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 Table of Contents  
Year : 2021  |  Volume : 12  |  Issue : 4  |  Page : 424-433

An expert opinion on the management of type 2 diabetes mellitus in children and adolescents

1 Department of Endocrinology, Pandit Bhagwat Dayal Sharma Postgraduate Institute of Medical Sciences, Medical Road, Rohtak, Haryana 124001, India
2 Institute of Endocrinology Diabetes and Metabolism, Max Super Specialty Hospital, South Block, 2, Press Enclave Road, Saket, New Delhi 110017, India
3 Metabolic and Critical Care Medicine, Department of Medicine, SLN Medical College, Pujariput, Koraput, Odisha 764020, India
4 King George Hospital, Andhra Medical College, Vishakhapatnam, Andhra Pradesh, India
5 ACODE and Sugar Clinics, Apollo Hospitals, Bhubaneswar, Odisha, India; Hitech Medical College and Hospital, Hi-Tech Hospital Road, Pandra, Rasulgarh, Bhubaneswar, Odisha 751025, India

Date of Submission03-Jun-2021
Date of Decision27-Jun-2021
Date of Acceptance13-Aug-2021
Date of Web Publication12-Jan-2022

Correspondence Address:
Dr. Sambit Das
ACODE and Sugar Clinics, Apollo Hospitals, Bhubaneswar, Odisha.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jod.jod_71_21

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Type 2 diabetes mellitus (T2DM) is an emerging epidemic among children and adolescents. There is a lack of comprehensive guidance to clinicians for the management of T2DM in this patient population. An expert panel of diabetes specialists from India reviewed the available literature, discussed, and proposed six recommendations on the identification of risk factors leading to the development of T2DM, diagnosis of T2DM, and non-pharmacological and pharmacological management of T2DM in children and adolescents. According to these recommendations, the most common risk factors leading to T2DM in children are obesity, metabolic syndrome, insulin resistance, family history, puberty, and genetic abnormalities. Diagnosis of T2DM in children and adolescents should be based on plasma glucose levels, with recommendation to test glycated hemoglobin levels quarterly. Lifestyle modifications may help in improving outcomes. Among pharmacological treatments, insulin and metformin are currently the approved first-line therapies and liraglutide is recommended if glycemic targets are no longer met with metformin or insulins. Early identification of risk factors, along with early diagnosis and initiation of insulin therapy with lifestyle modifications, may help in delaying the chronic complications associated with T2DM in children and adolescents.

Keywords: Adolescents, children, India, insulin, type 2 diabetes mellitus

How to cite this article:
Rajput R, Jha S, Panda JK, Subrahmanyam AK, Das S. An expert opinion on the management of type 2 diabetes mellitus in children and adolescents. J Diabetol 2021;12:424-33

How to cite this URL:
Rajput R, Jha S, Panda JK, Subrahmanyam AK, Das S. An expert opinion on the management of type 2 diabetes mellitus in children and adolescents. J Diabetol [serial online] 2021 [cited 2022 Aug 13];12:424-33. Available from: https://www.journalofdiabetology.org/text.asp?2021/12/4/424/335597

  Introduction Top

Early onset type 2 diabetes mellitus (T2DM) is an alarming health concern observed among children, adolescents, and young adults, with unique challenges in research and clinical care. The incidence and prevalence of T2DM in children and adolescents are increasing globally, echoing the epidemic of childhood obesity.[1]

It is estimated that a four-fold increase in the burden of T2DM in the US population aged <20 years will be seen by year 2050. Based on this projection, 178% increase in the prevalence rate from 0.27/1000 to 0.75/1000 is expected.[2] In India, the risk factors contributing to the development of early onset T2DM include generalized obesity, abdominal obesity, hypertriglyceridemia, and family history of T2DM.[3] Furthermore, a high prevalence of dyslipidemia has been noted in this population and has been associated with an increased risk of development of microvascular complications.[4],[5]

New strategies should be implemented on working with children suffering from diabetes and their families, in order to make changes to their lifestyle or to cope with societal aspect of living with a long-term condition.[6]

Despite T2DM being an emerging epidemic in the pediatric population, there is dearth of data pertaining to this condition in children and adolescents when compared with adults.[6] However, a population-based study conducted in south India reported the prevalence of dysglycemia among children and adolescents to be 3.7%.[7] Furthermore, currently, there is a lack of comprehensive evidence-based guidelines on the therapeutic management of T2DM in the pediatric population. Hence, the objective of the current review is to guide the clinicians on the management of T2DM in children as well as adolescents to ensure optimal clinical outcomes.

