Introduction

Diabetic nephropathy is one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and the leading cause of end-stage renal disease worldwide (Lopes, 2009; Ohga et al., 2007). Diabetic kidney disease (DKD) is a thoughtful complication that takes place in 20% to 40% of all diabetics (Chen, 2014; Gheith, Farouk, Nampoory, Halim, & Al-Otaibi, 2016). The prevalence of diabetes around the world has reached epidemic proportions. While diabetes is already estimated to affect more than 8% of the global population (nearly more than 350 million people), this is predictable to grow to over 550 million people by the year 2035 (Andersen, Christiansen, Andersen, Kreiner, & Deckert, 1983). Many factors contribute to the development of diabetic nephropathy, including hyperglycemia, hypertension, obesity, a sedentary lifestyle, hereditary, smoking, and advancing age (Romero-Aroca, Mendez-Marin, Baget-Bernaldiz, Fernandez-Ballart, & Santos-Blanco, 2010; Rossing, 2006). Diabetic nephropathy is characterized by morphological and ultrastructural changes in the kidney, including an expansion of the molecular matrix and loss of the charge barrier on the glomerular basement membrane.

The progression from normal albuminuria to microalbuminuria is considered the initial step in diabetic nephropathy, which further progresses to macroalbuminuria as the renal function continues to deteriorate and glomerular filtration rate (GFR) starts to decline (Hovind, Rossing, Tarnow, Smidt, & Parving, 2001; Parving, 2001). The World Health Organization (WHO) defines "drug utilization" as the marketing, distribution, prescription, and use of the drugs in a society considering its medical, social, and economic consequences (Sharma, Sharma, Gaur, Chhabra, & Kaur, 2017). Drug utilization studies help to assess whether the drug treatment is rational or not and to determine rational drug use, especially in poorer and rural populations (Mandal et al., 2016). The few studies published on the prevalence of diabetic nephropathy in India have all been clinic-based (Elmarakby & Sullivan, 2012; Parving, 2001). Indeed, the Diabetes Atlas 2006 (2) does not list a single population-based study on diabetic nephropathy from South Asia. This article reports on the first population-based data on the prevalence of diabetic nephropathy in India.

Materials and Methods

For this purpose, a cross-sectional observational study was carried out at the outpatients department of Dr. Pinnamaneni Siddhartha Institute of Medical Sciences & Research Foundation, Gannavaram, Andhra Pradesh, South India (Bazroy & Singh, 2015). The study was initiated after approval by the Institutes Ethical Review Committee, KVSR Siddhartha College of Pharmaceutical Sciences (SCOPS), Vijayawada, India. KVSR SCOPS was recognized by All India Council of Technical Education (AICTE) and Pharmacy Council of India (PCI), New Delhi, Govt. of India. The protocol approval number was KVSRSCOPS/IEC/ PG/231/2017.

Selection of participants

Patients of either sex diagnosed with or without T2DM of any duration (as per ADA guidelines) and willing to participate were included in the study. A total of 613 patients (359 patients with T2DM and 254 patients with diabetic nephropathy) were enrolled in the study.

Inclusion criteria

Patients of either sex diagnosed with type 2 diabetes mellitus of any duration, established as per American Diabetes Association (ADA) guidelines. Patients who are visiting a public endocrine hospital in the duration of six months would be recruited.

Exclusion criteria

Patients with incomplete case reports. Patients having type 1 diabetes mellitus, gestational diabetes, and maturity-onset diabetes of the young were excluded from the study.

Data collection

Physicians were requested to report the clinical and biochemical data not exceeding 6 months before the observation. The information regarding demographics (age, sex), socioeconomic, and lifestyle characteristics (smoking, alcohol consumption) were collected by interviewing the participant. Biochemical parameters were derived from the latest laboratory investigation reports documented in the clinical records. Socioeconomic status was assessed using the modified Kuppuswamy’s scale, which considers the education qualification, occupation of the family head, and family income per month of the participant. The diagnosis of nephropathy was confirmed from the clinical records (if already documented) or if an estimated 24-h protein excretion was ≥150 mg/day. All the relevant data were collected in a predesigned paper case record form with the prior consent of the participant. Data was collected from a total of 613 patients (359 patients with T2DM and 254 patients with diabetic nephropathy).

