Presented by – Dr. Rishika Gaur
Jr2
Internal medicine ,
KGMU
 Principal Guide
• Dr. Madhukar Mittal
 Co-Guides
• Prof Ravi Misra
• Prof Arvind Mishra
• Dr. Vivek Kumar
• Prof A.A.Mahdi
 Known since years:
The adverse association between low serum vitamin D
levels and bone and calcium metabolism
 Recently researched:
Inverse relation between serum vitamin D levels and
metabolic syndrome, diabetes mellitus , hypertension
and cardiovascular disease
 Insulin secretion
Research shows that severe vitamin D deficiency may inhibit
insulin secretion
 Insulin Resistance
Vitamin D deficiency also associated with insulin resistance in
humans
 Vitamin D supplementation
Conflicting data on whether supplementation improves glycemic
control in T2D
Inconsistent results regarding supplementation and prevention of
progression of prediabetes to diabetes
 IL-6 levels correlate negatively with insulin sensitivity
 TNF α levels increase with insulin resistance
 hsCRP-directly associated with insulin resistance
 Fetuin A
 Fetuin A
Peptide molecule
Secreted from hepatocytes
Binds to Insulin receptor present on adipose cells and
muscles
Higher serum Fetuin A levels are associated with
insulin resistance
 Comparison of 25(OH)D and Fetuin A levels
• Impaired Fasting Glucose/Impaired Glucose
Tolerance(IFG/IGT)
• Type 2 Diabetes mellitus(T2D), No CAD
• Type2 Diabetes Mellitus with Coronary artery
disease
 Effect of Vitamin D supplementation on
glycemic parameters
 Study Design-
• Observational Cross sectional study
• Prospective open label study
 Duration of study-one year
 Study population- 3 groups
• IFG/IGT
• T2D, No CAD
• T2D with CAD
 Age : >18 and <70 years
 Blood sugar
 CAD: Coronary artery disease- previous h/o myocardial
infarction, cardiomyopathy, stable angina, unstable angina
IFG: FBS -100-125
IGT: PPBS-140-199
T2D 1.FBS: ≥ 126
2.PPBS: ≥200
3.RBS: ≥200 with symptoms
Holick’s Classification Lip’s Classification
 1.Sufficiency :≥ 30 ng/ml
 2.Insufficiency: 20-29 ng/ml
 3.Deficiency :<20 ng/ml
 1. Mild- 25-50 ng/ml
 2. Moderate- 12.5-25 ng/ml
 3. Severe- <12.5ng/ml
• Chronic kidney disease
• Vitamin D Supplementation in last 3 month
• Vitamin D Fortified food
• Malabsorption
• Primary hyperparathyroidism
• Pregnancy
• Breast feeding
• Antiepileptics, Steroids, Antifungal, ATT, ART
• Complete Blood Count
• Liver function test
• Kidney function test
• HbA1c
• 25(OH) D : Chemiluminescence (CLIA)
• Fetuin A: Human Fetuin A ELISA kit(Booster
Immunoleader)
• ECG and USG
Sno. Publication Study design Interventi
on
Effect Remarks
1. Mittal M et al.
(Journal of diabetes
&metabolic
disorder)
Systematic
review
- - No improvement with
vitamin D supplementation
on glycemic parameters
2. George PS, Pearson
ER,Witham Md et
al(2012)
Systematic
review and
meta analysis
- - Further studies need to
establish relation between
25(OH) D and T2D
S No. Publication Study design Intervention Change in
glycemic
parameters
REMARKS
1. Jehle et al, 2014,
Switzerland
RCT, N=55 300,000 IU
IM once in 3
month x 6mo
HOMA-IR - ↓ by
12.8% ± 5.6% in
the D3 group and ↑
by 10% ± 5.4% in
placebo group
(p = 0.032) 0
Improved
HOMA-IR
2. Al-Daghri et al,
2012, Saudi
Prospective
longitudinal,
N=92
Vitamin D3
oral 2000 IU
daily for 18
months
HOMA-B: 52 ± 9
vs. 97 ± 15
(p=0.002)
S No. Publication Study design Intervention Change in
glycemic
parameters
Remarks
3. Talaei et al,
2013, Iran
Longitudinal
study, N=100
50,000 U
vitamin
D3
orally/weekly
for 8 weeks
HOMA-IR:
3.57±3.18
and
2.89±3.28
(P=0.008)
4. Nikooyeh et al
, 2011, Iran
RCT,N = 90 500 IU
vitamin D+
calcium
twice daily
for12 weeks
HbA1c(8.7±
1.4 v/s
7.3±1.3(p<0.
