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BRIEF REPORT
Year : 2006  |  Volume : 54  |  Issue : 1  |  Page : 43-44

Relation between increased anaerobic glycolysis and visual acuity in long-standing type 2 diabetes mellitus without retinopathy


1 Regional Institute of Ophthalmology, Kolkata, India
2 Department of Biochemistry, B. C. Roy Post Graduate Institute of Basic Medical Sciences, Kolkata, India
3 Indian Institute of Chemical Biology, Kolkata, India

Correspondence Address:
G Bhaduri
Regional Institute of Ophthalmology, Kolkata - 700073
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0301-4738.21615

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  Abstract 

In long-standing diabetes mellitus, blood flow to essential organs including the retina is reduced owing to macrovascular and/or microvascular changes. Poor glycolytic pathway of glucose metabolism owing to tissue hypoxia caused by ischemia at capillary bed of essential organs produces excessive lactic acid and less of adenosine triphosphate, which lead to poor cellular function. The purpose of the study was to evaluate the relationship between increased anaerobic glycolysis and visual acuity in type 2 diabetes mellitus without retinopathy. Fifty patients of type 2 diabetes mellitus of 10-12 years duration, without retinopathy, constituted the study group. The controls were 50 age-matched healthy persons without diabetes mellitus. Blood lactate level and best-corrected visual acuity (BCVA) were measured in both the groups. The mean blood lactate level was 1.05 mM/l in the control group and 2.32 mM/l in the study group. BCVA of 20/20 (log MAR 0) was seen in 48 (96%) patients of the control group and in 27 (54%) patients of the study group. BCVA of 20/30 (log MAR 0.2) was seen in 23 (46%) patients in the study group and 2(4%) in the control group. Association of higher blood lactate level with decreased BCVA in the study group was statistically significant (P<0.001).

Keywords: Blood lactate, type 2 diabetes mellitus, visual acuity


How to cite this article:
Mondal L K, Baidya K P, Bhattacharya B, Giri A, Bhaduri G. Relation between increased anaerobic glycolysis and visual acuity in long-standing type 2 diabetes mellitus without retinopathy. Indian J Ophthalmol 2006;54:43-4

How to cite this URL:
Mondal L K, Baidya K P, Bhattacharya B, Giri A, Bhaduri G. Relation between increased anaerobic glycolysis and visual acuity in long-standing type 2 diabetes mellitus without retinopathy. Indian J Ophthalmol [serial online] 2006 [cited 2019 Oct 22];54:43-4. Available from: http://www.ijo.in/text.asp?2006/54/1/43/21615



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It is now established that under anaerobic conditions, tissue hypoxia shows poor glycolytic pathway because reoxidation of NADH by transfer of reducing equivalents through the respiratory chain to oxygen is prevented. Pyruvate is reduced to lactate by NADH, which is generated increasingly owing to inactive terminal electron transport chain.[1]

Excessive amounts of lactic acid produced by increased anaerobic glycolysis owing to tissue hypoxia result in poor cellular function. On the other hand, it has been proved that retinal ischemia and hypoxia play a major role in the pathogenesis of visual as well as vascular dysfunction in type 2 diabetes mellitus.[2] Changes in the capillary blood flow occurs before morphological changes in retina of long-standing type 2 diabetes mellitus. It is also highlighted by some studies that functional abnormalities may precede ophthalmoscopic evidence of retinopathy.[3],[4],[5],[6]

We have noticed some patients of long-standing type 2 diabetes mellitus with mildly decreased visual acuity who did not have retinopathy ophthalmoscopically. The aim of this study was to see the association between mildly decreased visual acuity without retinopathy and increased anaerobic glycolysis, which is one of the biochemical markers of tissue hypoxia in diabetes mellitus patients.


  Materials and Methods Top


Fifty patients of type 2 diabetes mellitus of 10-12 years duration, without retinopathy, were included in the study group. Controls were 50 age-matched healthy persons without having diabetes mellitus. Patients having hypertension, cardiovascular diseases, glaucoma, or any other ocular abnormalities that might affect visual function were excluded from the study. All subjects underwent detailed ocular and systemic examinations. Dilated fundoscopic examination by direct or indirect ophthalmoscope and slit-lamp biomicroscope with Goldman-3 mirror and + 90 D lens were done serially to rule out any retinal abnormality. Cycloplegic refraction was performed and best-corrected visual acuity (BCVA) was recorded by the early treatment of diabetic retinopathy study (ETDRS) chart at 4 m in a "forced-choice" manner. BCVA was assessed using letter-by-letter scoring in logarithmic units (log MAR) for statistical analysis and a change in visual acuity was defined as a change of greater than five letters or 0.2 log MAR.

Enzymatic method was used for measuring the blood lactate level. Venous blood was collected without tourniquet and was immediately delivered into a pre-measured amount of chilled protein precipitant perchloric acid. Initially, lactate was oxidized to pyruvate by lactate dehydrogenase in the presence of NAD+. The NADH formed in this reaction was measured spectrophotometrically at 340 nm and served as a measure of lactate concentration.

