European Journal of Cardiovascular Medicine

Diabetes Mellitus is one of the most common metabolic conditions.¹ Diabetes mellitus is defined as a group of metabolic disorders of various etiologies, which is characterized by chronic hyperglycemia and is associated with disturbance in carbohydrate, fat, and protein metabolism. According to the ADA (American Diabetes Association), an HbA1c value of 6.5 % is the cut-off point for diagnosing diabetes mellitus.²

HbA1c is recommended as the standard laboratory assessment of glycaemic control and efficacy of treatment of patients with type 1 and type 2 diabetes mellitus. Diabetic complications can be related directly to the HbA1c levels of the patients. A reaction between the glucose and the N terminal region of hemoglobin alpha or beta chains in vivo results in the formation of glycosylated hemoglobin. The amount of glycosylated hemoglobin is directly proportional to the average glucose concentration over the last three months.³ HbA1c measurements can be done by separation by molecular charge, high-performance liquid chromatography (HPLC) which yields excellent precision and rapid hemoglobin separation.⁴

It is seen that HbA1c assays give incorrect values in patients with hemoglobinopathies.⁵ In hemoglobinopathies, there is a change in net charge on the hemoglobin, and it interferes with the detection of HbA1c by HPLC.

The North Eastern region has the highest frequency of HbE. In Assam, the fact that HbE is prevalent in both tribal and non-tribal populations of Assam was reported by Deka⁶ and Flatz et al.⁷. As HbE disorder is prevalent in this part of the country and there are not many studies on the interference of HbE disorder on HbA1C estimation, this study is taken with the following aims and objectives.

AIM:

• To estimate serum fructosamine in diabetic patients with normal adult haemoglobin and HbE disorder.

Objective:

• To correlate serum fructosamine and HbA1c in diabetic patients with normal adult haemoglobin and HbE disorder.

The study was carried out at Assam Medical College & HospitalospitalH, Dibrugarh, India for a period of 12 months. A prospective, observational, cross-sectional, study was carried out in the inpatient and outpatient medicine departments. The total sample size was calculated to be 90. The protocol was approved by the institutional ethics committee. The subjects agreed to sign a formal informed consent form covering the details of the research. The medical history and patient profile questionnaires were used to collect the patient’s data.  

 Inclusion Criteria:

• All diabetes mellitus patients who attended various outpatient departments and patients admitted to medicine wards were included in the study
• Diabetic patients will be diagnosed by ADA criteria 2020

Fasting plasma glucose >/= 126mg/dl. Fasting is defined as no food intake for at least 8 hours.

                                            Or

2-hour plasma glucose>/=200mg/dl during an oral glucose tolerance test. The test is performed as described by the World Health Organisation, using a glucose load containing the equivalent of 75gm anhydrous glucose dissolved in water.

                                             Or

In a patient with classic symptoms of hyperglycemia or hyperglycemia crisis, a random plasma glucose >/=200mg/dl

                                              Or

HbA1C >/=6.5%. The test will be performed in a laboratory using a method that is NGSP-certified and standardized to the DCCT assay.

• Age>/=13years

Exclusion Criteria:

• Conditions that alter HbA1C levels like
• Chronic liver disease
• Chronic kidney disease
• Patients receiving a blood transfusion in recent three months
• Patients on drugs like aspirin, iron, vitamin C or vitamin E
• Patients with hemoglobinopathies other than HbE disease or trait
• Pregnant patients with diabetes mellitus.

Fasting blood sugar, postprandial sugar, glycosylated hemoglobin, and serum fructosamine levels were tested in each case. The datasets were analyzed and evaluated using IBM SPSS Statistics 20 software. Statistical significance was considered at p-values less than 0.05. The Pearson correlation coefficient(r) was utilized to determine how closely the continuous variables were related.

TABLE 1: Distribution Of Hbe Disorder Among Total Diabetic Patients.

It was observed that out of 90 diabetic patients, 60 (66.66 %) patients had adult hemoglobin,  24 ( 26.67%) had HbE trait, and 6 (6.67  %) of the total diabetic patients were HbE disease patients.

TABLE 2: Hba1c Level In Diabetic Patients

From the above table and Figure, it was observed that the majority of patients, 51.67% of diabetic patients with adult haemoglobin had HbA1C between 6.5-7.4%, and 79.17% of HbE trait patients had HbA1C levels within percentage 5.5-6.4%.

For HbE disease patients, there was no HbA1C peak in the chromatogram, so it was not measurable.

TABLE 3: Serum Fructosamine Level In Diabetic Patients

From the above table and Figure, it was observed that the majority of patients, the majority (78.33%) of diabetic patients with adult hemoglobin had serum fructosamine levels between 0.27-0.36mmol/L and 91.67% of HbE trait patients had serum fructosamine level within 0.27-0.36 mmol/L.

