|Year : 1994 | Volume
| Issue : 1 | Page : 23-25
Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus
PK Khosla, K Sharma, HK Tewari, JS Bajaj, MC Vaidya
R.P. Centre for Ophthalmic Sciences, and Departments of Medicine and Anatomy, ARMS, New Delhi, India
Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 002
Source of Support: None, Conflict of Interest: None
Thirty-five patients of insulin-dependent diabetes mellitus (IDDM) were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS) was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI) levels and serum C-peptide radioimmunoreactivity (CPR) as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM
Keywords: Diabetes mellitus - Juvenile onset - Retinopathy - Metabolic factors
|How to cite this article:|
Khosla P K, Sharma K, Tewari H K, Bajaj J S, Vaidya M C. Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus. Indian J Ophthalmol 1994;42:23-5
The most frequent complication of type I diabetes (IDDM) is retinopathy. After a lag period of about 4 years, the risk of background retinopathy increases rapidly with the duration of diabetes.  Incidence of proliferative retinopathy increases between 10th and 15th year of diabetes after background retinopathy has developed .  The effect of metabolic derangements of diabetes on the long-term microvascular complications remains controversial. The present study deals with the relationship between certain metabolic risk factors and juvenile diabetic retinopathy.
| Material and methods|| |
This study included 35 patients of IDDM (25 males; 10 females), selected on the basis of age of onset of diabetes (40 years) and the requirement of insulin supplementation. The diagnosis of IDDM was established by the absence of beta cell function (fasting CPR levels less than 0.06 pmol/m1 3). The IDDM patients were divided into various groups depending on the severity of retinopathy; Group I - no retinopathy (20 patients) and Group II - patients with retinopathy (15 patients). Group II was further subdivided into Gr IIa - mild retinopathy ( 6 patients) and Gr IIb - severe retinopathy (9 patients). A control group consisting of 10 healthy individuals matched for age and sex was subjected to extended oral glucose tolerance test (OGTT).
A detailed history and physical examination was performed with regard to duration, age of onset and family history of diabetes, visual involvement, peripheral vascular disease, and neuropathy. Detailed ophthalmologic evaluation was carried out including determination of visual acuity, examination of anterior segment, measurement of intraocular pressure and fundus examination for diabetic retinopathy. Fluorescein angiography was done on a Retinophot Carl Zeiss fundus camera with automatic robot equipment. Three millilitre of 20% sodium fluorescein dye was injected as a bolus and photographs of the disc and macular area were taken at a rapid sequence (one/sec) using a black and white (400 ASA) film. A late phase photograph was taken at an interval of 5 minutes.
Metabolic investigations: Fasting blood sugar (Technicon autoanalyser; method No. SF4-0002 FF4), serum cholesterol (ferric chloride methods), serum triglyceride,  and extended OGTT were done to assess metabolic status. During extended OGTT, serum IRI, CPR and blood sugar levels were estimated at 30 minute intervals for 3 hours after a 75 gm glucose load. Serum IRI was assayed by dextran-coated charcoal radioimmunoassay (RIA)' using anti-insulin antiserum (Novo Research Institute) and WHO international reference preparation. Serum was pretreated with polyethylene glycol (PEG) to remove endogenous anti-insulin antibody for free insulin level assay in IDDM patients on insulin treatment. Serum CPR was measured by RIAB (Novo Research Institute, Denmark). All the values were expressed as mean ± SD.
Statistical analysis: Various metabolic factors studied were correlated with presence, absence and severity of retinopathy. Individual parameters were evaluated by linear regression analysis. Comparison between groups was assessed by Student's t-test and chi-square test. Statistical analysis was carried out on computer using a 'Statwork' software package.
| Results|| |
Average age at the time of diagnosis of IDDM was 18.8 years in Gr I (no retinopathy), 20.3 years in Gr IIa (mild retinopathy) and 26.2 years in' Gr IIb (severe retinopathy). The frequency and severity of retinopathy correlated well with the age of onset of IDDM (R=0.525; p<0.005). Mean duration of diabetes was 6.5 years in Gr I and 9 years in Gr II. Majority of patients with retinopathy (54%) had diabetes for more than 10 years (33% of Gr IIa and 66.7% of Gr IIb) as against 15% of patients without retinopathy (Gr I). There was an increase in the severity of retinopathy with duration of diabetes but was not statistically significant (R=0.263; p<0.1). Incidence of peripheral neuropathy was higher in Gr II as compared to Gr I, but failed to be statistically significant (x2 = 3.29; 0.1>p>0.05).
