Prevalence and complications of diabetes mellitus In India - A systematic review

Background Diabetes is progressively becoming a vital chronic disease burden worldwide, mainly in developing countries such as India; this necessitates a shift in healthcare priorities and advanced data on the epidemiology and impact of diabetes to help plan and prioritize health programs. We systematically reviewed the literature on diabetes prevalence and its complications in India. Methods This systematic review focuses on diabetes prevalence and complications in India from January 2000 to September 2021. Literature searches were conducted using electronic databases. Results Diabetes prevalence ranged from 2.02% in rural Madhya Pradesh to 40.3% in Tamil Nadu. Diabetes prevalence was signi�cantly higher in urban areas than in rural areas. The prevalence of pre-diabetes varied across Indian states ranging from 2.4% in Meghalaya to 47.6% in Delhi. The prevalence of chronic diabetes complications ranged from 4.8–21.7% for retinopathy, 0.9–62.3%% for nephropathy, and 10.5–44.9% for neuropathy.


Introduction
Diabetes mellitus (DM) is persistent metabolic anarchy described by hyperglycemia resulting from defects in insulin secretion, insulin action, or in the combination of both [1].Diabetes mellitus occurs throughout the world but is common primarily type 2 in developing and developed countries [2].The incidence of diabetes has been steadily increasing during the last few decades.International Diabetes Federation (IDF) guesstimates that virtually 500 million people worldwide are presently living with diabetes, a number that is expected to increase by a further 30% in 2045.Diabetes, jointly with its host of micro and macrovascular complications, is a widespread cause of morbidity, reduced quality of life, and early mortality.It is anticipated that nearly 10% of the global allcause mortality (20-99 years age group) is attributable to diabetes [3].
India has reported a pointed augment in the prevalence of diabetes and pre-diabetes in the past few years.In 2019 the projected 77 million Indians were living with diabetes, with an estimated prevalence of 8.9% among adults according to IDF.India has turned into the country with the second-largest diabetes inhabitants, with 1 in 6 adults with diabetes in the world impending from India [4] It is mandatory to precisely understand the urban and rural diversity and drifts in the prevalence of Diabetes in India by a systematic combination of results from individual prevalence studies to understand the up-to-date situation and help take appropriate, evidence-based improvement strategies and public health strategies.At present, no studies compare and contrast the rural and urban differences in the prevalence of diabetes and pre-diabetes among Indian adults.In addition, India comprises twenty-eight states and eight union territories [5].Thus, preceding studies have exposed wide variations in the overall prevalence of diabetes across India's different states and union territories, with the highest rate of augment being reported in less developed low epidemiological transition level states [6].Consequently, it is essential to have an accurate portrait of the magnitude of diabetes and pre-diabetes in the different states, with urban-rural comparisons to enable planning for targeted policy.At present, no studies compare and contrast the rural and urban differences in the prevalence of diabetes and pre-diabetes among Indian adults.Thus, in the current study, we carried out a systematic review to portray the most recent prevalence and trends of prediabetes and diabetes in urban and rural India.

Materials And Methods
The present systematic review was done according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-A-lyses) guidelines.The PRISMA checklist is attached as an additional le (Supplementary File 1).
The literature search was performed in a systematic process.The online PubMed database search was done using the MeSH (Medical Subject Heading) combination terms "diabetes mellitus, type 2/ epidemiology, diabetic complication" and "India".The search consisted of studies listed from January 2000 and up to September 2021.The articles were screened for eligibility, using inclusion and exclusion criteria by reading article Title, Abstract, and Full-text.Only studies available in the English language and studies done with human beings and age ≥18 years included in this systematic review.

