Table 2. Open in new tab B Vitamin...

	Normoglycemia, n = 1856	Hyperglycemia
Vitamin B12; serum total B12, pmol/L	272 (266–277)^a	275 (269–280)^a	239 (224–254)^b	<0.001
Deficiency: ≤148 pmol/L, n (%)	213 (12)	244 (12)	59 (19)	0.005
Plasma holoTC, pmol/L	59.7 (58.4–61.1)	61.2 (59.9–62.5)	60.0 (56.4–63.5)	0.30
Deficiency: ≤35 pmol/L, n (%)	323 (17)	361 (18)	67 (21)	0.15
Plasma homocysteine, µmol/L	15.5 (15.2–15.7)^a	14.9 (14.7–15.2)^b	15.4 (14.7–16.0)^a	0.007
Elevated: ≥15 µmol/L, n (%)	697 (38)	823 (41)	147 (46)	0.003
cB12 index^c ≤−1, n (%)	341 (18)	389 (20)	84 (26)	0.005
Folate; RBC,^d nmol/L	1009 (987–1031)^a	968 (947–989)^b	954 (894–1013)^a^,^b	0.02
Deficiency: ≤340 nmol/L, n (%)	53 (3)	48 (2)	5 (2)	0.42
Serum folate, nmol/L	30.3 (29.3–31.2)	29.6 (28.7–30.5)	28.4 (25.9–31.0)	0.34
Deficiency: <10 nmol/L, n (%)	219 (12)	251 (13)	38 (12)	0.72
Vitamin B6; plasma PLP, nmol/L	68.6 (66.7–70.3)^a	66.3 (64.6–68.0)^a	59.8 (55.1–64.6)^b	0.003
Deficiency: <30.0 nmol/L, n (%)	234 (13)	310 (16)	68 (21)	<0.001
Riboflavin; EGRac^e	1.35 (1.34–1.36)	1.36 (1.35–1.37)	1.38 (1.35–1.40)	0.23
Deficiency: ≥1.40, n (%)	536 (29)	572 (29)	114 (36)	0.03

Normoglycemia, n = 1856

Hyperglycemia

Not on Metformin, n = 1986

On Metformin, n = 318

Vitamin B12; serum total B12, pmol/L

272 (266–277)^a

275 (269–280)^a

239 (224–254)^b

<0.001

Deficiency: ≤148 pmol/L, n (%)

213 (12)

244 (12)

59 (19)

0.005

Plasma holoTC, pmol/L

59.7 (58.4–61.1)

61.2 (59.9–62.5)

60.0 (56.4–63.5)

0.30

Deficiency: ≤35 pmol/L, n (%)

323 (17)

361 (18)

67 (21)

0.15

Plasma homocysteine, µmol/L

15.5 (15.2–15.7)^a

14.9 (14.7–15.2)^b

15.4 (14.7–16.0)^a

0.007

Elevated: ≥15 µmol/L, n (%)

697 (38)

823 (41)

147 (46)

0.003

cB12 index^c ≤−1, n (%)

341 (18)

389 (20)

84 (26)

0.005

Folate; RBC,^d nmol/L

1009 (987–1031)^a

968 (947–989)^b

954 (894–1013)^a^,^b

0.02

Deficiency: ≤340 nmol/L, n (%)

53 (3)

48 (2)

5 (2)

0.42

Serum folate, nmol/L

30.3 (29.3–31.2)

29.6 (28.7–30.5)

28.4 (25.9–31.0)

0.34

Deficiency: <10 nmol/L, n (%)

219 (12)

251 (13)

38 (12)

0.72

Vitamin B6; plasma PLP, nmol/L

68.6 (66.7–70.3)^a

66.3 (64.6–68.0)^a

59.8 (55.1–64.6)^b

0.003

Deficiency: <30.0 nmol/L, n (%)

234 (13)

310 (16)

68 (21)

