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Carenza di Vitamina D Carenza di Vitamina D

e diabete e diabete

26 Ottobre 2013

Emanuele Miraglia del Giudice

Seconda Università degli Studi di Napoli Dipartimento della Donna del Bambino e

di Chirurgia Generale e Specialistica

(2)

The condicion of obesity in Italy is worrying:

The condicion of obesity in Italy is worrying:

23,6% of children are overweight and 12,3% are obese 23,6% of children are overweight and 12,3% are obese

More than 1 children out of 3 weights more than he should do for his age More than 1 children out of 3 weights more than he should do for his age

Overweight and obesity: the state of Italian Overweight and obesity: the state of Italian children described by

children described by “ “OK OKKIO alla SALUTE” KIO alla SALUTE”

(3)

SUNLIGHT IN ITALY: DATA FROM 1994 TO 2003

(4)

The

The conditioncondition ofof obesityobesity in Italy in Italy isis worryingworrying::

23,6%

23,6% ofof childrenchildren are are overweightoverweight and 12,3% are obeseand 12,3% are obese

More

More thanthan 11 childrenchildren out out ofof 33 weightsweights more more thanthan hehe shouldshould do do forfor hishis ageage

Overweight and obesity: the state of Italian Overweight and obesity: the state of Italian children described by

children described by “ “OK OKKIO alla SALUTE” KIO alla SALUTE”

(5)

Overweight and obesity: the state of Italian Overweight and obesity: the state of Italian children described by

children described by“ “OK OKKIO alla SALUTE” KIO alla SALUTE”

In Campania there are about 80.000 obese children aged 6 through 11 yr!

In Campania there are about 80.000 obese children aged 6 through 11 yr!

(6)

ETÀ

MEDIA CRITERI PREVALENZA (%) REFERENZA

Dietz et al 2003 14 NCEP 28.7 APAM 157;821

METABOLIC SYNDROME IN CHILDHOOD METABOLIC SYNDROME IN CHILDHOOD

THE PREVALENCE OF THE SYNDROME

Weiss et al 2004 12 NCEP* 49 NEJM 50;2362

Goodman et al 2004 15.2 NCEP 19.5 J.Ped 145;445

Goodman et al 2004 15.2 WHO 38.9 J.Ped 145;445

Miraglia del Giudice et al 2006 10.4 NCEP* 40 JCEM 91;4641

*Modified criteria by NCEP (National Cholesterol Education Panel)

(7)

We can say that metabolic syndrome affects We can say that metabolic syndrome affects

about

about 30.000 30.000-- 35.000 35.000 children in Campania! children in Campania!

CHILDHOOD METABOLIC

CHILDHOOD METABOLIC

SYNDROME IN CAMPANIA

SYNDROME IN CAMPANIA

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Psychological

•Reduced self-esteem

•Social isolation and stigmatization

•Eating disorders

•Depression

Neurological

•Pseudotumor cerebri

Cardiovascular

•Hypertension

•Atherosclerosis

Respiratory

•Asthma

•OSAS

•Poor exercise tolerance

Gastrointestinal Endocrine

•Metabolic syndrome

Insulin resistance IGT

Dyslipidemia Hypertension

•Diabetes Mellitus

•Polycystic Ovary Syndrome

COMORBIDITY

COMORBIDITY of of PEDIATRIC OBESITY PEDIATRIC OBESITY

Gastrointestinal

•Gallstone

•Gastroesophageal Reflux

•NASH

Orthopedic

•Flat Foot

•Valgus Knee

•Ankle sprain

•Head femoral epiphysiolysis

•Forearm fracture

•Tibia vara (M. di Blount)

(9)

DIAGNOSTIC CRITERIA FOR METABOLIC DIAGNOSTIC CRITERIA FOR METABOLIC

SYNDROME IN CHILDREN SYNDROME IN CHILDREN

IGT

<5th percentile

>95°°°° percentile

>95th percentile ZS BMI 2

Weiss et al Weiss et al

HDL IGT Cholesterol Triglycerid

es Blood

Pressure Obesity

Definizione da:

