Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors

doi:10.4239/wjd.v15.i1.53

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World Journal of Diabetes

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Retrospective Study

World J Diabetes. Jan 15, 2024; 15(1): 53-71
Published online Jan 15, 2024. doi: 10.4239/wjd.v15.i1.53

Table 1 Characteristics of 97 new-onset type 2 diabetes patients of normal weight, overweight and obesity

	NW (33)	OW (42)	OB (22)	F value	P value
Sex: M/F [n (%)]	20/13 (33)	24/18 (42)	13/9 (22)	0.095	0.954
Age (yr, mean ± SD)	43.64 ± 6.95	42.21 ± 9.76	36.77 ± 10.32^a	4.054	0.020^a
T2DM onset (d)	46.1 ± 96.8	41.8 ± 90.3	8.5 ± 20.2	1.569	0.214
Medication (Y/N)	13/20	13/29	6/16	1.016	0.602
Metformin equiv dose (g, mean ± SD)	176 ± 221	214 ± 225	546 ± 34	1.384	0.256
Weight (kg)	60.53 ± 6.87	73.49 ± 9.71^b^,^c	85.64 ± 11.35^b^,^c	49.593	0.000^b
Height (cm)	165.3 ± 8.26	168.5 ± 9.05	164.4 ± 6.91	1.407	0.250
BMI index	22.23 ± 1.60	25.88 ± 1.07^b^,^c	31.23 ± 2.31^b^,^c	208.086	0.000^b
Waist circumference (cm)	84.85 ± 6.21	89.76 ± 6.07^b^,^c	99.61 ± 7.05^b^,^c	35.920	0.000^b
Waist: Height ratio	0.514 ± 0.042	0.535 ± 0.034^a	0.604 ± 0.041^b^,^c	37.279	0.000^b
Systolic blood pressure (mmHg)	122.1 ± 17.6	125.6 ± 13.2	130.7 ± 18.2	12.68	0.07
Diastolic blood pressure (mmHg)	81.9 ± 12.8	83.8 ± 8.7	82.5 ± 15.7	0.509	0.602

^aP < 0.05 compared with normal weight.

^bP < 0.01, compared with normal weight.

^cP < 0.01, compared with overweight.

Data are numbers (n) of individuals (%) unless otherwise indicated. NW: Normal weight (body mass index: 18.5-23.9); OB: Obesity (body mass index: ≥ 28.0); OW: overweight (body mass index: 24.0-27.9); BMI: Body mass index; M: Male; F: Female.

Table 2 One-way/two-way ANOVA of serum amino acids in newly onset type-2 diabetes mellitus patients of normal weight, overweight and obesity (mean ± SD)