<0.001

Riboflavin; EGRac^e

1.35 (1.34–1.36)

1.36 (1.35–1.37)

1.38 (1.35–1.40)

0.23

Deficiency: ≥1.40, n (%)

536 (29)

572 (29)

114 (36)

0.03

	Normoglycemia, n = 1856	Hyperglycemia
Vitamin B12; serum total B12, pmol/L	272 (266–277)^a	275 (269–280)^a	239 (224–254)^b	<0.001
Deficiency: ≤148 pmol/L, n (%)	213 (12)	244 (12)	59 (19)	0.005
Plasma holoTC, pmol/L	59.7 (58.4–61.1)	61.2 (59.9–62.5)	60.0 (56.4–63.5)	0.30
Deficiency: ≤35 pmol/L, n (%)	323 (17)	361 (18)	67 (21)	0.15
Plasma homocysteine, µmol/L	15.5 (15.2–15.7)^a	14.9 (14.7–15.2)^b	15.4 (14.7–16.0)^a	0.007
Elevated: ≥15 µmol/L, n (%)	697 (38)	823 (41)	147 (46)	0.003
cB12 index^c ≤−1, n (%)	341 (18)	389 (20)	84 (26)	0.005
Folate; RBC,^d nmol/L	1009 (987–1031)^a	968 (947–989)^b	954 (894–1013)^a^,^b	0.02
Deficiency: ≤340 nmol/L, n (%)	53 (3)	48 (2)	5 (2)	0.42
Serum folate, nmol/L	30.3 (29.3–31.2)	29.6 (28.7–30.5)	28.4 (25.9–31.0)	0.34
Deficiency: <10 nmol/L, n (%)	219 (12)	251 (13)	38 (12)	0.72
Vitamin B6; plasma PLP, nmol/L	68.6 (66.7–70.3)^a	66.3 (64.6–68.0)^a	59.8 (55.1–64.6)^b	0.003
Deficiency: <30.0 nmol/L, n (%)	234 (13)	310 (16)	68 (21)	<0.001
Riboflavin; EGRac^e	1.35 (1.34–1.36)	1.36 (1.35–1.37)	1.38 (1.35–1.40)	0.23
Deficiency: ≥1.40, n (%)	536 (29)	572 (29)	114 (36)	0.03

		Risk of B Vitamin Deficiency
Vitamin B12 deficiency (cB12 index ≤ −1)	Reference category	0.94 (0.79–1.12)	0.50	1.45 (1.03–2.02)	0.03
Folate deficiency (RBC ≤340 nmol/L)	Reference category	0.89 (0.58–1.37)	0.60	0.85 (0.30–2.44)	0.77
Vitamin B6 deficiency (PLP <30 nmol/L)	Reference category	1.05 (0.86–1.28)	0.62	1.48 (1.02–2.15)	0.04
Riboflavin deficiency (EGRac ≥1.40)	Reference category	1.04 (0.90–1.21)	0.60	1.28 (0.95–1.73)	0.11

Risk of B Vitamin Deficiency

OR (95% CI)

Vitamin B12 deficiency (cB12 index ≤ −1)

Reference category

0.94 (0.79–1.12)

0.50

1.45 (1.03–2.02)

0.03

Folate deficiency (RBC ≤340 nmol/L)

Reference category

0.89 (0.58–1.37)

0.60

0.85 (0.30–2.44)

0.77

Vitamin B6 deficiency (PLP <30 nmol/L)

Reference category

1.05 (0.86–1.28)

0.62

1.48 (1.02–2.15)

0.04

Riboflavin deficiency (EGRac ≥1.40)

Reference category

1.04 (0.90–1.21)

0.60

1.28 (0.95–1.73)

0.11

		Risk of B Vitamin Deficiency
Vitamin B12 deficiency (cB12 index ≤ −1)	Reference category	0.94 (0.79–1.12)	0.50	1.45 (1.03–2.02)	0.03
Folate deficiency (RBC ≤340 nmol/L)	Reference category	0.89 (0.58–1.37)	0.60	0.85 (0.30–2.44)	0.77
Vitamin B6 deficiency (PLP <30 nmol/L)	Reference category	1.05 (0.86–1.28)	0.62	1.48 (1.02–2.15)	0.04
Riboflavin deficiency (EGRac ≥1.40)	Reference category	1.04 (0.90–1.21)	0.60	1.28 (0.95–1.73)	0.11

Table 2.

