Serum Concentrations and Dietary Intake of Vitamin B12 in Children and Adolescents on Metformin: A Case–Control Study
Abstract
:1. Introduction
2. Results
2.1. Vitamin B12 Status, Hormonal Assays, and Vitamin D
2.2. Dietary Intake Results
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Ethical Permission
4.3. Anthropometric Measurements
4.4. Dietary Intake
4.5. Blood Samples and Assays
4.5.1. Insulin Resistance (IR)
4.5.2. Vitamin B12 Deficiency
4.6. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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MET (n = 23) | Controls (n = 46) | p-Value | |
---|---|---|---|
Vitamin Β12 (pg/mL) | 284 (197–421) | 363 (235–522) | 0.135 |
Biochemical vitamin B12 deficiency (n, %) † | 4 (17%) | 0 (0%) | 0.016 § |
Total serum 25(OH)D3 (ng/mL) | 26.0 (22.7–30.4) | 25.5 (17.7–28.3) | 0.330 |
Fasting glucose (mg/dL) | 88 (81–95) | 86 (82–93) | 0.994 |
Fasting insulin (μIU/mL) | 10.9 (7.7–18) | 9.4 (8.1–13.8) | 0.485 |
HOMA-IR | 2.4 (1.8–4) | 2 (1.5–2.8) | 0.357 |
Hb (g/dL) | 13.3 (12.6–14.5) | 12.9 (12.3–13.7) | 0.116 |
HbA1c (%) | 5.1 (5–5.3) | 5.2 (4.9–5.4) | 0.676 |
MCV (fl) | 86.1 (83.5–89.3) | 81.8 (79.2–85.8) | 0.001 |
Ca2+ (mg/dL) | 10.0 (9.6–10.2) | 9.8 (9.5–10) | 0.197 |
P (mg/dL) | 3.9 (3.6–4.3) | 4.7 (4.0–5.1) | 0.001 |
ALP (IU/L) | 91 (79–128) | 230 (132–294) | 0.000 |
SHBG (nmol/L) | 22.9 (15.2–37.6) | 30.2 (16.5–38.3) | 0.626 |
Δ4-Androstenedione (ng/mL) | 2.1 (1.4–2.9) | 0.7 (0.4–1.2) | <0.001 |
DHEA-S (μg/dL) | 264 (225–334) | 171 (88–224) | <0.001 |
Daily Nutrient Intake | MET (n = 23) | Controls (n = 46) | p-Value |
---|---|---|---|
Energy intake (EI) (kcal/day) | 1522 (1183–1814) | 1162 (823–1452) | 0.004 |
Estimated energy expenditure (EER) (kcal/day) | 1753 (1471–1969) | 2008 (1699–2171) | 0.007 |
EI (% of EER) | 99.4 (58.5–119.0) | 59.8 (40.3–74.2) | 0.001 |
Carbohydrates (% of the EI) | 45 (36–50) | 50 (40–53) | NS |
Proteins (% of the EI) | 16 (13–18) | 15 (13–21) | NS |
Fats (% of the EI) | 40 (35–45) | 33 (29–43) | 0.032 |
MUFA (g) | 20 (16–32) | 14 (10–19) | 0.004 |
PUFA (g) | 6.4 (4.4–8.4) | 4.8 (2.8–8.3) | NS |
n-3 fatty acids (g) | 0.8 (0.5–0.9) | 0.4 (0.3–0.7) | 0.001 |
SFA (g) | 23.4 (15.0–30.7) | 16.8 (7.8–23.3) | 0.006 |
Trans fats (g) | 1.2 (0.6–2.2) | 0.6 (0.2–1.1) | 0.002 |
Cholesterol (mg) | 143 (74–197) | 89 (59–133) | NS |
Vitamin B1 (% of the RDA) | 102 (65–127) | 81 (74–128) | NS |
Vitamin B2 (% of the RDA) | 115 (72–158) | 109 (54–144) | NS |
Vitamin Β6 (% of the RDA) | 112 (75–162) | 91 (42–122) | 0.025 |
Vitamin Β12 (% of the RDA) | 112 (55–181) | 54 (20–118) | 0.010 |
Vitamin Β9 (% of the RDA) | 74 (48–110) | 64 (39–99) | ΝS |
Vitamin A (% of the RDA) | 46 (27–75) | 37 (20–54) | NS |
Vitamin D (% of the RDA) | 9 (4–27) | 8 (2–32) | NS |
Vitamin E (% of the RDA) | 30 (15–49) | 52 (29–66) | 0.009 |
Calcium (Ca) (% of the RDA) | 47 (28–66) | 44.5 (28–74) | NS |
Iron (Fe) (% of the RDA) | 54 (37–82) | 80 (54–124) | 0.037 |
