RSSDI-ESI clinical practice recommendations for the management of type 2 diabetes mellitus 2020

Abstract

DIAGNOSIS OF DIABETES RECOMMENDATIONSTable: No title available.Table: No title available.NOTE Estimation of HbA1c should be performed using NGSP standardized method. Capillar y glucose estimation methods are not recommended for diagnosis Venous plasma is used for estimation of glucose Plasma must be separated soon after collection because the blood glucose levels drop by 5%–8% hourly if whole blood is stored at room temperature. For more details on glucose estimation visit: http://www.ncbi.nlm.nih.gov/books/NBK248/ *FPG is defined as glucose estimated after no caloric intake for at least 8–12 hours. **Using a method that is National Glycohaemoglobin Standardization Program (NGSP) certified. For more on HbA1c and NGSP, please visit http://www.ngsp.org/index.asp BACKGROUND The diagnostic criteria of diabetes have been constantly evolving. Both type 1 and type 2 Diabetes mellitus (DM) are diagnosed based on the plasma glucose criteria, either the fasting plasma glucose (FPG) levels or the 2-h plasma post-prandial glucose (2-h PPG) levels during a 75-g oral glucose tolerance test (OGTT), or the newer glycosylated haemoglobin (HbA1c) criteria which reflects the average plasma glucose concentration over the previous 8–12 weeks.[12] The International Expert Committee Report recommend a cut-point of ≥6.5% for HbA1c for diagnosing diabetes as an alternative to fasting plasma glucose (FPG ≥7.0 mmol/L).[3] HbA1c testing has some substantial advantages over FPG and OGTT, such as convenience, pre-analytical stability, and less day-to-day fluctuations due to stress and illness.[3] Additionally, HbA1c has been recognized as marker to assess secondary vascular complications due to metabolic derailments in susceptible individuals.[245] However, given ethnic differences in sensitivity and specificity of HbA1c population-specific cut-offs might be necessary.[67] Moreover, measuring HbA1c is expensive as compared to FPG assessments and standardization of measurement techniques and laboratories are poorly practiced across the country.[8] Also, in several countries including India, HbA1c demonstrated inadequate predictive accuracy in the diagnosis of diabetes, there is no consensus on a suitable cut-off point of HbA1c for diagnosis of diabetes in this high-risk population.[9] In lieu of this, the panel expressed concerns on using HbA1c as sole criteria for diagnosis of diabetes particularly in resource constraint settings. Therefore, a combination of HbA1cand FPG would improve the identification of individuals with diabetes mellitus and prediabetes in limited resource settings like India. CONSIDERATIONS The decision about setting diagnostic thresholds values was based on the cost-effective strategies for diagnosing diabetes that were reviewed in Indian context. RATIONALE AND EVIDENCE Glycosylated haemoglobin cut off for diagnosis of diabetes in Indian patients The RSSDI expert panel suggests [WHITE SMALL SQUAREHbA1c ≥6.5% as optimal level for diagnosis of diabetes in Indian patients [WHITE SMALL SQUAREHbA1c cannot be used as 'sole' measurement for diagnosis of diabetes in Indian settings. These recommendations are based on the Indian evidences A recent study conducted in Singapore residents of Chinese, Malay and Indian race to assess the performance of HbA1c as a screening test in Asian populations suggested that HbA1c is an appropriate alternative to FPG as a first-step screening test, and a combination of HbA1c with a cut-off of ≥6.1% and FPG level ≥100 mg/dL would improve detection in patients with diabetes.[6] A study to assess the diagnostic accuracy and optimal HbA1c cutoffs for diabetes and prediabetes among high-risk south Indians suggested that HbA1c ≥6.5% can be defined as a cut-off for diabetes and HbA1c ≥5.9% is optimal for prediabetes diagnosis and value <5.6% excludes prediabetes/diabetes status.[8] Data from a community based randomized cross sectional study in urban Chandigarh suggest that HbA1c cut point of 6.5% has optimal specificity of 88%, while cut off point of 7.0% has sensitivity of 92% for diagnosis of diabetes.[10] The results of the Chennai Urban Rural Epidemiology Study (CURES) demonstrated 88.0% sensitivity and 87.9% specificity for detection of diabetes when HbA1c cut off point is 6.1% (based on 2-h post load plasma glucose) and 93.3% sensitivity and 92.3% specificity when HbA1c cut off point is 6.4% (when diabetes was defined as FPG ≥7.0 mmol/l).