		NW	OW	OB	Obesity, F, P (1-way ANOVA)	Obesity, F, P (2-way ANOVA)	Sex, F value, P value	Obesity × sex interaction, F value, P value	Age-adjusted F value, P value	Onset-adjusted, F value, P value	Metf. dose-adjusted, F value, P value
HbA1c (%)	Pooled	10.96 ± 2.73	9.91 ± 2.69	9.09 ± 2.40^a	3.471, 0.035^a	2.888, 0.061^d	1.603, 0.209	0.376, 0.688	NS	NS	NS
	Male	11.51 ± 2.93	10.07 ± 2.78	9.25 ± 2.16	3.012, 0.058^d
	Female	10.12 ± 2.24	9.70 ± 2.64	8.85 ± 2.82	0.661, 0.522
TC (mmol/L)	Pooled	4.82 ± 1.36	4.68 ± 1.65	4.55 ± 1.10	0.229, 0.796	0.239, 0.788	1.020, 0.315	0.035, 0.965	NS	NS	NS
	Male	4.91 ± 1.24	4.80 ± 1.96	4.73 ± 1.14	0.053, 0.948
	Female	4.68 ± 1.58	4.52 ± 1.15	4.29 ± 1.04	0.243, 0.786
TG (mmol/L)	Pooled	3.12 ± 6.77	2.73 ± 3.18	4.66 ± 4.20	1.161, 0.318	0.992, 0.375	1.758, 0.188	0.253, 0.777	NS	NS	NS
	Male	3.85 ± 8.61	2.91 ± 3.94	5.45 ± 4.99	0.711, 0.496
	Female	2.00 ± 1.64	2.49 ± 1.80	3.53 ± 2.54	1.683, 0.200
HDL (mmol/L)	Pooled	1.07 ± 0.27	1.03 ± 0.27	0.86 ± 0.22	4.744, 0.011^a	4.478, 0.014^a	0.998, 0.320	0.337, 0.715	NS	NS	NS
	Male	1.07 ± 0.26	0.98 ± 0.23	0.84 ± 0.24	3.602, 0.034^a
	Female	1.08 ± 0.31	1.09 ± 0.32	0.88 ± 0.19	1.635, 0.209
LDL (mmol/L)	Pooled	2.82 ± 1.10	2.81 ± 0.87	2.34 ± 1.02	1.922, 0.152	1.670, 0.194	0.009, 0.925	0.121, 0.887	NS	NS	NS
	Male	2.83 ± 0.96	2.87 ± 0.84	2.29 ± 0.99	1.870, 0.164
Histidine (μg/L)	Pooled	188.42 ± 40.62	197.28 ± 57.63	219.62 ± 53.34	2.488, 0.089	2.010, 0.140	3.614, 0.060^d	0.651, 0.524	NS	NS	NS
	Male	190.30 ± 45.33	205.95 ± 62.41	234.87 ± 49.68	2.680, 0.078^d
	Female	185.53 ± 33.68	185.72 ± 49.92	197.59 ± 53.32	0.234, 0.792
Arginine (μg/L)	Pooled	458.53 ± 180.93	480.08 ± 198.77	507.06 ± 127.36	0.487, 0.616	0.423, 0.656	0.219, 0.641	0.044, 0.957	NS	NS	NS
	Male	459.85 ± 163.56	492.30 ± 231.02	516.31 ± 131.56	0.369, 0.693
	Female	456.51 ± 211.98	463.80 ± 150.31	493.70 ± 127.59	0.140, 0.870
β-Alanine (μg/L)	Pooled	436.45 ± 188.57	445.91, 188.70	394.88, 202.89	0.530, 0.591	0.402, 0.670	0.569, 0.452	0.942, 0.394	NS	NS	NS
	Male	454.86 ± 200.68	425.40 ± 177.60	357.16 ± 178.59	1.100, 0.340
	Female	408.11 ± 172.11	473.25 ± 204.50	449.37 ± 233.59	0.395, 0.676
Carnosine (μg/L)	Pooled	5.99 ± 1.37	5.98 ± 2.06	6.95 ± 1.50	2.671, 0.074	3.122, 0.049	0.013, 0.908	1.193, 0.308	NS	NS	NS
	Male	6.27 ± 1.41	5.93 ± 2.36	6.65 ± 1.34	0.632, 0.535
	Female	5.55 ± 1.22	6.04 ± 1.63	7.39 ± 1.69^a	4.035, 0.026^a
Serine (μg/L)	Pooled	268.73 ± 91.46	239.17 ± 83.33	283.56 ± 79.43	2.258, 0.110	2.182, 0.119	7.451, 0.008^b	0.567, 0.569	NS	NS	NS
