Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations

doi:10.4254/wjh.v14.i4.754

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Apr 27, 2022 (publication date) through Feb 21, 2025

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World Journal of Hepatology

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1948-5182

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

World J Hepatol. Apr 27, 2022; 14(4): 754-765
Published online Apr 27, 2022. doi: 10.4254/wjh.v14.i4.754

Table 1 Baseline characteristics of study participants

Characteristic	Testosterone group (n = 20)	Placebo group (n = 19)	P value
Age (yr)	62 (58-67)	60.4 (6.5)	0.5
Duration of type 2 diabetes (yr)	8 (6-14)	7 (5-9)	0.2
Insulin therapy, n (%)	3 (15)	2 (10.5)	> 0.9
Weight, kg	92 (86-101)	98 (92-105)	0.15
BMI, kg/m²	30.3 (27.3-31.9)	32.0 (29.7-35.4)	0.14
Waist circumference, cm	106 (102-116)	112 (106-119)	0.4
Fat mass, g	30788 (24875-38117)	31758 (29332-35286)	0.8
Lean mass, g	57090 (51658-62688)	62140 (66226-65844)	0.029
ALT, IU/L	34 (26-38)	32 (25-52)	0.8
ALP, IU/L	72 (60-82)	58 (54-69)	0.057
GGT, IU/L	30 (21-38)	32 (25-45)	0.5
TT, nmol/L (ECLIA)	9.8 (7.2-12.0)	7.8 (6.0-10.8)	0.2
cFT, pmol/L (ECLIA)	216 (151-272)	176 (146-224)	0.3
SHBG, nmol/L	28 (20-34)	28 (23-32)	0.8
LH, IU/L	4.5 (3.4-7.0)	4.3 (3.4-6.0)	0.7
Fasting glucose, mmol/L	8.9 (6.8-10.3)	8.5 (7.7-9.8)	0.6
HbA1c, %	6.6 (6.4-7.2)	7.0 (6.7-7.3)	0.071
Cholesterol, mmol/L	4.4 (4.0-5.0)	4.6 (4.0-4.9)	> 0.9
LDL, mmol/L	2.4 (2.0-3.0)	2.7 (2.0-3.0)	0.7
HDL, mmol/L	1.2 (1.0-1.4)	1.0 (0.7-1.2)	0.03

Data are median (IQR). ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TT: Total testosterone; cFT: Calculated free testosterone; SHBG: Sex hormone-binding globulin; LH: Luteinising hormone; LDL: Low-density lipoprotein; HDL: High density lipoprotein.

Table 2 Baseline characteristics of our participants who had magnetic resonance imaging scans compared to index study participants who did not have magnetic resonance imaging scans

Characteristic	Non-MRI scan group (n = 49)	MRI scan group (n = 39)	P value
Age, yr	62 (58-68)	62 (58-67)	0.6
Duration of type 2 diabetes, yr	9 (4-12)	8 (5-11)	> 0.9
Insulin therapy, n (%)	13 (26.5)	5 (12.8)	0.19
Weight, kg	102 (89-111)	95 (90-104)	0.12
BMI, kg/m²	33.4 (31.2-35.9)	31.5 (28.2-35.3)	0.012
Waist circumference, cm	116 (109-123)	111 (104-118)	0.024
Fat mass, g	32696 (29299-39109)	31832 (26820-37809)	0.2
Lean mass, g	62004 (58056-66170)	60,049 (54278-64848)	0.12
ALT, IU/L	34 (25-50)	32 (25-42)	0.7
ALP, IU/L	71 (56-82)	66 (54-75)	0.2
GGT, IU/L	30 (24-43)	32 (24-43)	0.8
TT, nmol/L (ECLIA)	8.5 (7.3-10.5)	8.1 (6.7-11.4)	0.8
cFT, pmol/L (ECLIA)	176 (151-230)	194 (148-253)	0.6
SHBG, nmol/L	28 (24-32)	29 (22-34)	> 0.9
LH, IU/L	4.5 (3.5-6.2)	4.5 (3.4-6.4)	0.9
Fasting glucose, mmol/L	8.2 (7.0-10.6)	8.6 (7.3-9.9)	> 0.9
HbA1c, %	7.1 (6.6-7.7)	6.9 (6.5-7.3)	0.4
Cholesterol, mmol/L	4.1 (3.5-4.7)	4.6 (4.0-4.9)	0.005
LDL, mmol/L	2.0 (1.6-2.4)	2.7 (2.0-3.1)	< 0.001
HDL, mmol/L	1.0 (0.9-1.2)	1.1 (0.9-1.2)	0.5
SAT, cm³	4095 (3526-5593)	4661 (3137-5385)	0.7
VAT, cm³	4786 (3,642-5,617)	3634 (2780-4823)	0.044

Data are median (IQR). MRI: Magnetic resonance imaging; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TT: Total testosterone; cFT: Calculated free testosterone; SHBG: Sex hormone-binding globulin; LH: Luteinising hormone; LDL: Low-density lipoprotein; HDL: High density lipoprotein; SAT: Subcutaneous adipose tissue; VAT: Visceral adipose tissue.