001) and
HOMA-IR
(5.5±3.7 v/s
3.0±1.5)(p<
0.001)
Significant
improvemen
t in
HbA1c and
HOMA-IR
S No. Publication Study
design
Intervention Change in glycemic
parameters
Remarks
5. Tabesh et al ,
2014, Iran
RCT, N =
70
Cholecalcifero
l for 8 weeks
changes from baseline,
HbA1c (-0.70 ± 0.19%,
(p = 0.02), HOMA-IR (-
0.46 ± 0.20, p = 0.001)
QUICKI (0.025 ± 0.01,( p
= 0.004)
improved
HbA1c,
HOMA-IR
6. Shab-bidar et
al, 2011, Iran
RCT, N =
100
1,000 IU
vitamin
D3 orally daily
for12 weeks
QUICKI- 0.27±0.02 V/S
0.30±0.02,HBA1c-
8.7±1.8 v/s
7.8±1.3(p=0.015)
QUICKI only
showed
improvement,
rest no
significant
change.
S No. Publication Study
design
Interventio
n
Change in glycemic
parameters
Remarks
7. Chan et al ,
2013, Hong
Kong
RCT, N =
100
5000 IU
Vitamin
D3 daily
for 12
weeks
HbA1c -7.35 vs.
7.20,
p = 0.08
No change in
HBA1C and
other
glycemic
parameters
8. Hassan et al,
2011, Iran
RCT, N =
70
Calcitriol
0.25 μg
daily
orally for
12 weeks
HbA1c -7.1 ± 1.6
vs. 7.9 ± 2.1,
p=0.004,QUICKI-
0.33±0.03
v/s0.31±0.02
(p=0.002)
Attenuated the
increase
in glycemic,
and QUICKI
1. N, % 14 (87.5)
2.BMI 27.21±4.37 27.57(23.84-30.36)
3.25(OH)D,
ng/ml
15.29±14.69 9.03(4.45-24.44)
4.HBA1c, % 6.31±0.86 6.30(5.62-6.87)
5.Fasting insulin,
mU/L
11.04±7.43 9.92(5.79-13.20)
6.HOMAIR
2.893±1.914 2.642(1.68-3.29)
7.QUICKI 0.341±0.040 0.330(0.320-0.352)
Values are means ± SD or median (inter-quartile range)
1. N,% 43(63.2)
2.BMI 27.24±6.50 25.77(22.56-31.00)
3.25(OH)D,
ng/ml
14.62±9.67 12.67(7.277-19.91)
4.HBA1c,% 9.16±2.63 8.65(6.70-11.28)
5.Fasting insulin,
mU/L
13.12±18.65 8.17(4.60-14.70)
6.HOMAIR
4.201±6.561 2.57(1.28-4.00)
7.QUICKI 0.339±0.0488 0.331(0.311-0.368)
Values are means ± SD or median (inter-quartile range)
1. N,% 5(31.2)
2.BMI 27.55±7.27 25.96(25.00-27.63)
3.25(OH)D, ng/ml 16.12±13.25 12.56(5.89-24.47)
4.HBA1c,% 9.54±2.25 9.50(8.80-10.60)
5.Fasting insulin,
mU/L
7.16±4.17 5.46(4.60-10.76)
6.HOMAIR
2.297±1.566 1.600(1.30-3.68)
7.QUICKI 0.354±0.047 0.355(0.315-0.368)
Values are means ± SD or median (inter-quartile range)
Characteristic Deficient
(N=92)
Non
deficient
(N=8)
P
value
1. N,% 57(91.93) 5(8.06) 0.976
2.BMI 27.48±6.42 25.96(23.68-
30.08)
25.20±4.65 25.61(21.22-
27.18)
0.332
3.25(OH)D, ng/ml 12.57±7.30 10.97(5.8-
18.77)
42.55±10.01 40.91 0.00
4.HBA1c,% 8.89±2.64 8.60(6.6-
10.7)
7.30±1.60 6.70(6.07-8.35) 0.097
5.Fasting insulin,
mU/L
10.933±9.425 8.38(4.81-
13.5)
22.422±47.21
3
5.56(4.18-10.75) 0.049
6.HOMAIR
3.262±2.933 2.57(1.38-
3.80)
6.822±15.016 1.60(0.94-2.77) 0.074
7.QUICKI 0.340±0.043 0.331(0.313-
0.36)
0.359±0.074 0.355(0.328-
0.387)
0.272
Values are means ± S D or median (inter-quartile range)
Characteristic Female
(N=62)
Male
(N=38)
P value
1. N, % 62(100) 8(0)
2.BMI 28.54±6.89 26.66(18.00-
27.00)
25.22±4.59 25.39(21.98-
27.38)
0.012
3.25(OH)D, ng/ml 15.38±11.58 12.76(5.48-
21.52)
14.28±10.34 11.68(6.96-
19.03)
0.631