	Male	297.99 ± 77.49	256.57 ± 87.30	295.74 ± 64.80	1.817, 0.172
	Female	223.72 ± 95.80	215.97 ± 73.74	265.98 ± 98.35	1.038, 0.364
Taurine (μg/L)	Pooled	71.97 ± 18.22	78.96 ± 30.38	75.98 ± 22.23	0.721, 0.489	1.054, 0.353	1.714, 0.194	0.685, 0.507	9.335, 0.003^b	NS	NS
	Male	72.61 ± 17.85	74.52 ± 30.24	76.10 ± 21.65	0.083, 0.921
	Female	71.00 ± 19.47	84.88 ± 30.39	75.81 ± 24.38	1.131, 0.334
Alanine (μg/L)	Pooled	130.77 ± 49.32	139.06 ± 40.66	168.94 ± 56.03^a	4.531, 0.013^a	3.967, 0.022^a	0.007, 0.934	0.812, 0.447	NS	NS	NS
	Male	123.80 ± 46.98	143.52 ± 40.18	170.88 ± 56.72^a	4.013, 0.024^a
	Female	141.51 ± 52.77	133.10 ± 41.67	166.14 ± 58.32	1.357, 0.270
Asparagine (μg/L)	Pooled	36.73 ± 13.82	30.17 ± 16.07	40.40 ± 13.67^c	3.900, 0.024^a	3.817, 0.026^a	7.684, 0.007^b	0.586, 0.559	NS	NS	NS
	Male	38.32 ± 15.37	34.05 ± 18.30	45.52 ± 11.83	2.161, 0.125
	Female	34.28 ± 11.16	25.01 ± 10.95	33.01 ± 13.30	2.865, 0.070^d
Glutamine (μg/L)	Pooled	464.62 ± 156.05	450.21 ± 188.81	489.96 ± 120.18	0.422, 0.657	0.530, 0.590	0.652, 0.421	0.857, 0.428	NS	NS	NS
	Male	459.31 ± 156.09	486.60 ± 219.88	495.68 ± 135.66	0.192, 0.826
	Female	472.80 ± 162.00	401.70 ± 127.29	481.70 ± 100.88	1.534, 0.229
Glutamate (μg/L)	Pooled	2812.36 ± 1104.11	2768.39 ± 1153.78	3588.65 ± 1138.22^a^,^e	4.259, 0.017^a	4.028, 0.021^a	5.188, 0.025^a	0.176, 0.839	NS	NS	NS
	Male	2949.39 ± 1011.65	3028.47 ± 1234.29	3866.48 ± 1088.44	3.039, 0.056^d
	Female	2601.55 ± 1245.38	2421.62 ± 962.57	3187.33 ± 1147.67	1.470, 0.243
Lysine (μg/L)	Pooled	341.06 ± 128.62	365.48 ± 152.71	423.72 ± 142.42	2.262, 0.110	2.087, 0.130	6.688, 0.011^a	0.376, 0.687	NS	NS	NS
	Male	357.60 ± 124.07	406.28 ± 172.85	462.00 ± 157.70	1.831, 0.170
	Female	315.62 ± 136.32	311.08 ± 101.65	368.42 ± 100.58	0.833, 0.443
Hydroxyproline (μg/L)	Pooled	21.09 ± 11.77	14.33 ± 11.68^a	21.41 ± 12.09	4.050, 0.021^a	3.901, 0.024^a	9.074, 0.003^b	0.614, 0.543	NS	NS	NS
	Male	22.84 ± 12.69	17.00 ± 12.59	26.07 ± 12.48	2.472, 0.094
	Female	18.39 ± 10.06	10.78 ± 9.55	14.67 ± 7.98	2.490, 0.097
Threonine (μg/L)	Pooled	201.17 ± 88.38	208.93 ± 86.51	236.53 ± 82.51	1.173, 0.314	0.950, 0.390	3.035, 0.085^d	0.293, 0.746	NS	NS	NS
	Male	209.66 ± 92.11	217.95 ± 89.86	258.54 ± 87.84	1.259, 0.292
	Female	188.12 ± 84.22	196.90 ± 82.80	204.73 ± 66.12	0.118, 0.889
Citrulline (μg/L)	Pooled	95.53 ± 32.87	90.68 ± 34.25	94.71 ± 27.50	0.237, 0.790	0.527, 0.592	6.414, 0.013^a	0.001, 0.999	6.232, 0.014^a	NS	NS
	Male	101.68 ± 34.73	96.78 ± 38.17	98.59 ± 30.95	0.105, 0.901
