International Journal of Clinical Biochemistry and Research

Print ISSN: 2394-6369

Online ISSN: 2394-6377

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Sadashiv Jankar: Association of glycated haemoglobin and serum ferritin levels in type 2 diabetics of rural population


Introduction

Diabetes mellitus, a chronic metabolic and endocrine condition that affects people all over the world, is a major public health concern in both developing and developed countries. Diabetes mellitus (DM), one of the most common endocrine disorders in the world, has now reached pandemic proportions worldwide. In this regard, India, a forerunner, has a very large number of diabetics and has won the dubious distinction of being the world's diabetes hub. The earliest evidence that systemic iron overload could contribute to abnormal glucose metabolism was that patients with classic hereditary hemochromatosis (HH) had increased frequency of diabetes mellitus.

However, with the discovery of new iron metabolism disorders, it is clear that iron overload, regardless of the aetiology, contributes to an increased occurrence of type 2 diabetes. a) An increased occurrence of type 2 diabetes due to various sources of iron overload, and b) a reversal or improvement of diabetes (glycemic control) with a decrease in iron load accomplished by phlebotomy or iron chelation therapy, suggest that iron plays a role in diabetes aetiology. The increased insulin sensitivity and secretion associated with regular blood donation, as well as lower iron levels, suggest that iron excess is a causal factor.1, 2

Recent research has linked the onset of glucose intolerance, gestational diabetes, type 2 diabetes, and insulin resistance syndrome to increased body iron storage.3, 4, 5, 6, 7

Insulin resistance is the predominant symptom of type 2 diabetes, followed by a growing degree of -cell dysfunction.8 Many people die as a result of DM complications.9  The HbA1c percentage represents the average glucose levels during the previous 6 to 8 weeks.

In chronic diabetes patients, the HbA1c fraction is higher, and it correlates with glycemic control.10 Insulin resistance, metabolic syndrome, and type 2 diabetes have all been linked to chronic systemic subclinical inflammation. Inflammation causes the creation of several acute phase proteins in the liver, including serum ferritin, which has a role in insulin resistance and atherosclerosis. High blood ferritin levels have been linked to an increased risk of type 2 diabetes. Insulin resistance is defined by elevated blood glucose and insulin levels, which are frequently caused by bodily iron excess, resulting in a rise in serum ferritin.11, 12 Elevated iron reserves can cause diabetes by a variety of processes, including oxidative damage to pancreatic beta cells, disruption of hepatic insulin extraction by the liver, and insulin suppression of hepatic glucose synthesis. Hepcidin affects iron metabolism; hepcidin induces excessive production of cytokines IL-6 in chronic inflammatory diseases, including type 2 diabetes mellitus, by directly activating hepatocytes.13 Glycation of proteins, including haemoglobin, is enhanced in chronic hyperglycemia, culminating in the production of Advanced Glycated End Products (AGE).14 It has been claimed that there is a link between elevated serum ferritin and poor glycemic control, as measured by greater HbA1c, in diabetes individuals.15

Raised serum ferritin may cause long-term microvascular and macrovascular problems in diabetics.16 Iron is a transitional metal with high pro-oxidant activity, which results in the generation of reactive oxygen species, which raises oxidative stress levels.17 It's uncertain what role ferritin plays as an iron overload marker in hyperglycemia caused by pancreatic injury or peripheral insulin resistance.18 There are few research that indicate the optimal serum ferritin cut-off value in type 2 diabetes mellitus.

The aim of the current study was to assess long-term glycemic control (HbA1c) among subjects with type 2 diabetes mellitus and the correlation among HbA1c as well as serum ferritin levels which are responsible for diabetes mellitus complications.

Aim

To correlate Glycated Haemoglobin and serum Ferritin levels in Type 2 Diabetes Mellitus

Material and Methods

The present study was carried out at clinical biochemistry laboratory, Dept. of Biochemistry of a tertiary teaching hospital of Vidarbha region, India.

Study group

50 diagnosed patients of type 2 diabetes mellitus of duration more than 1 year, aged 30 years and above from Medicine indoor and outdoor will be recruited in the study.

Cut off values for Fasting Blood Sugar Level >126 mg/dl and Post Meal Blood Sugar > 200 mg/dl will be considered as diagnostic criteria.

Patients with history of Hypertension (HT), Obesity, Renal diseases, Liver disease, Valvular heart diseases, smoking, Family history of Diabetes will be excluded.

50 Healthy controls of same age will be included for comparison.

Study period

Study period will be for the duration of 6 months.

Study type

Case-control study.

Sample size

Cases: 50 newly diagnosed patients of type 2 diabetes mellitus

Control: 50 healthy controls of same age

Blood sample collection

5 ml (2.5 + 2.5 ml) random blood sample will be collected in dry plain and EDTA tubes for the estimation of Serum ferritin and Glycated haemoglobin levels simultaneously.