FBS levels in IDDM patients did not correlate with the severity or presence of retinopathy (R = 0.083; p>0.5). There was no significant difference in the serum cholesterol (205 ± 31.6 mg% vs 214.8 ± 35.6 mg%; t =0.81, p>0.1) and triglyceride levels (122.5 ± 15.7 mg% vs 126.8 ± 4.4 mg%; t=0.83, p>0.1) or the incidence of hypercholesterolemia (x2 = 1.88, p>0.1) and hypertriglyceridemia (x2 = 0.67: p> 0.2) between the groups with or without retinopathy.
Extended OGTT was performed to assess residual beta cell function in IDDM patients and was compared with 10 normal controls. IDDM patients as a group showed severe loss of beta cell function. Degree of carbohydrate intolerance; IRI and CPR levels in blood (baseline and after glucose load) were similar in patients with 'no', 'mild', or 'severe' retinopathy. Thus, insulin secretory response was not different in the 3 groups (I,Ila, IIb) of patients studied. The baseline IRI in IDDM patients was 2.08 ± 0.17 µU/ml (Gr I - 1.97 ± 0.87 µU/ml; GrII - 2.33 ± 1.901 µU/ ml) did not rise above 4.13 ± 0.83.tU/ml (Gr 1 - 4.13 ± 0.83 µU/ml, Gr II- 3.91 ± 0.95 gU/ml) after glucose load (normal IRI: fasting 7.4 ± 0.76 µU/ml; stimulated 61.6 ± 6.8 .tU/ml). The fasting CPR in diabetic patients was 0.013 ± 0.001 pmol/ml (Gr 1 - 0.012 ± 0.002 pmol/ml; Gr II - 0.013 ± 0.001 pmol/ml) and increased to 0.021 ± 0.002 pmol/ml (Gr I - 0.019 ± 0.003 pmol/ml, Gr II - 0.023 ± 0.002 pmol/ml) during GTT (normal CPR: fasting 0.272 ± 0.11 pmol/ml; stimulated 0.673 ± 0.1 pmol/ml).
| Discussion|| |
Duration of diabetes is a predictor of retinopathy., The present data shows a trend of increase in the incidence and severity of retinopathy with duration of diabetes. But patients with the longest duration of IDDM i.e. 23 and 25 years did not show evidence of retinopathy. Age of the patient at the time of diagnosis of diabetes is another determinant of retinopathy. In the present study, higher age of onset of IDDM was related to the severity and prevalence of retinopathy. In the literature, retinopathy has been reported to correlate with higher age of onset of IDDM 9 The association between retinopathy and neuropathy as suggested by the present data may be the result of a common pathogenetic mechanism for diabetic microangiopathy.
The evidence demonstrating an association between diabetic control and occurrence of retinopathy has been a point of controversy. Microangiopathic complications including retinopathy have been reported to correlate with the severity of metabolic derangements due to IDDM. , The present study shows that FBS levels as an index of metabolic control, correlated neither with the presence/absence nor with the severity of retinopathy. Even some randomized prospective studies have failed to demonstrate beneficial effect of diabetic control on retinopathy.  Studies that include patients with different types of diabetes and combinations of different complications are difficult to interpret. The patients included in the present study formed a homogenous group with very low post-glucose CPR blood levels, supporting the diagnosis of IDDM. Single measurements of FBS or even of glycosylated Hb may not be an accurate and reliable index of long-term diabetic control.
The serum lipid levels were similar in diabetics with or without retinopathy in the present study. Diabetic retinopathy is reported to be associated with higher levels of low-density lipoprotein cholesterol but not with triglyceride or high- density lipoprotein.  But the evidence implicating lipid abnormalities in the aetiology of diabetic retinopathy is not very strong. Studies from India  and the West  do not indicate plasma lipids to play any major role in the development of diabetic retinopathy.
Serum IRI levels following insulin antibody removal with PEG have been used to measure glucose stimulated insulin secretion in IDDM patients on insulin therapy by various workers,  Insulin secretory response during OGTT in the present study showed no correlation with the incidence or severity of retinopathy. Non-insulin-dependent diabetics with or without retinopathy have been reported to have similar pancreatic beta cell reserve.  Juvenile diabetics who have measurable blood C-peptide levels and insulin secretion , have been found to have less prevalence and severity of retinopathy. Other workers, however, have found similar insulin secretory response  and C-peptide , levels in IDDM patients with or without retinopathy. This suggests that insulin secretory reserve is not related to the development of retinopathy. The data in the present study also does not show a direct relationship between the various metabolic factors studied and juvenile diabetic retinopathy.
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