[11] However, panel emphasized that HbA1c can be used in settings where an appropriate standardized method is available. IMPLEMENTATION Individuals should be educated on the advantages of early diagnosis and should be encouraged to participate in community screening programs for diagnosis. PREVENTION RECOMMENDATIONSTable: No title available.Table: No title available.BACKGROUND Chronic hyperglycaemia is associated with significantly higher risk of developing diabetes related micro-and macrovascular complications. Early detection of diabetes/prediabetes through screening increases the likelihood of identifying asymptomatic individuals and provides adequate treatment to reduce the burden of diabetes and its complications. Through a computer simulated model on the data from the Anglo-Danish-Dutch study of intensive treatment in people with screen-detected diabetes in primary care (ADDITION-Europe), Herman et al. have demonstrated that the absolute risk reduction (ARR) and relative risk reduction (RRR) for cardiovascular (CV) outcomes are substantially higher at 5 years with early screening and diagnosis of diabetes when compared to 3 years (ARR: 3.3%; RRR: 29%) or 6 years of delay (ARR: 4.9%; RRR: 38%).[12] Adopting a targeted approach and utilizing low-cost tools with meticulous planning and judicious allocation of resources can make screening cost-effective even in resource-constrained settings like India.[13] Furthermore, in a systematic review and meta-analysis, screening for type 2 DM (T2DM) and prediabetes has been found to be cost-effective when initiated at around 45–50 years of age with repeated testing every 5 years.[14] 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 PG in the 75-g OGTT: 140-199 mg/dL) or IFG (FPG: 100-125 mg/dL). It is a state of intermediate hyperglycaemia with increased risk of developing diabetes and associated CV complications and therefore early detection and treatment of 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 ADA recommends screening for prediabetes and T2DM through informal assessment of risk factors or with an assessment tool.[1] To prevent the progression of pre-diabetes to T2DM, ADA recommends an intensive behavioural lifestyle intervention (BLI) programme (eg, medical nutrition therapy (MNT) and physical activity) in susceptible individuals.[15] Based on the Indian Council of Medical Research-INdiaDIABetes (ICMR-INDIAB) study conducted in 15 states, the overall prevalence of diabetes and prediabetes was 7.3% (95% CI: 7.0, 7.5) and 10.3% (10.0, 10.6), respectively.[16] Another study conducted among residents of urban areas of east Delhi-The Delhi Urban Diabetes Survey (DUDS) demonstrated a strikingly high prevalence of diabetes (18.3%: known, 10.8%; newly detected, 7.5%) and prediabetes (21% [WHO criteria], 39.5% [ADA criteria]).[17] Given the high prevalence rates of prediabetes in our country, the RSSDI panel holds the opinion that including screening and management aspects of prediabetes is logical and will provide an important opportunity for prevention of diabetes in India. CONSIDERATIONS The decision about conducting a screening program should be based on the following local factors that 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, fast conversion rates from population 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. RATIONALE AND EVIDENCE Opportunistic screening The panel suggests that screening should be opportunistic but not community-based as they are less effective outside health care setting and poorly targeted, i. e., it may fail to identify individuals who are at risk. In a cross-sectional study on 215 participants in a tertiary care hospital in Haryana, opportunistic screening showed that for every seven patients with known diabetes, there are four undiagnosed diabetes patients.[18] In the ICMR-INDIAB study, the ratio of known-to-unknown diabetes was at least 1:1, with rural areas being worse than urban.[16] Opportunistic screening is more cost-effective with better feasibility within the health care system while minimizing the danger of medicalization of a situation. Furthermore, patients diagnosed through this screening have good prognosis over those diagnosed by clinical onset of symptoms.[19] Risk assessment questionnaire There are two risks cores specific for Indians developed by Madras Diabetes Research Foundation (MDRF) and by Ramachandran et al.[20] [Annexures 1 and 2]. Both risk scores are validated and are being used widely in our country. The MDRF-Indian Diabetes Risk Score (IDRS) tool has been found to be useful for identifying undiagnosed patients with diabetes in India and could make screening programs more cost-effective.[21] It is also used in several national programs for prevention of not only diabetes but also cardiometabolic diseases such as stroke. Also its applicability in identifying prevalence of diabetes-related complications such as CAD, peripheral vascular disease (PVD), and neuropathy among T2DM patients has been found to be successful.