INTRODUCTION:

Many researchers studied the relationship between the ABO blood group and different diseases, in France a large prospective study found no association between risk of DMII and Rh blood group, but those in blood group O had the lowest risk of DMII while blood group B individuals were at the highest risk, followed by group AB and then group A people, but the risk for group AB individuals did not reach statistical significance. When ABO and Rh groups were evaluated together, blood group B+ individuals had the highest risk, followed by group AB+, then A– and then A+ individual, but no difference in risk was seen for the other groups¹. When adjusted for metabolic covariates (fasting blood glucose and lipids), blood group AB individuals had the highest risk of DMII². Another study in Yemen reported that the highest random blood sugar and insulin levels were found in blood group A, while blood group AB showed a protective effect³, and a study in Iraqi individuals reported higher total cholesterol, higher blood glucose, and higher blood pressure in blood group O individuals,

followed by lower risk in group A, group B, and then group AB individuals, who had the lowest risk¹.

Researchers have also investigated the association between ABO blood group antigens and dyslipidemia. One study reported that total cholesterol, LDL cholesterol, and triglycerides (TG) were higher, and high-density lipoprotein cholesterol (HDLc) was lower, in blood groups A and B, and that blood group AB was protective for dyslipidemia³, while another study reported that blood group A was associated with higher total cholesterol and LDL cholesterol, but there was no association with HDL cholesterol².

The most interesting finding by D Rose Ewald et al. was the association of ABO and secretor blood groups with serum levels of intestinal alkaline phosphatase (I-ALP) and apolipoprotein B-48 (Apo B-48); I-ALP is required for transport of chylomicrons from the intestines into the circulation and is therefore a marker for chylomicron absorption, and Apo B-48 is a protein that stabilizes the chylomicron membrane, and is therefore a marker for chylomicron production. There are significant differences in serum I-ALP and Apo B-48 between blood group O and B secretors and all other blood groups; the O and B secretors have very elevated serum levels of these markers compared with blood group A/AB secretors and non- secretors of all blood groups⁴.

Blood group A individual also have lower serum Apo B-48 levels, which may be due to a genetic down-regulation of I-ALP activity in their intestines, resulting in reduced chylomicron secretion⁴.

Hypertension can have many different causes, EI-Sayed MIK et al., found that the rate of hypertension was highest in blood group B, followed by blood group A, and that blood group AB had the lowest rate of hypertension³.

In essential hypertension due to abnormal erythrocyte sodium and potassium transport, no association was found with the ABO, Rh, Duffy, Kidd, P, or MNS blood groups, or with the major histocompatibility HLA antigens⁵.

Historically, non-O blood groups have been associated with greater incidence of vascular disorders such as cerebral arterial ischemia, venous thromboembolism, peripheral vascular disease, angina, and myocardial infarction, and these associations were confirmed in 2008 with a systematic and meta-analysis, and further validated by subsequent GWAS studies. Von Willebrand factor (VWF) and Factor VIII (FVIII) are plasma coagulation glycoproteins, which act by forming a non- covalently bound complex; vWF stabilizes FVIII and transports it to the site of vascular injury, and then interacts with platelets as part of the clotting process. VWF is partially regulated by the cleavage action of a metalloprotease, which clears it from the plasma; it is thought that the A and B antigens interfere with access to the cleavage site, thereby reducing clearance of vWF⁶.

FVIII and vWF are approximately 25% lower in the plasma of blood group O people (specifically, < O < B < A < AB, with A/O and B/O having less than A/A and B/B individuals), and group O individuals are therefore at lower risk for venous and arterial thromboembolism, but at greater risk of excessive bleeding than group A individuals. Higher average levels of FVIII in blood group A individuals increase the risk of ischemic heart disease and venous thromboembolism, and group A people are more likely to thrombosis or have myocardial infarctions than group O individuals. The risk for myocardial infarction in the presence of coronary atherosclerosis is 44% lower for group O individuals than for other blood groups⁷. Non-O blood group individuals have an 11% greater relative risk of developing coronary heart disease than blood group O individuals⁸, and group AB individuals have a high risk of stroke compared to group O individuals, and Zakai NA et al., found that 60% of stroke risk in blood group AB individuals was associated with FVIII levels⁹.

