J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 12, Number 6, June 2020, pages 377-388

Associations Between Cannabis Use, Abdominal Fat Phenotypes and Insulin Traits

Figure 1. Fat phenotypes measurements for a 78-year-old European man who was never smoker and had low-to-moderate average alcohol consumption. (a, b) Intra-pancreatic fat deposition measurement by region of interest placement in the head, body and tail of the pancreas on out-of-phase and fat images. (c, d) Intra-hepatic fat deposition measurement with placement of the voxel within the liver and spectroscopy data using fat and water signals collected at the time of scan acquisition. (e, f) Skeletal muscle fat deposition measurement with selection of total erector spinae muscle area and quantification of fat pixels using the thresholding function of ImageJ.

Figure 2. Contribution of cannabis use to variance in each of the fat phenotypes in the study cohort. Data are presented as the R² metric (%). SFV: subcutaneous fat volume; VFV: visceral fat volume; IPFD: intra-pancreatic fat deposition; IHFD: intra-hepatic fat deposition; SMFD: skeletal muscle fat deposition.

**Table 1.** Baseline Characteristics of the Study Cohort
Characteristics	Never cannabis users	Non-regular cannabis users	Regular cannabis users	P-value
Data are presented as median and interquartile range or frequency counts and percentages. BMI: body mass index; HbA1c: glycated hemoglobin.
No. of individuals	91	21	8
Age, years	58 (47 - 69)	52 (43 - 61)	54 (45 - 63)	0.015
Sex				0.203
Men	59 (64.8%)	17 (81%)	7 (87.5%)
Women	32 (35.2%)	4 (19%)	1 (12.5%)
BMI, kg/m²	26.8 (22.3 - 31.3)	27.9 (24.9 - 30.9)	34.3 (30.3 - 38.3)	0.170
Ethnicity				0.092
European	40 (44%)	10 (47.6%)	1 (12.5%)
Maori	14 (15.4%)	6 (28.6%)	4 (50%)
Pacific Islander	2 (2.1%)	0	1 (12.5%)
Asian	16 (17.6%)	3 (14.3%)	0
Other	19 (20.9%)	2 (9.5%)	2 (25%)
HbA1c, mmol/mol	39 (36 - 42)	37 (34 - 40)	35 (33 - 37)	0.293
Insulin, mU/L	9.80 (6.23- 16.38)	12.0 (6.25 - 17.5)	12.9 (5.35 - 14.2)	0.072
C-peptide, nmol/L	0.57 (0.40 - 0.83)	0.58 (0.43 - 0.92)	0.48 (0.22 - 0.61)	0.108
Diabetes status				0.437
Normoglycemia	65 (71.4%)	15 (71.4%)	5 (62.5%)
Prediabetes	19 (20.9%)	5 (23.8%)	3 (37.5%)
Diabetes	5 (5.5%)	1 (4.76%)	0 (0%)
Physical activity (n = 96)				0.049
Inactive (< 2.5 h/week)	16 (22.5%)	7 (33.3%)	4 (66.7%)
Active (> 2.5 h/week)	55 (77.5%)	12 (66.7%)	2 (33.3%)
Tobacco smoking				0.024
Never	44 (48.4%)	3 (10.4%)	0
Former	30 (33.0%)	11 (51.7%)	4 (50%)
Light	8 (8.8%)	4 (20.7%)	2 (25%)
Moderate-heavy	9 (9.8%)	3 (17.2%)	2 (25%)
Alcohol consumption (n = 113)				0.192
None (0 g/day)	28 (33.3%)	9 (44.8%)	4 (50%)
Low-moderate (< 40 g/day)	44 (52.4%)	9 (34.5%)	1 (12.5%)
Excess (≥ 40 g/day)	12 (14.3%)	3 (20.7%)	3 (37.5%)

Table 1. Baseline Characteristics of the Study Cohort

Characteristics

Never cannabis users

Non-regular cannabis users

Regular cannabis users

P-value

Data are presented as median and interquartile range or frequency counts and percentages. BMI: body mass index; HbA1c: glycated hemoglobin.