Table 3 Changes in body composition and metabolic parameters

	Testosterone group (n = 20)	Placebo group (n = 19)	P value
Weight, kg
Baseline	92 (86-101)	98 (91-105)	0.55
40 wk	90 (86-100)	96 (94-100)
BMI, kg/m²
Baseline	30.3 (27.3-31.9)	32.0 (29.7-35.4)	0.64
40 wk	29.3 (27.4-31.8)	31.8 (30.0-34.4)
Waist circumference, cm
Baseline	106 (102-116)	112 (106-118)	0.15
40 wk	108 (101-115)	114 (110-118)
Fasting glucose, mmol/L
Baseline	8.9 (6.8-10.3)	8.6 (7.7-9.8)	0.93
40 wk	8.3 (6.5-10.5)	9.1 (7.7-9.9)
HbA1c, %
Baseline	6.6 (6.4-7.2)	7.0 (6.8-7.4)	0.95
40 wk	7.0 (6.3-7.4)	7.3 (7.0-7.7)
Fat mass, g
Baseline	30788 (24875-38117)	31758 (29332-35286)	< 0.001^a
40 wk	27272 (21948-34558)	32089 (29869-34492)
Lean mass, g
Baseline	57090 (51658-62688)	62140 (66226-65844)	< 0.001^a
40 wk	58236 (55150-63077)	61070 (57408-64833)
SAT, cm³
Baseline	4445 (2928-5669)	4302 (3828-5254)	0.004^a
40 wk	4140 (2769-5046)	4330 (3741-5179)
VAT, cm³
Baseline	3574 (2460-4711)	3864 (3267-4703)	0.63
40 wk	3248 (2280-4634)	3966 (3462-4699)
ALT, U/L
Baseline	34 (26-38)	32 (25-52)	0.27
40 wk	32 (25-36)	44 (29-61)
GGT, U/L
Baseline	30 (21-38)	32 (25-45)	0.28
40 wk	28 (20-41)	33 (28-56)
ALP, U/L
Baseline	72 (60-82)	58 (54-69)	0.04^a
40 wk	70 (60-78)	60 (58-72)
Total cholesterol, mmol/L
Baseline	4.4 (4.0-5.0)	4.6 (4.0-4.9)	0.008^a
40 wk	3.7 (3.5-4.5)	4.5 (4.1-5.1)
LDL, mmol/L
Baseline	2.4 (2.0-3.0)	2.7 (2.0-3.0)	0.21
40 wk	2.1 (1.8-2.7)	2.4 (1.9-3.2)
HDL, mmol/L
Baseline	(1.01-1.40)	1.02 (0.74-1.18)	0.02^a
40 wk	1.19 (0.93-1.36)	0.98 (0.82-1.09)
Triglycerides, mmol/L
Baseline	1.6 (1.3-2.0)	2.0 (1.4-2.4)	0.25
40 wk	1.4 (1.0-1.9)	1.9 (1.6-3.0)

^aP values are an exploratory univariate analysis of between-group week 40 values after adjusting for baseline. No adjustment for multiple comparisons were made given the exploratory nature. Data are median (IQR). BMI: Body mass index; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; TT: Total testosterone; cFT: Calculated free testosterone; SHBG: Sex hormone-binding globulin; LH: Luteinising hormone; LDL: Low-density lipoprotein; HDL: High density lipoprotein; SAT: Subcutaneous adipose tissue; VAT: Visceral adipose tissue.

Table 4 Univariate analysis table of factors affecting change in hepatic steatosis

Characteristic	n	Beta	95%CI	P value
Testosterone	38¹	-0.66	-1.0, -0.37	< 0.001
Age (yr)	38	-0.03	-0.05, 0.00	0.075
BMI (kg/m²)	38	0.06	0.02, 0.10	0.003
Baseline liver fat proportion	38	4.6	3.3, 6.0	< 0.001
Baseline total testosterone (nmol/L)	38	-0.03	-0.09, 0.03	0.3
Baseline free testosterone (nmol/L)	38	0.00	0.00, 0.00	0.5
Baseline visceral fat (g)	38	0.00	0.00, 0.00	0.4
Follow up total testosterone (nmol/L)	37	-0.05	-0.09, -0.02	0.006
Follow up free testosterone (nmol/L)	37	0.00	0.00, 0.00	0.005
Follow up visceral fat (g)	38	0.00	0.00, 0.00	0.2

¹One participant did not have follow-up testosterone concentration. BMI: Body mass index.

Citation: Apostolov R, Gianatti E, Wong D, Kutaiba N, Gow P, Grossmann M, Sinclair M. Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations. World J Hepatol 2022; 14(4): 754-765
URL: https://www.wjgnet.com/1948-5182/full/v14/i4/754.htm
DOI: https://dx.doi.org/10.4254/wjh.v14.i4.754