[22] Risk scores by Ramachandran et al. is simple with few risk variables listed and can be applied at any worksite by a paramedical personnel and help identification of the high risk group by the presence of a minimum of 3 or more of the risk variables used in the risk score.[23] Random plasma glucose level The panel endorse the IDF recommendation on the need to measure FPG and perform OGTT based on random plasma glucose levels which are associated with the development of diabetes (2-h PG ≥200 mg/dL) or prediabetes (2-h PG ≥140 to <200 mg/dL).[24] According to IDF guidelines, FPG values ≤100 mg/dL are considered normal and FBG >100 mg/dL is considered to be at risk of developing diabetes. Further, individuals with FPG between 100-125 mg/dL have IFG, suggesting an increased risk of developing T2DM. Confirming the FPG levels ≥126 mg/dL by repeating tests on another day, confirm diabetes.[25] In a cross-sectional study on 13,792 non-fasting National Health and Nutrition Examination Surveys (NHANES) in participants without diagnosed diabetes, random blood sugar level of ≥100 mg/dL was strongly associated with undiagnosed diabetes.[26] Prediction of diabetes carried out on the basis of this data showed that random blood glucose ≥100 mg/dL was 81.6% (95% CI: 74.9%, 88.4%) sensitive and 78% (95% CI: 76.6%, 79.5%) specific to detect undiagnosed diabetes, which is better than current screening guidelines.[27] Evidence from community-based opportunistic screening in India suggests that random capillary blood glucose level of ≥110 mg/dL can be used to identify those individuals who should undergo definitive testing for diabetes or prediabetes.[28] In patients with no history of diabetes or prediabetes, random blood glucose screening is effective in promoting additional screening among high-risk age groups and encourages patients to make lifestyle changes.[29] The panel suggest that although the present criteria of IFG (100-125 mg/dL) may be sensitive and has lesser variability, measuring 2-h PG levels may give more accuracy and confidence in targeting this population for prevention strategies. Glycosylated haemoglobin as criteria for screening A meta-analysis of 49 studies involving patients aged ≥18 years reported that HbA1c as a screening test for prediabetes has lesser sensitivity (49%) and specificity (79%).[30] Moreover, the use of ADA recommended HbA1c threshold value of 6.5% for diagnosis of diabetes may result in significant under diagnosis.[31] The predictive value of HbA1c for T2DM depends on various factors such as ethnicity, age, and presence of iron deficiency anaemia (IDA).[32333435] In a cohort study on individuals from Swedish and Middle-East ancestry, HbA1 ≥48 mmol/mol had a predictive sensitivity of 31% and 25%, respectively, for T2DM.[34] Furthermore, HbA1c values ≥42 and ≥39 mmol/mol as predictors for prediabetes were associated with a sensitivity of 15% and 34% in individuals of Swedish and 17% and 36% in individuals of Middle-East ancestry. Similarly, a systematic review and meta-analysis of 12 studies including 49,238 individuals without T2DM reveal that HbA1c values are higher in Blacks (0.26% (2.8 mmol/mol), p <0.001), Asians (0.24% (2.6 mmol/mol), p <0.001), and Latinos (0.08% (0.9 mmol/mol); p <0.001) when compared to Whites.[33] Moreover, significantly high HbA1c levels are observed in patients with IDA when compared to healthy subjects (5.51±0.696 vs 4.85±0.461%, p <0.001) and HbA1c levels decline significantly after treatment with iron supplements in IDA subjects (5.51±0.696 before treatment vs 5.044±0.603 post-treatment; p <0.001).[35] The panel recommends the use of HbA1c as sole criteria for screening of diabetes/prediabetes would be inappropriate in most settings in India, at this time. However, HbA1c may be utilized for screening if it is being done from a laboratory known to be well-equipped with external quality assurance.[36] The panel expresses concerns of high prevalence of anaemia and high prevalence of haemoglobinpathies in certain regions/populations particularly from the North East as these can have significant impact when HbA1c is used as diagnostic test for screening. Diagnosis of prediabetes The panel endorses the ADA criteria for diagnosis of prediabetes for Indian context [Table 1]:[1] Table 1: Glycaemic values for Indian patients with type 2 diabetes mellitusPregnancy as a critical target for diabetes prevention strategies Gestational diabetes mellitus (GDM) is a known risk factor for T2DM. Women with GDM have a 7-fold higher risk of developing T2DM and are at a higher risk of developing metabolic syndrome and CVD.