No. of individuals

Age, years

58 (47 - 69)

52 (43 - 61)

54 (45 - 63)

0.015

Sex

0.203

Men

59 (64.8%)

17 (81%)

7 (87.5%)

Women

32 (35.2%)

4 (19%)

1 (12.5%)

BMI, kg/m²

26.8 (22.3 - 31.3)

27.9 (24.9 - 30.9)

34.3 (30.3 - 38.3)

0.170

Ethnicity

0.092

European

40 (44%)

10 (47.6%)

1 (12.5%)

Maori

14 (15.4%)

6 (28.6%)

4 (50%)

Pacific Islander

2 (2.1%)

1 (12.5%)

Asian

16 (17.6%)

3 (14.3%)

Other

19 (20.9%)

2 (9.5%)

2 (25%)

HbA1c, mmol/mol

39 (36 - 42)

37 (34 - 40)

35 (33 - 37)

0.293

Insulin, mU/L

9.80 (6.23- 16.38)

12.0 (6.25 - 17.5)

12.9 (5.35 - 14.2)

0.072

C-peptide, nmol/L

0.57 (0.40 - 0.83)

0.58 (0.43 - 0.92)

0.48 (0.22 - 0.61)

0.108

Diabetes status

0.437

Normoglycemia

65 (71.4%)

15 (71.4%)

5 (62.5%)

Prediabetes

19 (20.9%)

5 (23.8%)

3 (37.5%)

Diabetes

5 (5.5%)

1 (4.76%)

0 (0%)

Physical activity (n = 96)

0.049

Inactive (< 2.5 h/week)

16 (22.5%)

7 (33.3%)

4 (66.7%)

Active (> 2.5 h/week)

55 (77.5%)

12 (66.7%)

2 (33.3%)

Tobacco smoking

0.024

Never

44 (48.4%)

3 (10.4%)

Former

30 (33.0%)

11 (51.7%)

4 (50%)

Light

8 (8.8%)

4 (20.7%)

2 (25%)

Moderate-heavy

9 (9.8%)

3 (17.2%)

2 (25%)

Alcohol consumption (n = 113)

0.192

None (0 g/day)

28 (33.3%)

9 (44.8%)

4 (50%)

Low-moderate (< 40 g/day)

44 (52.4%)

9 (34.5%)

1 (12.5%)

Excess (≥ 40 g/day)

12 (14.3%)

3 (20.7%)

3 (37.5%)

**Table 2.** Associations Between Cannabis Use and the Studied Fat Phenotypes
Fat phenotype	Cannabis use	Mean ± SD	Model 1	Model 2	Model 3
Model 1 was unadjusted. Model 2 was adjusted for age, sex and ethnicity. Model 3 was adjusted for age, sex, ethnicity, HbA1c level, tobacco smoking, alcohol consumption and physical activity. SD: standard deviation; B: beta coefficient; CI: confidence interval.
Subcutaneous fat volume, cm³	Never	2,769 ± 1,421	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	2,928 ± 266	-0.008	-759.8	706.9	0.943	-0.043	-911.6	617.3	0.702	-0.066	-1037.0	583.5	0.579
	Regular	4,061 ± 1,644	0.246	174.3	2467.1	0.024	0.180	-190.4	2118.9	0.100	0.143	-496.1	2031.9	0.230
Visceral fat volume, cm³	Never	2,390 ± 1,134	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	2,190 ± 350	0.006	-596.7	631.7	0.955	-0.032	-674.7	495.9	0.762	-0.028	-702.8	545.3	0.802
	Regular	2,522 ± 1,653	0.072	-647.4	1272.9	0.519	0.048	-674.8	1093.4	0.639	0.023	-872.3	1074.7	0.836
Intra-pancreatic fat deposition, %	Never	9.7 ± 1.7	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	9.9 ± 1.7	-0.070	-1.37	0.71	0.529	-0.028	-1.24	0.97	0.811	-0.046	-1.39	0.96	0.714
	Regular	9.1 ± 1.8	0.007	-1.53	1.63	0.952	0.034	-1.38	1.87	0.764	0.032	-1.56	2.02	0.798
Intra-hepatic fat deposition, %	Never	9.2 ± 8.4	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	7.2 ± 2.0	0.097	-2.00	5.42	0.361	0.096	-2.43	5.83	0.415	0.069	-2.88	5.32	0.554
	Regular	12.6 ± 7.8	0.336	3.45	15.03	0.002	0.370	3.96	16.39	0.002	0.313	2.28	14.96	0.008
Skeletal muscle fat deposition, %	Never	16.1 ± 5.0	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	8.4 ± 1.9	-0.147	-6.20	1.19	0.181	0.070	-1.93	4.32	0.448	0.085	-1.95	4.84	0.399
	Regular	11.3 ± 5.5	-0.135	-9.38	2.16	0.217	0.017	-4.28	5.16	0.853	0.030	-4.48	6.10	0.760