Methods:

Subjects:

The study was carried out on patients with clinical already diagnosed as having DM II without and with complication such as nephropathy, retinopathy and neuropathy admitted to the medicine unit in Medical City -Baghdad Teaching Hospital and Al_ Imamein Al_ Kadhimaein Medical city from (July 2018 to September 2018). A total of fifty-two 52 patients (29 male, 23 female) without complication of DMII, two hundred sixteen 216 patients (107 male, 109 female) with complication of DMII were included in the study: (nephropathy 59 patients, retinopathy 61 patients, and neuropathy 96 patients), with seventy one 71 person as healthy control (34 male, 37 female), all DM II patients are detected by (history, signs, symptoms and laboratory diagnosis).

Exclusion criteria:

i. Subject with DMI as defined by American Diabetes Association (ADA).

ii. Gestational DM as defined by ADA.

ABO blood group detection:

Principle:

The ABO grouping test is based on the principle of haemagglutination reaction¹⁰.

Statistical Analysis:

The following statistical data analysis approaches were done by using the Statistical Package for Social Sciences (SPSS 24): Statistical tables, chi-square was used to examine the degree of significance in distribution. P values equal or less than 0.05 was considered significant and to compare between groups lowest significant difference test (LSD) was used.

RESULTS:

Age and gender distribution of subjects are illustrated in table (1).

Distribution of ABO blood groups in healthy group:

Table (2) shows the distribution of ABO blood groups in healthy subjects with highest percent for group A in males (38.2) % and for group O in females (46) %.

Table 2: Distribution of ABO blood groups in healthy group

	A	B	AB	O
Male	13(38.2)%	8(23.5)%	4 (11.8)%	9(26.5)%
Female	9 (24.3)%	8(21.6)%	3(8.1)%	17(46)%
Total	22(31)%	16(22.5)%	7(9.9 )%	26(36.6)%

Distribution of ABO blood groups in DM II patients without complication:

According to table (3), in diabetic patients without complication group A and group AB were the high percent for males (27.6) %, while in females the high percent was group B(43.5) %.

Table 3: Distribution of ABO blood groups in DM II without complication

	A	B	AB	O
Male	8(27.6 )%	6(20.7)%	8(27.6)%	7(24.1 )%
Female	5(21.7 )%	10(43.5)%	2(8.7)%	6(26.1)%
Total	13(25 )%	16(30.8)%	10(19.2)%	13(25 )%

Distribution of ABO blood groups in DM II patients with complication:

According to table (4) the distribution of ABO blood group in DM II with complication group shows a high percentage in group O for both males (48.6) %, and a high percentage in group O for females (56.9) %.

Table 4: Distribution of ABO blood groups in DM II patients with complication

	A	B	AB	O
Male	32(29.9%)	8(7.5%)	15(14%)	52(48.6%)
female	8(22.2)%	2(5.6)%	2(5.6)%	24(66.6)%
Total	15( 24.6)%	3( 4.9 )%	7( 11.5)%	36(59 )%

Distribution of ABO blood groups in DM II with Nephropathy:

table (5) shows the distribution of ABO blood groups in DM II with nephropathy subjects and group O represent the highest percentage for both males (51.4) %, females.

Table 5: Distribution of ABO blood groups in DM II with Nephropathy

	A	B	AB	O
Male	9(24.3)%	5(13.5)%	4(10.8)%	19(51.4)%
Female	8(36)%	3(14)%	0(0)%	11(50)%
Total	17(28.8)%	8(13.6 )%	4(6.8)%	30(50.8)%

Distribution of ABO blood groups in DM II with Neuropathy:

Table (6) shows the distribution of ABO blood groups in DM II with neuropathy subjects and group O represent the highest percentage for both males (46.6) %, females.

Table 6: Distribution of ABO blood groups in DM II with Neuropathy

	A	B	AB	O
Male	16(35.6)%	2(4.4)%	6(13.4)%	21(46.6)%
Female	12(23.6)%	7(13.7)%	5(9.8)%	27(52.9)%
Total	28(29.1)%	9(9.4 )%	11(11.5 )%	48(50)%

Distribution of ABO blood groups in DM II with Retinopathy:

Table (7) shows the distribution of ABO blood groups in DM II with retinopathy subjects and group O represent the highest percentage for both males (48) % and females (66.6) %.

Table 7: Distribution of ABO blood groups in DM II with Retinopathy

	A	B	AB	O
Male	7(28)%	1(4)%	5(20)%	12(48)%
Female	8(22.2)%	2(5.6)%	2(5.6)%	24(66.6)%
Total	15(24.6)%	3(4.9 )%	7(11.5)%	36(59 )%

DISCUSSION:

Distribution of ABO blood group in DM II subjects:

The present study supports the hypothesis that DM II and blood groups are interrelated. We found that the frequency of blood group O was significantly higher among DM II subjects, compared with distribution of ABO blood groups in healthy group.

