RSSDI clinical practice recommendations for the management of type 2 diabetes mellitus 2017

Management of diabetes, a disease which is assuming epidemic proportions, remains a challenge despite the availability of numerous guidelines. According to International Diabetes Federation (IDF) 2015 estimates, globally 415 million people are suffering from diabetes and this figure may reach up to 642 million in 2040 [1]. Currently, 78.3 million people with diabetes are in Southeast Asia (SEA) region and this may rise up to 140.2 million in 2040 if proper measures are not taken [1]. India has the second largest population (69.2 million) with diabetes in the world after China (109.7 million) [2]. In addition, approximately 52% adults with diabetes remain undiagnosed in India. Large-scale surveys, such as District Level Household and Facility Survey (DLHS) 2012–2013 and Annual Health Survey (AHS) 2014, have reported that around 7% Indian adults are suffering from diabetes and the prevalence is higher in urban (9.8%) compared to rural areas (5.7%) [3].

Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by abnormal insulin secretion and utilization. Indian patients with T2DM have distinctive clinical and biochemical characteristics, which makes them the so-called Asian Indian Phenotype [4–7]. These abnormalities include more insulin resistance (IR), elevated abdominal adiposity (i.e., higher visceral fat in spite of lower body mass index [BMI]), lower level of adiponectin, and a higher level of highly sensitive C-reactive protein [4–7]. Moreover, they have greater propensity to develop cardiovascular (CV) complications such as coronary artery disease (CAD) and atherosclerosis at any age point [4, 8] and have significant pro-coagulant affinities [9–11]. At the same BMI, more Asian Indians develop metabolic syndrome (MS) and diabetes compared to their western counterparts [12]. In spite of a relatively lower rate of obesity as defined by international BMI cut-off points, Indians tend to have larger waist circumference (WC) and waist-to-hip ratios (WHR), indicating a greater degree of central body obesity [13]. Asian Indians also have increased metabolic risk compared to their western counterparts due to high leptin levels [14], greater IR [6, 15, 16], higher insulin sensitivity index and lower acute insulin response to glucose [17], early loss of β-cell function [6], “concept of thin-fat Indian,” or “sarcopenic obesity” [18].

Numerous international and national guidelines are in place for the management of T2DM. Adopting country-specific guidelines improves treatment outcomes in diabetes. The Research Society for the Study of Diabetes in India (RSSDI) therefore published the clinical practice recommendations for the management of T2DM in 2015, which was adapted from the 2014 global guidelines for type 2 diabetes by IDF. The recommendations were specifically designed considering the diverse socioeconomic and cultural background of Indians. The 2015 RSSDI guidelines were very well accepted by the healthcare practitioners across India and helped in decision-making.

However, diabetes research is continuously evolving. Every year, several publications are being added to the literature which can significantly impact holistic diabetes care. Addition of new medicines to the diabetes management armamentarium, which is beneficial in terms of reduction in morbidity and mortality risk, is transforming the treatment of T2DM. Keeping this in mind, in the 2017 update, all of the sections have been updated with recent evidence. Moreover, three new sections, Hypoglycemia, Diabetes and CV risk, and Technologies, have been incorporated and some of the annexures revised. The objective of this updated RSSDI 2017 clinical practice recommendations is to provide evidence-based recommendations for the treatment of patients with T2DM. It is expected that these recommendations will help define practically implementable best practices not only for the management of T2DM but also help in timely prevention of acute and chronic complications of diabetes by primary care physicians across India.

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The methodology followed to develop the current recommendations is similar to that used to prepare RSSDI 2015 recommendations. A steering committee of RSSDI involving experienced diabetologists and endocrinologists across India was constituted, which met twice in the year 2017. The steering committee deliberated and defined the scope of the recommendations. As in the case of 2015 version, for all sections of the recommendations, expert panel groups were constituted including one steering committee member as a coordinator with several national experts to review all available Indian, Asian, and global evidence and make suitable recommendations.

The members of the expert panel reviewed the previous RSSDI recommendations and formulated recommendations based on available research evidence and economic and logistic constraints prevalent in India. Where there was little or no evidence, the group relied on their clinical experience and expertise, judgment, and consensus to make the recommendations. The recommendations of the expert panel groups were reviewed by the steering committee and were then finalized by the writing group as a draft consensus document.

The decision on the analytical reevaluation of the recommendations proposed by RSSDI 2017 was based on the Indian evidence published between 1990 and 2017 and following a review of relevant local factors in the Indian context. This included Indian evidence from indexed literature searches, articles published in the International Journal of Diabetes in Developing Countries (IJDDC), RSSDI Textbook of Diabetes (third edition) [1, 2], Journal of Association of Physicians of India (JAPI), and personal communications from authors. Where Indian evidence was not available, Asian/global evidence was considered where available.

Similar to the 2015 document, only “Recommended care” and “Limited care” setting of the IDF guidelines have been considered while the “Comprehensive care” was omitted. This practical approach facilitates implementation of cost-effective evidence-based care in limited resource settings like India.

References

Diabetes can be diagnosed with any of the following criteria:

Diabetes can be diagnosed with any of the following criteria:

*FPG is defined as glucose estimated after no caloric intake for at least 8–12 h.