Statistical Analysis

Statistical analyses were performed using SPSS version 20 (SPSS Inc., Chicago, IL, USA) and Graph Pad Prism 5.0 software (San Diego, CA). Estimates were expressed as mean ± SD. One-way analysis of variance or Student’s t-test was used to compare groups for continuous variables, and χ² test was used to compare proportions between the two groups. Univariate logistic regression analysis was used to examine the association between various exposures (age, gender, place of residence, generalized obesity, cigarette smoking, alcohol consumption, income status, and literacy level) and outcome (T2DM). P-value < 0.05 was considered significant.

Results and Discussion

A total of 613 subjects (359 with type 2 diabetes and 254 with diabetic nephropathy) were included in the study, and the clinical characteristics of T2DM

were presented in Table 2; Table 1 and Table 3 show the socio-demographic and lifestyle characteristics of subjects with and without diabetic nephropathy, respectively.

The prevalence of diabetic nephropathy was significantly higher in subjects who are married(98.8%,P=0.0211), uneducated(61%, p<0.0001), nature of work (house wives 44.4%,P=0.0120), rural residents(51.2%) and risk factors were co-morbidities(HTN 37.44%, P<0.0001, other diseases 36.51%, P<0.0001, endocrine diseases 9.53%, P=0.009, history of CVDs 7.90%, P< 0.0001), no physical activity (64.9%, P<0.0001), soft drinks (taking occasionally 31.9%, P<0.0001), habit of taking tea /coffee (twice without sugar 42.3%, p=0.0208), HbA1C(7-9% 42%, P<0.0001), FBS (>200 29.3%, P=0.0113), low HDL(23%, P=0.0470), high triglyceride levels (39.8%,P=0.0293), high serum creatinine (28.3%, P<0.0001), duration of T2DM(5-10years 39.8% & >10 years 37% , p<0.0001). Gender, age, BMI, body weight, monthly income, food habits, the habit of smoking, alcohol, stress levels, blood glucose levels are not significantly associated with the development of diabetic nephropathy.

Univariate regression analysis was performed to determine the odds ratios for the modifiable and non modifiable risk factors for T2DM (Table 4).

The analysis showed that married (OR, 3.903; 95% CI, 1.125-13.54, P=0.0211), poorly educated (OR, 0.3670;95%CI, 0.2635-0.5112, P<0.0001), house wives (OR, 0.5492; 95% CI, 0.3432 - 0.8789, P=0.0120), rural residents (OR, 0.3943; 95% CI, 0.2820-0.5513, P<0.0001), hypertension (OR, 4.131; 95% CI, 2.687-6.350, P<0.0001), other diseases (OR, 4.963; 95% CI, 3.202 -7.692, P<0.0001), Endocrine diseases (OR, 2.460; 95% CI, 1.433- 4.224, P=0.0009), history of CVD (OR, 17.20; 95% CI, 7.049- 41.95, P<0.0001), HbA1c (OR, 3.380; 95% CI,2.157- 5.295, P<0.0001), low HDL (OR, 0.5961; 95% CI, 0.3572 - 0.9947 , P=0.0470), high FBS levels (OR, 6.111; 95%CI, 1.283 -29.10, P=0.0113), high triglyceride levels (OR, 0.6077; 95%CI, 0.3878 -0.9523, P=0.0293), high serum creatinine (OR, 154.3; 95% CI, 37.92- 627.7, P<0.0001), duration of T2DM (5-10years OR, 2.653;95% CI 1.778 - 3.958, & >10 years , OR, 3.606 ; 95% CI, 2.362-5.504, P<0.0001). physical inactivity(OR, 0.5188;95% CI, 0.3727-0.7220 , P<0.0001), soft drinks occasionally (OR, 2.253; 95% CI,1.531-3.315, P<0.0001), habit of taking tea /coffee twice without sugar(OR, 1.845; 95% CI, 1.094 to 3.112, P=0.0208).

Drug utilization pattern was assessed and presented the results in Table 5. Metformin, combination of Glimepiride and Metformin, combination of insulin isophane and insulin regular, Teneligliptin, insulin regular were the anti-diabetic medications mostly given to the T2DM patients with nephropathy.

The present study’s results suggested that subjects who are married, uneducated, nature of work (housewives), rural residents and risk factors were co-morbidities(HTN, other diseases, endocrine diseases, history of CVDs), no physical activity, soft drinks (taking occasionally), habit of taking tea /coffee (twice without sugar),poor glycemic control, FBS (>200), low HDL, high triglyceride levels, high serum creatinine, duration of T2DM are major risk factors for the development of nephropathy complications.