There are conflicting results reported by different researchers on the hypothesis that there is an association between ABO blood types and diabetes.

Studies in Malaysia¹¹ and India¹² reported higher frequency of blood group B among diabetic patients. In addition, Quershi and Bhatti study from Pakistan also had demonstrated an interrelationship between diabetes and ABO blood group with highest distribution of blood group B in DM II¹³. On the contrary, the frequencies of blood groups A and B were lower among diabetic patients as compared with healthy Algerian population¹⁴. Another study by Okon UA et al., from Nigeria reported a strong association between blood group A and diabetes¹⁵.

Blood groups and DM are interrelated in Qatar¹⁶, and blood group B was more dominant and blood group O was less common among diabetic group as compared with non-diabetic healthy population, and specifically Blood group B was more common in diabetic men, whereas blood groups A and B were higher in diabetic women compared with non-diabetic healthy population. But in the population of Pakistan¹⁷, Iraq¹⁸and Japan¹⁹, it was blood group O that has the highest distribution among diabetics. Significant association between blood group B and diabetes was reported in a research conducted in Iran, which is consistent with other investigations²⁰. In contrast, Waseem et al. had suggested a negative relationship between blood groups A and B and diabetes. They also had found high frequency of blood group AB in diabetic group¹⁷.

In addition, studies in Italy²¹and Trinidad²²showed an increased frequency of blood group B among diabetics, but studies in Germany²³and in Glasgow²⁴it was concluded that there was no significant association between ABO blood groups and diabetes.

A study in Malaysia had showed a negative association between A and O blood groups and DMII, with both groups being less common in the diabetic group¹².

The association between ABO blood groups and DM could be due to racial and geographical variations playing role in the genetic expression of the disease. That the frequency of ABO blood group varies across different populations¹⁶.

The possible mechanism in the development of an association among “ABO”, Rhesus blood types and incidence of DMII is still not well defined. The recent genome-wide that “ABO” blood group antigen enhances the general body inflammatory state. Single nucleotide polymorphisms at the “ABO” locus are linked with two serum markers of inflammation, tumor necrosis factor- α (TNF- α and soluble intercellular adhesion molecule -1(ICAM-1)²⁵. Increased expression of tumor necrosis factor- α has been associated with inflammation. It is well known that the systemic inflammation is the main cause of insulin resistance and ultimately plays a role in the development of DMII²⁶. ABO blood groups and DMII may be interrelated because of broad genetic and immunologic basis. The genetic makeup, which may lead to a link between the high association of blood group B with the incidence of DMII and blood group O, has less association with diabetes mellitus²⁵.

Distribution of ABO blood group in DM II with microvascular complications:

The purpose of this research was to find out the association between different ABO blood groups and diabetic mellitus with complication. The distribution of ABO blood group in DM patients with complication shows a high percentage in group O (53.24%). In addition; distribution of ABO blood groups in diabetic nephropathy subjects results O blood group is the highest percentage (50.8%), in diabetic neuropathy subjects results O blood group is the highest percentage (50%), then in diabetic retinopathy subjects results O blood group is the highest percentage (59%). Comparison of ABO blood group distribution among diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy are shows non- significant difference.

Study by Biplab Mandal et al., reported that the Nephropathy was the most common complication observed among different blood groups (high blood group type B, O, A and AB), and when relative risk (RR) has been calculated with blood group O as reference it has been observed that blood group AB and blood group A were less likely to develop neuropathy compare to blood group O²⁷.

Unal A et al., from Turkey conducted by a study on diabetic subjects with microvascular complications that the Blood group A is more commonly associated with diabetic nephropathy²⁸, Blood group B is more likely & blood group O & A are less likely to be associated with diabetic retinopathy and the overall complications were more common with blood group A²⁹.

The Raph Human Blood Group system (RAPH group consist of a single antigen, MER2. MER2 was initially classified as a high-incidence antigen in the 901 series of blood groups) is the most recent blood group detected which have a single antigen MER2. This MER2 gene has also been mentioned in nephron membrane abnormality, nor to correlate it with Diabetic Nephropathy²⁸.