  Materials and Methods Top

A panel of experts in the field of diabetes and endocrinology from India convened to discuss on the management of T2DM in children and adolescents. The expert panel provided recommendations on the following topics [Figure 1]:
Figure 1: Topics for the expert opinion on the diagnosis and management of T2DM in children and adolescents

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  1. Risk factors leading to T2DM in children and adolescents;

  2. Diagnosis of T2DM in children and adolescents;

  3. Non-pharmacological management of children and adolescents with T2DM;

  4. Pharmacological treatment of T2DM in children and adolescents.

Each of the above topics was presented and evaluated based on the views from the published literature and established guidelines from the American Diabetes Association (ADA), American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE), the National Institute for Health and Care Excellence (NICE), Indian Academy of Pediatrics (IAP), and the International Society for Pediatric and Adolescent Diabetes (ISPAD). These evaluations were then factored into the national context based on the opinion from the expert panel and the current clinical and therapeutic practices followed in India. The evaluations were then discussed within the expert committee, and the final consensus-based recommendations and key takeaways were collectively documented in a clear and concise manner.

  Pathophysiology and Risk Factors for T2DM in Children and Adolescents Top

Literature views

The risk factors that contribute to the development of insulin resistance in children and adolescents with T2DM include obesity/sedentary lifestyle, race/ethnicity, family history, puberty, polycystic ovarian syndrome, and intra-uterine factors.[8] Obesity/sedentary lifestyle is a major cause of insulin resistance in children and adolescents. Adipose tissue expanding in the obese state synthesizes and secretes metabolites and signaling proteins, such as adiponectin, leptin, and tumor necrosis factor-α. These factors are responsible for the alteration of insulin secretion and sensitivity in the body and hence cause insulin resistance under experimental and clinical conditions.[9],[10] Race and ethnicity are other factors that may influence insulin sensitivity in childhood.[11],[12] Parental history of T2DM leads to a greater chance of offspring developing insulin resistance.[13] Growth hormone/insulin-like growth factor-1 (IGF-I) axis is an important contributor to insulin resistance during puberty.[14] Polycystic ovary syndrome (PCOS) associated with insulin resistance is common in youths with T2DM. Diabetes during pregnancy is also a complicated risk factor that affects both mother and the newborn.[15] The clinical presentation of T2DM differs between adults and children/adolescents.[16],[17],[18] Acanthosis nigricans (AN) was once considered a rare paraneoplastic dermatosis but is now frequently observed in obese adolescents. Current understanding suggests that it is associated with insulin resistance and has a unique role in secondary prevention.[19]

The chronic complications associated with T2DM include pancreatic β-cell dysfunction, microalbuminuria, hypertension, dyslipidemia, retinopathy, and depressive symptoms. The natural history of early onset T2DM and its associated complications differ from that of adult-onset T2DM.[7] A slower decline in β-cell function has been noted among adults (7–11% per year) than in youths (20–35% per year).[20],[21] Microalbuminuria and hypertension are more common in adults when compared with the younger population. In a prospective study, 38% of adults with T2DM developed microalbuminuria.[22] In another study, 67% of adults developed hypertension.[23] A study conducted among youths showed that 6.3% and 11.6% of the younger population had microalbuminuria and hypertension at baseline, respectively, which increased to three-fold in 4 years (16.6% and 33.8%).[24] Dyslipidemia is another complication more commonly seen among adults when compared with the pediatric population with T2DM. In a study conducted among adults, ~50% of adults showed elevated levels of triglycerides (≥150 mg/dL),[25] compared with 23.3% in youths.[26] Although the prevalence of retinopathy in the pediatric population has been noted to be about 13.7%,[27] it is noted to be 12.6% among adults.[28] Prevalence of depressive symptoms in the pediatric population has been reported to be 14.8%,[29] whereas the same was 17.6% in case of adults.[30] Furthermore, when therapeutic response to metformin monotherapy was assessed, poor glycemic control was observed in approximately 50% of adolescents, whereas better glycemic control was observed among the adult population.[31] Henceforth, a serious thought needs to be given for the proper management of complications associated with T2DM.