	Female	86.06 ± 28.48	82.54 ± 27.12	89.11 ± 22.12	0.195, 0.824
Proline (μg/L)	Pooled	2313.70 ± 644.63	2244.77 ± 716.36	2561.43 ± 555.47	1.707, 0.187	3.138, 0.048^a	0.941, 0.335	3.279, 0.042^a	6.754, 0.011^a	NS	NS
	Male	2176.16 ± 572.03	2404.58 ± 839.03	2604.08 ± 534.61	1.560, 0.220
	Female	2525.30 ± 714.13	2031.68 ± 448.42^a	2499.81 ± 611.56	3.418, 0.043^a
Homocysteine (μg/L)	Pooled	2.50 ± 1.71	2.68 ± 1.64	2.27 ± 1.33	0.481, 0.620	0.800, 0.453	0.194, 0.661	1.812, 0.169	NS	NS	NS
	Male	2.26 ± 1.66	2.39 ± 1.43	2.61 ± 1.52	0.205, 0.815
	Female	2.88 ± 1.78	3.06 ± 1.85	1.77 ± 0.82	1.916, 0.161
Valine (μg/L)	Pooled	3839.99 ± 883.13	3718.96 ± 851.75	4259.02 ± 820.20	2.938, 0.058^d	2.627, 0.078^d	1.547, 0.217	1.385, 0.256	NS	NS	NS
	Male	3763.81 ± 926.69	3876.21 ± 837.88	4465.80 ± 583.75	3.144, 0.051^d
	Female	3957.18 ± 833.97	3509.28 ± 847.57	3960.35 ± 1041.61	1.264, 0.294
Methionine (μg/L)	Pooled	2.44 ± 1.86	2.48 ± 1.97	3.21 ± 2.24	1.201, 0.306	0.754, 0.473	3.091, 0.082^d	2.568, 0.082^d	NS	NS	NS
	Male	2.23 ± 1.92	2.84 ± 2.11	3.99 ± 2.50	2.658, 0.079^d
	Female	2.76 ± 1.78	2.01 ± 1.70	2.09 ± 1.15	0.879, 0.424
Isoleucine (μg/L)	Pooled	306.68 ± 75.83	326.23 ± 81.56	357.51 ± 75.72	2.778, 0.067	2.325, 0.104	6.977, 0.010^b	0.786, 0.459	NS	NS	NS
	Male	313.67 ± 73.98	343.49 ± 87.07	386.75 ± 75.14^a	3.283, 0.045^a
	Female	295.93 ± 80.37	303.21 ± 69.32	315.27 ± 56.43	0.200, 0.820
Leucine(μg/L)	Pooled	492.26 ± 136.62	518.94 ± 147.01	577.40 ± 153.91	2.301, 0.106	1.909, 0.154	8.751, 0.004^b	0.856, 0.428	NS	NS	NS
	Male	511.46 ± 137.96	548.74 ± 163.13	638.14 ± 137.20	2.896, 0.064^d
	Female	462.73 ± 134.45	479.21 ± 114.87	489.66 ± 138.87	0.129, 0.879
Tyrosine (μg/L)	Pooled	155.13 ± 57.40	166.00 ± 63.14	203.68 ± 74.79^a	3.998, 0.022^a	3.370, 0.039^a	5.255, 0.024^a	1.448, 0.240	NS	NS	NS
	Male	154.79 ± 57.19	182.95 ± 70.70	225.47 ± 58.95^b	4.857, 0.011^a
	Female	155.65 ± 60.07	143.39 ± 43.65	172.21 ± 87.10	0.685, 0.511
Phenylalanine (μg/L)	Pooled	664.47 ± 163.17	699.89 ± 172.50	785.74 ± 197.37^a	3.223, 0.044^a	2.909, 0.060^d	2.806, 0.097^d	0.384, 0.682	NS	NS	NS
	Male	688.44 ± 154.62	709.87 ± 191.09	828.45 ± 208.14	2.534, 0.089^d
	Female	627.58 ± 175.24	686.60 ± 148.44	724.03 ± 173.28	1.002, 0.377
Tryptophan(μg/L)	Pooled	658.00 ± 150.01	694.36 ± 188.43	790.15 ± 162.27^a	4.082, 0.020^a	4.277, 0.017^a	13.121, 0.000^b	0.051, 0.951	NS	NS	NS
	Male	702.38 ± 151.16	746.40 ± 193.72	847.94 ± 127.90	3.062, 0.055^d
	Female	589.72 ± 124.48	624.97 ± 161.06	706.66 ± 176.95	1.567, 0.222