Table 2. Associations Between Cannabis Use and the Studied Fat Phenotypes

Fat phenotype

Cannabis use

Mean ± SD

Model 1

Model 2

Model 3

95% CI

P-value

95% CI

P-value

95% CI

P-value

Lower

Upper

Lower

Upper

Lower

Upper

Model 1 was unadjusted. Model 2 was adjusted for age, sex and ethnicity. Model 3 was adjusted for age, sex, ethnicity, HbA1c level, tobacco smoking, alcohol consumption and physical activity. SD: standard deviation; B: beta coefficient; CI: confidence interval.

Subcutaneous fat volume, cm³

Never

2,769 ± 1,421

Ref

Non-regular

2,928 ± 266

-0.008

-759.8

706.9

0.943

-0.043

-911.6

617.3

0.702

-0.066

-1037.0

583.5

0.579

Regular

4,061 ± 1,644

0.246

174.3

2467.1

0.024

0.180

-190.4

2118.9

0.100

0.143

-496.1

2031.9

0.230

Visceral fat volume, cm³

Never

2,390 ± 1,134

Ref

Non-regular

2,190 ± 350

0.006

-596.7

631.7

0.955

-0.032

-674.7

495.9

0.762

-0.028

-702.8

545.3

0.802

Regular

2,522 ± 1,653

0.072

-647.4

1272.9

0.519

0.048

-674.8

1093.4

0.639

0.023

-872.3

1074.7

0.836

Intra-pancreatic fat deposition, %

Never

9.7 ± 1.7

Ref

Non-regular

9.9 ± 1.7

-0.070

-1.37

0.71

0.529

-0.028

-1.24

0.97

0.811

-0.046

-1.39

0.96

0.714

Regular

9.1 ± 1.8

0.007

-1.53

1.63

0.952

0.034

-1.38

1.87

0.764

0.032

-1.56

2.02

0.798

Intra-hepatic fat deposition, %

Never

9.2 ± 8.4

Ref

Non-regular

7.2 ± 2.0

0.097

-2.00

5.42

0.361

0.096

-2.43

5.83

0.415

0.069

-2.88

5.32

0.554

Regular

12.6 ± 7.8

0.336

3.45

15.03

0.002

0.370

3.96

16.39

0.002

0.313

2.28

14.96

0.008

Skeletal muscle fat deposition, %

Never

16.1 ± 5.0

Ref

Non-regular

8.4 ± 1.9

-0.147

-6.20

1.19

0.181

0.070

-1.93

4.32

0.448

0.085

-1.95

4.84

0.399

Regular

11.3 ± 5.5

-0.135

-9.38

2.16

0.217

0.017

-4.28

5.16

0.853

0.030

-4.48

6.10

0.760

**Table 3.** Associations Between Cannabis Use and the Studied Insulin Traits
Insulin traits	Cannabis use	Mean ± SD	Model 1	Model 2	Model 3
Model 1 was unadjusted. Model 2 was adjusted for age, sex and ethnicity. Model 3 was adjusted for age, sex, ethnicity, HbA1c level, tobacco smoking, alcohol consumption and physical activity. SD: standard deviation; B: beta coefficient; CI: confidence interval.
Indices of insulin sensitivity
HOMA-IS (fasting)	Never	0.68 ± 0.42	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	0.61 ± 0.35	-0.020	-0.536	0.480	0.911	0.002	-0.594	0.599	0.992	-0.253	-0.991	0.288	0.266
	Regular	0.45 ± 0.27	-0.079	-0.745	0.480	0.662	0.064	-0.700	0.913	0.788	0.038	-0.739	0.886	0.870
Raynaud index (fasting)	Never	3.30 ± 2.56	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	9.28 ± 20.77	0.281	-0.79	15.38	0.076	0.374	1.13	18.28	0.028	0.234	-2.64	14.77	0.165
	Regular	1.99 ± 1.71	-0.054	-26.76	12.33	0.728	0.031	-14.02	16.98	0.847	-0.038	-16.30	12.67	0.800
Matsuda index (post-prandial)	Never	0.72 ± 0.53	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	0.74 ± 0.35	-0.032	-0.732	0.609	0.854	-0.034	-0.834	0.702	0.861	-0.243	-1.262	0.326	0.236
	Regular	0.46 ± 0.38	-0.072	-0.976	0.643	0.366	0.032	-0.966	1.111	0.887	0.001	-1.007	1.005	0.999
Indices of insulin secretion
HOMA-β (fasting)	Never	142.6 ± 75.2	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	223.8 ± 134.6	0.212	-31.78	126.42	0.232	0.089	-70.14	109.81	0.654	0.334	-19.01	167.79	0.112
	Regular	155.9 ± 44.3	0.167	-50.49	140.20	0.345	0.115	-90.79	152.59	0.606	0.167	-72.25	162.24	0.434
Insulinogenic index 30’ (post-prandial)	Never	0.66 ± 1.27	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	-0.03 ± 0.25	-0.128	-2.823	1.475	0.524	-0.096	-3.036	2.027	0.681	0.046	-3.075	3.555	0.879
	Regular	1.91 ± 0.76	-0.026	-2.284	2.015	0.898	-0.145	-3.756	2.237	0.602	-0.025	-3.751	3.485	0.939
Insulinogenic index 60’ (post-prandial)	Never	0.53 ± 1.12	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref	Ref
	Non-regular	0.28 ± 0.72	-0.156	-2.203	0.980	0.433	-0.350	-3.032	0.298	0.101	0.085	-3.491	0.634	0.399
	Regular	1.76 ± 1.49	0.408	0.010	3.187	0.049	1.016	1.620	6.330	0.003	1.091	1.676	6.855	0.004

