European Journal of Cardiovascular Medicine

Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both . ¹ Diabetes is a major lifestyle disorder, the prevalence of which is increasing globally. Asian countries contribute to more than 60% of the world’s diabetic population as the prevalence of diabetes is increasing in these countries.²

Symptoms of marked hyperglycemia include polyuria, polydipsia, weight loss, sometimes with polyphagia, and blurred vision. Impairment of growth and susceptibility to certain infections may also accompany chronic hyperglycemia. Acute, life-threatening consequences of uncontrolled diabetes are hyperglycemia with ketoacidosis or the nonketotic hyperosmolar syndrome. ¹

The onset of type 2 diabetes (T2DM) is often silent and insidious. Pathogenic processes causing T2DM range from autoimmune destruction of cells of pancreas with consequent insulin deficiency to abnormalities that result in resistance to insulin action. Asymptomatic phase of hyperglycemia accounts for the relatively high prevalence of complications at initial presentation.^1,3

The primary driver of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity as evident from the higher prevalence of  diabetes in the urban population. Even though the prevalence of  microvascular complications of diabetes like retinopathy and nephropathy are comparatively lower in Indians, the prevalence of premature coronary artery disease is much higher in Indians compared to other ethnic groups. The most disturbing trend is the shift in age of onset of diabetes to a younger age in the recent years. This could have long lasting adverse effects on nation’s health and economy. Diabetes is the leading cause of blindness, end-stage renal disease, and non traumatic amputations in adults. Because diabetes is a progressive disorder, the importance of early and appropriate treatment cannot be overemphasized.⁴

Type 2 diabetes is frequently not diagnosed until complications appear, and approximately one third of all people with the disease may be undiagnosed. Epidemiologic evidence suggests the relationship between diabetes and complications begins early in the progression from normal glucose tolerance to impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) to diabetes than previously thought. These observations indicate that early identification and management of individuals with diabetes and pre-diabetes have the potential to reduce both the incidence of diabetes and its related complications.

In January 2010, the ADA now includes HbA1C as an appropriate diagnostic test. The levels of HbA1c in the blood reflect the glucose levels to which the erythrocyte has been exposed during its lifespan (approximately 117 days in men and 106 days in women). Therefore, the HbA1c is an index of the level of glycaemic control over the preceeding  2 to 3 months. Of this period, the immediately preceding 30 days contribute 50% to HbA1c^..1 HbA1C  a widely used marker of chronic glycaemia  plays a critical role in the management of the patient with diabetes, since it correlates well with both microvascular and  to a lesser extent ,macrovascular complications and is widely used as the standard biomarker for the adequacy of  glycaemic management. HbA1C assays are now highly standardized so that their results can be uniformly applied both temporally and across populations. The diagnostic test should be performed using a method that is certified by the National  Glycohemoglobin Standardization Program (NGSP) and standardized or traceable to the Diabetes Control and Complications Trial reference assay.¹

The diagnostic HbA1C cut point of  6.5% is associated with an inflection point for retinopathy prevalence, as are the diagnostic thresholds for FPG and 2-h PG. Individuals with an HbA1C of  5.7–6.4%  are at increased risk for diabetes as well as cardiovascular disease . As with glucose measurements, the continuum of risk is curvilinear, so that as HbA1C rises, the risk of diabetes rises disproportionately. ¹Early intervention and avoidance or delay of progression to Type 2 DM is of enormous benefit to patients in terms of increasing life expectancy and quality of life, and potentially in economic terms for society and health-care payers.

 Diabetes Mellitus is a major public health problem in India. It often go unnoticed and diagnosed when complications have already developed. HbA1c is an index of the level of glycaemic control over the preceeding  2 to 3 months;  it can be  used  as a marker of chronic glycaemia and as chronic hyperglycemia causes microvascular and macrovascular complications even in asymptomatic newly diagnosed cases of type 2 diabetes mellitus.

This study is conducted for estimation of  HbA1C  in all newly diagnosed Type 2 diabetes mellitus patients so that we can easily assess the degree of chronic hypergycaemia and also to assess the presence of  earliest fundus changes in eye and renal changes as an early markers of diabetic blindness and chronic renal dysfunction respectively. Prevent the further progression of these complications  by optimum glycaemic control. Thus this study has been taken up to establish the possible relationship of  Glycosylated Haemoglobin (HbA1c) with all such target organ damages in the form of  retinopathy and nephropathy, so that  HbA1c can be used as a marker to predict the extend of target organ damage that may have already taken place at the time of diagnosis in a case of newly detected type 2 diabetes mellitus.