The presence of 3 of these 5 abnormalities allows MS diagnosis The presence of 3 of these 5 abnormalities allows MS diagnosis

percentile percentile

Fasting gluc. 110mg/dl

OR IGT

40 mg/dl

110 mg/dl

90th percentile WC 90th

percentile

Cook et al Cook et al

Fasting gluc. 100mg/dl

OR IGT

10°°°° percentile

110 mg/dl

90°°°° percentile WC 90th

percentile

Ford et al Ford et al

(10)

METABOLIC SYNDROME:

The link among these abnormalities

The link among these abnormalities

(11)

INSULIN RESISTANCE:

Definition

INSULIN RESISTANCE:

Definition

“Inability of insulin to induce an adequate

“Inability of insulin to induce an adequate utilization of glucose in the periphery and to utilization of glucose in the periphery and to

adequately suppress the hepatic glucose adequately suppress the hepatic glucose

production production ” production production ”

Insulina Insulina

(12)

When the adipocytes reach their maximum When the adipocytes reach their maximum

storage capacity of lipids and their proliferation storage capacity of lipids and their proliferation process is exhausted,

process is exhausted,

the fat is accumulated in other tissues the fat is accumulated in other tissues

INSULIN RESISTANCE INSULIN RESISTANCE

The pathogenesis of fat ectopic deposition

the fat is accumulated in other tissues the fat is accumulated in other tissues

Van Gaal et al, Nature, 2006 Van Gaal et al, Nature, 2006

(13)

PKCθθθθ

IR

IRS-1 IRS-1

Y

Y SS

IRS-1 IRS-1

Y

Y P SS

INSULIN

LCACoA LCACoA DAG

PKCθθθθ

PI- 3K

McGarry JD Diabetes 2002

GLUT4

IRS-1 IRS-1

Y S P

FFA

GLUT4

(14)

Vitamin D in the New Millennium Vitamin D in the New Millennium

Curr Osteoporos Rep. 2012 Mar;10(1):4 Curr Osteoporos Rep. 2012 Mar;10(1):4--15.15.

(15)

SERUM 25(OH)D LEVELS

DEFINITION ng/mL nmol/L

Severe Deficiency <10 <25

Deficiency 10-19 25-49

Vitamin D in the New Millennium Vitamin D in the New Millennium

Deficiency 10-19 25-49

Insufficiency 20-29 50-74

Optimal 30-60 75-150

Intoxication >100 >250

Curr Osteoporos Rep. 2012 Mar;10(1):4 Curr Osteoporos Rep. 2012 Mar;10(1):4--15.15.

(16)

Prevalence and associations of 25

Prevalence and associations of 25--hydroxyvitamin D deficiency in US hydroxyvitamin D deficiency in US children: NHANES 2001

children: NHANES 2001--2004.2004.

Pediatrics. 2009 Sep;124(3):e362 Pediatrics. 2009 Sep;124(3):e362--70.70.

PREVALENCE OF DEFICIENCY AND INSUFFICIENCY OF 25(OH)D IN FEMALE( 3012 PZ)

(17)

Prevalence and associations of 25

Prevalence and associations of 25--hydroxyvitamin D deficiency in US hydroxyvitamin D deficiency in US children: NHANES 2001

children: NHANES 2001--2004.2004.

Pediatrics. 2009 Sep;124(3):e362 Pediatrics. 2009 Sep;124(3):e362--70.70.

PREVALENCE OF DEFICIENCY AND INSUFFICIENCY OF 25(OH)D IN MALE ( 3263 PZ)

(18)

Prevalence and associations of 25

Prevalence and associations of 25--hydroxyvitamin D deficiency in US hydroxyvitamin D deficiency in US children: NHANES 2001

children: NHANES 2001--2004.2004.

Pediatrics. 2009 Sep;124(3):e362 Pediatrics. 2009 Sep;124(3):e362--70.70.

CHARACTERISTICS OF

PATIENTS AND 25(OH)D LEVELS (6275 patients aged 1-21yr)

(19)

Prevalence and associations of 25

Prevalence and associations of 25--hydroxyvitamin D deficiency in US hydroxyvitamin D deficiency in US children: NHANES 2001

children: NHANES 2001--2004.2004.

Pediatrics. 2009 Sep;124(3):e362 Pediatrics. 2009 Sep;124(3):e362--70.70.

