469
WHR	0.93	0.05	0.90	0.05	0.022	0.065	0.83	0.05	0.83	0.05	0.949
SBP (mmHg)	125	12.7	126	12.5	0.911		116	13.6	117	13.0	0.677
DBP (mmHg)	79	8.4	77	7.6	0.324		72	10.1	71	7.4	0.276
HDL (mmol/l)	1.4	0.3	1.5	0.4	0.033	0.057	1.8	0.4	1.9	0.5	0.757
TC/HDL	3.9	1.2	3.4	1.0	0.005	0.097	2.8	0.7	2.8	0.8	0.639
LDL (mmol/l)	3.2	1,0	3.0	0.8	0.039	0.053	2.8	0.9	2.8	0.7	0.909
Triglycerides (mmol/l)	1.4	1.0	1.0	0.6	0.059		0.9	0.5	0.8	0.3	0.166
CRP (mg/l)	1.6	1.8	1.2	1.9	0.176		2.0	4.0	1.0	1.6	0.163
Insulin (mU/l)	9.1	5.2	5.9	3.6	0.001	0.125	5.8	2.0	5.3	2.4	0.760
Glucose (mmol/l)	4.9	0.4	5.3	0.5	0.003	0.107	4.6	0.3	4.9	0.5	< 0.001	0.183
HbA1c (%)	4.1	0.3	4.1	0.3	0.780		4.0	0.3	4.1	0.3	0.147
Cortisol (nmol/l)	7.1	6.1	6.5	9.2	0.703		4.8	5.8	6.7	8.17	0.152

Notes: BMI, body mass index; WHR, waist–hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, serum high-density lipoprotein; TC, serum total cholesterol; LDL, serum low-density lipoprotein; triglycerides, serum concentration; CRP, serum C-reactive protein; Insulin, serum concentration; glucose, plasma concentration; HbA1c, blood glycated haemoglobin; cortisol, mean morning salivary concentration; significant differences are indicated in bold; total n = 170 participants as there was a missing biomarker value for 10 of the original 180 participants.

Figure 1.  Two clusters were identified by multivariate analysis, including all 13 AL markers and 87 patients with stress-related exhaustion and 83 controls. (a) Relative importance of each AL biomarker for the two clusters and for the total model. (b) Characteristics of the two clusters illustrated by cluster mean values of standardized AL biomarker data; each biomarker has mean 0 and SD 1. Low AL (Cluster 1), n = 68 participants (29 patients; 39 controls); High AL (Cluster 2), n = 102 participants (58 patients; 44 controls). Note, total n = 170 participants as there was a missing Biomarker value for 10 of the original 180 participants. AL markers: BMI, body mass index; WHR, waist–hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, serum high-density lipoprotein; TC, serum total cholesterol; LDL, serum low-density lipoprotein; triglycerides, serum concentration; CRP, serum C-reactive protein; insulin, serum concentration; glucose, plasma concentration; HbA1c, blood glycated haemoglobin; cortisol, mean morning salivary concentration.