European Journal of Cardiovascular Medicine

Diabetes Mellitus type 2 is one of the commonly encountered non-communicable disease. Its worldwide prevalence has risen drastically over the last two decades owing to urbanization, industrialization, change in work culture, adoption of poor lifestyle practices and stress.. Based on current trends, International Diabetes Federation projects that 642 million individuals will have Diabetes Mellitus by the year 2040.1 In India, People living with Diabetes has increased from 32.6 million in 2000s to 74.2 million in 2021, amounting to a prevalence of 9.6%.2 Also, there are around 39.3 million undiagnosed cases of Diabetes in the country. To add to this, there are 5.4% prevalence of Impaired Glucose Tolerance (IGT) and 7.8% prevalence of Impaired Fasting Glucose (IFG).2 With all these statistics, there remains no wonder regarding India being called as “Diabetes capital of the world”. Diabetes Mellitus, being a chronic condition gives rise to multiple complications.3 They could be microvascular or macrovascular in nature. Macrovascular complications include Coronary Artery Disease (2.5%), Cerebrovascular disease (0.3%), heart failure 2 (0.2%) etc. Microvascular complications mainly include Neuropathy (10.6%), Nephropathy (5.9%) and Retinopathy (0.8%).2 Diabetic Nephropathy is one of the complications to be kept in priority as it is a major cause of chronic kidney disease (CKD). The condition requires early identification, timely management and a good prognosis assessor. Currently, as per the routine screening of DM patients for diabetic complications, renal function tests are to be done at least once a year. By the time Serum Creatinine shows changes, nephropathy would have started worsening. Therefore, more reliable early detector may be looked for. Owing to the fact that Diabetes is a pro-inflammatory state and that, it is associated with endothelial dysfunction, it is found that various inflammatory markers such as Erythrocyte sedimentation rate, C-reactive protein, Interleukins (especially IL-6), Serum Amyloid A, Fibrinogen etc. are elevated significantly in Diabetic population.3 With this background, current study is planned. 
The study aims at identifying whether there is any significant relationship between high sensitivity C-reactive protein and diabetic complications (in this case, diabetic 3 nephropathy). Also, the study is designed to assess if the severity of Diabetic Nephropathy may be projected on the levels of high sensitivity C-reactive protein. The findings of this study are expected to benefit the treating physician in multiple ways: suspecting Diabetic Nephropathy, assessing severity and planning timely management, thus providing a better care for the patients. Hence the study was planned.
OBJECTIVES
1. To assess the serum high sensitivity C reactive protein levels in patients with type 2 diabetes mellitus with diabetic nephropathy.
2. To estimate the levels of serum high sensitivity C reactive protein levels in different stages of diabetic nephropathy.

The study was conducted in the Department of General Medicine at K. R. Hospital (Mysore Medical College and Research Institute), Mysuru, Karnataka, on specific set of patients attending OPD or admitted patients with Diabetes Mellitus type 2 over a period of one and a half years.
Inclusion criteria:

A total of 60 diabetics with nephropathy at different stages, were selected for the study. Most of the study participants belonged to age group of 51 to 60 years. The mean (SD) was 60.23years, suggesting that most patients were elderly. Men constituted around 70% of study population and females being 30%.
Duration of Diabetes Mellitus is an important variable in the study, it influences both the kidney involvement and inflammatory markers. Groups were made of 5 years each. Proportion of diabetics with duration of less than 5 years, 6 to 10 years, 11 to 15 years, 16 to 20 years and more than 20 years were 5%, 28%, 33%, 27% and 7% respectively. Mean (SD) duration of Diabetes Mellitus was 13.02years.

Most of the patients [24 out of 60 i.e. 40.0%] belonged to the DN stage 3. Next most common DN stage was stage 4, with 18 patients constituting 30.0%. Out of the 18 remaining patients, 13 (i.e. 21.7%) patients had DN at stage 2 and 5 (i.e. 8.3%) had DN at stage 5. None of the patients taken up for the study had DN stage 1.