Guideline views

As per the position statement by the ADA, non-modifiable risk factors for youth-onset T2DM include first-or-second degree family history of T2DM, maternal gestational diabetes mellitus or obesity, race/ethnicity, and physiologic insulin resistance of puberty. Furthermore, the major modifiable risk factors include obesity/sedentary lifestyle, low physical activity, improper dietary patterns and consumption of junk foods, chronic stress/depression, and sleep disorders. Obesity and prediabetes have been implicated as risk factors for the development of T2DM, as per the 2020 AACE/ACE guideline.[32] According to the IAP, insulin resistance is that waist circumference, a surrogate marker for visceral fat, has been shown to be strongly predictive of cardiovascular risk factors in children.[33] ISPAD 2018 recommends testing to identify clinical cases of diabetes in children and adolescents, who have risk factors for diabetes.[1] Consistent with the views of the ISPAD guidelines, risk factors such as obesity; T2DM history in first- or second-degree relative; African, Arab, Asian, Hispanic, Indigenous, or South Asian descent; impaired glucose tolerance; PCOS; exposure to diabetes in utero; AN; hypertension and dyslipidemia; and non-alcoholic fatty liver disease can lead to the development of T2DM, as per the 2018 CJD guidelines.[34]

  Diagnosis of T2DM in Children and Adolescents Top

Literature views

A detailed history and physical examination generally provides clues for the diagnosis of T2DM in children and adolescents. Compared with adults, who are often asymptomatic at the time of diagnosis, children and adolescents with diabetes commonly show symptoms of hyperglycemia. Children and adolescents with T2DM are generally overweight, with markers of insulin resistance.[35] Other clues include presence of irregular menstrual period and PCOS in girls during adolescence and a positive family history of diabetes.[36] In addition to physical examination and detailed history, laboratory investigations may be necessary for confirmation of the diagnosis and identifying the type of diabetes.

The clinical features of pediatric patients with T2DM include overweight or obesity, weight gain, polydipsia, polyphagia, polyuria, family history of T2DM, increased production of insulin, signs of insulin resistance, and absence of diabetes-related autoantibodies.[36] In this context, it is pertinent to mention that infants who develop diabetes before 6 months of age are often misclassified as having T1DM.[37] Maturity-onset diabetes of the young (MODY) is an uncommon form of diabetes in children.[17] Diagnostic criteria of MODY include early onset of diabetes (<25 years of age)[37],[38]; insulin independence for at least 5 years from diagnosis[39]; very rare occurrence of ketoacidosis;[17] autosomal-dominant inheritance;[37],[38] and absence of typical features such as obesity or diabetes-related autoantibodies. Heterozygous mutations in the GCK, HNF1A, and HNF4A genes are very common among patients with MODY, and, hence, genetic testing in these patients is essential.[37]

Apart from clinical presentation and course of disease in most patients, certain tests such as fasting insulin or C-peptide determination and β-cell autoantibody measurements may be beneficial in distinguishing diabetes.[7],[16] Patients with T2DM show elevated levels of C-peptide and fasting insulin.[7],[16] In case of T1DM, specific autoantibodies to insulin, GAD-II, or tyrosine phosphatases insulin antibodies (IA)-2 and IA-2b are seen at presentation in most patients (85–98%).[8],[17]

Guideline views

According to the ICMR Guidelines for Management of Type 2 Diabetes 2018,[38] children and adolescents aged 18 years and below should be screened for diabetes if they are overweight (weight >120% of ideal body weight) and have any of the following risk factors:

  • Family history of type 2 diabetes in first-degree relatives;

  • Signs of insulin resistance (ANs);

  • Hypertension;

  • Dyslipidemia;

  • PCOS.