^aP < 0.05 vs normal weight (or male vs female).

^bP < 0.01, vs normal weight (or male vs female).

^cP < 0.1 vs overweight.

^dP < 0.1 vs normal weight.

^eP < 0.01, vs overweight.

NS: Not significant, NW: Normal weight; OB: Obesity; OW: Overweight; HbA1c: Hemoglobin A1c; TC: Total cholesterol; TG: Triglyceride; HDL: High-density lipoprotein; LDL: Low-density lipoprotein.

Table 3 Correlation coefficients between serum amino acids and adiposity, body weight and body mass index in 97 type 2 diabetes patients differing in body mass index categories

Amino acids	Pooled (n = 97)				Obese (n = 22)				Overweight (n = 42)				Normal weight (n = 33)
Amino acids	VAT	Body weight	BMI	HDL	VAT	Body weight	BMI	HDL	VAT	Body weight	BMI	HDL	VAT	Body weight	BMI	HDL
Valine	0.375^b	0.236^a	0.212^a	NS	0.311	0.217	0.009	NS	0.140	0.286^c	0.223	NS	0.150	0.008	0.167	NS
Isoleucine	0.443^b	0.287^b	0.255^a	-0.309^b	0.109	0.106	-0.095	NS	0.347^c	0.289^c	0.301^d	-0.417^b	0.351	0.047	0.114	NS
Leucine	0.396^b	0.315^b	0.249^a	-.276^b	0.120	0.201	-0.068	NS	0.312	0.320^a	0.340^a	-0.345^a	0.133	0.159	0.173	NS
Tyrosine	0.524^b	0.341^b	0.301^b	NS	0.447	0.136	0.002	NS	0.251	0.343^a	0.094	NS	-0.036	0.154	0.347^a	NS
Phenylalanine	0.508^b	0.264^b	0.262^a	-0.307^b	0.177	0.176	0.027	NS	0.607^b	0.096	0.171	-0.323^a	0.185	0.156	0.085	NS
Tryptophan	0.373^a	0.362^b	0.236^a	NS	0.382	0.076	-0.230	NS	0.107	0.339^a	0.114	NS	-0.042	0.280	-0.012	NS
Methionine	0.379^b	0.251^a	0.228^a	NS	0.229	0.223	0.105	NS	0.377^c	0.327^a	0.357^a	NS	-0.263	0.050	0.296^c	NS
Taurine	-0.367^a	-0.001	0.047	NS	-0.479^c	-0.043	-0.164	NS	-0.451^a	-0.153	0.142	NS	-0.345	0.083	-0.082	NS
Alanine	0.429^b	0.194^d	0.268^b	NS	0.640^a	0.178	0.078	NS	-0.027	-0.041	-0.095	NS	0.304	-0.171	0.043	NS
Asparagine	0.278^d	0.218^a	0.079	-0.222^a	0.200	0.333	0.049	-0.478^a	0.129	0.287^c	0.008	NS	-0.192	0.206	-0.052	NS
Glutamine	0.253^c	0.157	0.052	NS	0.422	0.075	0.042	NS	-0.021	0.282^c	0.043	NS	0.000	0.070	-0.072	NS
Glutamate	0.398^b	0.263^b	0.234^a	NS	0.147	0.172	0.133	NS	0.291	0.181	0.021	NS	-0.024	0.113	-0.053	NS
Lysine	0.390^b	0.272^b	0.203^a	NS	0.372	0.124	0.053	NS	0.237	0.277^c	0.090	NS	-0.246	0.059	-0.054	NS
Hydroxyproline	0.293^a	0.025	-0.008	NS	-0.428	0.080	0.015	-0.436^a	0.276	0.172	0.056	NS	0.192	-0.105	-0.171	NS
Threonine	0.388^b	0.237^a	0.190^c	NS	0.573^a	0.322	0.233	NS	0.108	0.190	0.177	NS	0.012	0.088	0.005	NS
Citrulline	0.118	0.035	-0.046	NS	-0.146	-0.114	-0.043	NS	0.068	0.231	0.015	NS	-0.120	-0.052	-0.233	NS
Proline	0.314^a	0.099	0.104	NS	0.295	-0.015	-0.162	NS	0.059	0.205	-0.061	NS	0.018	-0.310^c	0.047	NS
Homocysteine	-0.132	0.007	-0.011	NS	0.232	0.475^a	0.431	NS	-0.201	-0.109	-0.061	NS	0.251	-0.015	-0.020	NS
Histidine	0.278^d	0.331^b	0.250^a	NS	0.316	0.358	0.123	NS	0.085	0.275^c	0.231	NS	-0.274	0.100	0.012	NS
Arginine	0.167	0.042	0.042	NS	0.097	-0.189	-0.226	NS	0.122	0.078	-0.100	NS	-0.215	-0.182	-0.088	NS
β-Alanine	-0.134	-0.073	-0.108	NS	0.241	-0.108	0.069	NS	-0.360^c	-0.175	-0.329^a	NS	0.193	0.306^c	-0.037	NS
Carnosine	0.278^d	0.162	0.157	NS	0.113	-0.121	-0.143	NS	0.056	0.062	0.054	NS	-0.649^a	0.200	-0.156	NS
Serine	0.149	0.151	0.039	-0.240^a	-0.157	-0.031	-0.154	NS	0.121	0.159	-0.121	NS	-0.220	0.465^b	0.111	NS

^aP < 0.05.

^bP < 0.01.

^cP < 0.1.

^dP < 0.06.

BMI: Body mass index; HDL: High density lipoprotein; VAT: Visceral adipose tissue; NS: Not significant.

Citation: Wang M, Ou Y, Yuan XL, Zhu XF, Niu B, Kang Z, Zhang B, Ahmed A, Xing GQ, Su H. Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors. World J Diabetes 2024; 15(1): 53-71
URL: https://www.wjgnet.com/1948-9358/full/v15/i1/53.htm
DOI: https://dx.doi.org/10.4239/wjd.v15.i1.53