TABLE 4: Correlation Between Serum Fructosamine and Hba1c in Hbaa

It was observed from the above table that in diabetic patients with adult hemoglobin, there was a statistically significant correlation between serum fructosamine and HbA1C (r = 0.93).

TABLE 5: Correlation Between Serum Fructosamine And Hba1c In Hbae

It was observed from the above table that in diabetic patients with adult haemoglobin there was a statistically significant correlation between serum fructosamine and HbA1C (r = 0.522)

In our study patients aged 13 years or above were included. The majority of subjects belonged to 41-50 years of age group. It was observed that the mean age for the study subject was 49.83 ± 8.99 years. 55% of the study subjects were males, with a male-to-female ratio of 1.2:1.

It was observed that out of 90 diabetic patients, 60 (66.66 %) patients had adult hemoglobin,24 (26.67%) had HbE trait, and 6 (6.67 %) of the total diabetic patients were HbE disease patients. These findings are similar to those of Scott and Fischer (1938) ⁸, Mc Nair et al. (1981)⁹, and Yoon in 2008.¹⁰ The highest incidence of type 2DM in these studies was also in 41-50 years of age group.

 It was seen that 60% of the diabetic patients with adult hemoglobin,50% of HbE trait, and 50% of HbE disease had a duration of diabetes of 1-4 years at the time of presentation. In the study by W Srisurin et al.¹¹ in 2011, a mean duration of diabetes of 5.21 ± 2.98 years was observed.

In this study, it was also observed that the mean fasting blood sugar values of hemoglobin E trait and disease are 139.06 +/-17.77mg/dl and 146.5+/-16.8mg/dl, respectively. The mean FBS of diabetic patients with adult hemoglobin was 140.24+/-15.47 mg/dL. Similar results were also seen in the study by W Srisurin et al.¹¹in 2011. The mean FBS in their study was 142.60+48.9mg/dl. In this study, it was observed that the mean PPBS of diabetic patients with adult hemoglobin was 193.63± 40.23mg/dl and the mean PPBS levels were 177.63+/-31.12mg/dl and 190.5+/-19.78mg/dl for HbE trait and HbE disease respectively.

In the present study, it was observed that the majority of patients,51.67% of diabetic patients with adult hemoglobin and 20.83% of HbE trait patients, had HbA1C levels within 6.5-7.4. The mean HbA1C of HbE trait 6.32+/-0.38% was lower when compared with patients with adult hemoglobin 7.85+/-1.18%. For Hemoglobin E disease patients, there was no HbA1C peak in the chromatogram, so it was not measurable. In the study by W Srisurin et al.¹¹in 2011 it was observed that the mean HbA1C level in diabetic patients with adult haemoglobin was 7.50+/-1.88%, and for HbE trait, it was 7.43±1.76%.

In the present study, it was observed that the majority of patients, 78.33% of diabetic patients with adult hemoglobin and 91.67% of HbE trait patients, had serum fructosamine levels within 0.27-0.36 mmol/L. All diabetic patients with HbE disease had serum fructosamine levels between 0.37-0.46 mmol/L. The mean serum fructosamine values of the Haemoglobin E trait and disease were 337.92+/-36.99 micromol/L and 446.67+/-5.16micromol/L, respectively. The mean serum fructosamine of diabetic patients with adult hemoglobin was  343.73+/-36.99micromol/L. In the study by Baker JR et al. ¹², similar results were seen and a strong linear correlation was seen between serum fructosamine and HbA1c.

It was observed that in diabetic patients with adult hemoglobin, there was a statistically significant correlation between serum fructosamine and HbA1C (0.93), and in diabetic patients with the HbE trait also, there was a statistically significant strong correlation (r=0.522). In the study by Baker JR et al. ¹², similar results were seen, and a strong linear correlation was seen between serum fructosamine and HbA1c. P Koskinen et al. ¹³ in their study also found a good correlation between fructosamine with HbA1c and recommended that fructosamine is a simple and inexpensive test to assess glycemic control.

HbA1c is recommended as the standard laboratory assessment of glycaemic control and detection of diabetes mellitus. It is seen that HbE disorder is prevalent in this part of the country, and the presence of Haemoglobin E causes significant interference on HbA1C measurement. HbA1C could not be measured by the HPLC method in diabetic patients with Haemoglobin E disease.

We observed that serum fructosamine was detectable in all our patients, irrespective of their haemoglobin typing. Moreover, a significant correlation was seen between serum fructosamine and HbA1c in diabetic patients with normal adult haemoglobin as well as Haemoglobin E trait.

Thus, in the presence of HbE disease, serum fructosamine can be used in place of HbA1c to know the glycaemic status of the patient.

Conflict of Interest – None

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