Volume 6, Issue 10, October – 2021 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165

Effect of Variability of Hemoglobin Value on Type

and Severity of Diabetic Retinopathy in Adult
Type II Diabetes Mellitus Patients
Dr. Mehrin Samed1* (correponding author), Dr. Nashwa Abdul Gaffoor2, Dr. Babitha V3, Dr. Padma B Prabhu4
1,2
MBBS-Intern, 3Associate professor, 4Additional professor
1,2,3,4
Govt. Medical College Kozhikode, Kerala, India

Abstract:- I. INTRODUCTION
Background: Anemia has been identified as a risk factor
1
for Diabetic Retinopathy, a leading cause of blindness Diabetic retinopathy (DR), including diabetic
worldwide. However the "at risk" values of hemoglobin maculopathy, is a microvascular complication of DM and
in prognosticating diabetic retinopathy has not been the 2leading cause of blindness worldwide. 3,4,5Various
defined. This study intends to evaluate the relation factors are associated with the development and severity of
between level of hemoglobin and type and severity of DR including high blood pressure, proteinuria, duration of
diabetic retinopathy among type 2 DM. DM, administration of insulin, hyperglycemia and renal
disease. 6,7Anemia is more prevalent in persons with
Methodology: design - descriptive cross sectional study; diabetes. 3Many studies have shown a link between low Hb
duration-6months, study setting- tertiary care hospital in level and hypoxia induced organ damage.
North Kerala, study population- type II DM Patients,
age> 40years with diabetic retinopathy, sample size-87 We designed the study to assess the effect of variation
cases. Variables - gender, age, duration of disease, stages of haemoglobin level on type and severity of diabetic
of Retinopathy, Hb, HbA1C, RFT. p value <0.05 retinopathy and also its association with blood urea, serum
considered as statistically significant. Data analyzed creatinine and Hba1c values.
using chi square and one way anova with PASW
statistics 18.0.0. II. SUBJECTS AND METHODS

Results: Male female ratio=1.2:1. Mean age - 59.83 ± The study was conducted in a tertiary care hospital at
6.201, mean duration of disease- 11.06± 5.564. Mean Hb north Kerala among diabetic retinopathy patients with type
was 11.65 ± 1.89. 81.6% of subjects were anemic. 50.6% II diabetes mellitus and age >40 years having evidence of
subjects had PDR and others had NPDR. 69% of DR on fundus examination. Permission from the
patients had maculopathy. Anemia was more prevalent Institutional Research Committee and Ethical Committee
in PDR patients and those with maculopathy . Among was obtained. There was no financial burden to the study
NPDR and PDR, anemic had severe disease. The mean participants. A descriptive cross sectional study was
Hb values showed a statistically significant relationship conducted for duration of 6 months.
with type and severity of retinopathy irrespective of
gender and nephropathy. Mean Hb and type of A total of 87 cases (based on the formula 4pq/d2,
retinopathy had a statistically significant relationship where p=32, d= 10, p is the prevalence and q=100-p) by
among subjects with poor glycemic control. The lower convenient sampling was taken. DR patients with age of
mean Hb related to male gender and normal HbA1c onset of type II DM <40 years, gestational diabetes,
values among maculopathy cases. pancreatic disease induced diabetes, steroid induced
diabetes, type I diabetes mellitus were excluded.
Conclusion: Lower hemoglobin values correlated with
the severity of diabetic retinopathy and presence of Data about age, gender, duration of type II DM, type
maculopathy independent of gender and presence of of DR, value of hemoglobin, blood urea, serum creatinine,
nephropathy. Correcting anemia and maintaining a Hba1c were collected. Type of retinopathy was classified as
normal Hb value may delay the onset and progression of non proliferative diabetic retinopathy (NPDR) and
diabetic retinopathy and maculopathy in type 2 diabetic proliferative diabetic retinopathy ( PDR). Patients with
adults. NPDR were further grouped according to the severity as
mild, moderate, severe; and PDR as early PDR and high risk
Keywords:- Diabetic Retinopathy, Nephropathy, Anemia, PDR (HRPDR). Patients also evaluated for presence and
Maculopathy. absence of maculopathy. Data was collected using proforma,
lab values from records, and retinal examination. The data
was analysed using chi square test and one way anova. p
value< 0.05 is considered to be statistically significant.