4.HBA1c,% 8.72±2.44 8.45(6.47-
10.72)
8.83±2.88 8.60(6.50-
10.45)
0.844
5.Fasting insulin,
mU/L
13.49±19.36 8.80(4.66-
15.05)
9.18±6.55 6.94(4.43-
12.79)
0.194
6.HOMAIR
4.299±6.522 2.72(1.368-
4.454)
2.44±1.83 1.925(1027-
3.334)
0.134
7.QUICKI 0.336±0.045 0.328(0.307-
0.364)
0.352±0.048 0.346(0.319-
0.368)
0.123
Values are means ± SD or median (inter-quartile range)
Characteristic IFG
(N=16)
T2D
(N=84)
pvalue
1. N , % 14(87.5) 48(57.14) 0.025
2.BMI 27.21±4.37 27.57(23.84-
30.36)
27.30±6.60 25.77( 22.91-
29.47)
0.961
3.25(OH)D, ng/ml 15.29±14.69 9.03(4.45-
24.44)
14.90±10.37 12.76(6.44-
19.91)
0.899
4.HBA1c,% 6.31±0.86 6.30(5.62-6.87) 9.23±2.56 8.90(6.70-
11.24)
0.00
5.Fasting insulin,
mU/L
11.04±7.43 9.92(5.79-
13.20)
12.03±17.08 7.42,(4.51-
13.46)
0.822
6.HOMAIR
2.893±1.914 2.642(1.68-
3.29)
3.791±5.895 2.233(1.32-
3.80)
0.551
7.QUICKI 0.341±0.0404 0.330(0.320-
0.352)
0.3427±0.0485 0.338(0.3138-
0.3665)
0.895
Values are means ± SD or median (inter-quartile range)
25(oh) d levels, fetuin final
Sno. Publication Study design Fetuin A levels REMARKS
1. Liang Yin et al,
China ,2015
Cross Sectional
Study
T2D v/s NGT (368.5±15.6
vs. 152.7±7.1 mg/l (P<0.01)
2. Aiyun Song et
al,China,2011
Cross Sectional
Study
NGT v/s IFG/IGT v/s T2D
285.3 v/s291.0 v/s 307.7 (p
value= 0.0008)
Significant
difference
among three
group.

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25(oh) d levels, fetuin final

  • 1. Presented by – Dr. Rishika Gaur Jr2 Internal medicine , KGMU
  • 2.  Principal Guide • Dr. Madhukar Mittal  Co-Guides • Prof Ravi Misra • Prof Arvind Mishra • Dr. Vivek Kumar • Prof A.A.Mahdi
  • 3.  Known since years: The adverse association between low serum vitamin D levels and bone and calcium metabolism  Recently researched: Inverse relation between serum vitamin D levels and metabolic syndrome, diabetes mellitus , hypertension and cardiovascular disease
  • 4.  Insulin secretion Research shows that severe vitamin D deficiency may inhibit insulin secretion  Insulin Resistance Vitamin D deficiency also associated with insulin resistance in humans  Vitamin D supplementation Conflicting data on whether supplementation improves glycemic control in T2D Inconsistent results regarding supplementation and prevention of progression of prediabetes to diabetes
  • 5.  IL-6 levels correlate negatively with insulin sensitivity  TNF α levels increase with insulin resistance  hsCRP-directly associated with insulin resistance  Fetuin A  Fetuin A Peptide molecule Secreted from hepatocytes Binds to Insulin receptor present on adipose cells and muscles Higher serum Fetuin A levels are associated with insulin resistance
  • 6.  Comparison of 25(OH)D and Fetuin A levels • Impaired Fasting Glucose/Impaired Glucose Tolerance(IFG/IGT) • Type 2 Diabetes mellitus(T2D), No CAD • Type2 Diabetes Mellitus with Coronary artery disease  Effect of Vitamin D supplementation on glycemic parameters
