IRS-1 genetic polymorphism (r.2963G>A) in type 2 diabetes mellitus patients associated with insulin resistance

Figures & data

Table 1 Assessment of Hardy–Weinberg equilibrium for rs1801278 genotypes

	Control (N=120)		Cases (N=100)
	Observed	Expected	Observed	Expected
GG	108	108.3	70	68.9
GA	12	11.4	26	28.2
AA	0	0.3	4	2.9
P	0.564		0.432

Note: Deviations from Hardy–Weinberg equilibrium expectations were determined using the chi-squared test.

Table 2 Mean fasting serum glucose, insulin, HOMA and lipid profile concentration in T2DM patients and the control group

	Control (N=120)			T2DM (N=100)			P
	Median	Range		Median	Range
Triglyceridesa (mg/dL)	111.5	100	140	150.3	150	152	<0.001
Total cholesterolb (mg/dL)	183.5	165	200	201.4	201	202	<0.001
HDL-C (mg/dL)	51.0	40	70	24.7	25	25	<0.001
LDL-C (mg/dL)	107.4	95	127	146.5	66	148	<0.001
Fasting blood glucosec (mg/dL)	85.5	74	103	293.5	240	490	<0.001
FPI (IU/mL)	7.1	6.4	7.8	7.8	7.6	8.8	<0.001
HOMA-IR	1.3	1.4	1.7	5.7	4.5	9.8	<0.001
HBA1C (%)	4.9	4.1	5.6	7.0	6.6	7.5	<0.001
Waist circumference (cm)	87.5	76.3	99.3	79.4	66.9	91.9	0.03
	N	%		N	%
IR	0	0		66	66		<0.001

Notes: Numerical data are expressed as median, range, compared by Mann–Whitney test. Categorical data are expressed as number and percentage, compared by FET.

a SI conversion factors: to convert triglycerides to millimoles per liter and to multiply values by 0.0113.

b SI conversion factors: to convert cholesterol to millimoles per liter and to multiply values by 0.0259.

c SI conversion factors: to convert glucose to millimoles per liter and to multiply values by 0.0555.

Abbreviations: IS, insulin sensitive; FET, Fisher’s exact test; FPI, fasting plasma insulin; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostatic model assessment; IR, insulin resistance; LDL-C, low-density lipoprotein cholesterol; T2DM, type 2 diabetes mellitus.

Table 3 Comparison of rs1801278 (alleles and genotypes) in all the studied T2DM patients and healthy controls

	Control (N=120)		Cases (N=100)		P	OR	95% CI
	N	%	N	%
GG	108	90	70	70.0	–	R	–	–
GA	12	10	26	26.0	0.025	3.343	1.162	9.617
AA	0	0	4	4.0	0.999	–	–	–
GA+AA	12	10	30	30.0	0.011	3.857	1.366	10.890
GA+GG	120	100	96	96	0.041	–	–	–
GG+AA	108	90	74	74	0.002	0.489	0.310	0.770
G	228	95.0	166	83.0	–	R	–	–
A	12	5.0	34	17.0	0.004	3.892	1.471	10.294

Note: Logistic regression test was used.

Abbreviations: R, reference; T2DM, type 2 diabetes mellitus.

Figure 1 Identification of IRS1 gene polymorphism (r.2963G>A) using PCR-RFLP method.

Abbreviations: PCR, polymerase chain reaction; RFLP, restriction fragment length polymorphism.

Table 4 Comparison of laboratory data according to IR

	IS (N=34)			IR (N=66)			P
	Median	Range		Median	Range
Triglycerides (mg/dL)	149.9	150	151	150.4	150	152	0.448
Total cholesterol (mg/dL)	201.3	201	202	201.4	201	202	0.656
HDL-C (mg/dL)	24.7	25	25	24.7	25	25	0.958
LDL-C (mg/dL)	146.5	146	147	146.4	66	148	0.806
Fasting blood glucose (mg/dL)	258	240	275	315	268	490	<0.001
FPI (IU/mL)	7.7	7.6	8.4	8.1	7.6	8.8	0.005
HOMA-IR	4.9	4.5	5.1	6.3	5.2	9.8	<0.001
HBA1C (%)	7.0	6.6	7.5	7.0	6.6	7.5	0.742
Waist circumference (cm)	85.5	76.8	94.2	83.4	71.5	94.5	0.65

Note: Numerical data are expressed as median, minimum and maximum, compared by Mann–Whitney test.

Abbreviations: FPI, fasting plasma insulin; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostatic model assessment; IR, insulin-resistance; IS, insulin-sensitive; LDL-C, low-density lipoprotein cholesterol.