It is hospital based cross sectional observational study Patients of  newly detected diabetes mellitus type 2 attending outdoor and admitted in department of General Medicine  of Princess Esra and Owaisi Hospitals, Deccan College Of Medical Sciences  during the period between May 2017  to April  2019 were selected randomly and  included in the study after applying the inclusion and exclusion criteria. Serving and retired employees of South Eastern Railway zone and their dependent family members. South Eastern Railway zone includes the states of West Bengal, Jharkhand and Odisha.

Inclusion Criteria: Patients . Age group:30-60 years both genders with diagnosed for the first time with Diabetes mellitus type 2 in accordance with ADA recommendations for diabetes mellitus.

Exclusion Criteria: Known case of diabetes mellitus type 1 and type 2 who are already diagnosed or on treatment, Patient of  known hypertension with or without treatment, Cardiac diseases ( Ischemic heart disease, Cardiomyopathy, Valvular  heart disease, Heart failure, Chronic pulmonary illness, Severe anemia , Hemoglobinopathies, Retinal artery occlusion, Retinal vein occlusion, Retinal vasculitis and Sickle cell retinopathy and Pregnancy

Anthropometric measurements were taken for their weight, height, BMI (calculated by dividing body weight in kilograms by square of height in meters).

Based on BMI study population will be divided into 3 groups-

• normal -   20 - 24.99 kg/m²
• overweight -   25 – 29.99 kg/m² 
• obese     -     ≥30 kg/m²

Venous blood  collected in a test tube with Ethylene Diamine Tetra Acetic Acid (EDTA) for HbA1c. Particle enhanced immunoturbidimetric method for estimation of Hba1c. We compare the complication of diabetes in our study with reference to HbA1C <7 and > or = 7. Study by Axer-Siegel R ⁶ et al had showed patients having HbA1C level < 7%  are associated with better preservation of vision in patients with type 2 diabetes mellitus Fasting blood sugar (FBS) and  2 hour Post prandial blood sugar (PPBS)  aasay done by hexokinase (enzymatic UV ) method . Blood for FBS was collected after 8 hours of fasting.

8.) Patient eyes were examined via fundoscopy with direct ophthalmoscopic examination after dilatation  of pupils for diagnosis of diabetic retinopathy. Based on the findings of optic fundus study population was divided into   groups as according to ICDSS as mentioned in literature for Retinopathy.

1. No apparent retinopathy
2. Mild nonproliferative DR
3. Moderate nonproliferative DR
4. Severe nonproliferative DR
5. Proliferative DR

 Patients enrolled in the study were recommended not to have heavy exercise 24 hours before examination. 24 hours urine albumin excretion in milligram was estimated. 24 hours urine protein estimation by pyrogallol red method  done for assessing  Albuminuria . Microalbuminuria considered as urine albumin excretion rate(UAER) between 30-300mg/24hrs and macroalbuminuria as >=300mg/24hrs.

Statistical Analysis was performed with help of Epi Info (TM) 3.5.3 which is a trademark of the Centers for Disease Control and Prevention (CDC).

Using this software, basic cross-tabulation and frequency distributions were prepared.  test was used to test the association between different study variables under study. Z-test was used to test the significant difference between two proportions. t-test was also used to compare the means.  Odds ratio (OR) with 95% Confidence Interval (CI) was calculated to measure the different risk factor. Significance level was set at 0.05 and confidence intervals were at 95 percent level.

Also One Way Analysis of variance (ANOVA) followed by post hoc Tukey’s Test was performed with the help of Critical Difference (CD) or Least Significant Difference (LSD) at 5% and 1% level of significance to compare the mean values. p ≤0.05 was considered statistically significant.

Table-1: Demographic distribution in study

The mean age (mean ± s.d.) of the patients was 47.46±8.20 years with range 30 - 60 years and the median age was 47.0 years.  Most of the patients were with age between 41-60 years (77.4%) which was significantly higher (Z=7.74; p<0.0001).

