Effect of one time high dose “stoss therapy” of vitamin D on glucose homeostasis in high risk obese adolescents

Brar, Preneet Cheema; Contreras, Maria; Fan, Xiaozhou; Visavachaipan, Nipapat

doi:10.20945/2359-3997000000024

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Original Article • Arch. Endocrinol. Metab. 62 (2) • Mar-Apr 2018 • https://doi.org/10.20945/2359-3997000000024 copy

Effect of one time high dose “stoss therapy” of vitamin D on glucose homeostasis in high risk obese adolescents

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Objective

To study the effect of using a one time high dose “stoss therapy” of vitamin D2 (ergocalciferol: VD2) on indices of insulin sensitivity {whole body sensitivity index: WBISI} and secretion {insulinogenic index: IGI} measured during an oral glucose tolerance test (OGTT) in obese adolescents with VDD (25 OHD; serum metabolite of vit D: < 30 ng/dL).

Subjects and methods

In a randomized placebo controlled cross over design 20 obese adolescents with vitamin D deficiency (VDD) had baseline OGTT. Arm A received one time high dose 300,000 IU of ergocalciferol and Arm B received placebo. After 6 weeks the adolescents were reassigned to Arm A if they were in Arm B and vice versa. 25OHD, calcium, parathyroid hormone, comprehensive metabolic panel, urine calcium creatinine ratio were measured at each study visit. OGTTs to assess indices of sensitivity and secretion were done at baseline, 6 weeks and 12 weeks respectively.

Results

Adolescents were obese and insulin resistant (mean ± SD: mean age = 15.1 ± 1.9 years; BMI: 32.7 ± 9.8; homeostatic model of insulin resistance: HOMA-IR: 4.2 ± 2.8). Stoss therapy with VD2 increased 25OHD from baseline (16.7 ± 2.9 to 19.5 ± 4.5; p = 0.0029) when compared to the placebo. WBISI (2.8 ± 1.9) showed a trend towards improvement in Rx group (p = 0.0577) after adjustment for covariates. IGI (3 ± 2.2) showed an improvement in both Rx and placebo groups.

Conclusions

Our study demonstrated that using a high dose of VD2 (300,000 IU) did not have any beneficial effect on insulin sensitivity (whole body sensitivity index {WBISI}) and secretory indices (insulinogenic index {IGI}) in obese adolescents. High dose “stoss therapy” of VD2 did not appear to have any beneficial effect on glucose homeostasis on obese adolescents.

Keywords
Vitamin D; insulin resistance; prediabetes; obesity

Characteristics and clinical features		Study participants (n = 20)
Characteristics and clinical features		Mean/N	SD/%
Age (year)		15.1	1.9
Gender^* * Numbers of participants and percentage were calculated.
	Male	4	20
	Female	16	80
Ethnicity^* * Numbers of participants and percentage were calculated.
	African American	3	15
	Bangladesh	1	5
	Caucasian	1	5
	Hispanic	15	75
Height (cm)		162.5	7.8
Weight (kg)		90.7	19.2
BMI		32.7	9.8
25 OH vitamin D (ng/mL)		16.7	2.9
WBISI		2.8	1.9
IGI		3.0	2.2
Intact, PTH (pg/mL)		50.9	15.8
HbA1C		5.7	0.3
HOMA-B%		452.2	343.3
HOMA-IR		4.2	2.8
Serum calcium (mg/dL)		9.4	0.4
Albumin (g/dL)		4.2	0.3
Albumin-adjusted serum calcium (mg/dL)		9.2	0.4
Alkaline phosphatase (U/L)		110.0	46.8
AST (U/L)		29.2	14.1
ALT (U/L)		42.3	39.8
Serum phosphorus (mg/dL)		4.5	0.6
Random urine calcium (mg/dL)		6.5	4.6
Random urine creatinine (mg/dL)		217.9	107.2