  1. Estimation of Serum Ferritin Levels: It was done by roche cobas e411 analyzer with Electrochemiluminescence immunoassay (ECLIA).

  2. Estimation of Glycated Haemoglobin levels: It was done by Vitros 5600 dry chemistry analyzer with Turbidimetric Inhibition Immuno Assay method.

Statistical analysis

Statistical analysis was done by using descriptive and inferential statistics using Student’s unpaired t test and Pearson’s correlation coefficient and software used in the analysis were SPSS 27.0 version and Graph Pad Prism 7.0 version and p<0.05 is considered as level of significance.

Results

Table 1 shows gender wise distribution of patients with 62% of the cases and 56% of the control were males and 36% of the cases & 44% of the controls were females.

Table 1

Gender wise distribution of patients

Gender

Cases

Controls

Male

32(64%)

28(56%)

Female

18(36%)

22(44%)

Total

50(100%)

50(100%)

As shown in Table 2 mean serum ferritin levels in cases was 535.28 ± 146.40 and in controls it was 182±99.94 by using students unpaired t test. Statistically significant difference was found. (t=14.22, p=0.00015).

Table 2

Comparison of serum ferritin level(µg/L) in two groups student’s unpaired t test

Group

N

Mean

Std. Deviation

Std. Error Mean

t-value

Cases

50

535.28

146.40

20.70

14.22 P=0.0001,S

Controls

50

182.00

96.94

13.71

[i] N= No of subjects, S= significant

As given in Table 3, it was found that serum Ferritin Levels (µg/L) were positively correlated with HbA1c Levels (%) (r=0280, p=0.049)

Table 3

Correlation between serum ferritin levels (µg/L) with HbA1c levels (%) Pearson’s correlation coefficient

Mean

Std. Deviation

N

Correlation ‘r’

p-value

Sr. Ferritin Level

535.28

146.40

50

0.634

0.0001,S

HbA1c Level

6.59

0.44

50

[i] N= No of subjects, S= significant

As shown in Table 1, significant positive correlation was found between duration of type 2 diabetes mellitus and serum ferritin levels. (r = 0.280, p= 0.049)

Table 4

Correlation between serum ferritin levels (µg/L) with duration of diabetes in cases Pearson’s correlation coefficient

Mean

Std. Deviation

N

Correlation ‘r’

p-value

Duration of diabetes

7.70

3.18

50

-

-

Sr. Ferritin Level

535.28

146.40

50

0.280

0.049,S

[i] N= No of subjects, S= significant

Discussion

The majority of the diabetics in the study were men, with an average age of 49.3 years. The majority of the patients were on oral hypoglycemics. Only roughly 12% of the patients were left untreated.

When compared to controls, serum ferritin, a reflector of bodily iron reserves, was significantly higher in diabetic patients, and this increased dramatically as the duration of diabetes increased which is in consistence with our study. This could be due to the development of subclinical hemochromatosis in a diabetic patient with a prolonged history of diabetes.19 Increased body iron reserves are likely connected with the incidence of glucose intolerance, type-2 diabetes, and gestational diabetes, according to Fernandez et al.20

HbA1c had a positive correlation with serum ferritin. This represented the short- and long-term relationship between serum ferritin and glycemic control. In their studies, Cantur KZ et al. confirmed that patients with poorly controlled diabetes exhibited hyperferritinemia.21 This indicated that in diabetes, serum ferritin levels rose as long as glycemic control was not established. In addition, they discovered a link between ferritin levels and diabetic retinopathy. Eschwege et al. found a link between elevated serum ferritin and poor glycemic control, as measured by greater HbAIc, in diabetics.22

In diabetic patients, there was no link between serum ferritin and BMI or metabolic syndrome, according to our findings. S. ferritin had no relationship with age, sex, coexisting hypertension, total cholesterol, LDL, or serum triglycerides. Insulin resistance, hypertension, dyslipidemia with low HDL and elevated triglycerides, obesity, type 2 diabetes mellitus, and accelerated cardiovascular disease are all terms used to describe a cluster of metabolic derangements that include insulin resistance, hypertension, dyslipidemia with low HDL and elevated triglycerides, obesity, type 2 diabetes mellitus, and accelerated cardiovascular disease. Iron reserves, as measured by serum ferritin levels, have been suggested as a determinant in insulin resistance. Serum ferritin levels are considerably higher in men and women with a high BMI (>25 kg/m2), high cholesterol (>200 mg/dl), and high systolic (>160 mmHg) blood pressure, in women with diabetes, and in men with high diastolic (>95 mmHg) blood pressure, according to Wrede et al.23 This assertion is contradicted by our study.