With a significance level of 0.05% and a power of 80% we got an approximate total sample size of 100 subjects, which were divided into two groups of 50 each.

The data were entered and an initial descriptive analysis was done. Student's " t -test" was done to find any difference in the blood sugar and lactate levels. Chi-square test was done to find any difference in the prevalence of depressed visual acuity among the two groups and also in factors found in the descriptive analysis.


  Results Top


The mean age was 49.9 years (49.9 3.38) in the control group and 50.1 years (50.1 3.3) in the study group. The blood pressure, intraocular pressure, and the difference between two groups was statistically insignificant. The mean plasma glucose level was 101 mg/dl in the control group and 127 mg/dl in the study group. The difference between two groups was statistically significant ( P < 0.001). The mean blood lactate levels were 1.05 and 2.32 m M /l in the control and study groups, respectively [Table - 1].

This difference between two groups was statistically significant ( P =0.001). This analysis indicated that patients of long-standing diabetes mellitus had a higher blood-lactate level [Table - 2]. BCVA of 20/20 (log MAR 0.0) was seen in 48 (96%) patients of the control group (nondiabetic) and in 27 (54%) of the study group (diabetic). BCVA of 20/30 (log MAR 0.2) was seen in 23 (46%) patients of the study group and 2 (4%) of the control group. With an odds ratio of 20.44 (95% CI: 4.15-136.29; p < 0.001), it is evident from this observation that there is an association between decreased visual acuity and higher blood lactate level in type 2 diabetes mellitus.


  Discussion Top


In the retina of a diabetic patient of long duration, reduced capillary blood flow and increased perifoveal intercapillary areas are seen before retinopathy.[3]

Different studies have demonstrated visual field loss, loss of color sensitivity, and contrast sensitivity before morphological changes in retina of diabetic patients.[4],[5],[6]

Though decreased visual acuity is not a common finding in diabetic patients without retinopathy, meticulous testing by ETDRS chart in our cross-sectional study detected mildly decreased visual acuity in 23 (46%) patients of long-standing type 2 diabetes mellitus without retinopathy.

One study showed correlation of decreased visual acuity (20/50 or worse) with an enlarged perifoveal intercapillary area, which indicated macular ischemia and concluded that critical hypoxic threshold is responsible for visual loss.[7] From this study, it appears that functional disturbance of macula is caused by ischemia-induced hypoxia. It is assumed that visual acuity, which is not only the function of dioptric apparatus but also of neural factors of the eye, may be mildly reduced (20/30) in some diabetic patients.

We suggest that there may be some biochemical and ionical changes owing to ischemia at the capillary bed of retina, which are mentioned as follows. (1) Less production of ATP and diminished Na+-K+ ATPase pump owing to poor glycolytic pathways, (2) increased intracellular Na+, which blocks nodal depolarization, (3) glutamate-induced overexcitation of NMDA receptor and cell excitotoxicity by increased intracellular Ca 2sub+, and (4) excessive generation of free radicals which impair cellular function.

It is our corollary that higher blood lactate levels owing to metabolic derangement are correlated with the extent of ischemia and tissue hypoxia, which explain the association between two factors in our study.

There may be other mechanisms causing poor visual function owing to hypoxia.

In spite of weakness of the cross-sectional study, this study probably first brings to focus on the association between main metabolic derangement and visual dysfunction in patients with diabetes mellitus without retinopathy. This study invokes further longitudinal study for better understanding of hypoxia-induced biochemical changes, producing visual dysfunction in long-standing type 2 diabetes mellitus.

 
  References Top

1.
Mayes PA. Glycolysis and the oxidation of pyruvate. In : Marry RK, Graner DK, Mayers PA, Rodwell VW, editors. Harper's Biochemistry. 25th Edn. Stamford: Appleton and Lange Medical Publication; 2000. pp. 190-8.  Back to cited text no. 1
    
2.
Harris A, Arend O, Davis RP. Hyperoxia improves contrast sensitivity in early diabetic retinopathy. Br J Ophthalmol 1996;80:209-13.  Back to cited text no. 2
    
3.
Arend O, Wolfs S, Jung F. Retinal microcirculation in patients with diabetes mellitus: dynamic and morphologic analysis of perifoveal capillary network. Br J Ophthalmol 1991;75:514-8.  Back to cited text no. 3
    
4.
Roth JA. Central visual field in diabetes. Br J Ophthalmol 1969;53:16-25.  Back to cited text no. 4
[PUBMED]  [FULLTEXT]  
5.
Roy M, Gunkel R, Podgor M. Colour vision defect in early diabetic retinopathy. Arch Ophthalmol 1986;104:225-8.  Back to cited text no. 5
    
6.
Sokol S, Moskowitz A, Skarf R. Contrast sensitivity in diabetics with and without background retinopathy. Arch Ophthalmol 1985;103:51-4.  Back to cited text no. 6
    
7.
Arend O, Wolf S, Harris A, Reim M. The relationship of macular microcirculation to visual acuity in diabetic patients. Arch Ophthalmol 1995;113:610-4.  Back to cited text no. 7
[PUBMED]  [FULLTEXT]  



 
 
    Tables

  [Table - 1], [Table - 2]


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