Table 3. Associations Between Cannabis Use and the Studied Insulin Traits

Insulin traits

Cannabis use

Mean ± SD

Model 1

Model 2

Model 3

95% CI

P-value

95% CI

P-value

95% CI

P-value

Lower

Upper

Lower

Upper

Lower

Upper

Indices of insulin sensitivity

HOMA-IS (fasting)

Never

0.68 ± 0.42

Ref

Non-regular

0.61 ± 0.35

-0.020

-0.536

0.480

0.911

0.002

-0.594

0.599

0.992

-0.253

-0.991

0.288

0.266

Regular

0.45 ± 0.27

-0.079

-0.745

0.480

0.662

0.064

-0.700

0.913

0.788

0.038

-0.739

0.886

0.870

Raynaud index (fasting)

Never

3.30 ± 2.56

Ref

Non-regular

9.28 ± 20.77

0.281

-0.79

15.38

0.076

0.374

1.13

18.28

0.028

0.234

-2.64

14.77

0.165

Regular

1.99 ± 1.71

-0.054

-26.76

12.33

0.728

0.031

-14.02

16.98

0.847

-0.038

-16.30

12.67

0.800

Matsuda index (post-prandial)

Never

0.72 ± 0.53

Ref

Non-regular

0.74 ± 0.35

-0.032

-0.732

0.609

0.854

-0.034

-0.834

0.702

0.861

-0.243

-1.262

0.326

0.236

Regular

0.46 ± 0.38

-0.072

-0.976

0.643

0.366

0.032

-0.966

1.111

0.887

0.001

-1.007

1.005

0.999

Indices of insulin secretion

HOMA-β (fasting)

Never

142.6 ± 75.2

Ref

Non-regular

223.8 ± 134.6

0.212

-31.78

126.42

0.232

0.089

-70.14

109.81

0.654

0.334

-19.01

167.79

0.112

Regular

155.9 ± 44.3

0.167

-50.49

140.20

0.345

0.115

-90.79

152.59

0.606

0.167

-72.25

162.24

0.434

Insulinogenic index 30’ (post-prandial)

Never

0.66 ± 1.27

Ref

Non-regular

-0.03 ± 0.25

-0.128

-2.823

1.475

0.524

-0.096

-3.036

2.027

0.681

0.046

-3.075

3.555

0.879

Regular

1.91 ± 0.76

-0.026

-2.284

2.015

0.898

-0.145

-3.756

2.237

0.602

-0.025

-3.751

3.485

0.939

Insulinogenic index 60’ (post-prandial)

Never

0.53 ± 1.12

Ref

Non-regular

0.28 ± 0.72

-0.156

-2.203

0.980

0.433

-0.350

-3.032

0.298

0.101

0.085

-3.491

0.634

0.399

Regular

1.76 ± 1.49

0.408

0.010

3.187

0.049

1.016

1.620

6.330

0.003

1.091

1.676

6.855

0.004