Medications in type-2 diabetics and their association with liver fibrosis

Table 1 Demographic and clinical characteristics

Factor	Overall (n = 1183)		Fibrosis 0-2 (n = 802)		Fibrosis 3-4 (n = 381)		P value
	n	Statistics	n	Statistics	n	Statistics
Age at biopsy (yr)	1183	52.0 ± 11.6	802	50.3 ± 11.5	381	55.5 ± 11.1	< 0.0011
Gender	1183		802		381		0.0173
Female		777 (65.7)		545 (68.0)		232 (60.9)
Male		406 (34.3)		257 (32.0)		149 (39.1)
Race	1183		802		381		< 0.0013
Caucasian		1007 (85.1)		665 (82.9)		342 (89.8)
African American		109 (9.2)		97 (12.1)		12 (3.1)
Other		67 (5.7)		40 (5.0)		27 (7.1)
Smoking	1173		795		378		0.0413
Never		675 (57.5)		477 (60.0)		198 (52.4)
Former		426 (36.3)		274 (34.5)		152 (40.2)
Current		72 (6.1)		44 (5.5)		28 (7.4)
BMI	1183	35.4 ± 8.3	802	35.4 ± 8.1	381	35.2 ± 8.8	0.571
BMI group	1183		802		381		0.592
Normal weight		74 (6.3)		41 (5.1)		33 (8.7)
Overweight		233 (19.7)		161 (20.1)		72 (18.9)
Obese		596 (50.4)		413 (51.5)		183 (48.0)
Severely obese		280 (23.7)		187 (23.3)		93 (24.4)
SBP	1183	129.6 ± 17.1	802	129.5 ± 16.6	381	129.9 ± 18.2	0.661
DBP	1183	73.7 ± 11.0	802	74.5 ± 10.5	381	72.1 ± 11.7	< 0.0011
Hypertension	1183	781 (66.0)	802	561 (70.0)	381	220 (57.7)	< 0.0013
Hyperlipidemia	1183	734 (62.0)	802	547 (68.2)	381	187 (49.1)	< 0.0013
CKD	1183	89 (7.5)	802	37 (4.6)	381	52 (13.6)	< 0.0013
IBD type	1181		802		379		0.293
CD		29 (2.5)		18 (2.2)		11 (2.9)
UC		14 (1.2)		12 (1.5)		2 (0.53)
None		1138 (96.4)		772 (96.3)		366 (96.6)
IBD	1181	43 (3.6)	802	30 (3.7)	379	13 (3.4)	0.793
Stricturing disease	1183	17 (1.4)	802	10 (1.2)	381	7 (1.8)	0.433
DVT	1183	66 (5.6)	802	43 (5.4)	381	23 (6.0)	0.643

¹ANOVA.

²Kruskal-Wallis test.

³Pearson's χ² test. Statistics presented as mean ± SD or n (%). BMI: Body mass index; SBP: Systolic blood pressures; DBP: Diastolic blood pressures; CKD: Chronic kidney disease; CD: Crohn's disease; UC: Ulcerative colitis; IBD: Inflammatory bowel disease; DVT: Deep venous thrombosis.