Symptomatology of diabetic patients having nephropathy
In the present study, patients complained mainly of 3 symptoms. They are as listed below:
1. Easy fatiguability by 52 patients (86.7 %).
2.Lower limb swelling by 19 patients (31.7 %).
3. Facial puffiness by 18 patients (30.0 %).

The study was planned with the objectives to estimate the serum high sensitivity C reactive protein levels in patients with type 2 diabetes mellitus with diabetic nephropathy; and to determine the change in serum high sensitivity C reactive protein levels in different stages of diabetic nephropathy. A total of 60 patients were studied. Findings of this present study are compared with existing literature and are shared below in a concise manner.
Proportion of males in the present study was 70%. Similarly, in most studies, males share higher proportion of the study participants. Only in one study, proportion of males is lesser. The reasons for this could be varied: males may have more health seeking behavior / males may have more addictions such as consumption of tobacco or alcohol/ delayed onset of non-communicable diseases in females. But the explanation of addictions may not be valid as only handful of men had addictions in the present study.
Mean (SD) HbA1C measure in the present study was 10.4 (2.2) g%. Similarly, in other studies, mean estimates in other studies on similar topic showed elevated HbA1C in all scenarios like in the study conducted by Roy D et al. in Uttar Pradesh in 2017.
As for distribution of patients with respect to staging of diabetic nephropathy, majority of the patients belonged to stage 3 and stage 4 of diabetic nephropathy. This finding was similar to the study conducted by Adejumo OA et al. in 2016 in Southern Nigeria. Not many studies have classified their patients as this. So, there are not many studies to compare. Most studies have either taken overt nephropathy patients or have compared non-nephropathy patients to initial stages of nephropathy such as microalbuminurics.
In the present study, mean estimates of hs-CRP among those with diabetic nephropathy stage 2, 3, 4 and 5 were: 5.1, 9.0, 12.4 and 13.1 respectively. Mean measures keep increasing as the stage of DN worsens. Similarly, in other studies as shown in table 7.7, the pattern of mean CRP measures matches with that of the study. Other studies have also shown statistically significant difference between mean CRP of non-DN patients and DN patients; and also, between mean CRP among micro-albuminuric patients and macro-albuminuric patients. In the present study, all patients have their CRP measures more than 3 mg/L. But, in other studies, there have been some patients with nephropathy having normal CRP; such as the study conducted by Gupta R et al. in Madhya Pradesh in 2019, where proportion of patients with elevated CRP was only 58%. This aspect requires further studies and exploration of reasoning or influence of other factors.
Overall, findings of the present study are in line with the findings of the reviewed literature. With this, the study concludes that hs-CRP can be considered as an important biochemical marker to identify the severity of diabetic nephropathy.
LIMITATIONS
The study was limited by the duration of study and sample size. Moreover, patients with Diabetic nephropathy stage 1 were not to be found in the study setting. Measuring hs-CRP at this early stage would help in providing better management. Further studies are required to assess diagnostic accuracy of hs-CRP.

In conclusion, mean hs-CRP among all the patients in the study with type 2 diabetes with Diabetic Nephropathy was elevated. There was a significant correlation between mean Hs CRP levels and clinical stages of the diabetic nephropathy. Higher stages of diabetic nephropathy showed higher mean HsCRP levels. Also, hsCRP significantly correlates with elevated PPBS, HbA1C, S. Creatinine, and eGFR levels. Hence HsCRP as a highly sensitive marker of inflammation suggesting that, Diabetes mellitus is associated with inflammatory process and elevated levels of HsCRP act as an independent marker for the development and also a marker to assess severity of the diabetic complications like diabetic nephropathy. However further exploration and studies of larger magnitude are needed before universally bringing this concept to practice. Hence early estimation of serum HsCRP levels and good control of blood sugar levels possibly help in prevention of progression of Diabetic complications like diabetic nephropathy

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