**Using a method that is National Glycohemoglobin Standardization Program (NGSP) certified. For more on A1C and NGSP, please visit http://​www.​ngsp.​org/​index.​asp [10]

Note:

Traditionally, measuring FPG and OGTT is often considered for diagnosis [1] despite several international guidelines recommending A1C as a diagnostic tool for detecting diabetes/prediabetes [2, 3]. The optimal cut-off value of A1C to diagnose diabetes is determined in a way that individuals with A1C levels above a certain cut-off value have a much larger probability of having or developing diabetes-related complications [4]. However, in several countries including India, there is no consensus on a suitable cut-off point of A1C for diagnosis of diabetes. Moreover, measuring A1C is more expensive than FPG [5] and standardization of measurement techniques and laboratories is poorly practiced across the country [6]. Nonetheless, a recent review has included A1C as a criterion for the diagnosis of diabetes in India [7]. In lieu of this, the panel felt that using A1C as sole criteria for diagnosis of diabetes is inappropriate in resource constraint settings and framing recommendations based on fasting or 2-h plasma glucose or OGTT to detect or diagnose diabetes would be more appropriate in limited resource settings like India.

The decision about setting diagnostic thresholds values was based on the cost-effective strategies for diagnosing diabetes that were reviewed in Indian context.

Individuals should be educated on the advantages of early diagnosis and should be encouraged to participate in community screening programs for diagnosis.

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Prediabetes is defined as blood glucose concentration higher than normal but lower than established thresholds for diagnosis of diabetes. People with prediabetes are defined by having IGT (2-h plasma glucose in the 75-g OGTT = 140 to 199 mg/dL) or IFG (FPG = 100 to 125 mg/dL). It is a state of intermediate hyperglycemia with increased risk of developing diabetes and associated CV complications and therefore early detection and treatment of prediabetic IGT and IFG is necessary to prevent the rising epidemic of diabetes and its associated morbidity and mortality. Although IDF guideline does not deal with screening and management of prediabetes, the American Diabetes Association (ADA) recommends screening for prediabetes and T2DM through informal assessment of risk factors or with an assessment tool guidelines [4]. Given the high prevalence rates of prediabetes in our country, RSSDI panel members opine that including screening and management aspects of prediabetes is logical and will provide an important opportunity for prevention of diabetes in India.

The decision about conducting a screening program should be based on the following local factors than were reviewed in Indian context: limited resources, lack of quality assurance in labs, high-risk population for diabetes, large unrecognized burden of undiagnosed diabetes, high prevalence of prediabetes, among fastest converting population form prediabetes to diabetes, large rural–urban divide, largely sedentary population in urban areas, onset of T2DM at least a decade earlier that in western countries, newer technologies for screening, cost of early detection to the individual, capacity for carrying out screening, and capacity to treat/manage screen positive individuals with diabetes and prediabetes.

It has been observed that Indians are more prone to diabetes at a younger age and at a lower BMI compared to their western counterparts [21, 22]. The reason for this difference has been attributed to “Asian Indian phenotype” characterized by low BMI, higher body fat, visceral fat and WC, lower skeletal muscle mass, and profoundly higher rates of IR [23, 24]. The 10-year follow-up data of the CURES that assessed incident rates of dysglycemia in Asian Indians are now available [25]. According to the study, Asian Indians were found to have one of the highest incidence rates of diabetes (diabetes, prediabetes, and any dysglycemia = 22.2, 29.5, and 51.7 per 1000 person-years, respectively), with rapid conversion from normoglycemia to dysglycemia (45.1%). In a cross-sectional study on slum dwellers in Bangalore, prevalence of diabetes and prediabetes was identified as 12.33 and 11.57% in people aged 35 years or above [26]. Moreover, female gender, increasing age, overweight and obesity, sedentary lifestyle, tobacco consumption, and diet habits were strongly associated with prevalence of diabetes and prediabetes. Similarly, in a cross-sectional study in Tamil Nadu, prevalence of diabetes and prediabetes was identified as 10.1 and 8.5%, respectively [27]. Risk factors associated with prediabetes in this study were age of 40 years, male gender, BMI > 23 kg/m², WHR for men > 1 and women > 0.8, alcohol intake, and systolic blood pressure (SBP) > 140 mmHg. Likewise, in a household survey in Punjab using World Health Organization STEP wise Surveillance (WHO STEPS) questionnaire, prevalence of diabetes and prediabetes was identified as 8.3 and 6.3%, respectively [28]. Risk factors that were significantly associated with diabetes were age (45–69 years), marital status, hypertension, obesity, and family history of diabetes. A study on 163 north Indian subjects proposed severity of IR and family history of diabetes as determinants of diminished beta-cell function leading to diabetes in MS [29]. Predictors of progression to dysglycemia were advancing age, family history of diabetes, 2-h plasma glucose, A1C, low and high density lipoprotein (HDL) cholesterol, and physical inactivity. Despite the escalating burden, the current evidence on the prevention of T2DM and its complications in India still remain scanty. Though the general practitioners in India are well aware of symptoms and complications of T2DM, they are oblivious regarding the use of standard screening tests resulting in significant delay in diagnosis and treatment [30]. Considering significant resource constraints together with awareness levels of patients and physicians, there is a need for prevention strategies that are culturally relevant and cost-effective [31]. Following section covers evidence from India studies on various strategies that are helpful in detecting and minimizing the risk of development of diabetes and its associated complications.

A clear and transparent decision should be made about whether or not to endorse a screening strategy. If the decision is in favor of screening, this should be supported by local protocols and guidelines and public and healthcare professional education campaigns.