CARDIOVASCULAR RISK AND VITAMIN D DEFICIENCY

(20)

Low 25

Low 25--hydroxyvitamin D levels in adolescents: race, season, hydroxyvitamin D levels in adolescents: race, season, adiposity, physical activity, and fitness.

adiposity, physical activity, and fitness.

Pediatrics. 2010 Jun;125(6):1104 Pediatrics. 2010 Jun;125(6):1104--11.11.

(21)

High prevalence of vitamin D insufficiency and its association with High prevalence of vitamin D insufficiency and its association with BMI

BMI--forfor--age among primary school children in Kuala Lumpur, Malaysia.age among primary school children in Kuala Lumpur, Malaysia.

BMC Public Health. 2011 Feb 11;11:95.

BMC Public Health. 2011 Feb 11;11:95.

VITAMIN D AND BMI

(22)

Is vitamin D status known among children living in Northern Italy?

Is vitamin D status known among children living in Northern Italy?

Eur J Nutr. 2012 Mar;51(2):143 Eur J Nutr. 2012 Mar;51(2):143--9.9.

Serum 25(OH) D in Winter (November-May) and in Summer (June-October)

(23)

Is vitamin D status known among children living in Northern Italy?

Is vitamin D status known among children living in Northern Italy?

Eur J Nutr. 2012 Mar;51(2):143 Eur J Nutr. 2012 Mar;51(2):143--9.9.

Different characteristics associated to 25(OH) D status

(24)

VITAMIN D VITAMIN D LEVELS LEVELS AND AND OBESITY OBESITY

CAUSE?

CAUSE?

OR OR

EFFECT ?

EFFECT ? OR

OR

(25)

VITAMIN D VITAMIN D LEVELS AND LEVELS AND OBESITY OBESITY

1)

1) Vitamin D is trapped in Vitamin D is trapped in adipose tissue

adipose tissue

↓VITAMIN D LEVELS

↓VITAMIN D LEVELS

ARE A COSEQUENCE OF OBESITY ARE A COSEQUENCE OF OBESITY

1)

1) Vitamin D influences Vitamin D influences

↓VITAMIN D LEVELS

↓VITAMIN D LEVELS COULD CAUSE OBESITY COULD CAUSE OBESITY

adipose tissue adipose tissue 2)

2) There is a reduction in There is a reduction in hepatic synthesis of hepatic synthesis of 25(OH) Vit D due to 25(OH) Vit D due to NAFLD

NAFLD 3)

3) Obese children may Obese children may have a more sedentary, have a more sedentary, indoor lifestyle

indoor lifestyle 1)

1) Vitamin D influences Vitamin D influences the adipocytes

the adipocytes differentiation differentiation 2)

2) Vitamin D induces the Vitamin D induces the expression of lypolisis expression of lypolisis genes

genes

(26)

Causal Relationship between Obesity and Vitamin D Status: Bi Causal Relationship between Obesity and Vitamin D Status: Bi-- Directional

Directional MendelianMendelian Randomization Analysis of Multiple CohortsRandomization Analysis of Multiple Cohorts

PLoS Med. 2013 February; 10(2): e1001383.

PLoS Med. 2013 February; 10(2): e1001383.

Random effects meta-analysis of the BMI association with 25(OH)D in men (A) (n=20,950) and women (B) (n=21,074).

(27)

Causal Relationship between Obesity and Vitamin D Status: Bi Causal Relationship between Obesity and Vitamin D Status: Bi-- Directional

Directional MendelianMendelian Randomization Analysis of Multiple CohortsRandomization Analysis of Multiple Cohorts

PLoS Med. 2013 February; 10(2): e1001383.

PLoS Med. 2013 February; 10(2): e1001383.

Meta-analysis of the BMI allele score association with BMI (n=32,391), and the vitamin D synthesis (n=35,873) and metabolism (n=38,191) allele score association with 25(OH)D.

(28)

Causal Relationship between Obesity and Vitamin D Status: Bi Causal Relationship between Obesity and Vitamin D Status: Bi-- Directional

Directional MendelianMendelian Randomization Analysis of Multiple CohortsRandomization Analysis of Multiple Cohorts

PLoS Med. 2013 February; 10(2): e1001383.

