Is Glycosylated Haemoglobin a good marker for glycaemic control in diabetic patients with G6PDD? 

Background: 
Diabetes is a chronic progressive disease that leads to multiple complications.    Prospective   trials in patients with        diabetes1 have demonstrated that elevated glycosylated hemoglobin (HbA1C) levels are associated with these complications. Accordingly, The American Diabetes Association (ADA) recommends HbA1C as the standard marker of glycemic control2. Sometimes there are discrepancies between HbA1C and blood glucose values as in cases with     hemoglobinopathies3. 

Aim:
We conducted this study to determine the prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDD) among diabetic patients and to find out the relation between G6PDD and glycemic control in our population. 
  
Methods: 

Omani diabetic patients who have visited diabetic clinic at Bowsher polyclinic, Muscat, Oman in the period from 1st January 2004 to 1st Feb. 2017 were randomly included in the study. Patients who are    younger than 40, have T1DM or other known haemoglobinopathies and those  with incomplete data were excluded.  Patients were analyzed for glucose-6-phosphate dehydrogenase (G6PD) levels, HbA1c, Plasma and Capillary Fasting Blood Sugar (FBS), hemoglobin(Hb) and Total Bilirubin (T. Bil) and subjected to demographic and anthropometric features (age, gender, Body Mass Index(BMI).  We studied the Prevalence of G6PDD in relation to age, gender and BMI and we compared the levels of HbA1c, Plasma FBS, Capillary FBS, T. Bil and Hb in normal and G6PDD groups. Data were coded, entered, and analyzed using the statistical package SPSS version 15.  
   
Results: 
365 Omani patients (190   Men, and 175   Women) who have T2DM and are 40 years old or above are included. Among them, 90 (24.7%) have G6PDD (D group) and 275 (75.3%) have normal G6PD levels (N group). In the D Group, 57 are men (63.3%) and 33 are women (36.7%).  HbA1c was significantly lower in D group compared to N group.  However, there was no significant difference about Hb level between the 2 groups.   Nevertheless, T. Bil was significantly higher in D group compared to N group. The FBS whether Capillary or Plasma was slightly higher in D group compared to N group, but this was not statistically significant.  HbA1c was significantly correlated with both Capillary FBS and Plasma FBS in both groups (P < 0.001).


Discussion:

Glucose-6-Phosphate dehydrogenase deficiency (G6PDD) is an X-linked recessive disorder expressed mostly in males4. There are a few reports that link G6PDD to diabetes5.  Our study included 365 Omani patients (190   Men, and 175   Women) who have T2DM and are 40 years old or above.  Our study demonstrated high prevalence of G6PDD among    Omani diabetic population (24.7%) with significant gender difference [(men   63.3% and women    36.7%) (P=0.014)], and did not show significant difference among different age groups (P =0.728). The prevalence of G6PDD among     Omani general population was 16% as reported by another researcher6.  The higher prevalence of G6PDD among diabetic patients was seen in Saudi population (12.4%) as compared to healthy controls (2.0%) (p < 0.008)7. Similarly, another study, showed    a significantly (p<0.001) higher prevalence of G6PDD   among diabetic patients (19.6%) as compared to controls (10.4%)8.  We found significantly lower HbA1c in D group compared to the N group [ mean 7.44 vs 9.1(P < 0.001)]. However, this difference was not demonstrated by other researchers5.  We   reported also    that, FBS whether Capillary [ mean 10.93 vs10.75] or Plasma [ mean 11.27 vs 10.99] was slightly higher in D group   compared to N group but this was not statistically significant [ P values 0.895 and 0.916 respectively]. These figures of FBS indicates poor glycaemic control in both groups. The lower HbA1c in the presence of higher FBS   indicating that HbA1c is a misleading measuring tool of glycaemic control in D group. Despite this significant difference between the D and N   groups in terms of HbA1c, our study did not show significant difference in Hb level between the 2 groups [mean 12,23 vs 12.69   respectively (P= 0.060)].  Nevertheless, T. Bil was slightly but significantly higher in D group compared to the N group, [ Mean 13.94 vs 9.75 (P< 0.001)]. This higher bilirubin without lower Hb levels in the D group might not reflect actual haemolysis because the averages in both groups are still within normal average in our laboratory (5-21 umol/L) and we  used total   rather than indirect bilirubin and in addition, indirect bilirubin itself is not a specific marker for hemolysis because it could be raised by other causes like Gilbert disease9.  Therefore, the cause of lower HbA1c in the D group could be related to another factor(s) apart from hemolysis, an observation that merits further research. 

Conclusion: G6PDD is common among diabetic Omani population.    HbA1c is not a good marker for glycemic control in patients with G6PDD necessitating screening of diabetic patients with lower HbA1c for G6PDD. The cause of lower HbA1c in the deficient group could be related to another factor(s) apart from hemolysis, an observation that merits further research.  We recommend other tools as fructosamine level   as a marker for glycaemic control in diabetic patients with G6PDD. 



References

 
 

1. UKPDS. intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with T2DM. Lancet 1998; 352: 837–53

2. ADA: Standards of medical care in diabetes. Diabetes Care. 2007; 30: S4–S41. 

     3. Reynolds TM, et al; HbA1c monitoring. BMJ. 2006; 333:586-8. 

4. Nkhoma ET, et al. The global prevalence of G6PDD: a systematic review and meta-analysis. Blood Cells Mol Dis 2009; 42:267–278. 

5. Cappai G, et al. Increased prevalence of proliferative retinopathy in patients with T1DM who are deficient in G6PDD. Diabetologia 2011; 54:1539–1542.

 6. Al-Riyami A et al. Genetic Blood Disorders Survey in the Sultanate of Oman. J Trop Pediatr. 2003 ;49: i1-20.

7. Niazi G.A. G6PDD and DM. Int J Hematol. 1991 ;54:295-8.

8. Saeed TK, et al. Association of G6PDD  with DM . Diabet Med. 1985r; 2:110-2.

9. Schick P. Hemolytic Anemia. Medscape. Accessed in 27 Oct. 2017.

Is glycosylated hemoglobin a good marker for diabetic control in patients with G6PDD?