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Obesity is a highly prevalent metabolic disorder that is often associated with T2DM [1, 2]. Obesity is clinically defined as a BMI of ≥ 30 kg/m² (a BMI of 30 represents an overweight of approximately 30 lb. (14 kg) for any given height) [3]. However, WHO and International Obesity Task Force (IOTF) suggested BMI cut-offs of 23 and 25 kg/m² for Asian Indian adults for overweight and obesity, respectively [4, 5]. Furthermore, the guidelines defined generalized obesity (GO, BMI ≥ 25 kg/m²), AO (WC ≥ 90 cm for men and ≥ 80 cm for women), and combined obesity (CO, GO plus AO) for Asian population [5]. In India, the prevalence of obesity is rising at an alarming rate, especially affecting urban population [2, 6]. The Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study currently report that 135, 153, and 107 million individuals in India will have GO, AO, and CO, respectively, in extrapolation to the whole country. Furthermore, female gender, hypertension, diabetes, higher socioeconomic status, physical inactivity, and urban residence were significantly associated with GO, AO, and CO, in Indian populations [7]. Indians are at increased predisposition to diabetes that has been attributed to the “Asian Indian Phenotype” characterized by lesser GO as measured by BMI and greater central body obesity and more truncal fat as shown by greater WC and WHR [2, 8–11]. High AO contributes significantly to metabolic alterations such as IR, dysglycemia, and dyslipidemia [12–16, 17]. Obesity-induced IR may cause T2DM by increasing the allostatic load on the pancreas which eventually leads to failure of pancreas. High consumption of sugars among children and adults in India may also have clinical significance in view of the high tendency for Indians to develop IR, abdominal adiposity, and hepatic steatosis and the increasing “epidemic” of T2DM [2, 18]. Because Asian Indians tend to develop diabetes at a significantly lower BMI and WC than white Europeans, lower thresholds of BMI to define overweight (BMI = 23–24.9 kg/m²) and obesity (BMI ≥ 25 kg/m²) were proposed by IDF and National Institute of Health and Care Excellence (NICE) [19, 20].

In light of increasing prevalence of obesity in both developed and developing countries and a higher risk for developing IR, dyslipidemia, dysglycemia, and a higher CV risk at lower levels of BMI in Indians, a consensus meeting was convened in New Delhi in 2008 (published in 2009) to redefine the cut-offs for BMI and WC for diagnosing overweight and obesity in Indian population [21, 22]. According to this consensus statement, a BMI of 18–22.9 kg/m² should be considered as normal, a BMI of 23–24.9 kg/m² should be considered as overweight, and BMI more than 25 kg/m² indicates presence of obesity. The upper limit for WC for men and women was defined as 90 cm and 80 cm, respectively.

The following local factors were considered when framing recommendations for obesity that were reviewed in Indian context: high prevalence of obesity, high abdominal adiposity, increased fasting insulin and IR, nutritional factors, and atherogenic lipid profile [increased triglycerides and low density lipoprotein (LDL) and low HDL].

Nutritional and diet therapy remains an integral part of diabetes management. As there is no “one-size-fits-all” meal plan or eating pattern, RSSDI recommendations emphasis on development of individualized eating plan, based on individual’s health needs, personal and cultural preferences, access to healthful choices, health literacy, and numeracy [1, 2] in consonance with ADA [3]. The primary goal of the diet therapy is to improve health by providing calories for normal growth and development while achieving and maintaining optimal glycemia and normalizing dyslipidaemia [4]. Therefore, diets are often altered or/modified with respect to amount of carbohydrate, the type of fat, and the quantity and type of protein to meet these needs. Evidence from epidemiological and experimental studies focusing on nutritional intervention in the prevention of T2DM suggests that intake of foods with more non-starch polysaccharides and omega-3 fatty acids with low glycemic index (GI) may play a protective role, whereas excess intake of saturated fats and TFAs may contribute to the increased risk [2]. In people who are accustomed to consuming sugar sweetened foods, ADA recommends the use of non-nutritive sweeteners in moderate amounts as they have the potential to reduce overall calorie and carbohydrate intake [3]. However, the exact nature of diet appropriate for patients with T2DM still remains a matter of debate due to lack of tools and strategies that help to decide on healthy eating patterns to minimize the burden of disease [6]. Among Asian Indians from South Asia, intake of refined carbohydrate, saturated fatty acids (SFA) and n-6 PUFA as well as TFAs is higher and intake of n-3 PUFA and fiber is lower [7, 8]. In addition, attitudes, cultural differences, and religious and social beliefs and imbalances in dietary patterns pose significant barriers in effective prevention and management of T2DM [9]. Evidence suggest that intake of MUFAs among Asian Indians ranged from 4.7 to 16.4% that indirectly could contribute to increasing obesity, metabolic syndrome, and T2DM [10, 11]. In this context, it is felt that RSSDI recommendations on diet therapy can suggest approaches to the dietary management of diabetes in Asian Indians (Annexure III).

The panel endorse most of the IDF recommendations on diet therapy with a few modifications based on the local factors that were reviewed in Indian context including high prevalence of both obesity and undernutrition, poor access to healthy food choices, and inadequate physical activity in some.

Implementation of dietary management therapies demands knowledgeable and competent dietitians and nutritionists who are trained in providing effective dietary interventions that are consistent with individual’s needs and demands. Self-management and counselling in nutrition (for individuals or groups) should first include assessment, identification of the nutrition problem, and later implementation of nutritional strategies followed by nutrition monitoring and evaluation of individual outcomes. Nationwide community intervention programs aimed at creating awareness about the consequences of unhealthy food choices and replacing them with healthy food choices is urgently needed in India. Evidence from initial studies suggests that simple 4-week nutritional counselling provided to increase patient’s nutritional knowledge can significantly improve fasting and postprandial blood glucose levels in illiterate to semi-literate patients with T2DM [61], but long-term interventional studies are lacking. Increasing taxation on sugar-sweetened beverages has been shown to decrease the incidence of obesity and T2DM, suggesting that prevention strategies, encompassing multiple stakeholders (government, industry, and consumers), may decrease excessive sugar consumption in the Indian population [58].