Magnesium (Mg) (% of the RDA) | 50 (30–59) | 63.5 (41–76) | 0.010 |
Phosphorus (P) (% of the RDA) | 52 (34–73) | 60 (38–83) | NS |
Zinc (Zn) (% of the RDA) | 54 (30–66) | 71 (43–108) | 0.025 |
Sodium (Na) (% of the RDA) | 96 (65–152) | 138 (93–201) | 0.028 |
First Author | Origin | Design | Sample | Results |
---|---|---|---|---|
Anderson [30] | Australia | 12-month double-blind placebo-controlled RCT | N = 90 children and adolescents, >50th BMI PC, with T1DM | Vitamin B12 concentrations were lower in the MET group compared with placebo but were still within the reported reference range, with no change in tHcy concentrations. |
Azcona-Sanjulián [24] | Spain | Prospective cohort (6 months) | N = 21 pediatric patients with obesity, unresponsive to lifestyle treatment, on MET | No change was noted in the vitamin B12 concentrations after 6 months of MET use. |
Burgert [25] | USA | 4-month double-blind RCT | N = 28 adolescents with obesity and IR randomized to MET (n = 15, dose: 1500 mg/day) or placebo (n = 13); all patients received a daily MV with vitamin B12 | No difference was noted in vitamin B12 concentrations between subjects taking MET and those on placebo. |
der Aa [27] | Netherlands | 18-month RCT | N = 42 adolescents with obesity and IR randomized to MET (n = 23, 2000 mg/day) or placebo (n = 19) and physical training twice/week | At the end of treatment, 3 patients (13%) in the MET-receiving arm had vitamin B12 deficiency. |
Gourgari [31] | USA | Case report | N = 1 adolescent girl with obesity and PCOS on MET (2000 mg/day) | The girl exhibited vitamin B12 deficiency. Treatment with oral cyanocobalamin was initiated (1000 μg/day). After 1 month, normal B12 concentrations were attained. ONS with vitamin B12 was discontinued, and the patient returned after 5 months. Serum B12 concentrations had decreased, but remained within normal range. |
Lentferink [28] | Netherlands | Open-label extension of an 18-month double-blind RCT | N = 31 adolescents with obesity and IR on MET or placebo for 18 months | Low vitamin B12 concentrations were observed in 2 participants (1 on MET during RCT and extension and 1 on MET during RCT and placebo, on the extension study). |
Levy-Shraga [26] | Israel | Case–control | N = 49 children/adolescents with BMI >85 PC treated with DSRA allocated to MET and vitamin B12 (n = 31) and those on nothing (n = 18) | No difference was noted in the vitamin B12 concentrations between the groups. |
Taş [18] | Turkey | Prospective cohort (6 and 12 months) | N = 24 patients with T2DM, MetS, or PCOS with IR and/or IGT, treated with MET | At the 6-month follow-up, no difference was noted in the vitamin B12, tHcy, MMA, and holo-TC-II levels, although a 0.6% decline in vitamin B12 concentrations was noted. At 12 months (n = 11 patients: 6 with T2DM and 5 with MetS), no difference was noted in vitamin B12, tHcy, MMA, and holo-TC-II concentrations, but a 6% decline in vitamin B12, a 5.4% decrease in holo-TC-II, and a 10.9% increase in tHcy concentrations were noted. |