PLoS Med. 2013 February; 10(2): e1001383.

Meta-analysis of the BMI allele score association with 25(OH)D (n=31,120).

(29)

Causal Relationship between Obesity and Vitamin D Status: Bi Causal Relationship between Obesity and Vitamin D Status: Bi-- Directional

Directional MendelianMendelian Randomization Analysis of Multiple CohortsRandomization Analysis of Multiple Cohorts

PLoS Med. 2013 February; 10(2): e1001383.

PLoS Med. 2013 February; 10(2): e1001383.

Meta-analysis of the synthesis allele score association with BMI (A) (n=36,553) and the metabolism allele score association with BMI (B) (n=40,367).

(30)

Vitamin D Status and

Vitamin D Status and CardiometabolicCardiometabolic Risk Factors in the United Risk Factors in the United States Adolescent Population

States Adolescent Population

Pediatrics 2009;124;e371.

Pediatrics 2009;124;e371.

Vitamin D levels and cardiovascular desease in adolescents

(31)

Vitamin D deficiency in obese children and its relationship to glucose Vitamin D deficiency in obese children and its relationship to glucose

homeostasis.

homeostasis.

J Clin Endocrinol Metab. 2012 Jan;97(1):279 J Clin Endocrinol Metab. 2012 Jan;97(1):279--85.85.

Vitamin D and Glucose Homeostasis/Blood Pressure

(32)

Vitamin d deficiency in obese children and its relationship to insulin Vitamin d deficiency in obese children and its relationship to insulin

resistance and

resistance and adipokinesadipokines..

Journal of Obesity J Obes. 2011;2011:495101. doi: 10.1155/2011/495101.J Obes. 2011;2011:495101. doi: 10.1155/2011/495101.

25(OH) D levels and HOMA-IR

(33)

Vitamin d deficiency in obese children and its relationship to insulin Vitamin d deficiency in obese children and its relationship to insulin

resistance and

resistance and adipokinesadipokines..

Journal of Obesity J Obes. 2011;2011:495101. doi: 10.1155/2011/495101.J Obes. 2011;2011:495101. doi: 10.1155/2011/495101.

25(OH) D levels and QUICKI

(34)

Vitamin d deficiency in obese children and its relationship to insulin Vitamin d deficiency in obese children and its relationship to insulin

resistance and

resistance and adipokinesadipokines..

Journal of Obesity J Obes. 2011;2011:495101. doi: 10.1155/2011/495101.J Obes. 2011;2011:495101. doi: 10.1155/2011/495101.

25(OH) D levels and Adiponectin

(35)

Low serum 25

Low serum 25--hydroxyvitamin D is associated with increased risk of hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from the development of the metabolic syndrome at five years: results from

a national, population

a national, population--based prospective study (The Australian based prospective study (The Australian Diabetes, Obesity and Lifestyle Study:

Diabetes, Obesity and Lifestyle Study: AusDiabAusDiab).).

J Clin Endocrinol Metab. 2012 Jun;97(6):1953 J Clin Endocrinol Metab. 2012 Jun;97(6):1953--61.61.

Serum 25(OH) D and risk of MS development at 5 yr.

(36)

1,25

1,25--Dihydroxyvitamin D improved the free fattyDihydroxyvitamin D improved the free fatty--acidacid--induced insulin induced insulin resistance in cultured C2C12 cells.

resistance in cultured C2C12 cells.

Diabetes Metab Res Rev. 2008 Sep;24(6):459 Diabetes Metab Res Rev. 2008 Sep;24(6):459--64.64.

(37)

1,25

1,25--Dihydroxyvitamin D improved the free fattyDihydroxyvitamin D improved the free fatty--acidacid--induced insulin induced insulin resistance in cultured C2C12 cells.

resistance in cultured C2C12 cells.

Diabetes Metab Res Rev. 2008 Sep;24(6):459 Diabetes Metab Res Rev. 2008 Sep;24(6):459--64.64.

(38)

IR

IRS-1 IRS-1

Y

Y SS

IRS-1 IRS-1

Y

Y P SS

INSULIN

1,25 (OH)Vit D 1,25 (OH)Vit D

PI-3K

GLUT4 GLUT4

GLUT4

(39)
(40)

1.