Proportion of female (56.0%) was higher than that of male (44.0%) but it was not significant (Z=1.69; p=0.09).  The mean BMI (mean ± s.d.) of the patients was 27.01±1.87 kg/m² with range 24.34-33.31  kg/m² and the median was 26.62 kg/m².  Most of the patients were with over weight (88.1%) which was significantly higher (Z=11.11;p<0.0001).

Figure-1: Distribution of diabetic retinopathy

20.3% of the patients had retinopathy out of which 15.5% and 4.8% were mild NPDR and moderate NPDR respectively. Most of the patients were not having diabetic retinopathy (Z=9.10; p<0.0001)

No cases of severe NPDR and  PDR were found.

Figure-2: Distribution of diabetic nephropathy

19.1% of the patients had nephropathy out of which 15.5% and 3.6% were having Microalbuminuria and Macroalbuminuria respectively.

Table-2: Retinopathy and details of the patients

Diabetic retinopathy was evenly distributed over age, gender and BMI.

Figure-3: Nephropathy and mean level of HbA1c of the patients

Proportion of patients with Mild NPDR retinopathy and HbA1c ≥7% (100.0%) was significantly higher than that of no retinopathy (67.2%) (Z=6.26;p<0.001).

Also proportion of patients with Moderate NPDR retinopathy and HbA1c ≥7% (100.0%) was significantly higher than that of no retinopathy (67.2%) (Z=6.26;p<0.001).

Mean level of HbA1c for Mild NPDR was significantly higher than that of no retinopathy (p<0.05) and  the mean level of HbA1c for Moderate NPDR was significantly higher than that of no retinopathy (p<0.01).

Table-3: Retinopathy and level of FBS and PPBS of the patients

Proportion of patients with Mild NPDR retinopathy and FBS>126 mg/dl (100.0%) was higher than that of no retinopathy (98.5%) (Z=1.22;p>0.05).

However, proportion of patients with Moderate NPDR retinopathy and FBS>126 mg/dl (100.0%) was higher than that of no retinopathy (98.5%) (Z=1.22;p>0.05).

Proportion of patients with Mild NPDR retinopathy and PPBS>200 mg/dl (100.0%) was significantly higher than that of  no retinopathy (70.1%) (Z=5.92;p<0.001).

Proportion of patients with Moderate NPDR retinopathy and PPBS>200 mg/dl (100.0%) was significantly higher than that of  no retinopathy (68.3%) (Z=5.92;p<0.001).

Table-4: Nephropathy and age of the patients

Diabetic nephropathy was evenly distributed over age , gender and BMI there is no significance.

Figure-4: Nephropathy and mean level of HbA1c of the patients

However, proportion of patients with Microalbuminuria and HbA1c ≥7% (100.0%) was significantly higher than that of  no nephropathy (67.6%) (Z=6.21;p<0.001).

Also proportion of patients with Macroalbuminuria and HbA1c ≥7% (100.0%) was significantly higher than that of  no nephropathy (67.6%) (Z=6.21;p<0.001).

Mean level of HbA1c for Microalbuminuria was significantly higher than that of no nephropathy (p<0.05) and  the mean level of HbA1c for Macroalbuminuria was significantly higher than that of no nephropathy (p<0.01).

             Table-5: Nephropathy and level of FBS of the patients

Proportion of patients with Microalbinuria and FBS>126 mg/dl (100.0%) was higher than that of no nephropathy (98.5%) (Z=1.22;p>0.05).

Also, proportion of patients with Macroalbinuria and FBS>126 mg/dl (100.0%) was higher than that of no nephropathy (98.5%) (Z=1.22;p>0.05).

Proportion of patients with Microalbuminuria and FBS>126 mg/dl (100.0%) was higher than that of no nephropathy (70.6%) (Z=5.87;p>0.05).

Also proportion of patients with Macroalbuminuria and FBS>126 mg/dl (100.0%) was higher than that of no nephropathy (70.6%) (Z=5.87;p>0.05).