Marital status

The present study’s results revealed that marital status (98.8%, P=0.0211) was significantly associated and was the major risk factor for diabetic nephropathy (OR, 3.903; 95% CI, 1.125-13.54). Therefore, further studies are needed to evaluate the exact impact of marital status on risk for diabetic nephropathy.

Education

Education is one of the risk factors for the development of diabetic nephropathy. Abdulhakeemhamood et al. conducted a study on Prevalence and Risk Factors of Diabetic Nephropathy in Omani Type 2 Diabetics in Al-Dakhiliyah Region and concluded that decreased literacy was significantly related to the presence of diabetic nephropathy (Alrawahi, Rizvi, Al-Riyami, & Al-Anqoodi, 2012).

The present study’s results suggested that educational status was significantly associated with (61%, P<0.0001), and a risk factor for the development of diabetic nephropathy.

Nature of work

The present study's results revealed that housewives (44.4%, p=0.0120) were significantly associated and was the major risk factor for diabetic nephropathy (OR, 0.5492; 95% CI, 0.3432 - 0.8789). Therefore, further studies are needed to evaluate the exact impact of the nature of work on risk for diabetic nephropathy.

Rural residence

The present study’s results revealed that rural residents (51.2%, P<0.0001) were significantly associated and was the major risk factor for diabetic nephropathy. Therefore, further studies are needed to evaluate the exact impact of rural residence on risk for diabetic nephropathy.

Co-morbidities

Hypertension (P < 0.0001) was positively associated with diabetic nephropathy. Khalid Al-Rubeaan et al., conducted a study on “Diabetic Nephropathy and Its Risk Factors in a Society with a Type 2 Diabetes Epidemic: A Saudi National Diabetes Registry-Based Study” and concluded that the hypertension was the most significant risk factor for diabetic nephropathy in Saudi type 2 diabetic population (Al-Rubeaan et al., 2014).

The present study’s results are also supported that hypertension (37.44%, P < 0.0001) was a risk factor for diabetic nephropathy (OR, 4.131; 95% CI, 2.687-6.350).

Physical inactivity

The present study’s results revealed that physical inactivity (64.9%, P<0.0001) was significantly associated and was the major risk factor for diabetic nephropathy.Therefore, further studies are needed to evaluate the exact impact of physical inactivity on risk for diabetic nephropathy.

Soft drinks

The present study’s results revealed that habit of taking soft drinks occasionally (31.9%, P<0.0001) was significantly associated and was the major risk factor for diabetic nephropathy (OR, 2.253; 95% CI, 1.531-3.315). Therefore, further studies are needed to evaluate the exact impact of the habit of taking soft drinks on risk for diabetic nephropathy.

A habit of taking tea/coffee

The present study's results revealed that the habit of taking tea/coffee twice without sugar (42.3%, P =0.0208) was significantly associated and was the major risk factor for diabetic nephropathy (OR, 1.845; 95% CI, 1.094-3.112). Therefore, further studies are needed to evaluate the exact impact of the habit of taking tea/coffee on risk for diabetic nephropathy.

HbA1c

Poor glycemic control was significantly associated with the development of diabetic nephropathy. (Alrawahi et al., 2012) conducted a study on Prevalence and Risk Factors of Diabetic Nephropathy in Omani Type 2 Diabetics in Al-Dakhiliyah Region and concluded that poor glycemic control was a significant risk factor for the development of nephropathy (Alrawahi et al., 2012).

Another study conducted by Feng et al., (2008) on the prevalence and risk factors of diabetic nephropathy in taiwanese Type 2 diabetes–A hospital-based study and concluded that risk factors associated with diabetic nephropathy included the poor glycemic control. Other relevant studies conducted by (Al-Rubeaan et al., 2014) concluded that poor glycemic control is the most significant risk factor. In the present study, it was significant that poor glycemic control (42%, P<0.0001) was a major risk factor (OR, 2.488; 95% CI, 1.638-3.779).

Fasting blood glucose

The present study’s results revealed that FBS levels (29.3%, P=0.0113) was significantly associated and was the major risk factor for diabetic nephropathy (OR, 6.111; 95%CI, 1.283-29.10). Therefore, further studies are needed to evaluate the exact impact of FBS levels on risk for diabetic nephropathy.