1. Available Available scientific scientific evidence evidence supports supports a a key key role role of of calcium

calcium and and vitamin vitamin D D in in skeletal skeletal health health..

2.

2. Serum Serum Vitamin Vitamin D D levels levels of of at at least least 20 20 ng ng/ml /ml are are recommended

recommended..

1.

1. Available Available scientific scientific evidence evidence supports supports a a key key role role of of calcium

calcium and and vitamin vitamin D D in in skeletal skeletal health health..

2.

2. Serum Serum Vitamin Vitamin D D levels levels of of at at least least 20 20 ng ng/ml /ml are are recommended

recommended..

The 2011 report on dietary reference intakes for calcium and vitamin D The 2011 report on dietary reference intakes for calcium and vitamin D

from the Institute of Medicine: what clinicians need to know.

from the Institute of Medicine: what clinicians need to know.

3.

3. The The IOM IOM Commitee Commitee concluded concluded that that the the evidence evidence of of an an association

association between between vitamin vitamin D D deficiency deficiency and and risk risk of of nonskeletal

nonskeletal chronic chronic disease disease was was inconsistent inconsistent,, inconclusive,

inconclusive, and and did did not not meet meet criteria criteria for for estabilishing estabilishing cause

cause--and and--effect effect relashionship relashionship..

3.

3. The The IOM IOM Commitee Commitee concluded concluded that that the the evidence evidence of of an an association

association between between vitamin vitamin D D deficiency deficiency and and risk risk of of nonskeletal

nonskeletal chronic chronic disease disease was was inconsistent inconsistent,, inconclusive,

inconclusive, and and did did not not meet meet criteria criteria for for estabilishing estabilishing cause

cause--and and--effect effect relashionship relashionship..

J Clin Endocrinol Metab. 2011 Jan;96(1):53 J Clin Endocrinol Metab. 2011 Jan;96(1):53--8.8.

(41)

The 2011 report on dietary reference intakes for calcium and vitamin D The 2011 report on dietary reference intakes for calcium and vitamin D

from the Institute of Medicine: what clinicians need to know.

from the Institute of Medicine: what clinicians need to know.

J Clin Endocrinol Metab. 2011 Jan;96(1):53 J Clin Endocrinol Metab. 2011 Jan;96(1):53--8.8.

Calcium and vitamin D dietary reference intakes by life stage

(42)

1. The screening for vitamin D deficiency is recommended in individuals at risk for deficiency. Obese alduts and children are at risk of deficiency.

2. Serum levels of vitamin D at least of 30 ng/ml are recommended for the purpose of preventing the non-skeletal chronic desease.

1. The screening for vitamin D deficiency is recommended in individuals at risk for deficiency. Obese alduts and children are at risk of deficiency.

2. Serum levels of vitamin D at least of 30 ng/ml are recommended for the purpose of preventing the non-skeletal chronic desease.

Evaluation, treatment, and prevention of vitamin D deficiency: an Evaluation, treatment, and prevention of vitamin D deficiency: an

Endocrine Society clinical practice guideline.

Endocrine Society clinical practice guideline.

3. The patients who are at risk of deficiency, both adults and children, need a two times higher dose of vitamin D.

4. There is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

3. The patients who are at risk of deficiency, both adults and children, need a two times higher dose of vitamin D.

4. There is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

J Clin Endocrinol Metab. 2011 Jul;96(7):1911 J Clin Endocrinol Metab. 2011 Jul;96(7):1911--30.30.

(43)

Evaluation, treatment, and prevention of vitamin D deficiency: an Evaluation, treatment, and prevention of vitamin D deficiency: an

Endocrine Society clinical practice guideline.

Endocrine Society clinical practice guideline.

J Clin Endocrinol Metab. 2011 Jul;96(7):1911 J Clin Endocrinol Metab. 2011 Jul;96(7):1911--30.30.