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ISSN No:-2456-2165
From the data collected the patients were grouped into (NPDR), 18.6% (n=8) had mild, 34.9% (n=15) moderate
anemic and non anemic based on the Hb value. 8In males and 46.5% (n=20) severe NPDR. And among PDR 45.5% (n
Hb<13.5 g/dL (normal Hb value in males =13.5 to 17.5 20) had early PDR, 54.5% (n=24) had high risk PDR
g/dL) and in females Hb<12.0 g/dL (normal value in (HRPDR). 69% (n=60) had evidence of maculopathy.
females=12.0 to 15.5 g/dL) is considered as anaemic.
According to age, patients were divided into 2 groups as <60 Value of Hba1c varied between 4.6 to 14.6% with a
and ≥60 years, data also grouped into two as duration of DM mean of 8.06 ± 1.5 and median eight. Hba1c ≤7%
<10 and ≥10 years. Presence of nephropathy was determined considered as good control of DM. 78.2% (n=68) had poor
with blood urea level 9normal= 7 to 20 mg/dL) and serum short term control of DM. Hemoglobin value ranged from
creatinine level (8normal: males (M) = 0.9 TO 1.3 mg/dL, 8.4 to 15.6 g/dL with a mean of 11.65 ± 1.89 and median
females (F) = 0.6 to 1.1 mg/dL). Patients with blood urea 11.6. Among the subjects 81.6% (n=71) were anemic. The
>20 mg/dL and creatinine >1.3 mg/dL in males and >1.1 minimum blood urea level found in the subjects was
mg/dL in females were considered to have elevated RFT 14mg/dL and maximum 118 mg/dL, with a mean of 34
values. Hba1c values were used to assess whether the ±18.3 and median of 28. In which 86.2% (n=75) had
patient had uncontrolled or controlled DM. 10Hba1c ≤ 7 was elevated blood urea level. The serum creatinine level varied
considered as controlled (short term) diabetes. from 0.6 to 7.1 mg/dL with a mean of 1.42 ± 0.90 and
median equals 1.2. 47.1% (n 41) had high creatinine value.
III. RESULTS Patients with either elevated urea or creatinine were
considered to have nephropathy. Thus 86.2% (n=75) had
The study population included 87 diabetic nephropathy.
subjects. Among them 55.2% were male. The age varied
from 47 to 75 years, mean age was 59.83 ± 6.201 and The distribution of cases based on presence of anemia,
median 60 years. 44.8% were aged < 60yrs. Duration of type type of retinopathy and its severity is given in table-1.
II DM ranged from one year to 25 years with a mean of Presence of anemia showed statistically significant relation
11.06 ± 5.564 and median of ten years. Duration of type II with type of retinopathy (p=0.02) as well as severity of
DM >10yrs in 62.1% (n=54). PDR in 50.6% (n=44). Among NPDR (p=0.017) and severity of PDR (p=0.036).
the subjects with Nonproliferative diabetic retinopathy

Table 1: Relationship between presence of anemia, type of retinopathy and its severity
** p<0.05 (statistically significant)
Presence of anemia and maculopathy was compared. 86.7% (n=52) of patients with maculopathy had anemia while 70.4% (n=19)
Type of retinopathy N Non Anemic Anemic p value
n(%) n(%)

NPDR 43 12(27.9) 31(72.1)

Mild 8 5(62.5) 3(37.5)

0.017**
Moderate 15 5(33.3) 10(66.7)

Severe 20 2(10) 18(90)

PDR 44 4(9.1) 40(90.9)

Early 20 4(20) 16(80)

0.036**
HRPDR 24 0(0) 24(100)

Total 87 16(18.4) 71(81.6) 0.022

of diabetic cases without maculopathy had anemia. Though p value was 0.06, this observation is clinically relevant.

Relation between presence or absence of anemia and normal or abnormal creatinine and urea values is shown in table 2.