Table 2 Medication use

Factor	Overall (n = 1183)		Fibrosis 0-2 (n = 802)		Fibrosis 3-4 (n = 381)		P value
	n	Statistics	n	Statistics	n	Statistics
Oral hypoglycemic medications	1183	691 (58.4)	802	494 (61.6)	381	197 (51.7)	0.0012
Oral hypoglycemic duration (mo)	691	19.4 (5.0, 52.1)	494	20.6 (5.5, 54.4)	197	17.4 (3.4, 50.0)	0.0981
Metformin use	1183	631 (53.3)	802	461 (57.5)	381	170 (44.6)	< 0.0012
Metformin duration (mo)	631	20.0 (5.1, 53.3)	461	20.8 (5.4, 54.5)	170	18.3 (4.5, 52.1)	0.361
Glipizide use	1183	116 (9.8)	802	82 (10.2)	381	34 (8.9)	0.482
Glipizide duration (mo)	116	17.2 (5.6, 45.4)	82	19.2 (5.5, 47.7)	34	16.4 (6.0, 42.2)	0.851
Pioglitazone use	1183	136 (11.5)	802	100 (12.5)	381	36 (9.4)	0.132
Pioglitazone duration (mo)	136	15.5 (5.6, 44.8)	100	15.8 (6.1, 51.9)	36	12.5 (3.0, 40.8)	0.301
Sitagliptin/Januvia use	1183	147 (12.4)	802	100 (12.5)	381	47 (12.3)	0.952
Sitagliptin/Januvia duration (mo)	147	7.2 (1.6, 26.2)	100	7.4 (2.3, 26.6)	47	5.0 (0.30, 24.9)	0.231
Saxagliptin use	1183	10 (0.85)	802	9 (1.1)	381	1 (0.26)	0.132
Insulin	1183	370 (31.3)	802	253 (31.5)	381	117 (30.7)	0.772
Insulin duration (mo)	370	10.9 (2.7, 34.0)	253	11.9 (3.0, 36.8)	117	8.3 (2.5, 25.3)	0.121
Liraglutide use	1183	69 (5.8)	802	61 (7.6)	381	8 (2.1)	< 0.0012
Liraglutide duration (mo)	69	8.9 (2.6, 21.2)	61	8.6 (2.5, 17.9)	8	20.8 (5.0, 35.0)	0.131
Detemir/Levemir use	1183	67 (5.7)	802	48 (6.0)	381	19 (5.0)	0.492
Detemir/Levemir duration (mo)	67	5.9 (1.1, 17.7)	48	3.9 (0.85, 16.4)	19	9.0 (1.8, 17.7)	0.391
Lantus use	1183	202 (17.1)	802	127 (15.8)	381	75 (19.7)	0.102
Lantus duration (mo)	202	8.2 (0.80, 37.6)	127	9.2 (0.90, 42.8)	75	6.6 (0.20, 25.1)	0.171
Humulin use	1183	65 (5.5)	802	49 (6.1)	381	16 (4.2)	0.182
Humulin duration (mo)	65	12.0 (2.8, 34.0)	49	12.8 (2.0, 34.9)	16	8.4 (5.2, 18.7)	0.881
Byetta use	1183	119 (10.1)	802	83 (10.3)	381	36 (9.4)	0.632
Byetta duration (mo)	119	10.2 (3.8, 24.0)	83	11.9 (4.4, 24.0)	36	7.1 (2.5, 24.5)	0.211
Antihypertensive medications	1183	787 (66.5)	802	538 (67.1)	381	249 (65.4)	0.562
Antihypertensive duration (mo)	787	26.8 (4.7, 63.1)	538	31.3 (5.8, 65.8)	249	18.1 (3.1, 55.5)	0.0101
Lisinopril use	1183	377 (31.9)	802	274 (34.2)	381	103 (27.0)	0.0142
Lisinopril duration (mo)	377	16.1 (3.8, 49.0)	274	18.1 (3.6, 49.4)	103	12.4 (5.2, 48.6)	0.861
Losartan use	1183	112 (9.5)	802	71 (8.9)	381	41 (10.8)	0.292