Indications for 25(OH)D measurement

(44)

1. Bone health is assured when serum levels of 25(OH)D are 20ng/ml. A higher blood level of 25(OH)D,i.e. 30 ng/ml, isn’t beneficial for non- skeletal health

1. Bone health is assured when serum levels of 25(OH)D are 20ng/ml. A higher blood level of 25(OH)D,i.e. 30 ng/ml, isn’t beneficial for non- skeletal health

IOM committee members respond to Endocrine Society vitamin D IOM committee members respond to Endocrine Society vitamin D

guideline.

guideline.

2. There is no evidence that increases in vitamin D intake beyond the requirements for non obese persons can affect bone health or other health condictions among obese persons

2. There is no evidence that increases in vitamin D intake beyond the requirements for non obese persons can affect bone health or other health condictions among obese persons

J

J ClinClin EndocrinolEndocrinol MetabMetab. 2012 Apr;97(4):1146. 2012 Apr;97(4):1146--52.52.

(45)

1. It provides additional evidences in favor of the fact that the optimal concentration of Vitamin D for bone health must be greater than 30 ng/ml.

1. It provides additional evidences in favor of the fact that the optimal concentration of Vitamin D for bone health must be greater than 30 ng/ml.

Guidelines

Guidelines forfor preventingpreventing andand treatingtreating vitamin Dvitamin D deficiency and deficiency and insufficiency revisited.

insufficiency revisited.

2. These guidelines requires reconsideration in the future as additional data from ongoing longitudinal studies become available.

2. These guidelines requires reconsideration in the future as additional data from ongoing longitudinal studies become available.

J

J ClinClin EndocrinolEndocrinol MetabMetab. 2012 Apr;97(4):1153. 2012 Apr;97(4):1153--8.8.

(46)

Genetic association analysis of vitamin D pathway with obesity traits.

Genetic association analysis of vitamin D pathway with obesity traits.

Int

Int J J ObesObes ((LondLond). 2013 ). 2013 FebFeb 5. 5. doidoi: 10.1038/ijo.2013.6.: 10.1038/ijo.2013.6.

100 tagSNPs in the eight vitamin D pathway genes were studied.

(47)

Prospective association of 25(OH)D with metabolic syndrome.

Prospective association of 25(OH)D with metabolic syndrome.

Clin Endocrinol (Oxf). 2013 Mar 2. doi: 10.1111/cen.12190.

Clin Endocrinol (Oxf). 2013 Mar 2. doi: 10.1111/cen.12190.

Multivariate logistic regression analysis of associations of baseline 25(OH)D with incident MetS at follow-up (n=301).

(48)

Prospective association of 25(OH)D with metabolic syndrome.

Prospective association of 25(OH)D with metabolic syndrome.

Clin Endocrinol (Oxf). 2013 Mar 2. doi: 10.1111/cen.12190.

Clin Endocrinol (Oxf). 2013 Mar 2. doi: 10.1111/cen.12190.

Multiple linear regression analysis of associations of baseline 25(OH)D (nM) with components of the MetS at the 3-year follow-up, n=489

(49)

Background: Vitamin D deficiency has been linked to many of the characteristics of

metabolic syndrome. But whether supplementation with vitamin D2 would improve insulin sensitivity or metabolic risk factors is not known. Aim: To investigate effects of vitamin D2 supplementation on insulin sensitivity and metabolic parameters in metabolic syndrome patients. Subjects and Methods: An 8-week, prospective randomized, double-blind, double- dummy, parallel trial was conducted in patients with metabolic syndrome. Ninety patients were equally randomized to receive vitamin D2 40,000 IU per week, vitamin D2 20,000 IU per week, or placebo. Outcomes were assessed at baseline and at the end of the study.

Results: At week 8, serum 25(OH)D concentrations was increased significantly in both Background: Vitamin D deficiency has been linked to many of the characteristics of

metabolic syndrome. But whether supplementation with vitamin D2 would improve insulin sensitivity or metabolic risk factors is not known. Aim: To investigate effects of vitamin D2 supplementation on insulin sensitivity and metabolic parameters in metabolic syndrome patients. Subjects and Methods: An 8-week, prospective randomized, double-blind, double- dummy, parallel trial was conducted in patients with metabolic syndrome. Ninety patients were equally randomized to receive vitamin D2 40,000 IU per week, vitamin D2 20,000 IU per week, or placebo. Outcomes were assessed at baseline and at the end of the study.