	Baseline		Treatment group (N = 20)					Placebo group (N = 20)
			∆ after treatment					∆ after treatment
	Mean	SD	Mean	SD	Median^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	IQR^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	p^† † p values were calculated from exact comparison (paired t-test) of measurements to baseline.	Mean	SD	Median^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	IQR^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	p^† † p values were calculated from exact comparison (paired t-test) of measurements to baseline.	p^‡ ‡ p values were calculated from mixed regression models, adjusted for baseline measurements, age, gender, race, BMI, and season [winter: Dec-Feb; spring: Mar-May; summer: Jun-Aug; fall: Sep-Nov].	p^§ § p values were calculated from Koch's analysis testing for crossover effects.
25 OH vitamin D (ng/mL)	16.7	2.9	19.5	4.5	2.4	4.7	0.0029	17.2	4.7	0.0	2.2	0.5262	0.0059	0.4506
WBISI	2.8	1.9	2.7	1.4	-0.1	1.1	0.5377	3.1	1.5	0.3	1.9	0.3855	0.0577	0.4205
IGI	3.0	2.2	3.5	2.7	0.1	1.8	0.2878	4.3	6.3	0.1	1.2	0.3069	0.5971	0.0030
Intact, PTH (pg/mL)	50.9	15.8	45.6	11.8	-6.0	19.0	0.0538	50.3	14.3	0.5	16.0	0.8327	0.1290	0.1075
HbA1C	5.7	0.3	5.7	0.4	0.1	0.2	0.2674	5.7	0.4	0.1	0.3	0.3264	0.9052	0.2918
HOMA-B%	452.2	343.3	483.5	258.2	19.8	173.8	0.3889	543.9	532.2	34.2	288.5	0.2769	0.5740	0.0004
HOMA-IR	4.2	2.8	5.2	3.6	0.9	2.3	0.1079	4.9	4.5	0.2	1.3	0.2829	0.3403	0.3396
Serum calcium (mg/dL)	9.4	0.4	9.3	0.4	0.0	0.4	0.4936	9.2	0.3	-0.1	0.5	0.0909	0.1287	0.2258
Albumin (g/dL)	4.2	0.3	4.2	0.9	-0.3	0.4	0.8346	4.1	0.3	-0.2	0.3	0.1670	0.8932	0.0200
Albumin-adjusted serum calcium	9.2	0.4	9.1	0.7	0.1	0.4	0.8927	14.7	25.6	0.0	0.6	0.3750	0.3975	< 0.0001
Alkaline phosphatase (U/L)	110.0	46.8	103.6	43.5	-6.5	13.0	0.0344	99.6	37.6	-7.5	15.0	0.0034	0.3105	0.4072
AST (U/L)	29.2	14.1	25.2	11.9	-2.0	5.5	0.0209	29.1	15.8	-0.5	6.0	0.9374	0.0870	< 0.0001
ALT (U/L)	42.3	39.8	36.2	32.4	-4.0	9.5	0.0106	40.6	36.7	-1.0	9.0	0.6514	0.2704	< 0.0001
Serum phosphorus (mg/dL)	4.5	0.6	4.5	0.6	-0.1	0.5	0.7354	4.5	0.5	0.0	0.4	0.5965	0.6586	0.9649
Random urine calcium (mg/dL)	6.5	4.6	8.6	7.8	2.7	6.2	0.1733	14.0	21.4	1.0	7.0	0.1411	0.3369	0.0007
Random urine creatinine (mg/dL)	217.9	107.2	274.6	441.8	-12.7	106.5	0.5034	199.2	108.3	-9.9	89.7	0.4150	0.3292	< 0.0001

	Treatment group						Placebo group
	∆ after treatment						∆ after treatment
	N	Mean	SD	Median*	IQR*	p^†	N	Mean	SD	Median*	IQR*	p^†	p^‡	p^§
G_0 ≥ 100 mg/dL and/ or G_120 ≥ 140 mg/dL	5						5
WBISI		1.38	0.80	-0.20	0.30	0.1293		1.56	1.04	-0.10	0.50	0.6213	0.4718	0.5477
IGI		5.18	4.51	-0.70	1.20	0.5606		2.94	2.43	-0.60	1.60	0.1376	0.1236	0.1126
HOMA-IR ≥ 3.4 & HbA1C ≥ 5.7%	6						6
WBISI		2.27	1.44	-0.25	0.30	0.8226		2.32	1.06	0.25	0.90	0.4391	0.2516	0.1764
IGI		5.70	3.52	2.30	5.60	0.2714		8.40	10.69	0.95	5.60	0.2636	0.1735	0.8965
Intact, PTH ≤ 44 pg/mL	9						9
WBISI		2.15	1.18	0.10	0.35	0.5040		2.86	1.69	0.30	2.00	0.0765	0.3445	< 0.0001
IGI		3.26	2.20	-0.30	1.10	0.5722		2.64	1.88	-0.55	1.40	0.0389	0.3450	< 0.0001
Intact, PTH > 44 pg/mL	11						11
WBISI		3.05	1.43	-0.30	1.90	0.4458		3.34	1.46	0.20	1.60	0.7871	0.2312	0.4084
IGI		3.74	3.20	0.65	3.20	0.2286		5.61	8.24	0.50	1.50	0.1978	0.7405	0.1898