54.9% of anemic subjects had high serum creatinine (p=0.02). 87.3% had high urea levels (p=0.384). Presence of anemia did not
show statistically significant correlation with duration of diabetes( p=0.398) or short term glycemic control as evidenced by
HbA1C values ( p=0.093)

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Volume 6, Issue 10, October – 2021 International Journal of Innovative Science and Research Technology
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Table 2: Relation between presence or absence of anemia and RFT
** p<0.05 (statistically significant)
Serum creatinine Blood urea

n Normal High p n Normal High p

n(%) n(%) n(%) n(%)

Non anemic 16 14 2 16 13 13
(87.5) (12.5) 0.02** (18.8) (81.3) 0.384

Anemic 71 32 39 71 9 62
(45.1) (54.9) (12.7) (87.3)

Based on gender
The subjects were grouped based on gender and Hb Hb value and type of retinopathy based on
values were compared with type of retinopathy using one gender. A statistically significant relation was observed for
way anova. Table 3 and figure 1 represents the relation both males and females with p value 0.003 and 0.001
between respectively.

Figure 1: Relation between Hb value and type of retinopathy based on gender

Table 3: Relation between Hb value and type of retinopathy based on gender

** p<0.05 (statistically significant)

Mean 95% CI
Gender n Hb SD Min Max p
Lower Upper

NPDR 15 11.7 1.26 11.0 12.4 8.8 13.1

F 0.001**
PDR 24 10.3 1.15 9.8 10.7 8.4 12.3

Total 39 10.8 1.35 10.4 11.28 8.4 13.1

NPDR 28 13.0 1.57 13.6 13.6 9.0 15.6

M 0.003**
PDR 20 11.3 2.18 12.3 12.35 8.4 15.1

Total 48 12.3 2.01 12.8 12.89 8.4 15.6

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Among those with NPDR, as severity of the disease value was 12.7±2.05, 95% confidence interval =11.31 to
increased Hb value decreased but it was not found to be 14.24 and no extreme values present; for HPDR mean Hb
statistically significant in both genders. Among those with value was 9.88±1.08, 95% confidence interval = 9.10 to
PDR Hb was less when severity of disease increased in both 10.65 with two extreme values. Figure 2 shows a box plot
genders. But the observation was statistically significant representing relation between types of PDR and Hb value in
only in males (p=0.001). In males for early PDR mean Hb males.

Figure 2: Relation between types of PDR and Hb value in males.

Among males, those without maculopathy had a near significant with a p value of 0.007. In females no such
normal mean Hb value (13.43gm%). Those with relation was observed between presence of maculopathy and
maculopathy had a lower mean Hb value of 11.7± 2.07 Hb value. Figure 3 shows a box plot representing the
(95% CI= 10.37 to 11.47). The relation was statistically presence of maculopathy and Hb values in males.

Figure 3: Relation between presence of maculopathy and Hb values in males

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Based on variation in serum creatinine values retinopathy. The relation was found to be statistically
Serum creatinine is a more reliable indicator of renal significant in both high and normal creatinine groups with a
function than blood urea nitrogen because it is less p value 0.001 and 0.025 respectively. Table 4 shows an
influenced by diet and hydration. Hence the subjects were analysis between Hb values and type of retinopathy in
grouped based on presence or absence of elevated serum subjects with normal and elevated serum creatinine values.
creatinine and Hb values were compared with type of The same is represented by a box plot in figure 4.

Table 4: Relation between Hb and creatinine value with types of retinopathy

** p<0.05 (statistically significant)
95% CI
Serum creatinine n Mean SD Min Max p
Hb Lower Upper

NPDR 29 12.8 1.48 12.3 13.4 9 15.6

Normal 0.025**
PDR 17 11.7 1.82 10.79 12.6 9.3 15.1

Total 46 12.4 1.69 11.9 12.9 9 15.6

NPDR 14 11.8 1.63 10.9 12.8 8.8 13.3

0.001**
High PDR 27 10.17 1.44 9.5 10.7 8.4 13.9

Total 41 10.7 1.70 10.2 11.2 8.4 13.9

Figure 4: Relation between Hb and creatinine value with types of retinopathy

The subcategories of NPDR and PDR were compared 12.6 ± 1.67 (95% CI 11.4 to 13.8) and for HRPDR was 10.3
with Hb values. Even though the Hb values were less as ± 1.0 (95% CI 9.4 to 11.3). P value was 0.005. Mean Hb of
severity of NPDR increased in both groups no statistically patients with elevated creatinine was lower than those with
significant relation was found. In PDR for both groups, normal values.
mean Hb decreased as disease severity increased, but a
statistically significant relation was found only in patients Hb was lower in patients with maculopathy than
with normal creatinine value not in elevated creatinine without maculopathy in both groups irrespective of presence
value. Among them, the mean Hb value for early PDR was of elevated serum creatinine values. Anemia and presence of