De nitions, Inclusion, and Exclusion Criteria
The existence of diabetes Mellitus and Pre-diabetes (Impaired Fasting Glucose [IFG]) in the individual studies were considered if characterized according to World Health Organization (WHO) [7] and American Diabetes Association (ADA) [1] by examining capillary blood glucose via glucometer and plasma glucose.Non-institutionalized, population-based studies among adults (≥18 years including both men and women) from urban or rural populations, cross-sectional study design or being the rst phase of a longitudinal study, Total adequate sample size was more than a thousand persons for the prevalence of diabetes and two hundred persons for complication of diabetes.Studies reporting only self-reported Diabetes, Type-1 Diabetes or Gestational Diabetes, or any other variety of diabetes, being restricted to only a speci c community/age/patient/ethnic group, being hospital/clinic-based, and studies conducted among Indians residing somewhere else were excluded from this study.Studies available in English or with comprehensive summaries in English were included in this study.

Results
The combined keyword search on PUBMED identi ed 2,305 articles for the prevalence of Diabetes in India, of which 1,723 were excluded because studies were conducted outside the region of interest, described diabetes pathogenesis, included genetic research, reviewed another disease and review articles, data based on the analysis of patients records.Of the remaining 582 articles, forty-two papers met the inclusion criteria and were included for data on the prevalence of Diabetes in India.
One thousand two hundred thirteen papers were reviewed for data on microvascular diabetes complications (retinopathy, nephrology, and neuropathy ), of which 1,169 were excluded because they were based on management and screening options.Conditions such as periodontal problems, mental health problems, or sample size were outside of inclusion criteria (i.e., n<200).In total, fourteen articles met the inclusion criteria and were included for data on microvascular diabetic complications.

Discussion
This review demonstrates that diabetes is a widespread health problem in India.We observed massive dissimilarity in diabetes prevalence among different states in India.Almost majority of the studies which distinguished between urban and rural areas observed a higher diabetes prevalence in urban than rural areas.Most of the diabetic patients experienced microvascular complications of Diabetes in India.The prevalence of diabetes varied across Indian states ranging from 2.02% in rural Madhya Pradesh [8] to 40.3% in Tamil Nadu [11] It has been reported that the prevalence of diabetes and pre-diabetes are higher in both urban and rural areas of India compared with earlier studies.It has been revealed that the age-standardized prevalence of diabetes was 6.1% (95%CI, 6.0%-6.3%)among women and 6.5%(95%CI, 6.4%-6.7%)among men, and prevalence levels in India are towering across all geological settings and socioeconomic groups in middle and old age population [8].Apart from these studies, Anjana et al. reported that India has a massive pool of pre-diabetic subjects (77 million people) who have a high potential to develop type 2 diabetes [14].In this study, we observed that the prevalence of pre-diabetes varied across Indian states ranging from 2.4% in Meghalaya [12] to 47.6% in Delhi [15].
The complications related to diabetes account for most of the morbidity and mortality associated with the disorder.Microvascular complications affect the inner part of the eye; the retina is called diabetic retinopathy (DR), the kidney is termed as diabetic nephropathy (DN), and the peripheral nerves are termed as diabetic neuropathy [64].
It has been reported that diabetic retinopathy, considered the most speci c complication of diabetes, is the primary cause of new-onset blindness in adults in developed countries and rapidly becoming high in developing countries.The prevalence of diabetic retinopathy in India ranged from 4.8% [50]  Diabetic nephropathy ranged from 0.9% [51] to 62.3% [62] in India.Diabetic nephropathy is the foremost cause of end-stage renal disease worldwide, and it is projected that 20% of type 2 diabetic patients reach end-stage renal disease during their lifetime [75].Poor glycemic control, long duration of diabetes, and systolic blood pressure were the risk factors for overt nephropathy [59].
The prevalence of diabetic neuropathy in India ranged from 10.5% [50] to 44.9% [57].Studies in India observed that poor glycemic control and increased duration of diabetes were signi cantly associated with diabetic neuropathy [76,77].It has been documented that the augmentation of diabetes and the increasing burden of undiagnosed Diabetes in India increase the tendency to develop irreversible long-term vascular complications [64].