This is an observational study including a total of  84  patients with newly diagnosed type 2 Diabetes Mellitus as per our selection criteria.  The mean age (mean ± s.d.) of the patients was 47.46±8.20 years with range 30 - 60 years and the median age was 47.0 years.  Most of the patients were with age between 41-60 years (77.4%) which was significantly higher (Z=7.74; p<0.0001).  The mean age (mean ± s.d.) of the males was 48.86±7.80 years with range 30 - 60 years and the median age was 49.0 years.  The mean age (mean ± s.d.) of the females was 46.36±8.42 years with range 32 - 60 years and the median age was 47.0 years. t-test showed that there was no significant difference in mean age of the male and female (t₈₂ = 1.53;p= 0.13)

The mean BMI (mean ± s.d.) of the patients was 27.01±1.87 kg/m² with range 24.34-33.31  kg/m² and the median was 26.62 kg/m².  Most of the patients were with over weight (88.1%) which was significantly higher (Z=11.11;p<0.0001). 9.5% of them were having Class-I obesity.

It was found that there was no significant association between age and diabetic retinopathy (p=0.63), gender and  DR (p=0.29). BMI and DR of the patients (p=0.83) which was similar to study conducted by Atif et al  except  a significant association with BMI was seen in their study. 20.3% of the patients had retinopathy out of which 15.5% and 4.8% were mild NPDR and moderate NPDR respectively.  Prevalence of 17 % , 15 %, 20 % was seen in studies conducted by Atif et al , Wahab et al , Deepa DV et al. respectively.^3,7,8

Proportion of patients with Mild NPDR and Moderate NPDR  and HbA1c ≥7% was significantly higher( p<0.001)than that of no retinopathy. Overall there was a significant association between HbA1c and retinopathy .Study conducted by Jammal H ⁹ et al. had also shown a significant relation. One way ANOVA showed that there was significant difference in level of HbA1c of two categories of retinopathy and patients not having retiopathy (F_2,81 = 67.57;p<0.0001). As per the CD (CD₅=1.12 and CD₁=2.23 ) the mean level of HbA1c for Mild NPDR was significantly higher than that of no retinopathy (p<0.05) and  the mean level of HbA1c for Moderate NPDR was significantly higher than that of no retinopathy (p<0.01).

It was found that there was no significant association between age and DN (p=0.12) , gender and DN  (p=0.44), BMI and DN of the patients( p=0.19).   Whereas Navneet Agarwal et al¹⁰ showed a significant  association with all three variables. 19.1% of the patients had nephropathy out of which 15.5% and 3.6% were having Microalbuminuria and Macroalbuminuria respectively.  Prevalence of 17.34 % ,19 % was seen in studies conducted by Navneet Agarwal et al , Vaibhav shukla respectively.^10,11

The proportion of patients with Microalbuminuria and Macroalbuminuria with  HbA1c ≥7%  was significantly higher than that of  no nephropathy (Z=6.21;p<0.001) .Study conducted by A Varghese et al ¹², Navneet agarwal et al¹⁰, Deepa dv et al³  had also shown a significant relation. One way ANOVA showed that there was significant difference in level of HbA1c of two categories of nephropathy and patients not having nephropathy (p<0.0001). As per the CD (CD₅=1.02 and CD₁=2.06 ) the mean level of HbA1c for Microalbuminuria was significantly higher than that of no nephropathy (p<0.05) and  the mean level of HbA1c for Macroalbuminuria was significantly higher than that of no nephropathy (p<0.01).

Diabetes is fast gaining the status of a potential epidemic in India. Diabetes Mellitus is a major public health problem in India. HbA1c is an index of the level of glycaemic control over the preceeding  2 to 3 months;  it can be  used  as a marker of chronic glycaemia and play a critical role in the management of the patient with diabetes, since it correlates well with both microvascular and  to a lesser extent ,macrovascular complications.

HbA1C was significantly associated with  complications including retinopathy and nephropathy , even in asymptomatic newly diagnosed cases of type 2 diabetes mellitus.

Our study can suggest that  estimation of  HbA1C should be done in all newly diagnosed Type 2 diabetes mellitus cases so that we can easily assess the degree of chronic hypergycaemia and also to assess the presence of  earliest fundus changes in eye and renal changes as an early  markers  of     diabetic  blindness and  chronic  renal  dysfunction, respectively to prevent the further progression of these complications   by optimum glycaemic control (HbA1C <7%) since the establishment of diagnosis & regular  follow up there after.

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3. Deepa DV, Kiran BR, Gadwalkar Srikant R. Macrovascular and Microvascular Complications in Newly Diagnosed Type 2 DiabetesMellitus. Diabetologia 2014;25:644 -48.
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