The possible explanation of these conflicting findings may be the racial and geographical factors that probably have a role in genetic expression of disease. It has been suggested that the human ABO locus might influence endothelial or inflammation markers, such as the FVIII–vWF complex, which is present in higher levels in non-O individual³⁰. In addition, the ABO blood groups have been associated with plasma soluble ICAM-1 and TNF receptor 2 (TNF-R2) levels³¹. These markers have both been associated with an increased type 2 diabetes risk, thus providing a potential explanation for the observed relationships³².

A paper in 2012 suggested that the ABO blood group is one of the genetically determined host factors that modulate the composition of the intestinal microbiota³³, which participates in metabolism by affecting the energy balance, glucose metabolism and low-grade inflammation.

CONCLUSIONS:

There is a high distribution for blood group B in DMII without complications, while blood group O was in high distribution in DMII with complications and a significant difference in the distribution of ABO blood groups was observed between healthy and DMII subjects, and between DMII without complication and DMII with complication.

REFERENCES:

1. Fagherazzi G, Gusto G, Clavel-Chapelon F, Balkau B, Bonnet F. ABO and Rhesus blood groups and risk of diabetes II evidence from the large E3N cohort study. Diabetologia PubMed. 2015; 58: 519 – 522.

2. D Rose Ewald and Susan CJ Sumner Blood Type Biochemistry and Human Disease RTI International, Discovery Sciences, 3040 East Cornwallis Drive, Research Triangle Park, NC, 27709 Wiley Interdiscip Rev Syst Biol Med HHS Public Access. In PMC. 2017; 8 (6): 517 – 535.

3. El-Sayed MIK, Amin HK. ABO blood groups in correlation with hyperlipidemia, diabetes mellitus II, and essential hypertension. Asian J Pharm Clin Res. 2015; 8: 236 – 243.

4. Nakano T, Shimanuki T, Matsushita M, Koyama I, Inoue I, Katayama S, Alpers DH, Komoda T. Involvement of intestinal alkaline phosphatase in serum apolipoprotein B-48 level and its association with ABO and secretor blood group types. Biochem Biophys Res Co. 2006; 341: 33– 38.

5. Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, Bueno- de-Mesquita HB, Gross M, Helzlsouer K, Jacobs EJ, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet PubMed. 2009; 19: 648-918.

6. Daniels, G. Human blood groups. 3. Somerset, NJ: John Wiley and Sons; 2013.

7. Yamamoto F, Cid E, Yamamoto M, Blancher A. ABO research in the modern era of genomics. Transfuse Med Rev. 2012; 26: 103–118.

8. Liumbruno GM, Franchini M. Beyond immunohaematology: the role of the ABO blood group in human diseases. Blood Transfuse. 2013; 11: 491–499.

9. Zakai NA, Judd SE, Alexander K, McClure LA, Kissela BM, Howard G, Cushman M. ABO blood type and stroke risk the REasons for Geographic And Racial Differences in Stroke Study. J Thromb Haemost. 2014; 12: 564–570.

10. Clin Apher, Singmon JM Basic principle of the ABO and Rh blood group systems for hemapheresis practitioners PubMed. 1992; 7(3): 158-62.

11. Muhammad Kamil, Hamid Ali Nagi Al-Jamal and Narazah Mohd Yusoff Association of ABO blood groups with diabetes mellitus Universiti Sains Malaysia, Penang, Malaysia Published. 2010; 5: 48-47.

12. Jaggi S, Yadav AS. Distribution of ABO and Rh (D) Allele frequency among the type 2 Diabetes Mellitus patients. Am Int J Res Formal Appl Nat Sci. 2014; 1: 24‑6.

13. Qureshi MA, Bhatti R. Frequency of Blood Groups among the diabetes mellitus II patients. J Coll Physicians Surg Pak. 2003; 13: 453-5.

14. Dali Sahi M. Aour Metri A, Belmokhtar R, Bozza F. The relationship between ABO/rhesus blood groups and type 2 Diabetes in Mghnia/ Western Algeria, SAfr Fam Pract. 2011; 53: 568- 72.

15. Okon UA. Antai AB, Osim EE, Ita SO. The relative incidence of diabetes mellitus in ABO/Rhesus blood groups in South-Eastern Nigeria. Niger J Physiol Sci. 2008; 23: 1-3.

16. A Bener, MT Yousafzai the distribution of the ABO blood groups among the diabetes mellitus patients in Qatar Medical College, Qatar, Nigerian Journal of Clinical Practice. 2014; 37(5): 237-120.