Losartan duration (mo)	112	18.6 (3.2, 51.4)	71	24.1 (6.2, 54.3)	41	9.1 (2.1, 25.8)	0.0771
Furosemide use	1183	252 (21.3)	802	135 (16.8)	381	117 (30.7)	< 0.0012
Furosemide duration (mo)	252	8.7 (1.8, 39.4)	135	10.9 (2.3, 47.2)	117	7.9 (1.4, 30.0)	0.161
Hydrochlorothiazide use	1183	371 (31.4)	802	279 (34.8)	381	92 (24.1)	< 0.0012
Hydrochlorothiazide duration (mo)	371	32.9 (7.9, 65.6)	279	34.4 (9.2, 67.1)	92	22.6 (4.8, 58.0)	0.0891
Spironolactone use	1183	115 (9.7)	802	47 (5.9)	381	68 (17.8)	< 0.0012
Spironolactone duration (mo)	115	5.4 (0.90, 29.1)	47	18.7 (3.6, 46.9)	68	3.0 (0.25, 10.4)	< 0.0012
Amlodipine use	1183	180 (15.2)	802	128 (16.0)	381	52 (13.6)	0.302
Amlodipine duration (mo)	180	14.1 (3.0, 40.4)	128	14.7 (3.0, 40.9)	52	12.2 (3.5, 31.2)	0.451
Metoprolol use	1183	273 (23.1)	802	185 (23.1)	381	88 (23.1)	0.992
Metoprolol duration (mo)	273	11.4 (0.20, 45.1)	185	12.2 (0.20, 45.9)	88	10.0 (0.20, 36.1)	0.411
Carvedilol use	1183	50 (4.2)	802	28 (3.5)	381	22 (5.8)	0.0682
Carvedilol duration (mo)	50	8.9 (2.3, 22.3)	28	11.3 (1.4, 28.7)	22	8.4 (2.9, 13.5)	0.391
Antilipidemic medications	1183	522 (44.1)	802	380 (47.4)	381	142 (37.3)	0.0012
Antilipidemic duration (mo)	522	24.3 (5.3, 54.6)	380	24.8 (5.5, 62.4)	142	20.9 (4.4, 43.3)	0.0861
Rosuvastatin use	1183	84 (7.1)	802	61 (7.6)	381	23 (6.0)	0.332
Rosuvastatin duration (mo)	84	10.4 (2.7, 40.8)	61	10.8 (3.0, 35.4)	23	7.7 (2.2, 41.2)	0.581
Atorvastatin use	1183	243 (20.5)	802	179 (22.3)	381	64 (16.8)	0.0282
Atorvastatin duration (mo)	243	21.0 (5.3, 61.9)	179	23.5 (5.4, 66.7)	64	14.6 (4.4, 45.4)	0.301
Simvastatin use	1183	251 (21.2)	802	187 (23.3)	381	64 (16.8)	0.0102
Simvastatin duration (mo)	251	15.6 (3.4, 45.8)	187	15.6 (3.6, 51.1)	64	16.5 (1.6, 36.8)	0.211
Pravastatin use	1183	79 (6.7)	802	57 (7.1)	381	22 (5.8)	0.392
Pravastatin duration (mo)	79	13.8 (2.4, 33.9)	57	13.8 (2.0, 30.7)	22	15.4 (4.3, 34.7)	0.811
Gemfibrozil use	1183	38 (3.2)	802	27 (3.4)	381	11 (2.9)	0.662
Gemfibrozil duration (mo)	38	12.3 (3.0, 50.5)	27	7.9 (2.1, 49.0)	11	33.5 (5.8, 62.3)	0.121
Fenofibrate use	1183	109 (9.2)	802	78 (9.7)	381	31 (8.1)	0.382
Fenofibrate duration (mo)	109	17.2 (5.7, 40.7)	78	22.0 (6.0, 44.6)	31	12.6 (3.1, 28.7)	0.271
Aspirin use	1183	339 (28.7)	802	245 (30.5)	381	94 (24.7)	0.0372
Aspirin dose	335		241		94		0.982
81 mg		328 (97.9)		236 (97.9)		92 (97.9)
325 mg		7 (2.1)		5 (2.1)		2 (2.1)