[3738] Also children of GDM mothers are at higher risk of development of T2DM later in life compared with non-GDM mothers.[39] Given the high prevalence of GDM in Indian women, early detection and effective treatment can prevent all adverse outcomes of pregnancy and result in a normal and healthy postpartum course for both mother and baby.[40] Children and adolescents: Screening strategies Screening studies in obese adolescents have reported a prevalence of 0.4% up to 1% of type 2 diabetes mellitus in obese children ≥12 years.[41] Overweight (BMI >90 percentile) or obese children (BMI >99.5 percentile) with familial history of T2DM, children from a predisposed race/ethnicity such as Asian, American Indian, etc., with associated risk factors such as IR, dyslipidemia, polycystic ovarian syndrome must be screened periodically. Consistent with the recommendations for screening in adults, children at substantial risk for the development of T2DM should also be tested. The ADA recommends screening in high risk overweight children and adolescents at onset of puberty. The screening must be performed every 2 years from diagnosis using fasting glucose or OGTT. Rescreening The panel emphasize on striking balance between cost of screening and cost of treating complications. On the basis of expert opinion of the panel, general population should be evaluated for the risk of diabetes by their health care provider on annual basis beginning at age 30. Yearly or more frequent testing should be considered in individuals if the initial screen test results are in the prediabetes range or present with one or more risk factors that may predispose to development of diabetes. The panel opine that screening programs should be linked with health care system and ongoing national prevention programs that will facilitate effective and easy identification of people at high-risk of developing diabetes and its complications. Paramedical personnel Paramedical personnel play a key role as facilitators in imparting basic self-management skills to patients with diabetes and those at risk. They can be actively involved in implementing diet and lifestyle changes, behavioural changes, weight management, pre-pregnancy counselling, and other preventive education. Nurses or other trained workers in primary care and hospital outpatient settings can: [WHITE SMALL SQUAREHelp in identification of individuals at risk of diabetes [WHITE SMALL SQUAREHelp in recognition of symptoms of diabetes, hypoglycaemia, and ketosis [WHITE SMALL SQUAREHelp in timely referral of these cases. Nurses or nurse educators in secondary and tertiary care settings can: [WHITE SMALL SQUAREPerform all the above activities [WHITE SMALL SQUAREHelp in prevention and treatment of hypoglycaemia [WHITE SMALL SQUAREHelp in problems with insulin use. EVIDENCE 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.[4243] The reason for this difference has been attributed to the "Asian Indian phenotype" characterized by low BMI, higher body fat, visceral fat and WC; lower skeletal muscle mass and profoundly higher rates of IR.[4445] The 10-year follow-up data of the CURES that assessed incident rates of dysglycaemia in Asian Indians are now available.[46] 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.[47] Moreover, in case of 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.[48] 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 were identified as 8.3% and 6.3% respectively.[49] 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.[50] Predictors of progression to impaired glycaemia were advancing age, family history of diabetes, 2-h PPG, HbA1c, low density lipoprotein (LDL) and HDL, and physical inactivity. Despite the escalating burden, the current evidence on the prevention of T2DM and its complications in India is scarce. 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.[51] 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.[52] Following section covers evidence from Indian studies on various strategies that are helpful in detecting and minimizing the risk of development of diabetes and its associated complications. [WHITE SMALL SQUARESimplified tools for detection of diabetes such as IDRS developed by MDRF and Diabetes Risk Score for Asian Indians devised by Prof. A. Ramachandran are found to be useful for identifying undiagnosed patients with diabetes in India. Use of these tools could make screening programs more cost-effective.