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Lifestyle intervention is an integral part of diabetes management along with dietary and pharmacological interventions. Lifestyle interventions, which include increased physical activity, dietary modification, as well as weight reduction among overweight people, have potential to prevent T2DM in high-risk individuals [1, 2]. Obesity, which is one of the foremost reasons for T2DM development and associated with higher CV risk, can be controlled with significant lifestyle modifications. Major forms of lifestyle modifications considered for patients with T2DM include dietary modification and increasing physical activity (both aerobic and resistance training). A wealth of literature supports the fact that regular physical activity reduces morbidity and mortality in patients with T2DM. Regular aerobic training not only reduces glycemic burden but also helps to prevent atherosclerotic CVD by several mechanisms. In older adults with diabetes, regular walking was associated with reduced all-cause and CVD mortality [3–6]. Interestingly, regular exercise is shown to provide similar benefits in patients with T2DM when these exercises are done in single or multiple bouts, as long as the recommended length of activity is performed. Recent reports indicate positive effects of resistance training in patients with T2DM. All T2DM patients without complications and even those with complications can perform mild–moderate physical activity with appropriate caution. Yoga is also known to reduce glycemic parameters, improve insulin sensitivity, and reduce the use of OADs [4, 7]. Since Asians are considered to do less physical activity compared to their western counter parts [8], lifestyle modification is of paramount importance for blood glucose control and CV protection in patients with T2DM.

The panel endorsed most of the IDF recommendations on lifestyle modifications with additions on the specific role of yoga in the Indian context. The panel considered evidences of physical activity on glycemic parameters in view of the high predisposition of Asian Indians to develop T2DM and CAD. The benefits of yogic practices, individually and when combined with physical activity, are also considered.

Implementation of lifestyle management in patients with T2DM requires adequate awareness and education from the treating physician. It is imperative that all healthcare professionals encourage patients to practice the combined approach of diet and physical activity along with pharmacological intervention. In this regard, providing patients with structured educational programs using information leaflets on practices and procedures of physical activity could greatly enhance the adherence and overall health of patients with T2DM.

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Diabetes self-management education (DSME) is recognized as an important component of management of T2DM. Individuals with diabetes tend to make dramatic impact on the progression and development of diabetes by involving in their own diabetes self-care practices [1]. Moreover, diabetes education improves metabolic control, prevents or delay complications, improves QoL, and empowers people to make informed choices to manage their condition [2]. It is expected that patient who is well-educated has better understanding of the disease and self-manages the condition more effectively [3]. Evidence from literature suggests that implementation of DSME has been successful in lowering glycemic levels in uncontrolled patients [4, 5]. The DSME is an ongoing process that facilitates knowledge, skill, and ability necessary for diabetes self-care [5, 6]. It is guided by evidence-based standards while incorporating needs, goals, and life experiences of the person with diabetes [7]. India is a country with diverse social, economic, cultural, and educational patterns with majority of population residing in rural areas. Evidence has also revealed that rural people have less knowledge and awareness than urban Indian people [8]. It is presumed that the poor level of awareness on diabetes in India is due to high percentage of individuals with low or no literacy [9, 10].

The panel endorsed the IDF recommendations on education as such. However, evidence from India together with local factors such as cost, literacy, malnutrition, body weight, and BMI were reviewed in the Indian context and are reflected in the recommendations.

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The primary aims of controlling glycemic levels are to avoid acute symptoms of hyperglycemia, to avoid fluctuation in blood glucose over time, and to prevent/delay the development of various complications associated with diabetes without hampering QoL of patients. The treatment should also aim at preserving β-cell function and prevent or slow the rate of apoptosis that will in turn delay the natural progression of the disease. Particularly from a patient point of view stability of metabolic control over time may be another specific goal that needs to be considered. Given the progressive loss of β-cell function in T2DM, treatment with OADs is ensued if the target A1C is not achieved with initial lifestyle modification. However, the properties of any antidiabetic agent that play a role in the choice of drug(s) in individual patients may vary because diabetes itself has a different mechanism responsible for its pathophysiology. Several guidelines provide treatment algorithms on ways in which glucose-lowering agents can be used either alone or in combination. The current guideline based on the current clinical evidences provides overview on available OADs and tries to come up with some practically applicable recommendations for optimal management of T2DM in Asian Indians.

The decision on choice of OAD therapy in T2DM patients was based on the cost, safety, and efficacy factors that were reviewed in Indian context.

Insulin pump: Sufficient evidence from randomized controlled studies to support the use of insulin pump in patients with T2DM is lacking; however, it is a potential option in selected individuals [3]. Nonetheless, longitudinal data suggest that insulin pumps may be useful in patients with severe IR and poor glycemic control despite adhering to recommended insulin therapy, diet, and exercise [4]. Furthermore, pump therapy in appropriate patients may reduce risk of hypoglycemia and weight gain [4].