  • According to the 2018 ISPAD guidelines, diagnosis of T2DM is confirmed if an individual has fasting plasma glucose (FPG)≥126 mg/dL (7.0 mmol/L); 2-h plasma glucose during a 75-g oral glucose tolerance test (OGTT) of ≥200 mg/dL (11.1 mmol/L); random plasma glucose ≥200 mg/dL (11.1 mmol/L); unexplained weight loss; polyuria, polydipsia, and nocturia; and glycated hemoglobin (HbA1c) ≥6.5% (≥48 mmol/mol).[1],[40] According to the position statement by the ADA, risk-based screening for T2DM and/or prediabetes should be considered in children and adolescents who are overweight or obese and have additional risk factors for diabetes. In case of normal test results, repeat screening may be done after 3 years; the frequency may be increased in case of a noted increase in body mass index. The diagnosis of prediabetes is confirmed if HbA1c is 5.7–6.5%, FPG is 100–126 mg/dL (5.6–7.0 mmol/L), and 2-h plasma glucose is 140–200 mg/dL (7.8–11.1 mmol/L). The diagnosis of T2DM is confirmed when HbA1c is ≥6.5%, FPG≥126 mg/dL (7.0 mmol/L), 2-h plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT, and random plasma glucose >200 mg/dL (11.1 mmol/L) with classic symptoms of hyperglycemia or hyperglycemic crisis. As per the 2015 NICE guideline, T2DM is diagnosed when HbA1c is ≥6.5% (≥48 mmol/mol). It is recommended to measure HbA1c levels every 3 months in children and young people with T2DM.[31] Lastly, according to the 2018 CJA guideline, FPG≥7.0 mmol/L and HbA1c≥6.0% help in identifying and diagnosing children with T2DM.[32]

      Non-pharmacological Management of T2DM in Children and Adolescents Top

    The management of diabetes in children and adolescents causes a considerable amount of burden on the patients as well as the caregivers. Factors such as normal growth and development; variable exercise and eating patterns; fear of hypoglycemia; dependence on parents or other caregivers for injections and blood tests; difficulties assuring optimal diabetes care in schools; and the physiological and psychological burden of adolescence bring about immense stress, anxiety, and fear within the family.[41],[42]

    In general, the management of diabetes has always come with a challenge, as it involves a major change in lifestyle. This is particularly challenging for adolescents, as they face certain hormonal changes during this time, which further complicates the metabolic control.

    Literature views

    Several barriers to the successful treatment of T2DM in children and adolescents have been identified, including: (1) prevalence of high-risk lifestyle in family members (98%), (2) lack of immediate risk to life leading to reduced motivation in patients (89%), (3) lack of guidelines regarding ideal treatment, (4) prevalence of behavioral and/or psychiatric disorders (71%), and (5) language/cultural barriers.[43] Apart from these barriers, certain psychological challenges have also been noted in children and adolescents and their families [Table 1]. In addition to poor glycemic control, a higher rate of psychological complications, especially depression and anxiety, has been noted in youths with T2DM and obesity, particularly girls with obesity, relative to their healthy weight peers.[44],[45] Furthermore, the health-related quality of life of children and adolescents with T2DM has been found to be lower when compared with T1DM children (QoL scores: T1DM: 82.2 vs. T2DM: 76.7).[46] Recommendations for research in lifestyle management are as included in [Table 2].
    Table 1: Psychological challenges noted in children and their families toward successful management of T2DM

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    Table 2: Recommendations for research in lifestyle management

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    Guideline views

    According to the position statement by the ADA, youths with T2DM and their families should receive comprehensive diabetes self-management education/support by healthcare providers. They should also be provided with appropriate lifestyle programs with an encouragement to perform at least 30–60 min of moderate-to-vigorous physical activity at least 5 days per week and strength training on at least 3 days per week. Healthcare providers should guide youths on following healthy eating patterns. Providers should assess social context, including potential food insecurity, housing stability, as well as financial barriers, and apply that information in order to make treatment decisions. Finally, assessment of diabetes distress and mental/behavioral health in youth with T2DM should be performed using patient-appropriate standardized and validated tools. The multidisciplinary diabetes-care team should ensure regular contact with children and their families; in case if visits are being missed or infrequent, the patients or their families should be contacted via telephone or email. Furthermore, developmental progress should be assessed routinely.[48] The IAP guidelines suggest some lifestyle approaches to prevent excess weight gain and obesity that can be achieved by counseling about healthy eating patterns, increased physical activity levels, and decreased sedentary behavior.[33]