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Volume 6, Issue 10, October – 2021 International Journal of Innovative Science and Research Technology
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maculopathy showed a significant association in subjects Hb= 12.4± 1.73, 95% CI= 11.4 to 12.7. Figure 5 shows a
with no nephropathy (p 0.022). In this category, patients box plot showing relation between Hb value and presence of
without maculopathy had a mean Hb of 13.2± 1.34, 95% maculopathy in subjects with normal serum creatinine.
CI= 12.5 to 13.94, and for those with maculopathy mean

Figure 5: Relation between Hb value and presence of maculopathy in subjects with normal serum creatinine

Based on diabetic control PDR cases irrespective of the short term glycemic status. A
Subjects were divided on the basis of diabetes control, statistically significant relation was observed among those
and then the relation between Hb level and type of with poor control (table 5, figure 6).
retinopathy assessed. The mean Hb value was less among

Table 5: Relation between Hb and short term glycemic control with type of retinopathy
** p<0.05 (statistically significant)
95% CI
Control of DM n Mean SD Min Max p
Hb
Lower Upper

NPDR 13 12.9 1.5 12.0 13.88 9 15

Controlled 0.108
PDR 6 11.35 2.6 8.5 14.1 8.5 15.1

Total 19 12.4 2.03 11.47 13.4 8.5 15.1

NPDR 30 12.3 1.6 11.7 12.9 8.8 15.6

Uncontrolled 0.001**
PDR 38 10.6 1.6 10.1 11.2 8.4 14.6

Total 68 11.4 1.8 10.98 11.8 8.4 15.6

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Figure 6: Relation between type of retinopathy and Hb level in those with uncontrolled diabetes

In the case of NPDR, no relation was found between severity of disease and Hb value. In PDR, both controlled and
uncontrolled DM groups had statistically significant relations (table 6, figure 7).

Table 6: Relation between Hb value and severity of PDR based on short term glycemic control.
** p<0.05 (statistically significant)
95% CI
Control of DM n Mean SD Min Max p
Hb
Lower Upper

Early 2 14.5 0.8 6.8 22.1 13.9 15.1

Controlled 0.011**

HRPDR 4 9.7 1.3 7.6 11.8 8.5 11.6

Total 6 11.3 2.6 8.5 14.1 8.5 15.1

Early 18 11.4 1.7 10.5 12.2 8.6 14.5

Uncontrolled 0.006**

HRPDR 20 10 1.1 9.4 10.5 8.4 12.3

Total 38 10.6 1.6 10.1 11.2 8.4 14.6

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Figure 7: Relation between Hb value and severity of PDR based on short term glycemic control.

It was observed that the maculopathy and anemia had value of 13.6 gm% ± 1.23, 95% CI =12.7 to 14.5, and those
a significant relation among the subjects with controlled with maculopathy had a mean Hb value of 11.39 gm% ±
diabetes (p 0.011). Among patients with good short term 2.05, 95% CI= 9.9 to 12.8 ( figure 8)
glycemic control, those with no maculopathy had a mean Hb

Figure 8: Relation between presence of maculopathy and Hb in controlled diabetes patients