Table 5 Comparison of rs1801278 (genotypes and alleles) according to IS and IR in all the studied subjects

	Control (N=120)		IS (N= 34)		IR (N =66)		Prediction of IS in controls		Prediction of IR in controls		Prediction of IR in IS
							P	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)
	N	%	N	%	N	%
GG	108	90	30	88.2	40	60.6		R		R		R
GA	12	10	4	11.8	22	33.3	0.768	1.112 (0.548–2.257)	<0.001	2.690 (1.659–4.362)	0.076	2.317 (0.917–5.851)
AA	0	0	0	0	4	6.1	–	–	1	–	1
GA+AA	12	10	4	11.8	26	39.4	0.768	1.112 (0.548–2.257)	<0.001	2.979 (1.865–4.759)	0.043	2.536 (1.030–6.249)
GA+GG	120	100	34	100	62	93.9	–	–	0.015	–	0.296
GG+AA	108	90	30	88.2	44	66.7	0.768	0.899 (0.443–1.824)	<0.001	0.394 (0.243–0.637)	0.026	0.267 (0.083–0.852)
G	228	95	64	94.1	102	77.3		R		R		R
A	12	5	4	5.9	30	22.7	0.760	1.188 (0.370–3.807)	<0.001	5.588 (2.750–11.355)	0.034	4.706 (1.009–21.955)

Abbreviations: IR, insulin resistance; IS, insulin-sensitive.

Table 6 Regression analysis for prediction of insulin resistance within T2DM cases

	Univariable				Multivariable
	P	OR	95% CI		P	OR	95% CI
Age (years)	0.662	1.020	0.934	1.113
Gender	0.624	1.345	0.412	4.388
BMI (kg/m^2)	0.889	0.986	0.811	1.199
FH	0.488	1.560	0.445	5.474
Triglycerides (mg/dL)	0.699	1.194	0.485	2.943
Total cholesterol (mg/dL)	0.831	1.153	0.311	4.269
HDL-C (mg/dL)	0.950	1.142	0.018	7.010
LDL-C (mg/dL)	0.828	0.918	0.426	1.980
Fasting blood glucose (mg/dL)	0.035	1.392	1.023	1.893	0.247	1.054	0.964	1.153
FPI (IU/mL)	0.005	2.940	1.991	9.634	0.018	2.241	1.269	11.633
HOMA-IR	0.008	1.321	1.075	1.624	0.023	1.288	1.001	8.179
HBA1C (%)	0.710	1.456	0.201	10.528
rs1801278 (GA+AA)	0.043	2.536	1.030	6.249	0.018	0.895	0.429	1.867

Abbreviations: BMI, body mass index; FH, family history; FPI, fasting plasma insulin; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostatic model assessment; IR, insulin resistance; LDL-C, low-density lipoprotein cholesterol; T2DM, type 2 diabetes mellitus.

Table 7 Regression analysis for prediction of T2DM within healthy control subjects

	Univariable				Multivariable
	P	OR	95% CI		P	OR	95% CI
Age (years)	0.154	1.156	0.094	1.221
Gender	0.447	2.180	0.011	4.702
BMI (kg/cm^2)	0.017	1.155	1.027	1.299	0.027	1.396	1.192	1.900
Triglycerides (mg/dL)	<0.001	1.017	1.008	1.025	<0.001	1.003	1.002	1.005
Total cholesterol (mg/dL)	0.002	1.026	1.009	1.042	<0.001	1.009	1.007	1.011
HDL-C (mg/dL)	<0.001	0.978	0.967	0.989	<0.001	0.990	0.988	0.993
LDL-C (mg/dL)	<0.001	1.016	1.007	1.024	0.376	1.299	1.098	1.901
Fasting blood glucose (mg/dL)	<0.001	1.002	1.001	1.004	<0.001	1.003	1.002	1.005
FPI	0.002	1.552	1.170	2.058	0.004	1.075	1.023	1.130
HOMA-IR	<0.001	1.123	1.060	1.189	0.003	1.868	1.792	1.952
HBA1C (%)	<0.001	1.332	1.158	1.533	<0.001	1.150	1.120	1.181
rs1801278 (GA+AA)	0.011	3.857	1.366	10.890	<0.001	1.076	1.039	1.115

Abbreviations: BMI, body mass index; FPI, fasting plasma insulin; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostatic model assessment; IR, insulin resistance; LDL-C, low-density lipoprotein cholesterol; T2DM, type 2 diabetes mellitus.