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25(OH)D, Fetuin A levels in patients of IFG/IGT, Type 2
diabetes mellitus and Type 2 diabetes mellitus with
cardiovascular disease
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
Background
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
Role of Vitamin D
IL-6 levels correlate negatively with insulin sensitivity TNF α levels increase with insulin resistance hsCRP-directly associated with insulin resistance Fetuin A
Fetuin APeptide moleculeSecreted from hepatocytesBinds to Insulin receptor present on adipose cells and
musclesHigher serum Fetuin A levels are associated with
insulin resistance
Molecular markers in T2D
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
Aim & Objectives
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
Material & Methods
Age : >18 and <70 years
Blood sugar
CAD: Coronary artery disease- previous h/o myocardial infarction, cardiomyopathy, stable angina, unstable angina
Inclusion Criteria
IFG: FBS -100-125
IGT: PPBS-140-199
T2D 1.FBS: ≥ 126 2.PPBS: ≥200 3.RBS: ≥200 with symptoms
25(OH)D deficiency: Classification
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
Exclusion Criteria
• 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
Laboratory Investigations
Sno. Publication Study design Intervention
Effect Remarks
1. Mittal M et al. (Journal of diabetes &metabolic disorder)
Systematic review
- - No improvement with vitamin D supplementationon 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
Review of Literature: Systematic review & Metaanalysis
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
Prospectivelongitudinal,N=92
Vitamin D3 oral 2000 IU daily for 18 months
HOMA-B: 52 ± 9 vs. 97 ± 15 (p=0.002)
Individuals studies
S No. Publication Study design Intervention Change in glycemic parameters
Remarks
3. Talaei et al, 2013, Iran
Longitudinal study, N=100
50,000 U vitaminD3 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+ calciumtwice 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 improvement inHbA1c and HOMA-IR
S No. Publication Study design
Intervention Change in glycemic parameters
Remarks
5. Tabesh et al , 2014, Iran
RCT, N = 70
Cholecalciferol 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)
improvedHbA1c, HOMA-IR
6. Shab-bidar et al, 2011, Iran
RCT, N = 100
1,000 IU vitaminD3 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
Intervention
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 ± 1.6vs. 7.9 ± 2.1, p=0.004,QUICKI-0.33±0.03 v/s0.31±0.02 (p=0.002)
Attenuated the increasein glycemic, and QUICKI
Results: IFG/IGT1. 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.HOMAIR2.893±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.HOMAIR4.201±6.561 2.57(1.28-4.00)
7.QUICKI 0.339±0.0488 0.331(0.311-0.368)
Results: T2D No CAD
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.HOMAIR2.297±1.566 1.600(1.30-3.68)
7.QUICKI 0.354±0.047 0.355(0.315-0.368)
Results: T2D WITH CAD
Values are means ± SD or median (inter-quartile range)
Comparison of Vitamin D Deficient vs. Non DeficientCharacteristic 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±47.213
5.56(4.18-10.75) 0.049
6.HOMAIR3.262±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.HOMAIR4.299±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
Comparison of Female vs. Male
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.HOMAIR2.893±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
Comparison of IFG vs. T2D
Values are means ± SD or median (inter-quartile range)
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.
Individuals studies regarding Fetuin A-