Type 2 diabetes mellitus is a progressive disease in which patients nearly lose > 50% of their β-cell function by the time of diagnosis. Furthermore, this loss steadily continues to decline at approximately 3–5% per year [5, 6]. Intensive glycemic management has reduced the mortality, morbidity, and risk of diabetes-related complications in patients with T2DM [6, 7]. Most of the medications available to control glycemia have a final common pathway in the form of targeting β-cells or IR and are dependent upon the presence of insulin for their therapeutic effect. The durability of these medications varies and their safety is occasionally under scrutiny. Over a period, patients fail to achieve or maintain A1C levels even with multiple OADs and will require insulin therapy.

Most guidelines recommend early insulin therapy in patients with high A1C at the time of presentation [1, 8, 9]. The knowledge available through landmark trials in last decade warrants that glycemic control should be intensive in early stages of diabetes, preferably in first 4 years of diagnosis of diabetes [10–12]. This makes us understand that the indications of insulin therapy in T2DM should be more proactive, albeit not at the cost of severe symptomatic hypoglycemia, especially in patients where hypoglycemia may be deleterious.

The traditional postponement of insulin therapy up to prolonged failure of lifestyle and oral agents to achieve glycemic control has been revised in the last decade to incorporate insulin therapy much earlier, often in combination with OADs or GLP-1 analogues. All healthcare professionals and primary care physicians must understand the significance of legacy effect that was very clearly demonstrated in the long-term cohorts of UK Prospective Diabetes Study (UKPDS) trial [6]. An Indo-centric way of defining legacy effect is metabolic karma [14].

Non-insulin injectables such as GLP-1 analogues and amylin analogues (pramlintide) have been approved in various countries. The GLP-1 analogues improve glycemic control through multiple mechanisms, with low risk of hypoglycemia and clinically relevant weight loss [13]. As pramlintide is not available in India, it is not covered in these recommendations.

The decision on choice of injectable therapy in T2DM patients is based on clinical, pharmacological, as well as psychosocial factors. Apart from these, local factors such as cost, quality, cold chain maintenance, and perennial availability of insulin preparations as well as delivery devices must be considered in the Indian context.

Timely initiation and appropriate intensification of injectable therapy is a challenging aspect of diabetes care. This must be addressed by focusing on patient education and motivation, as well as updating knowledge of healthcare professionals. Lifestyle modification, self-monitoring, and insulin education should be integral parts of insulin therapy in T2DM. Structured guidelines and protocols should be shared and glycemic audits of persons on oral medications performed to address the issue.

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As diabetes is a disease which is chronic and controllable, rather than curable, patients are often daunted by the possibility of lifelong allopathic medications. Therefore, some patients use complementary and alternative medicinal (CAM) therapies for its prevention and management [1]. Ayurveda, yoga, unani, siddha, homeopathy, and naturopathy systems of medicine are often integrated into diabetes healthcare delivery. More than 300 Indian plant and mineral products have been reported, with sub-optimal therapeutic effects in diabetes. Evidence has established a few beneficial effects of methi, vijaysar, gurmar, neem, amla, ghritkumari, turmeric, black pepper, date fruit, onion, and karela in diabetes [1–17]. Moreover, yoga, pranayama, meditation, acupuncture, massage therapy, aromatherapy, and many relaxation techniques are being practiced in India, for prevention and management of diabetes [17–19]. Furthermore, some dietary supplements including chromium, alpha-lipolic acid, omega-3 fatty acids, magnesium, and zinc are also having some beneficial effects in the management of diabetes [1]. Although they do not substitute physical activity, they may supplement non-pharmacologic therapies in diabetes. Many of these alternative therapies have not been subjected to or have not withstood the rigorous scientific studies such as RCTs. Hence, the use of these agents may be considered as an adjunct to standard care. Moreover, there is a need to generate evidence on the benefits as well as toxicity of these agents by rigorously conducted clinical trials.

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Choice of any antidiabetic agent should take into account the patient’s general health status and associated medical disorders. This patient-centric approach may be referred to as the ABCD (EFGH) approach for diabetes management. As shown in the figure, for any T2DM patients, first line of therapy should be metformin unless it is not tolerated by the patient or contraindicated.

Poorly controlled diabetes is associated with increased risk of micro- and macrovascular complications which further depend upon both fasting and PPG levels [1–4]. Evidence from large controlled clinical trials suggest that intensive glycemic control can significantly decrease the development and/or progression of these complications [1, 5–8]. However, tight glycemic control needs to be instituted early in the disease course so that legacy effect can be seen as reduced number of complications even after many years. The relationship between hyperglycemia and CVD is complex with evidence suggesting that an acute increase of glycemia, particularly after a meal, contributes to the increased risk of diabetes-related complications and have a direct detrimental effect on CVD in patients with T2DM [9–11]. Until recently, the predominant focus of diabetes treatment has been on lowering A1C levels, with emphasis on FPG [12, 13]. Nevertheless, control of fasting hyperglycemia alone is insufficient to obtain optimal glycemic control. Emerging evidence suggests that reducing PPG excursion is as important or perhaps more important for achieving desired glycemic targets [14]. Usually A1C is supposed to be largely contributed by FPG when it is away from target. As and when it comes closer to the target, PPG starts taking upper hand and contributes predominantly. But in Asian Indians, scenario remains quite different. In Indians, the PPG remains relatively high all across the A1C spectrum and especially very high even at higher A1C values [15–17]. Relative contribution of postprandial hyperglycemia to A1C levels in patients with T2DM is higher than FPG levels when the A1C levels are below 7.5% and it decreases progressively as A1C levels increase [18]. Therefore, targeting both PPG and FPG is an important strategy for achieving optimal glycemic control. The purpose of these recommendations is to assist clinicians in developing strategies to consider and effectively manage postmeal glucose in people with T2DM in Asian countries.