  • 7.  Study Design- • Observational Cross sectional study • Prospective open label study  Duration of study-one year  Study population- 3 groups • IFG/IGT • T2D, No CAD • T2D with CAD
  • 8.  Age : >18 and <70 years  Blood sugar  CAD: Coronary artery disease- previous h/o myocardial infarction, cardiomyopathy, stable angina, unstable angina IFG: FBS -100-125 IGT: PPBS-140-199 T2D 1.FBS: ≥ 126 2.PPBS: ≥200 3.RBS: ≥200 with symptoms
  • 9. Holick’s Classification Lip’s Classification  1.Sufficiency :≥ 30 ng/ml  2.Insufficiency: 20-29 ng/ml  3.Deficiency :<20 ng/ml  1. Mild- 25-50 ng/ml  2. Moderate- 12.5-25 ng/ml  3. Severe- <12.5ng/ml
  • 10. • Chronic kidney disease • Vitamin D Supplementation in last 3 month • Vitamin D Fortified food • Malabsorption • Primary hyperparathyroidism • Pregnancy • Breast feeding • Antiepileptics, Steroids, Antifungal, ATT, ART
  • 11. • Complete Blood Count • Liver function test • Kidney function test • HbA1c • 25(OH) D : Chemiluminescence (CLIA) • Fetuin A: Human Fetuin A ELISA kit(Booster Immunoleader) • ECG and USG
  • 12. Sno. Publication Study design Interventi on Effect Remarks 1. Mittal M et al. (Journal of diabetes &metabolic disorder) Systematic review - - No improvement with vitamin D supplementation on glycemic parameters 2. George PS, Pearson ER,Witham Md et al(2012) Systematic review and meta analysis - - Further studies need to establish relation between 25(OH) D and T2D
  • 13. S No. Publication Study design Intervention Change in glycemic parameters REMARKS 1. Jehle et al, 2014, Switzerland RCT, N=55 300,000 IU IM once in 3 month x 6mo HOMA-IR - ↓ by 12.8% ± 5.6% in the D3 group and ↑ by 10% ± 5.4% in placebo group (p = 0.032) 0 Improved HOMA-IR 2. Al-Daghri et al, 2012, Saudi Prospective longitudinal, N=92 Vitamin D3 oral 2000 IU daily for 18 months HOMA-B: 52 ± 9 vs. 97 ± 15 (p=0.002)
  • 14. S No. Publication Study design Intervention Change in glycemic parameters Remarks 3. Talaei et al, 2013, Iran Longitudinal study, N=100 50,000 U vitamin D3 orally/weekly for 8 weeks HOMA-IR: 3.57±3.18 and 2.89±3.28 (P=0.008) 4. Nikooyeh et al , 2011, Iran RCT,N = 90 500 IU vitamin D+ calcium twice daily for12 weeks HbA1c(8.7± 1.4 v/s 7.3±1.3(p<0. 001) and HOMA-IR (5.5±3.7 v/s 3.0±1.5)(p< 0.001) Significant improvemen t in HbA1c and HOMA-IR
  • 15. S No. Publication Study design Intervention Change in glycemic parameters Remarks 5. Tabesh et al , 2014, Iran RCT, N = 70 Cholecalcifero l for 8 weeks changes from baseline, HbA1c (-0.70 ± 0.19%, (p = 0.02), HOMA-IR (- 0.46 ± 0.20, p = 0.001) QUICKI (0.025 ± 0.01,( p = 0.004) improved HbA1c, HOMA-IR 6. Shab-bidar et al, 2011, Iran RCT, N = 100 1,000 IU vitamin D3 orally daily for12 weeks QUICKI- 0.27±0.02 V/S 0.30±0.02,HBA1c- 8.7±1.8 v/s 7.8±1.3(p=0.015) QUICKI only showed improvement, rest no significant change.