Conclusion

Based on our results, it can be observed that serum ferritin levels were positively correlated with glycemic control of the patient. Serum ferritin levels can be used as one the control indices for patients of diabetes.

Need of the research in this field

Unfortunately, Serum ferritin levels are not done routinely in rural population of India. Anaemia is prevalent and recognized, and often there is dispensing of Iron and Folic Acid capsules openly and arbitrarily, irregardless of the hemoglobin status even by grass root level workers in persons with Type 2 DM pre-existing, which could hamper an already existing version of a critical situation if it leads to iron overload.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.

References

1 

R Jiang J Ma A Ascherio MJ Stampfer WC Willett FB Hu Dietary iron intake and blood donations in relation to risk of type 2 diabetes in men: a prospective cohort studyAm J Clin Nutr2004791705

2 

JM Fernandez-Real A Lopez-Bermejo W Ricart Clin Chem Iron stores, blood donation, and insulin sensitivity and secretionClin Chem200551712015

3 

JM Fernandez-Real A López-Bermejo W Ricart Cross talk between iron metabolism and diabetesDiabetes2002518234854

4 

K Dmochowski D T Finegood W Francombe B Tyler B Zinman Factors determining glucose tolerancein patients with thalassemia majorJ Clin Endocrinol Metab199377478483

5 

P Cavallo-Perin G Pacini F Cerutti A Bessone C Condo L Sacchetti Insulin resistance and hyperinsulinemia in homozygous ß-thalassemiaMetabolism19954432816

6 

CE Wrede R Buettner LC Bollheimer J Scholmerich KD Palitzsch C Hellerbrand Association between serum ferritin and the insulin resistance syndrome in a representative populationEur J Endocrinol2006154233340

7 

J Suvarna H Ingle CT Deshmukh Insulin resistance and beta cell function in chronically transfused patients of thalassemia majorIndian Pediatr2006435393400

8 

AK Abbas A Maitra V Kumar A Abbas N Fauto The endocrine pancreasRobbins and Cotranpathologic basis of disease7th EditionElsevierNew Delhi200511891207

9 

G Roglic N Unwin Mortality attributable to diabetes: estimates for the year 2010Diabetes Res Clin2010871159

10 

HB Chandalia PR Krishnaswamy Glycated hemoglobinCurr Sci20028312152232

11 

S Raj GV Rajan Correlation between elevated serum ferritin and HbA1c in type 2 diabetes mellitusInt J Res Med Sci201311125

12 

A Sengror N Bharathya JS Kumar Serum Ferritin, Iron, TIBC, Hb in male patient with dysglycemiaInt J Biol Med Res201232160911

13 

LW Oberley Free radicals and diabetesFree Radiac BiolMed19885211324

14 

E Eschwege R Saddi H Wacjman Haemoglobin AIc in patients on venesection on therapy for haemochromatosisDiabetes Metab198282137140

15 

JK Shetty M Prakash MS Ibrahim Relationship between free iron and glycated hemoglobin in uncontrolled type 2 diabetes patients associated with complicationsIndian J Clin Biochem20082316770

16 

H Yaghootkar C Lamina RA Scott Z Dastani MF Hivert LL Warren Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetesDiabetes20136210358998

17 

F Sharifi Serum ferritin in type 2 diabetes mellitus andits relationship with HbA1cActa Medica20044221425

18 

AR Nawrocki MW Rajala E Tomas UB Pajvani AK Saha ME Trumbauer Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonistsJ Biol Chem20062815265460

19 

DK Moczulski W Grzeszczak B Gawlik Role of hemochromatosis C282Y and H63D mutations in HFE gene in development of type 2 diabetes and diabetic nephropathyDiabetes Care2001247118791

20 

JM Fernández-Real G Peñarroja A Castro F García-Bragado A López-Bermejo W Ricart Blood letting in high ferritin type 2 diabetes: effects on vascular reactivityDiabetes Care20022512224955

21 

KZ Cantur B Cetinarslay I Tarkun NZ Canturk Serum ferritin levels in poorly- and well-controlled diabetes mellitusEndocr Res2003293299306

22 

E Eschwege R Saddi H Wacjman R Levy N Thibult A Duchateau Haemoglobin AIc in patients on venesection therapy for haemochromatosisDiabete Metab19828213740

23 

CE Wrede R Buettner LC Bollheimer J Scholmerich KD Palitzsch C Hellerbrand Association between serum ferritin and the insulin resistance syndrome in a representative populationEur J Endocrinol2006154233340



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© This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Article type

Original Article


Article page

304-307


Authors Details

Jayshri Sadashiv Jankar*


Article History

Received : 15-12-2021

Accepted : 28-12-2021

Available online : 05-01-2022


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