A study to investigate genetic factors associated with weight gain in people with diabetes: analysis of polymorphisms in four relevant genes

Figures & data

Table 1. Description of BMI increase category by diagnosis and by gender.

		Gender (Female %)	N	Mean age of diagnosis (y) Male	Mean age of diagnosis or equivalent age if controls (y) Female	Mean duration of follow-up (y) Female	Mean duration of follow-up (y) Male	Mean (sd) BMI at diagnosis (kg/m^2) or equivalent age if controls Female	Mean (sd) BMI at diagnosis (kg/m^2) or equivalent age if controls Male	BMI last recorded Female (kg/m^2)	BMI last record Male (kg/m^2)
BMI increase <=10%	Control	51.7	22	43.0	50.6	17.0	16.0	28.5 (8.8)	27.8 (4.5)	27.4 (9.3)	27.5 (4.3)
	T1D	38.8	30	39.4	31.5	19.3	37.0	31.0 (14.8)	33.5 (15.9)	27.6 (15.4)	25.5 (4.7)
	T2D	39.4	92	52.4	53.6	16.8	17.0	33.3 (8.7)	33.6 (10.8)	29.3 (7.2)	29.4 (7.1)
BMI increase >10%	Control	72.0	24	33.8	27.6	19.9	26.4	24.0 (3.5)	23.9 (3.5)	29.8 (5.1)	27.7 (4.6)
	T1D	43.8	81	25.5	36.3	32.3	23.4	25.0 (6.8)	24.5 (5.8)	30.9 (7.8)	28.7 (5.9)
	T2D	44.0	130	52.9	48.6	16.7	20.2	30.3 (7.4)	28.4 (7.0)	35.5 (9.7)	32.7 (7.1)

BMI, body mass index.

Table 2. Genotype distributions by diagnosis.

	N	BDNF rs6265		CAV-1 rs926198		FTO rs9939609		LEPR rs1137101
Controls	230	C/C	47.8%	C/C	7.8%	A/A	16.5%	A/A	63.0%
		C/T	50.9%	C/T	29.1%	A/T	63.5%	A/G	25.2%
		T/T	1.3%	T/T	63.0%	T/T	20.0%	G/G	11.7%
T1D	122	C/C	57.4%	C/C	13.1%	A/A	10.7%	A/A	51.6%
		C/T	39.3%	C/T	34.4%	A/T	56.6%	A/G	28.7%
		T/T	3.3%	T/T	52.5%	T/T	32.8%	G/G	19.7%
T2D	241	C/C	53.9%	C/C	9.5%	A/A	18.3%	A/A	53.5%
		C/T	43.2%	C/T	35.3%	A/T	55.2%	A/G	34.9%
		T/T	2.9%	T/T	55.2%	T/T	26.6%	G/G	11.6%
C vs T1D		p-Value	NS	p-Value	NS	p-Value	NS	p-Value	NS
C vs T2D		p-Value	NS	P-Value	NS	p-value	NS	p-Value	NS

C, control; T1D,  type 1 diabetes; T2D, type 2 diabetes; A, adenine; T, thymine; G, guanine; C, cytosine.

Table 3. Genotype frequency for BMI change category by diagnosis.

			BMI increase 10% or less		BMI increase more than10%
			Frequency %	N	Proportion %	N
BDNF rs6265	Control	CC	18.2	22	37.5	24
		CT	81.8		62.5
		TT	0.0		0.0
	T1D	CC	56.7	30	61.7	81
		CT	40.0		34.6
		TT	3.3		3.7
	T2D	CC	63.0	92	50.8	130
		CT	32.6		46.9
		TT	4.3		2.3
CAV-1 rs926198	Control	CC	0.0	22	8.3	24
		CT	9.1		20.8
		TT	90.9		70.8
	T1D	CC	10.0	30	14.8	81
		CT	46.7		30.9
		TT	43.3		54.3
	T2D	CC	12.0	92	9.2	130
		CT	39.1		31.5
		TT	48.9		59.2
FTO rs9939609	Control	AA	4.5	22	4.2	24
		AT	90.9		83.3
		TT	4.5		12.5
	T1D	AA	6.7	30	13.6	81
		AT	60.0		54.3
		TT	33.3		32.1
	T2D	AA	19.6	92	15.4	130
		AT	53.3		57.7
		TT	27.2		26.9
LEPR rs1137101	Control	AA	95.5	22	91.7	24
		AG	0.0		8.3
		GG	4.5		0.0
	T1D	AA	50.0	30	50.6	81
		AG	26.7		30.9
		GG	23.3		18.5
	T2D	AA	47.8	92	60.0	130
		AG	39.1		30.0
		GG	13.0		10.0

Differences by diagnosis are highlighted in bold.