  • 16. S No. Publication Study design Interventio n Change in glycemic parameters Remarks 7. Chan et al , 2013, Hong Kong RCT, N = 100 5000 IU Vitamin D3 daily for 12 weeks HbA1c -7.35 vs. 7.20, p = 0.08 No change in HBA1C and other glycemic parameters 8. Hassan et al, 2011, Iran RCT, N = 70 Calcitriol 0.25 μg daily orally for 12 weeks HbA1c -7.1 ± 1.6 vs. 7.9 ± 2.1, p=0.004,QUICKI- 0.33±0.03 v/s0.31±0.02 (p=0.002) Attenuated the increase in glycemic, and QUICKI
  • 17. 1. N, % 14 (87.5) 2.BMI 27.21±4.37 27.57(23.84-30.36) 3.25(OH)D, ng/ml 15.29±14.69 9.03(4.45-24.44) 4.HBA1c, % 6.31±0.86 6.30(5.62-6.87) 5.Fasting insulin, mU/L 11.04±7.43 9.92(5.79-13.20) 6.HOMAIR 2.893±1.914 2.642(1.68-3.29) 7.QUICKI 0.341±0.040 0.330(0.320-0.352) Values are means ± SD or median (inter-quartile range)
  • 18. 1. N,% 43(63.2) 2.BMI 27.24±6.50 25.77(22.56-31.00) 3.25(OH)D, ng/ml 14.62±9.67 12.67(7.277-19.91) 4.HBA1c,% 9.16±2.63 8.65(6.70-11.28) 5.Fasting insulin, mU/L 13.12±18.65 8.17(4.60-14.70) 6.HOMAIR 4.201±6.561 2.57(1.28-4.00) 7.QUICKI 0.339±0.0488 0.331(0.311-0.368) Values are means ± SD or median (inter-quartile range)
  • 19. 1. N,% 5(31.2) 2.BMI 27.55±7.27 25.96(25.00-27.63) 3.25(OH)D, ng/ml 16.12±13.25 12.56(5.89-24.47) 4.HBA1c,% 9.54±2.25 9.50(8.80-10.60) 5.Fasting insulin, mU/L 7.16±4.17 5.46(4.60-10.76) 6.HOMAIR 2.297±1.566 1.600(1.30-3.68) 7.QUICKI 0.354±0.047 0.355(0.315-0.368) Values are means ± SD or median (inter-quartile range)
  • 20. Characteristic Deficient (N=92) Non deficient (N=8) P value 1. N,% 57(91.93) 5(8.06) 0.976 2.BMI 27.48±6.42 25.96(23.68- 30.08) 25.20±4.65 25.61(21.22- 27.18) 0.332 3.25(OH)D, ng/ml 12.57±7.30 10.97(5.8- 18.77) 42.55±10.01 40.91 0.00 4.HBA1c,% 8.89±2.64 8.60(6.6- 10.7) 7.30±1.60 6.70(6.07-8.35) 0.097 5.Fasting insulin, mU/L 10.933±9.425 8.38(4.81- 13.5) 22.422±47.21 3 5.56(4.18-10.75) 0.049 6.HOMAIR 3.262±2.933 2.57(1.38- 3.80) 6.822±15.016 1.60(0.94-2.77) 0.074 7.QUICKI 0.340±0.043 0.331(0.313- 0.36) 0.359±0.074 0.355(0.328- 0.387) 0.272 Values are means ± S D or median (inter-quartile range)
  • 21. Characteristic Female (N=62) Male (N=38) P value 1. N, % 62(100) 8(0) 2.BMI 28.54±6.89 26.66(18.00- 27.00) 25.22±4.59 25.39(21.98- 27.38) 0.012 3.25(OH)D, ng/ml 15.38±11.58 12.76(5.48- 21.52) 14.28±10.34 11.68(6.96- 19.03) 0.631 4.HBA1c,% 8.72±2.44 8.45(6.47- 10.72) 8.83±2.88 8.60(6.50- 10.45) 0.844 5.Fasting insulin, mU/L 13.49±19.36 8.80(4.66- 15.05) 9.18±6.55 6.94(4.43- 12.79) 0.194 6.HOMAIR 4.299±6.522 2.72(1.368- 4.454) 2.44±1.83 1.925(1027- 3.334) 0.134 7.QUICKI 0.336±0.045 0.328(0.307- 0.364) 0.352±0.048 0.346(0.319- 0.368) 0.123 Values are means ± SD or median (inter-quartile range)
  • 22. Characteristic IFG (N=16) T2D (N=84) pvalue 1. N , % 14(87.5) 48(57.14) 0.025 2.BMI 27.21±4.37 27.57(23.84- 30.36) 27.30±6.60 25.77( 22.91- 29.47) 0.961 3.25(OH)D, ng/ml 15.29±14.69 9.03(4.45- 24.44) 14.90±10.37 12.76(6.44- 19.91) 0.899 4.HBA1c,% 6.31±0.86 6.30(5.62-6.87) 9.23±2.56 8.90(6.70- 11.24) 0.00 5.Fasting insulin, mU/L 11.04±7.43 9.92(5.79- 13.20) 12.03±17.08 7.42,(4.51- 13.46) 0.822 6.HOMAIR 2.893±1.914 2.642(1.68- 3.29) 3.791±5.895 2.233(1.32- 3.80) 0.551 7.QUICKI 0.341±0.0404 0.330(0.320- 0.352) 0.3427±0.0485 0.338(0.3138- 0.3665) 0.895 Values are means ± SD or median (inter-quartile range)
  • 24. Sno. Publication Study design Fetuin A levels REMARKS 1. Liang Yin et al, China ,2015 Cross Sectional Study T2D v/s NGT (368.5±15.6 vs. 152.7±7.1 mg/l (P<0.01) 2. Aiyun Song et al,China,2011 Cross Sectional Study NGT v/s IFG/IGT v/s T2D 285.3 v/s291.0 v/s 307.7 (p value= 0.0008) Significant difference among three group.