17. Waseem Abdul Ghani, Iqbal Muhammad, Awwabkhan Omar, Tahir Muhammad Association of Diabetes Mellitus with ABO and Rh Blood groups. Pakistan. 2012; 8(2): 134 – 136.

18. Jassim WE. Association of ABO blood group in Iraqis with hypercholesterolemia, hypertension and diabetes mellitus. East Mediterr Health J. 2012; 18: 888 ‑ 91.

19. Kanazawa Y, Furusho T, Nakajima H,Amemiya S,Akanuma Y, Kosaka K. Blood groups and diabetes mellitus A possible tool in the analysis of the hereditary background of diabetes mellitus. Tohoku J Exp Med. 1983; 141 (l): 295‑9.

20. Moinzadeh F, Mahdieh Najafabady G, Toghiani A. Type 2 diabetes mellitus and ABO/Rh blood groups. J Res Med Sci. 2014; 19(4): 382.

21. Tedeschi G, Cavazzuti F. Contributo casistico allo studio dei rapporti tra diabete mellito e gruppi sanguigni. ABO & Rh Prog Med (Napoli). 1959; (15): 76−82.

22. Henry MU, Poon-King T. Blood groups and diabetes. West Ind Med J. 1961; (10): 156−60.

23. Maehr G. Distribution of ABO blood groups in diabetes mellitus. Wien Klin Wochenschr. 1959; 71: 536−8.

24. Craig J, Wang J. Blood groups in diabetes mellitus. Glasgow Med J. 1955; 36: 261−6.

25. S.A Meo, F.A. Rouq, F. Suraya, S.Z. Zaidi Association of ABO and Rh blood groups with diabetes mellitus II College of Medicine, King Saud University City, Riyadh, Saudi Arabia European. 2016; 20: 237-242.

26. Meigs JB, Hu FB, Rifai N, et al. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004; 291(16): 1978‒1986.

27. Biplab Mandal, Ravindra Shukla, AK Basu, Anirban Sinha, Animesh Maiti, Kingshuk Bhattacharjee Association ABO Blood groups with diabetic mellitus II and its complication Services, Biocon LTD, India. 2018; 5(1): 1-7.

28. Ünal A et al: ABO blood Groups and Diabetic Nephropathy. Turkish nephrology, dialysis and transplantation. Journal. 2015; 10: 03-06.

29. Sushma T V and Ajoy Krishnamurthy Study of relationship between ABO and Rh blood group with diabetes mellitus II and its complications- is there any association Department of General Medicine, M V J Medical College & Research hospital, Hoskote 562114, Karnataka, International Journal of Current Advanced Research, Published 28th. 2018; 7 (7): 14150-14152.

30. M Shusterman, E Golub, WB Mowrey and A Broder the association between ABO blood types and venous thromboembolism in individuals with a positive antiphospholipid profile is varied by sex Division of Rheumatology, Montefiore Medical Center, New York, USA journals Permissions. 2017; 10 (11): 1-8.

31. Barbalic M, Dupuis J, Dehghan A, et al. Large-scale genomic studies reveal central role of ABO in sP-selectin and sICAM-1 levels. Hum Mol Genet. 2010; 19(9): 1863‒1872.

32. Thorand B, Baumert J, Chambless L, et al. Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population. Arterioscler Thromb Vasc Biol. 2006; 26(2): 398‒405.

33. Mäkivuokko H, Lahtinen SJ, Wacklin P, et al. Association between the ABO blood group and the human intestinal microbiota composition. BMC Microbiol. 2012; 12: 94.

Received on 17.10.2019 Modified on 23.04.2021

Research J. Pharm. and Tech. 2022; 15(8):3518-3522.

DOI: 10.52711/0974-360X.2022.00590

Parameters			Studied groups
Parameters			Control	DM II without Complication	DM II with Complication
Age / Year	30 - 50	N / %	50 / 70.5 %	10 / 19.3 %	44 / 20.3 %
	51 - 80	N / %	21 / 29.5 %	42 / 80.7 %	172 / 79.7 %
	Total	N / %	71 / 100 %	52 / 100 %	216 / 100 %
Gender	Male	N / %	34 / 47.8 %	29 / 55.8 %	107 / 49.5 %
	Female	N / %	37 / 52.2 %	23 / 44.2 %	109 / 50.5 %
	Total	N / %	71 / 100 %	52 / 100 %	216 /100 %