C, control; T1D,  type 1 diabetes; T2D, type 2 diabetes; A, adenine; T, thymine; G, guanine; C, cytosine..

Table 4. p-Value for Table 3.

		C vs T1D p value	Odds ratio (95%CI)	C vs T2D p value	Odds ratio (95% CI)
BDNF rs6265	BMI increase ≤10%	0.05	1.05 (1.01–1.10)	0.001	1.13 (1.05–1.20)
	BMI increase >10%	0.17	0.97 (0.91–1.09)	0.68	0.85 (0.82–1.10)
CAV-1 rs926198	BMI increase ≤10%	0.01	1.12 (1.06–1.18)	0.01	1.15 (1.11–1.19)
	BMI increase >10%	0.72	0.95 (0.90–1.10)	0.87	1.09 (0.79–1.21)
FTO rs9939609	BMI increase ≤10%	0.15	0.94 (0.89–1.11)	0.03	1.01 (0.89–1.12)
	BMI >10%	0.16	0.95 (0.90–1.10)	0.22	1.08 (0.78–1.21)
LEPR rs1137101	BMI increase ≤10%	0.01	1.13 (1.06–1.20)	0.002	1.21 (1.15–1.27)
	BMI increase >10%	0.01	1.17 (1.05–1.32)	0.06	1.03 (0.99–1.07)

C, control; T1D, type 1 diabetes; T2D, type 2 diabetes.

Table 5. Allele frequency for BMI change category by diagnosis.

			BMI increase ≤10%		BMI increase >10%
			Allele frequency %	2N	Allele frequency %	2N
BDNF rs6265	Control	C	59.4	44	68.8	48
		T	40.6		31.3
	T1D	C	77.5	60	79.0	162
		T	22.5		21.0
	T2D	C	79.9	184	74.2	260
		T	20.2		25.8
CAV-1 rs926198	Control	C	2.9	44	18.8	48
		T	97.1		81.3
	T1D	C	35.0	60	30.3	162
		T	65.0		69.8
	T2D	C	31.0	184	25.0	260
		T	69.0		75.0
FTO rs9939609	Control	A	53.5	44	45.8	48
		T	46.5		54.2
	T1D	A	38.8	60	40.7	162
		T	61.3		59.3
	T2D	A	45.1	184	44.2	260
		T	55.0		55.8
LEPR rs1137101	Control	A	97.1	44	95.8	48
		G	2.9		4.2
	T1D	A	62.5	60	66.1	162
		G	37.5		34.0
	T2D	A	67.9	184	75.0	260
		G	32.1		25.0

Differences by diagnosis are highlighted in bold.

C, control; T1D,  type 1 diabetes; T2D, type 2 diabetes; A, adenine; T, thymine; G, guanine; C, cytosine..

Figure 1. Significantly different Allele Frequencies for BMI change category by diagnosis for the CAV1 rs926198 and LEPR rs1137101 candidate genes.

Table 6. Chi-squared and p values for Table 5.

		C vs T1D p-value	Odds ratio (95%CI)	C vs T2D p-value	Odds ratio (95% CI)
BDNF rs6265	BMI increase ≤10%	NS	1.05 (0.95–1.15)	NS	1.13 (0.93–1.33)
	BMI increase >10%	NS	0.97 (0.92–1.02)	NS	0.85 (0.82–0.88)
CAV-1 rs926198	BMI increase ≤10%	0.004	1.12 (1.06–1.18)	0.005	1.15 (1.11–1.19)
	BMI increase >10%	NS	0.96 (0.90–1.03)	NS	1.09 (0.79–1.39)
FTO rs9939609	BMI increase ≤10%	NS	0.94 (0.84–1.04)	NS	1.01 (0.89–1.12)
	BMI increase >10%	NS	0.98 (0.96–1.03)	NS	1.08 (0.88–1.28)
LEPR rs1137101	BMI increase ≤10%	0.002	1.18 (1.06–1.30)	0.004	1.21 (1.15–1.27)
	BMI increase >10%	0.002	1.20 (1.07–1.33)	0.04	1.03 (0.99–1.07)

C, control; T1D, type 1 diabetes; T2D, type 2 diabetes.

Data availability statement

The participant data for this study is located in a data safe haven environment. The authors will provide a fully anonymized extract of the original data upon reasonable request.