Open in new tab

B Vitamin Status in Participants in Relation to Hyperglycemia and Metformin Use

	Normoglycemia, n = 1856	Hyperglycemia
	Normoglycemia, n = 1856	Not on Metformin, n = 1986	On Metformin, n = 318	P
Vitamin B12; serum total B12, pmol/L	272 (266–277)^a	275 (269–280)^a	239 (224–254)^b	<0.001
Deficiency: ≤148 pmol/L, n (%)	213 (12)	244 (12)	59 (19)	0.005
Plasma holoTC, pmol/L	59.7 (58.4–61.1)	61.2 (59.9–62.5)	60.0 (56.4–63.5)	0.30
Deficiency: ≤35 pmol/L, n (%)	323 (17)	361 (18)	67 (21)	0.15
Plasma homocysteine, µmol/L	15.5 (15.2–15.7)^a	14.9 (14.7–15.2)^b	15.4 (14.7–16.0)^a	0.007
Elevated: ≥15 µmol/L, n (%)	697 (38)	823 (41)	147 (46)	0.003
cB12 index^c ≤−1, n (%)	341 (18)	389 (20)	84 (26)	0.005
Folate; RBC,^d nmol/L	1009 (987–1031)^a	968 (947–989)^b	954 (894–1013)^a^,^b	0.02
Deficiency: ≤340 nmol/L, n (%)	53 (3)	48 (2)	5 (2)	0.42
Serum folate, nmol/L	30.3 (29.3–31.2)	29.6 (28.7–30.5)	28.4 (25.9–31.0)	0.34
Deficiency: <10 nmol/L, n (%)	219 (12)	251 (13)	38 (12)	0.72
Vitamin B6; plasma PLP, nmol/L	68.6 (66.7–70.3)^a	66.3 (64.6–68.0)^a	59.8 (55.1–64.6)^b	0.003
Deficiency: <30.0 nmol/L, n (%)	234 (13)	310 (16)	68 (21)	<0.001
Riboflavin; EGRac^e	1.35 (1.34–1.36)	1.36 (1.35–1.37)	1.38 (1.35–1.40)	0.23
Deficiency: ≥1.40, n (%)	536 (29)	572 (29)	114 (36)	0.03

	Normoglycemia, n = 1856	Hyperglycemia
	Normoglycemia, n = 1856	Not on Metformin, n = 1986	On Metformin, n = 318	P
Vitamin B12; serum total B12, pmol/L	272 (266–277)^a	275 (269–280)^a	239 (224–254)^b	<0.001
Deficiency: ≤148 pmol/L, n (%)	213 (12)	244 (12)	59 (19)	0.005
Plasma holoTC, pmol/L	59.7 (58.4–61.1)	61.2 (59.9–62.5)	60.0 (56.4–63.5)	0.30
Deficiency: ≤35 pmol/L, n (%)	323 (17)	361 (18)	67 (21)	0.15
Plasma homocysteine, µmol/L	15.5 (15.2–15.7)^a	14.9 (14.7–15.2)^b	15.4 (14.7–16.0)^a	0.007
Elevated: ≥15 µmol/L, n (%)	697 (38)	823 (41)	147 (46)	0.003
cB12 index^c ≤−1, n (%)	341 (18)	389 (20)	84 (26)	0.005
Folate; RBC,^d nmol/L	1009 (987–1031)^a	968 (947–989)^b	954 (894–1013)^a^,^b	0.02
Deficiency: ≤340 nmol/L, n (%)	53 (3)	48 (2)	5 (2)	0.42
Serum folate, nmol/L	30.3 (29.3–31.2)	29.6 (28.7–30.5)	28.4 (25.9–31.0)	0.34
Deficiency: <10 nmol/L, n (%)	219 (12)	251 (13)	38 (12)	0.72
Vitamin B6; plasma PLP, nmol/L	68.6 (66.7–70.3)^a	66.3 (64.6–68.0)^a	59.8 (55.1–64.6)^b	0.003
Deficiency: <30.0 nmol/L, n (%)	234 (13)	310 (16)	68 (21)	<0.001
Riboflavin; EGRac^e	1.35 (1.34–1.36)	1.36 (1.35–1.37)	1.38 (1.35–1.40)	0.23
Deficiency: ≥1.40, n (%)	536 (29)	572 (29)	114 (36)	0.03