HDL

Feng et al. (2008) conducted a study on the prevalence and risk factors of diabetic nephropathy in taiwanese Type 2 diabetes–A hospital-based study and concluded that risk factors associated with diabetic nephropathy include HDL- cholesterol. The present study’s results are also supported that HDL (23%, P=0.0470) was a significant risk factor for diabetic nephropathy (OR, 0.5961; 95% CI, 0.3572-0.9947).

Triglycerides

Serum triglycerides levels are significantly associated with the development of diabetic nephropathy. Feng et al. (2008) conducted a study on the prevalence and risk factors of diabetic nephropathy in taiwanese Type 2 diabetes–A hospital-based study and concluded that triglyceride levels were the most significant risk factor associated with the development of diabetic nephropathy.

Another study conducted by (Al-Rubeaan et al., 2014) on “Diabetic Nephropathy and Its Risk Factors in a Society with a Type 2 Diabetes Epidemic: A Saudi National Diabetes Registry-Based Study” and concluded that the most significant risk factors for diabetic nephropathy in Saudi type 2 diabetic population was hyperlipidemia. In the present study, it was also significant that high serum triglyceride levels (39.8%, P=0.0293) were a major risk factor (OR, 0.6077; 95% CI, 0.3878-0.9523) for the development of diabetic nephropathy.

Serum creatinine

Feng et al. (2008) conducted a study on the prevalence and risk factors of diabetic nephropathy in taiwanese Type 2 diabetes–A hospital-based study and concluded that serum creatinine levels was a significant risk factor associated with the development of diabetic nephropathy. The present study’s results are also supported that serum creatinine levels (28.3%, P<0.0001) were the most significant risk factor for diabetic nephropathy (OR, 154.3; 95% CI, 37.92-627.7).

Duration of T2DM

Alrawahi et al. (2012) conducted a study on Prevalence and Risk Factors of Diabetic Nephropathy in Omani Type 2 Diabetics in Al-Dakhiliyah Region and concluded that long-standing diabetes was one of the significant risk factors for diabetic nephropathy. Other relevant studies conducted by Feng et al. (2008) also conclude that long-standing diabetes was the most significant risk factor for the development of diabetic nephropathy. The present study’s results are also supported that long-standing diabetes (39.8%, P<0.0001) was the significant risk factor (OR, 2.653; 95% CI, 1.778 -3.958).

Conclusions

Subjects who are married, uneducated, nature of work (housewives), rural residents and risk factors were co-morbidities(HTN, other diseases, endocrine diseases, history of CVDs), no physical activity, soft drinks (taking occasionally), habit of taking tea /coffee (twice without sugar), HbA1C(7-9%), FBS (>200), low HDL, high triglyceride levels, high serum creatinine, duration of T2DM(5-10years & 10 years) were significant risk factors for development of nephropathy. Metformin, a combination of Glimepiride and Metformin, a combination of Insulin Isophane and Insulin Regular, Teneligliptin, Insulin Regular, were the anti-diabetic medications mostly given to the T2DM patients with nephropathy.

Key findings

• The prevalence of nephropathy was found to be 20.58%.

• Nephropathy prevalence was higher in females compared to males (P=0.2985).

• The prevalence of nephropathy was significantly higher in subjects who are married (98.8%, P=0.0211) when compared to unmarried.

• The prevalence of nephropathy was significantly higher in subjects who are poorly educated (61%, p<0.0001) when compared to educated.

• The prevalence of nephropathy was significantly higher in subjects who are not doing any work when compared to others.

• The major comorbidities for the development of nephropathy complications include Hypertension (P<0.0001), other diseases (P<0.0001), endocrine diseases (P=0.009), history of CVDs (P< 0.0001).

• Locality, physical inactivity, soft drinks, a habit of taking tea /coffee are significantly associated with the development of diabetic nephropathy.

• Poor glycemic control, blood glucose levels, HDL, Triglycerides, serum creatinine levels are significantly associated with the development of diabetic nephropathy.

• Duration of T2DM (5-10years 39.8 %, P<0.0001, >10 years 37%, P<0.0001) was significantly associated with the development of diabetic nephropathy.

• Metformin, a combination of Glimepiride and Metformin, a combination of Insulin Isophane and Insulin Regular, Teneligliptin, Insulin Regular, were the anti-diabetic medications mostly given to the T2DM patients with nephropathy.