India has a high prevalence of diabetes and onset of diabetes is a decade early. Postprandial hyperglycemia is more prominent in Indians due to high traditional diets with high glycemic index. Literature is limited regarding postprandial hyperglycemia despite a definite role in micro and macrovascular complications.

Frequent monitoring of glucose levels using techniques such as SMBG can significantly improve glycemic control besides detecting PPG excursion. SMBG is currently the optimal method for assessing plasma glucose levels. Evidence suggests that structured SMBG followed by therapeutic interventions results in greater A1C reduction in people with T2DM compared with programs without structured SMBG [41–43]. Therefore, the panel opined that SMBG with appropriate patient education is necessary for optimal management of postmeal hyperglycemia.

References

Monitoring of blood glucose levels is critically important to ensure good glycemic control. It is considered the cornerstone of diabetes care that helps both physicians and patients to adjust the therapy according to patient’s need. Following clinical testing to assess levels of control and progression of T2DM, most guidelines recommend clinicians to perform frequent monitoring of glycemic status by measurement of A1C as a follow-up care of individuals with diabetes [1, 2]. Moreover, A1C measurement is the gold standard for the therapeutic management of diabetes in both research and in clinical settings, which involves assessing glycemic control over the previous 2–3 months [3, 4]. Long-term hyperglycemia as measured by A1C has been shown to be strongly related to development of diabetic microvascular complications though its relation to development of macrovascular complications is less clear. Therefore, patients who are not at targets or at increased risk of developing complications require more intensive monitoring, ranging from frequent self-monitored glucose [3, 5] to continuous glucose monitoring (CGM) [6, 7] to assess daily variations in blood glucose levels [8]. The current recommendations provide an insight on the importance and frequency of monitoring to be performed in order to facilitate medication and lifestyle changes when average A1C values remain above targets levels.

The decision on clinical monitoring of glycemic levels in T2DM patients was based on the local factors such as availability of newer technologies and cost of monitoring that were reviewed in Indian context.

There should be access to a laboratory or site-of-care test monitored by certified quality assurance schemes for measurement of A1C. People in whom A1C measurement is inappropriate must be identified by careful review of hematological parameters and other factors that can affect A1C values. Provision of capillary blood glucose meters and strips needs to be assured in hospitals and clinics. It is important to ascertain whether there are contraindications for use of a particular type of glucose meter in a particular patient. It is essential to establish whether meters report values for plasma or blood and to ensure that schemes for monitoring the quality of their output are in place. Blood glucose meters should be calibrated on regular basis and their use in hospitals should be restricted to trained personnel.

References

Frequent and precise blood glucose monitoring and concomitant optimal adjustment of insulin to carbohydrate intake and exercise are the basis of diabetes treatment. The SMBG is an essential component of the modern diabetes treatment and the most uncomplicated and commonly used strategy of interim glucose monitoring across the globe [1]. Established advantages with SMBG include achieving target A1C, reducing glucose variability, and prediction of severe hypoglycemia [2]. Therefore, it has been recommended for achieving a specific level of glycemic control and to prevent hypoglycemia in people with diabetes. The objective of SMBG is to assemble detailed information about blood glucose levels at various time points to enable maintenance of a more constant glucose level by more precise regimens. It can be used to aid in the adjustment of a therapeutic regimen in response to blood glucose values and to benefit individuals regulate their dietary intake, physical activity, and insulin doses to improve glycemic control on a day-to-day basis [2, 3]. SMBG serves as a vital adjunct to A1C as it can differentiate the fasting, preprandial, and postprandial hyperglycemic levels; detect the glycemic excursions; recognize and contribute in monitoring resolution of hypoglycemia; and provide immediate feedback to patients about the effects of food choices, activity, and medication on glycemic control [4].

In diabetes patients on intensive insulin regimens, SMBG is suggested at premeals, during snack, and bedtime, occasionally after eating, preexercise, when suspicion of and after correction of hypoglycemia, and before tasks like driving [5, 6]. There is also a positive relationship between frequency of SMBG and improvements in A1C and early detection of lower glucose values prior to symptomatic hypoglycemia may allow correction with a reduced risk for hyperglycemia [7]. Use of SMBG during exercise may also allow improved insulin management and reduce risk for hypoglycemia during and following exercise [8]. Measurement of blood glucose at different times in a day helps in management of improving blood glucose profiles, confirming hypoglycemia, monitoring recovery, and preventing hyperglycemic crises [3].

In patient who have stable oral regimen with A1C within the target range, SMBG data can be used as biofeedback at times of increased stress or changes in diet or physical activity. While patients whose diabetes is not in control or have initiated medication, SMBG data can be helpful in modifying or creating the diabetes management regimen [10].

SMBG has been well studied among individuals with diabetes and has proved to be a useful tool in improving glycemic control effectively and recognizing low blood glucose levels before the development of severe hypoglycemia [5]. Landmark clinical trials of insulin-treated patients have included SMBG as part of the multifactorial interventions to demonstrate the benefit of intensive glycemic control on diabetes complications [11, 12]. Clinical evidence supports a correlation between greater SMBG frequency and lower A1C. Moreover, patient’s specific needs and goals should not only determine but in fact should dictate SMBG frequency and timing [13].