		Risk of B Vitamin Deficiency
		OR (95% CI)	P	OR (95% CI)	P
Vitamin B12 deficiency (cB12 index ≤ −1)	Reference category	0.94 (0.79–1.12)	0.50	1.45 (1.03–2.02)	0.03
Folate deficiency (RBC ≤340 nmol/L)	Reference category	0.89 (0.58–1.37)	0.60	0.85 (0.30–2.44)	0.77
Vitamin B6 deficiency (PLP <30 nmol/L)	Reference category	1.05 (0.86–1.28)	0.62	1.48 (1.02–2.15)	0.04
Riboflavin deficiency (EGRac ≥1.40)	Reference category	1.04 (0.90–1.21)	0.60	1.28 (0.95–1.73)	0.11

		Risk of B Vitamin Deficiency
		OR (95% CI)	P	OR (95% CI)	P
Vitamin B12 deficiency (cB12 index ≤ −1)	Reference category	0.94 (0.79–1.12)	0.50	1.45 (1.03–2.02)	0.03
Folate deficiency (RBC ≤340 nmol/L)	Reference category	0.89 (0.58–1.37)	0.60	0.85 (0.30–2.44)	0.77
Vitamin B6 deficiency (PLP <30 nmol/L)	Reference category	1.05 (0.86–1.28)	0.62	1.48 (1.02–2.15)	0.04
Riboflavin deficiency (EGRac ≥1.40)	Reference category	1.04 (0.90–1.21)	0.60	1.28 (0.95–1.73)	0.11

Data presented are adjusted means (95% CI) unless stated otherwise. χ² for categorical variables; ANCOVA for continuous variables adjusted for age, sex, BMI, GFR, education, socioeconomic status [measured as area-level deprivation (35) and relevant drug use (PPIs, H₂-receptor antagonists, and glucose-lowering drugs other than metformin] with Tukey post hoc comparisons. Binary logistic regression model (outcome: risk of B vitamin deficiency) adjusted for covariates.

Abbreviation: cB12, combined B12.

^a,b

Different letters within a given row denote statistically significant differences between any two specific groups for that variable.

cB12 index was calculated with serum total vitamin B12, plasma holoTC, and plasma homocysteine values in combination to provide a diagnostic indicator, with a score ≤−1 being defined as deficient status (26).

For serum folate <10 nmol/L and RBC folate ≤340 nmol/L, an internationally accepted reference range was used (32). For other B vitamin biomarkers, reference ranges from analytical laboratory where assay was performed; for serum total B12 ≤148 pmol/L, plasma holoTC ≤35 pmol/L (30), plasma PLP <30.0 nmol/L (31). Elevated plasma homocysteine was classified as ≥15 µmol/L (33).

Riboflavin status was assessed with the EGRac; a higher EGRac ratio indicates a lower riboflavin status, with deficient status generally indicated by a coefficient of ≥1.40 (29).

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