[2021] Studies from different regions of India including Jammu, Kashmir, Chennai, Haryana, Delhi, Jabalpur, and Kerala estimated the utility of in identifying risk for DM and prediabetes in Indian population and found significant between IDRS and DM patients to be tool to screen and the of undiagnosed in [WHITE SMALL is also found by that identifying the presence of risk factors could be used as a simple measure of identifying people at high risk of [WHITE SMALL panel suggests that individuals with diabetes or at risk of developing diabetes should be on lifestyle and implementing strategies on and weight to prevent the risk of progression and complications of [WHITE SMALL studies have that lifestyle intervention could prevent the progression to T2DM by about Evidence from suggests that initial lifestyle are and can significantly reduce the of diabetes in Asian Indians with IGT or with The evidence from the program showed that in a to lifestyle is an effective method for or diabetes in with prediabetes, even in a the 3 years of the was (95% CI: in intervention participants compared with The by prediabetes type p and was in patients aged years, or [WHITE SMALL patients in is such as or may be as they lesser compared to other Furthermore, lifestyle intervention with diet and in those with IGT can significantly the of diabetes and its while for up to [WHITE SMALL studies have reported an between low levels of and increased risk for T2DM, and a few clinical studies that could improve the function of which However, in the recent study, for a years not significantly prevent T2DM development in a high-risk [WHITE SMALL systematic review and meta-analysis of identified that lifestyle intervention risk of progression to diabetes by 36% over 6 to 6 years which to by the of follow-up results of the were Another systematic review and meta-analysis showed that physical in prediabetes subjects oral glucose FPG and HbA1c and and body that physical and the progression of disease and the morbidity and associated with T2DM. has been to metabolic in weight and insulin while or of was associated with increased risk of results were observed in a systematic review and meta-analysis of which that the relative risks for T2DM were (95% CI: for among individuals who and for of among individuals who when compared to [WHITE SMALL based on and are found to be effective in the risk of developing diabetes and its and also in of individuals with prediabetes and was found to be an and most effective alternative to and and lifestyle in high-risk studies have the advantages of using strategies in of prevention of The has recommended the use of such strategies for large [WHITE SMALL such as and were found to have role in prevention of diabetes. Furthermore, of whole and and such as and are associated with lower risk of developing [WHITE SMALL from the CURES and and diabetes suggests that awareness and regarding diabetes is inadequate among patients in India and of programs at level can improve the awareness on diabetes and its associated Moreover, mass awareness and screening programs through community were found to prevent and diabetes and its complications such as [WHITE SMALL randomized study of conducted in people with prediabetes demonstrated a significant reduction in and and showed [WHITE SMALL the role of and in the prevention of diabetes is being evaluated in the Indian prevention of Diabetes Study by IMPLEMENTATION A and decision should be about or not to endorse a screening the decision is in of screening, this should be by local and guidelines, and and 1: (MNT) AND RECOMMENDATIONSTable: No title available.Table: No title available.BACKGROUND diet and sedentary lifestyle have been identified as risk factors in T2DM. and of that high of and have the local in with increasing physical these adverse have been associated with on the onset and progression of T2DM in is a systematic approach to intake in to metabolic and treatment outcomes in T2DM. and recommendations from a under the of the clinical for T2DM from the American of and IDF the of in the management of T2DM as a therapy and provide recommendations for day-to-day is a lifestyle that is and of in India is to its and of high of including with sugar or are to the standard Indian diet and have escalating the of diet as a of in India should and factors as these have a on the of by the of medical nutrition therapy in prevention and management and of diet and have been associated with lower rates of incident diabetes in Indian men with impaired glucose health programs and of model in rural and urban populations from and North of India have in and in several including BMI, fasting blood glucose and A Diabetes Program the risk of diabetes by (95% CI: in obese Asian Indian with any of These studies including few involving Indians with risk factors for diabetes reported of such as high or of with whole and increased intake of and The lifestyle intervention the of diet and reduce intake of such as and high on and