Despite being recommended in various guidelines [13, 14], a large gap between recommended to current practices of SMBG is observed in both developed and developing countries. In India, this strategy is still not properly understood or implemented. Lunch and dinner are our major meals of the day and glycemic variations are not recorded during routine tests which are invariably done in the morning. Availability of meals with varying glycemic indices and affordability of glucose meters and strips are major factors that play a dominant role either in recommending or practicing SMBG. Fortunately, the advent of less expensive meters and a reduction in the cost of the strips has considerably brightened the scenario. Apart from this, SMBG use is also associated with improved cost-effectiveness [15]. In this consensus, we have evaluated various literature and recommendations on SMBG available online and drawn statement to fit Indian scenario.

The decision including SMBG in clinical practice was based on the factors such as availability of and access to glucose meters and foods with varying glycemic indices that were reviewed in Indian context.

It is essential to establish whether glucometers report values for plasma or blood and to ensure that schemes for monitoring the quality of their output are in place. Blood glucose meters should be calibrated on a regular basis. Low-cost glucose strips and meters should be developed and made available for wider implementation of SMBG. Strategies that can lower PPG excursions in people with postprandial hyperglycemia should be implemented.

References

Diabetic retinopathy (DR) is a microvascular complication of diabetes and one of the leading causes of blindness or vision impairment in India [1, 2]. Visual loss from DR could be due to diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). Global data suggests that the overall prevalence as 35.4% for any DR and around 7.5% for PDR [3]. Factors such as longer duration of diabetes and poorer glycemic and BP control were found to be strongly associated with DR [3, 4]. In a cross-sectional study carried out by All India Ophthalmological Society, prevalence of DR was 21.7% and the rate was high in males (p = 0.007), in patients with diabetes duration > 5 years (p = 0.001), in patients with age > 40 years (p = 0.01), in insulin users (p = 0.001), and in patients with history of vascular accidents (p = 0.0014) [2]. Furthermore, in the cross-sectional survey of Indian patients with T2DM in chronic complications in newly diagnosed patients with type 2 diabetes mellitus in India (CINDI) and cardiovascular risk factors, micro- and macrovascular complications at diagnosis in patients with young onset type 2 diabetes in India (CINDI 2) studies DR was prevalent in 6.1 and 5.1% patients, respectively [5, 6]. Moreover, the socioeconomic burden resulting from DR induced visual impairment or blindness, particularly in the working age group, is a serious concern [7]. Therefore, it is high time to devise the means of managing DR and bring the problem under control. Early diagnosis, optimization of risk factors, and timely photocoagulation at appropriate places could entirely prevent the blindness from diabetes [8]. Moreover, a systematic approach to health education and creating awareness among patients and various health personnel and matching it with appropriate screening and service delivery mechanisms will go a long way in preventing blindness due to DR. Furthermore, early detection and management of DR with quick referrals and a highly coordinated teamwork between the endocrinologists and the ophthalmologists could reduce the prevalence of DR in India [9]. In addition, these recommendations will provide insights on the management of DR while promoting awareness and thus preventing vision impairment due to DR through cost-effective interventions.

The recommendations on management of DR were taken from IDF 2014. However, few of the IDF recommendations were modified based on the local factors such as limited resources, high prevalence of DR, lack of quality assurance in labs, and availability of newer technologies and therapies for eye screening and treatment which were reviewed in Indian context.

Though evidence from past studies suggests that prevalence of DR is low in Indians compared to other ethnic groups, emerging data indicate significant increase in prevalence of retinopathy in South Asians compared to Caucasians [17]. Data from a population-based study (CURES) indicate that the overall prevalence of DR in urban South Indian population was 17.6%, with higher prevalence among men than in women (21.3 vs 14.6%; p < 0.0001) and among subjects with proteinuria (p = 0.002) [18]. Similarly, prevalence of DR in western India was found to be 33.9% [19]. Data from a recent population-based cross-sectional study suggests that one of 10 individuals in rural South India, above the age of 40 years, had evidence of DR [20]. A meta-analysis of seven studies from India found 14.9% of known diabetes patients aged ≥ 30 years and 18.1% among those aged ≥ 50 years had DR. Furthermore, no linear trend was observed between age and the proportion with DR [21]. Duration of diabetes, A1C, male gender, macroalbuminuria, and insulin therapy were found to be strongly associated with increased risk of DR among South Indians [22, 23]. Moreover, the risk of nephropathy (OR, 5.3; p < 0.0001) and neuropathy (OR, 2.9; p < 0.0001) was significantly higher among T2DM patients with DR compared to those without DR [24]. After adjusting for age, gender, A1C, SBP, serum triglycerides, and duration of diabetes, DR was significantly associated with nephropathy (p = 0.005) than with neuropathy [24].

Sufficient number of trained general ophthalmologists and general physicians is required to develop an integrated DR model that facilitates early detection and create awareness on DR. Medical camps should be conducted for screening of diabetes and DR screening camps, which will help to identify people at risk of sight-threatening DR and initiate treatment including laser photocoagulation or vitreous surgery. Mobile vans with a fundus camera or other low-cost tools that can be used in remote rural areas should also be explored. However, successful implementation of program requires team approach, involving both administrative and voluntary organizations.