Yanovski [29] | USA | 6-month RCT with a 6-month follow-up | N = 100 children/adolescents with obesity and IR, randomized to 1000 mg MET (n = 53) or placebo (n = 47) twice/day | Serum vitamin B12 levels remained within the normal range in all subjects throughout the 12-month study, but decreased in the MET-treated arm, compared with the increase observed among placebo-treated children. |
Yu [17] | USA | Prospective cohort (6, 12, 24, and 36 months) | N = 151 pediatric patients with >3 months of consecutive MET use | No decrease in vitamin B12 concentrations was noted at 6, 12, 24, or 36 months among those treated with MET. A reduction in vitamin B12 was only noticeable in patients on a high-MET dose, with good compliance; however, levels remained within the normal range. Of the 151 patients, only 1 demonstrated deficiency after a year of MET use. |
Characteristics | MET Arm (n = 23) | Controls (n = 46) | p-Value |
---|---|---|---|
Age (years) | 15.4 ± 1.6 | 12.4 ± 2.7 | <0.001 |
Boys/girls (n) | 5/18 | 20/26 | NS |
Body weight (kg) | 82.5 ± 18.2 | 63.0 ± 22.9 | 0.001 |
Stature (cm) | 165.4 ± 9.8 | 153.9 ± 13.2 | 0.001 |
BMI (kg/m2) | 30.3 ± 7.8 | 25.8 ± 6.7 | 0.032 |
BMIz | 2.16 ± 1.37 | 1.97 ± 1.52 | NS |
Caucasian/Roma (n) | 22/1 | 45/1 | NS |
Normal weight/overweight/obese (n) | 4/7/12 | 14/9/23 | NS |
Menstrual disorders/premature adrenarche/thelarche/precocious puberty (n) | 2/0/0/0 | 0/4/1/1 | |
GH deficiency/short stature/microphallus/gynecomasty (n) | 1/0/0/0 | 0/1/1/1 | |
PCOS/prediabetes/IR/hyperglycemia (n) | 2/3/14/0 | 1/0/12/1 | |
Hypothyroidism/thyroid dysfunction (n) | 0/0 | 7/1 | |
Duration of MET use (months) | 22.7 ± 13.3 | - | |
Daily MET dose (mg/day) | 1494 ± 443 | - |
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Tsiroukidou, K.; Paschalidou, E.G.; Grammatikopoulou, M.G.; Androulakis, J.; Vamvakis, A.; Gkouskou, K.K.; Tzimos, C.; Sergentanis, T.N.; Vassilakou, T.; Roilides, E.; et al. Serum Concentrations and Dietary Intake of Vitamin B12 in Children and Adolescents on Metformin: A Case–Control Study. Int. J. Mol. Sci. 2023, 24, 4205. https://doi.org/10.3390/ijms24044205
Tsiroukidou K, Paschalidou EG, Grammatikopoulou MG, Androulakis J, Vamvakis A, Gkouskou KK, Tzimos C, Sergentanis TN, Vassilakou T, Roilides E, et al. Serum Concentrations and Dietary Intake of Vitamin B12 in Children and Adolescents on Metformin: A Case–Control Study. International Journal of Molecular Sciences. 2023; 24(4):4205. https://doi.org/10.3390/ijms24044205
Chicago/Turabian StyleTsiroukidou, Kyriaki, Eleni G. Paschalidou, Maria G. Grammatikopoulou, John Androulakis, Anastasios Vamvakis, Kalliopi K. Gkouskou, Christos Tzimos, Theodoros N. Sergentanis, Tonia Vassilakou, Emmanuel Roilides, and et al. 2023. "Serum Concentrations and Dietary Intake of Vitamin B12 in Children and Adolescents on Metformin: A Case–Control Study" International Journal of Molecular Sciences 24, no. 4: 4205. https://doi.org/10.3390/ijms24044205