¹Kruskal-Wallis test.

²Pearson's χ² test. Statistics presented as median (P25, P75) or n (%).

Table 3 Assessment of associations between clinical factors and advanced fibrosis

Factor	Unadjusted		Adjusted1
	OR (95%CI)	P value	OR (95%CI)	P value
Hypertension	0.59 (0.46, 0.76)	< 0.001	0.52 (0.39, 0.68)	< 0.001
Hyperlipidemia	0.45 (0.35, 0.58)	< 0.001	0.42 (0.32, 0.54)	< 0.001
CKD	3.3 (2.1, 5.1)	< 0.001	2.6 (1.7, 4.2)	< 0.001
IBD	0.91 (0.47, 1.8)	0.79	0.94 (0.47, 1.9)	0.85
DVT	1.1 (0.67, 1.9)	0.64	0.99 (0.58, 1.7)	0.97
Oral Hypoglycemic medications	0.67 (0.52, 0.85)	0.001	0.69 (0.53, 0.89)	0.004
Metformin use	0.60 (0.47, 0.76)	< 0.001	0.64 (0.49, 0.82)	< 0.001
Glipizide use	0.86 (0.57, 1.3)	0.48	0.93 (0.60, 1.4)	0.75
Pioglitazone use	0.73 (0.49, 1.10)	0.13	0.71 (0.47, 1.08)	0.11
Sitagliptin/Januvia use	0.99 (0.68, 1.4)	0.95	0.95 (0.65, 1.4)	0.79
Insulin	0.96 (0.74, 1.3)	0.77	1.02 (0.77, 1.3)	0.91
Liraglutide use	0.26 (0.12, 0.55)	< 0.001	0.30 (0.14, 0.64)	0.002
Detemir/Levemir use	0.82 (0.48, 1.4)	0.49	0.94 (0.53, 1.7)	0.83
Lantus use	1.3 (0.95, 1.8)	0.10	1.3 (0.92, 1.8)	0.14
Humulin use	0.67 (0.38, 1.2)	0.18	0.75 (0.41, 1.4)	0.35
Byetta use	0.90 (0.60, 1.4)	0.63	1.1 (0.72, 1.7)	0.65
Antihypertensive medications	0.93 (0.72, 1.2)	0.56	0.77 (0.59, 1.02)	0.064
Lisinopril use	0.71 (0.55, 0.93)	0.014	0.74 (0.56, 0.97)	0.031
Losartan use	1.2 (0.83, 1.9)	0.30	1.09 (0.71, 1.7)	0.70
Furosemide use	2.2 (1.6, 2.9)	< 0.001	1.9 (1.4, 2.5)	< 0.001
Hydrochlorothiazide use	0.60 (0.45, 0.79)	< 0.001	0.57 (0.43, 0.76)	< 0.001
Spironolactone use	3.5 (2.4, 5.2)	< 0.001	3.1 (2.0, 4.6)	< 0.001
Amlodipine use	0.83 (0.59, 1.2)	0.30	0.74 (0.51, 1.07)	0.11
Metoprolol use	1.00 (0.75, 1.3)	0.99	0.87 (0.64, 1.2)	0.37
Carvedilol use	1.7 (0.96, 3.0)	0.071	1.6 (0.89, 3.0)	0.12
Antilipidemic medications	0.66 (0.51, 0.85)	0.001	0.58 (0.45, 0.76)	< 0.001
Rosuvastatin use	0.78 (0.48, 1.3)	0.33	0.66 (0.40, 1.1)	0.12
Atorvastatin use	0.70 (0.51, 0.96)	0.029	0.62 (0.44, 0.86)	0.004
Simvastatin use	0.66 (0.48, 0.91)	0.011	0.61 (0.44, 0.85)	0.003
Pravastatin use	0.80 (0.48, 1.3)	0.39	0.75 (0.44, 1.3)	0.28
Gemfibrozil use	0.85 (0.42, 1.7)	0.66	0.92 (0.44, 1.9)	0.82
Fenofibrate use	0.82 (0.53, 1.3)	0.38	0.73 (0.47, 1.1)	0.18
Aspirin use	0.74 (0.56, 0.98)	0.037	0.58 (0.43, 0.78)	< 0.001

¹Adjusted for age at time of biopsy, gender, race and body mass index. CKD: Chronic kidney disease; IBD: Inflammatory bowel disease; DVT: Deep venous thrombosis; OR: Odds ratio; CI: Confidence interval.