		Baseline		Treatment group (N = 20)					Placebo (N = 20)
				∆ after treatment					∆ after treatment
		Mean	SD	Mean	SD	Mean^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	SD^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	p^† † p values were calculated from exact comparison (paired t-test) of measurements to baseline.	Mean	SD	Mean^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	SD^* * Medians and IQR of the difference between treatment/placebo group and baseline were calculated.	p^† † p values were calculated from exact comparison (paired t-test) of measurements to baseline.	p^‡ ‡ p values were calculated from mixed regression models, adjusted for baseline measurements, age, gender, race, BMI, and season [winter: Dec-Feb; spring: Mar-May; summer: Jun-Aug; fall: Sep-Nov].	p^§ § p values were calculated from Koch's analysis testing for crossover effects.
Plasma glucose
	At fasting	82.0	7.2	82.0	5.6	0.0	8.5	0.9698	81.2	5.5	-0.5	7.0	0.4466	0.3645	0.2856
	At 10 min	102.4	16.1	100.6	13.3	1.5	9.5	0.5910	96.7	13.5	-2.5	12.0	0.0589	0.2423	0.1161
	At 30 min	139.8	25.4	133.4	22.6	-5.5	33.0	0.2162	122.5	22.1	-18.5	25.0	0.0007	0.0236	0.4265
	At 60 min	139.8	28.5	128.7	38.9	-3.5	55.5	0.1202	119.8	34.0	-21.0	37.0	0.0067	0.2243	0.0452
	At 90 min	127.5	29.4	123.4	34.9	-10.5	53.0	0.5524	117.7	39.9	-10.5	29.0	0.2737	0.4540	0.1342
	At 120 min	123.3	31.2	110.5	31.0	-13.5	28.5	0.0568	111.8	35.1	-11.0	19.0	0.0419	0.9691	0.0700
	Mean	119.1	18.4	113.1	20.1	-6.9	27.0	0.0684	108.3	22.0	-10.7	19.4	0.0037	0.1754	0.1741
Insulin
	At fasting	20.9	13.3	25.2	16.7	4.0	10.0	0.0749	24.1	21.7	0.5	6.5	0.2686	0.4555	0.7516
	At 10 min	77.7	63.4	74.2	49.5	5.0	27.0	0.7478	71.9	61.7	3.5	52.0	0.6103	0.8206	0.6579
	At 30 min	183.5	147.6	176.9	110.1	9.0	117.0	0.7864	151.4	116.7	-6.0	108.5	0.1270	0.0197	0.3541
	At 60 min	213.9	183.6	187.0	181.3	-8.0	95.0	0.2746	145.8	136.3	-41.5	105.5	0.0178	0.1340	0.3023
	At 90 min	207.6	253.6	204.7	253.6	-17.5	133.0	0.3248	148.0	185.0	-58.0	117.0	0.0245	0.0604	0.0242
	At 120 min	231.3	352.4	138.7	116.3	-37.0	109.5	0.1919	165.7	250.4	-31.0	80.5	0.0487	0.6277	0.0135
	Mean	156.0	158.9	136.0	115.7	-5.5	54.4	0.2027	117.8	121.6	-2970.0	59.8	0.0215	0.2580	0.1541
	First-phase (≤ 30 m)	49.3	35.3	52.1	34.9	5.5	17.8	0.6396	48.0	40.3	0.8	33.0	0.8336	0.5587	0.5024
	Second-phase (> 30 m)	211.8	225.3	175.4	153.8	-20.3	83.3	0.1284	152.7	164.2	-36.8	87.0	0.0167	0.2367	0.3730

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[1] Correspondence to: Preneet Cheema Brar 160 East 3^nd street, L3, New York 100016, New York, United States of America Preneet.Brar@nyumc.org