Limitations
In the reviewed studies, different methods were used to analyze diabetes that could have led to differences in Diabetes prevalence in and among India, making it impossible to carry out a meta-analysis of the results.In addition, the reviewed studies were conducted in different years, varying from 2000 to 2020.In order to make an accurate estimate of prevalence differences among states, it would be ideal to compare studies conducted in the same period, which was impossible because of the limited availability of data on the prevalence of diabetes for a particular period for all states in India.Regardless of these limitations, this current review still offers helpful information about one of India's vital chronic disease conditions and its complications.

Conclusion
This review suggests that diabetes and related complications are the most common problems in India.In addition, prevalence estimates specify that prediabetes is much higher, resulting in a substantial burden of diabetes in the future Indian inhabitants.State-wise study of incidence observed a wide variation in the prevalence of diabetes in both rural and urban populations among the different regions, particularly between the North and the South of India.We observed a contraction of the gap between urban and rural incidence.It is imperative to plan urgent strategies to reduce a further augment in diabetes in areas with a high prevalence of pre-diabetes, while consequent prevention will play a critical role in rural and urban Indian populations with a high prevalence of diabetes.

Table 1
Prevalence of type 2 diabetes in India 2000-2021 ADA: American Diabetes Association, WHO: World Health Organization, FBG: Fasting Blood Glucose.RBG: Random Blood Glucose, OGTT: Oral Glucose Tolerance Test.ADA: American Diabetes Association, WHO: World Health Organization, FBG: Fasting Blood Glucose.RBG: Random Blood Glucose, OGTT: Oral Glucose Tolerance Test.ADA: American Diabetes Association, WHO: World Health Organization, FBG: Fasting Blood Glucose.RBG: Random Blood Glucose, OGTT: Oral Glucose Tolerance Test.ADA: American Diabetes Association, WHO: World Health Organization, FBG: Fasting Blood Glucose.RBG: Random Blood Glucose, OGTT: Oral Glucose Tolerance Test.

Table 2
Chronic Complication of diabetes mellitus in India.
[23]eepa  et al.documented that the prevalence of diabetes has increased in both urban and rural areas, with a steeper augment in the urban areas possibly due to rapid epidemiological transition involving globalization, alteration in dietary habits, and increased physical inactivity in urban contrasted to that in rural areas.Individuals who earlier had vigorous occupations in rural areas got employed in sedentary occupations in urban areas.Moreover, they now have access to urban facilities such as automated transport and appliances for household everyday jobs, consequently further decreasing physical activity levels[64].With greater urbanization, growth of the middle class, and population aging, we can anticipate sharp increases in the numbers of people with Diabetes in India in the future[14].Dasappa et al. documented that the prevalence of diabetes and pre-diabetes increased with the increasing age and physical inactivity and with a switch from a traditional to a Western diet[23].The higher prevalence of diabetes is linked with smoking [65] and alcohol consumption[66].Previous cohort studies have revealed that light and moderate alcohol consumption was linked with a lower risk of Type 2 Diabetes, while heavy alcohol consumption was not interrelated with the risk of Type 2 Diabetes [67].The elevated incidence of diabetes in vegetarians nds no clear answers unless this group has a family history coupled with a sedentary lifestyle and is subjected to a stressful life.Eating only vegetables does not necessarily relate to good nutrition because if these vegetables are composed primarily of foods with a high glycemic index that is low in ber and other nutrients and increased intake, these could be harmful to health and amplify the risk of diabetes[68].Another prospect is that the vegetables consumed may contain high amounts of pesticide/herbicide residues, triggering diabetic circuits in the body.A recent report con rms that the incidence of diabetes among farmers was coupled with pesticide exposure[69].Fast food with processed carbohydrates, such as [71]d, noodles, cornstarch, high-calorie drinks, and vegetable fat, contributes signi cantly to urban diabetes[70].Meyer et al. found that vegetable fat (saturated fats) intake remained a signi cant predictor of new diabetes[71].
[72][73][74].The high prevalence was observed in rural areas could be due to setbacks in diagnosis, poor self-care, poor health-seeking behavior[64].It has been documented that approximately one in every ve diabetic individuals has diabetic retinopathy in the rural Indian population[72][73][74].