References

Neuropathies are the most common complication of diabetes, affecting up to 50% of patients with T2DM [1]. Metabolic disruptions in the peripheral nervous system (altered protein kinase C activity and increased polyol pathway activity) due to hyperglycemia play a key role in the development of DN [2, 3]. Approximately 30% patients either with known or newly diagnosed diabetes are suffering from DN [4, 5]. In the cross-sectional survey of Indian patients with T2DM in CINDI and CINDI 2 studies, DN was prevalent in 13.15 and 13.2% patients, respectively [6, 7]. The most common form of DN is the distal symmetrical polyneuropathy that involves both tibial and sural nerves [8]. Presence of neuropathy is associated with significant morbidity, including recurrent foot infection and ulcers, impotence in men with diabetes, and sudden death in individuals with CV autonomic neuropathy. Neuropathic pain in patients with diabetes is commonly encountered in clinical practice. Therefore, timely screening and early detection ensure prevention of the progression of DN [9]. The present recommendations provide insights on the management aspects of DN while exploring newer therapeutic options that have emerged in recent years.

The panel endorsed the IDF 2014 recommendations for diagnosis and management of DN. However, few of the recommendations were modified based on local factors such as limited resources, which helps in clinical diagnosis of DN, lack of quality assurance in labs, and need for cost-effective diagnostic techniques which were reviewed in Indian context.

Appropriate protocols should be developed for sensory testing and may include formal assessment using the NSS and NDS. Recommended medications should be available according to the level of resources. Medical teams need to remain trained in the diverse manifestations of autonomic neuropathy.

References

Diabetic nephropathy is a leading cause of ESRD affecting ∼ 20–30% diabetes patients and is associated with increased CV mortality [3]. It affects 10–40% of T2DM patients who eventually suffer from kidney failure [4, 5]. In the cross-sectional survey of Indian patients with T2DM in CINDI and CINDI 2 studies, DN was prevalent in 1.06 and 0.9% patients, respectively [6, 7]. Cost of treatment for advanced CKD is substantial. Less than 10% of ESRD patients have access to any kind of renal replacement therapy [8, 9]. Thus, in a country with limited resources, it becomes appropriate to direct efforts towards prevention of CKD rather than the treatment. In India, with an increase in the prevalence of diabetes, it becomes imperative to evolve definite guidelines for detection of diabetic nephropathy and suggest practical clinical recommendations to combat it. Improving glycemic control, aggressive antihypertensive treatment, and the use of ACE inhibitors or ARBs will slow down the rate of progression of nephropathy [10, 11]. In addition, protein restriction and other treatment modalities such as phosphate lowering may have benefits in selected patients [12].

The panel endorsed the IDF 2014 recommendations for diagnosis and management of diabetic nephropathy. However, few of the recommendations were modified based on local factors such as limited resources, lack of quality assurance in labs, higher prevalence of diabetic kidney disease, and hypertension and cost of treatment of kidney failure through dialysis or transplantation which were reviewed in Indian context.

Management of CKD requires access to healthcare professional, laboratory for ACR and creatinine estimations, and availability of multiple blood pressure-lowering medications in particular renin-angiotensin system blockers.

References

Diabetic foot problems are one of the most common reasons for hospitalization of patients with diabetes (about 30% of admissions) and consume about 20% of the total healthcare costs of the disease compared to all other diabetic complications [1, 2, 3]. In India, prevalence of foot ulcers in patients with diabetes in clinic population varies from 3 to 14% [4–6]. Peripheral neuropathy, Charcot arthropathy, foot ulcers, infections, and lower extremity amputations are the various lower limb complications seen in diabetes patients [6]. Strategies aimed at preventing foot ulcers are cost-effective and can even be cost-saving if increased education and efforts are focused on those patients with recognized risk factors for the development of foot problem. The management of diabetic foot disease may seem poorly defined by comparison with complications such as nephropathy, hyperlipidemia, and retinopathy, for which clear guidelines exist. A multidisciplinary team approach, particularly in specialized diabetic foot clinics, is very successful in avoiding and treating foot complications. Present guideline focuses on the various mechanisms of managing diabetic foot disease.

The panel endorsed the IDF 2014 recommendations for diagnosis and management of diabetic foot complications. However, few of the recommendations were modified based on local factors such as limited resources and lack of quality assurance in labs, which were reviewed in Indian context.

Availability of basic equipment, appropriate protocols, structured records, and recall systems needs to be supported by appropriate training for professionals providing screening and management services. Liaison needs to be established with orthoptists, footwear suppliers, and cast technicians.

References

The risk of developing infectious diseases due to diabetes is now being considered an important complication of diabetes [1, 2]. Diabetes increases the risk of infection by two to three times in comparison to the non-diabetic population. The morbidity and mortality associated with infectious diseases such as influenza, pneumonia, and hepatitis, which is usually preventable by appropriate vaccination, also appear to be very high in diabetes subjects [3]. Patients with T2DM, especially those with PVD, are at high risk for many types of typical and atypical infections due to immune dysfunction, DN, and poor circulation [4]. Furthermore, skin breakdown in patients with advanced diabetes and PVD provides a portal of entry for bacteria. Longer duration of diabetes and poor glycemic control causes increased risk of pneumonia related hospitalizations in diabetes subjects due to compromised immune system of the host [5]. A recent study demonstrated that patients with high blood glucose level are at increased risk of community-acquired pneumonia [6, 7]. Even certain viral infections can lead to new onset of diabetes in the population who are genetically prone to develop diabetes.

The decision about conducting a screening program should be based on local factors such as limited resources and high prevalence of diabetes-related infections factors that were reviewed in Indian context.

Apart from the micro- and macrovascular events in diabetes, infections due to influenza and pneumococci should be considered as significant public health concern. All clinics providing vaccinations shall maintain the records to assess the efficacy of vaccines regarding occurrence of various complications in vaccinated individuals compared to non-vaccinated subjects. Vaccination strategies in diabetes should evolve as part of routine care and a central registry needs to be maintained.

References