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IV. DISCUSSION 1.22-2.69) is an independent risk factor for development of
anemia.
Type II Diabetes mellitus is a common disease with an
increased incidence in recent decades. Diabetic retinopathy Anemia was more prevalent in subjects with deranged
(DR), including diabetic maculopathy, is a microvascular RFT values. 13E Ritz and others has noted that anaemia is a
complication of DM and the leading cause of blindness frequent complication of diabetic nephropathy. In diabetic
worldwide. 11The lesions observed in these patients are patients anemia is seen not only in preterminal renal failure,
secondary to microangiopathy and result in increased but also frequently in patients with only minor derangement
vascular permeability in the form of edema. Hypoxia is a of renal function. 14Maurizio Li Vecchi and others mentions
stimulus for the production of erythropoietin (EPO) and for that anemia is more frequent in the diabetic patients with
vascular endothelial growth factor (VEGF). Both EPO and CKD than in the non-diabetic patients with CKD (61.7 vs.
VEGF are neuroprotective factors that possess likely 52%, p < 0.05).
angiogenic potential, leading to an increase in the
proliferation of new retinal vessels and thus inducing the Anemia was more common in subjects with poor
development of proliferative retinopathy. Macular edema diabetic control than that of others. 6Sharif A and others
(ME) may appear at any stage of DR. It is an increase in noticed a higher incidence and risk of anemia poorly
tissue fluid, which causes a thickening of the retina and controlled diabetes (49.5%) compared to those with
secondarily causes structural and functional alterations of controlled diabetes (p < 0.05).
retina. 12Anemia can lead to falsely low HbA1c levels,
which may result in under treatment of hyperglycemia, Among both genders, PDR patients were more anemic
which in turn will contribute to the progression of both than NPDR. In either group, as the disease severity
microvascular and macrovascular diabetic complications. increased the Hb was found to decrease. In the study by
11
The etiology of low hemoglobin (Hb) level in diabetes is Travaset and others, it is observed that Individuals with
multifactorial and includes inflammation, nutritional severe DR showed significantly lower hemoglobin,
deficiencies, renal disease, concomitant autoimmune hematocrit, and erythrocyte levels compared with those with
disease, drugs and hormonal changes. Anemia is associated mild disease. Hemoglobin was the only factor that showed a
with hypoxia. Retinal hypoxia is observed in DR. significant inverse association with the severity of DR [beta-
coefficient = -0.52, P value = 0.003]. 15Irace C Et al found
The study assessed the association of hemoglobin level that Haemoglobin, haematocrit and whole blood viscosity
and diabetic retinopathy among patients with type II DM significantly decreased with increasing severity of
and age more than 40 years. It was found that PDR patients retinopathy.
were more anemic than NPDR. As the hemoglobin level
decreased the disease severity increased. As blood urea can be affected by hydration and diet,
serum creatinine was considered a more reliable parameter
A positive relationship was observed between anemia than blood urea value for determining nephropathy.
and diabetic retinopathy in individuals with type 2 DM. Hemoglobin level in PDR was lower than NPDR
Similar observations were made by 3Chung JO et irrespective of presence of nephropathy. The same was
al. Anemia was prevalent in the majority of the cases. observed in the severity of NPDR and PDR. Among
Anemia causes tissue hypoxia, which is a critical etiology of subjects with PDR, a significant relation occurred only in
diabetic retinopathy. Retinal hypoxia is proposed to case of non nephropathic patients. Thus anemia can be an
stimulate synthesis of vascular endothelial growth factor independent risk factor determining the type and severity of
(VEGF), a strong stimulant of neovascularization. This diabetic retinopathy. 16Wang J and others reports that DKD
factor also increases vascular permeability and retinal severity and anemia had joint effect on NPDR (OR = 2.29,
exudates. Individuals with anemia have been reported to 95% CI = 1.32–3.96) and PDR (OR = 11.31, 95% CI =
have increased systemic levels of VEGF. Therefore, 5.95–21.51). 17according to Lee w j and others proliferative
decreased oxygen delivery due to anemia might have diabetic retinopathy is associated with microalbuminuria
detrimental effects on the retina of individuals with diabetes. and DR is associated with overt nephropathy in DM
Additionally, anemia might contribute to increased oxidative patients.
stress due to a decrease in the absolute number of red blood
cells with antioxidant defense and enhanced free radical In subjects with uncontrolled diabetes mellitus,
production. Irace C and others reported association among hemoglobin was lower in those with PDR than NPDR.
low whole blood viscosity, haematocrit, haemoglobin Among those with poor glycemic control, a lower Hb value
and diabetic retinopathy in subjects with type 2 diabetes. was observed as the disease severity of NPDR and PDR
The author comments that Haemoglobin, haematocrit and increased. Anemia with uncontrolled sugar level may
whole blood viscosity were significantly lower in subjects determine the type and severity of diabetic retinopathy.
18
with retinopathy compared to subjects without retinopathy Chatziralli IP and others have shown that glycemic control
in both gender. A multiple logistic regression analysis remains an important factor for the presence and progression
confirmed the independent inverse association among of DR. HbA1c seems to be an indicator which cannot
viscosity, haematocrit, haemoglobin and retinopathy demonstrate exactly the degree of glycemic control, while
(p<0.01). 12Padmaja Kumari Ranil and others observed that sudden variations of blood glucose may play an important
presence of diabetic retinopathy with OR 1.82 (95% CI

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Volume 6, Issue 10, October – 2021 International Journal of Innovative Science and Research Technology
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