Results: At week 8, serum 25(OH)D concentrations was increased significantly in both

Effects of Vitamin D2 Supplementation on Insulin Sensitivity and Effects of Vitamin D2 Supplementation on Insulin Sensitivity and

Metabolic Parameters in Metabolic Syndrome Patients.

Metabolic Parameters in Metabolic Syndrome Patients.

Results: At week 8, serum 25(OH)D concentrations was increased significantly in both

vitamin D2 groups (i.e., 20,000 IU and 40,000 IU) when compared with placebo group (11.72 ng/mL vs. 2.80 ng/mL; p < 0.001 and 15.74 ng/mL vs. 2.80 ng/mL; p < 0.001, respectively).

Serum 25(OH)D concentrations in both vitamin D2 treatment groups were also significantly different (p = 0.04). Insulin sensitivity assessed by homeostasis model assessment of insulin resistance (HOMA-IR) at week 8 in all 3 groups were not significantly different (p = 0.36).

Results: At week 8, serum 25(OH)D concentrations was increased significantly in both

vitamin D2 groups (i.e., 20,000 IU and 40,000 IU) when compared with placebo group (11.72 ng/mL vs. 2.80 ng/mL; p < 0.001 and 15.74 ng/mL vs. 2.80 ng/mL; p < 0.001, respectively).

Serum 25(OH)D concentrations in both vitamin D2 treatment groups were also significantly different (p = 0.04). Insulin sensitivity assessed by homeostasis model assessment of insulin resistance (HOMA-IR) at week 8 in all 3 groups were not significantly different (p = 0.36).

Conclusions: Vitamin D2 20,000 IU per week and 40,000 IU per week given for 8 weeks, were able to increase serum 25(OH)D concentrations higher than placebo group significantly.

However, HOMA-IR was not significantly different in all three groups. Our results do not support a positive effect of vitamin D2 on metabolic risk factors.

Conclusions: Vitamin D2 20,000 IU per week and 40,000 IU per week given for 8 weeks, were able to increase serum 25(OH)D concentrations higher than placebo group significantly.

However, HOMA-IR was not significantly different in all three groups. Our results do not support a positive effect of vitamin D2 on metabolic risk factors.

J

J EndocrinolEndocrinol Invest. 2013 Feb 4.Invest. 2013 Feb 4.

(50)

Correcting vitamin D insufficiency improves insulin sensitivity in Correcting vitamin D insufficiency improves insulin sensitivity in

obese adolescents: a randomized controlled trial.

obese adolescents: a randomized controlled trial.

Am J

Am J ClinClin NutrNutr. 2013 Apr;97(4):774. 2013 Apr;97(4):774--81. 81. doidoi: 10.3945/ajcn.112.050013.: 10.3945/ajcn.112.050013.

Mean (±±±±SE) serum concentrations of 25(OH)D.

(51)

Correcting vitamin D insufficiency improves insulin sensitivity in Correcting vitamin D insufficiency improves insulin sensitivity in

obese adolescents: a randomized controlled trial.

obese adolescents: a randomized controlled trial.

Am J

Am J ClinClin NutrNutr. 2013 Apr;97(4):774. 2013 Apr;97(4):774--81. 81. doidoi: 10.3945/ajcn.112.050013.: 10.3945/ajcn.112.050013.

Serum markers of insulin sensitivity and resistance in participants at baseline and at 6 mo.

(52)

Correcting vitamin D insufficiency improves insulin sensitivity in Correcting vitamin D insufficiency improves insulin sensitivity in

obese adolescents: a randomized controlled trial.

obese adolescents: a randomized controlled trial.

Am J

Am J ClinClin NutrNutr. 2013 Apr;97(4):774. 2013 Apr;97(4):774--81. 81. doidoi: 10.3945/ajcn.112.050013.: 10.3945/ajcn.112.050013.

Association between 6-mo change in serum 25(OH)D concentration and 6-mo change in HOMA-IR (A) and ratio of leptin to adiponectin (B) for all participants completing the 6-

mo follow-up (n=29).

(53)

Emanuele Miraglia del Giudice

Seconda Università degli Studi di Napoli

Dipartimento della Donna del Bambino e di Chirurgia Generale e Specialistica

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