      Pharmacological Treatment Options for Children with T2DM Top

    Literature views

    Poor glycemic control leads to serious microvascular (retinopathy, glaucoma, cataracts, end-stage renal disease) and macrovascular (stroke, angina, chronic heart disease) complications and early death. Furthermore, reduced life expectancy has been reported in individuals with T2DM. A 2010 report by Diabetes UK claims that T2DM reduces life expectancy by approximately 10 years.[49]

    Pharmacological treatments, such as basal and prandial insulin, have offered several benefits in children and adolescents with T2DM. Compared with neutral protamine Hagedorn, basal insulin exhibits a more predictable insulin effect with less day-to-day variation, besides a decreased rate of hypoglycemia and greater treatment adherence. Similarly, prandial insulin can be administered shortly after meals. It not only reduces postprandial hyperglycemia, but also reduces hyperglycemia that occurs during nighttime. For those infants and toddlers who are reluctant to eat, approved prandial insulin is a good option, as it can be given after food, when required.[32] Regarding oral antidiabetic (OAD) treatment, currently, metformin is the only approved oral therapy for children and adolescents with T2DM in the majority of countries. It is recommended as an initial pharmacological therapy among adolescents with mild hyperglycemia and without ketosis/ketoacidosis or severe hyperglycemia. Before initiating metformin, it is important to (1) assess whether an individual with a new diagnosis has T1DM or T2DM and (2) provide caution in uncertain cases. Comparing the advantages of insulin over metformin, insulin offers a more rapid metabolic control in comparison to metformin; it also provides an improved metabolic control while preserving β-cell function or reversing β-cell damage. Furthermore, the initial use of insulin may lead to a sense of seriousness about the disease among patients.[40] As the prevalence of T2DM in youths is increasing rapidly, treatment options beyond metformin and insulin are necessary. The ADA 2020 guidelines recommend that if glycemic targets are no longer met with metformin (with or without basal insulin), liraglutide (a glucagon-like peptide 1 receptor agonist) therapy should be considered in children 10 years of age or older if they have no past medical history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.[50] The ELLIPSE trial results have shed new hope for expanding the treatment regimen for T2DM in adolescents.[51]

    Substantial gaps in diabetes care have been reported during the transition period between pediatric and adult care. These gaps include (1) challenges with access to a new provider, with less involvement of the family and more responsibilities; (2) loss of parental supervision, higher priorities of work/school, dietary/exercise routine changes, alcohol/smoking/drug exposure; (3) multiple psychosocial issues (depression, anxiety, eating disorder, fear of hypoglycemia); and (4) lost to follow-up (disengagement with health care, emerging complications). It is important that a comprehensive and coordinated plan be made to manage the transition from pediatric to adult diabetes care.[52]

    Guideline views

    Multiple hypoglycemic agents are currently available and approved for use in adults with T2DM; however, for youth-onset T2DM, treatment choices are limited. Th current status of the OADs, DPPs, SGLTs, and insulins approved in the treatment of T2DM in children and adolescents have been presented in [Table 3].[53],[54]
    Table 3: Current status of the pharmacological therapies approved in the treatment of T2DM in children and adolescents[52],[53]

    Click here to view

    According to the 2020 position statement by ADA, in addition to lifestyle therapy, pharmacologic therapy should be initiated at diagnosis. In metabolically stable patients (HbA1c <8.5% and asymptomatic), metformin is the preferred choice if renal function is normal.[50] If the glycemic targets are not achieved on metformin alone, or in case of contraindications or intolerable side-effects to metformin, basal insulin therapy may be initiated. Furthermore, in youths with marked hyperglycemia (≥8.5% and symptomatic), basal insulin should be started while metformin is initiated and titrated. Patients with ketoacidosis should be treated with subcutaneous or intravenous insulin to rapidly correct hyperglycemia and metabolic derangement. If the combination of metformin and basal insulin is ineffective, more intensive approaches of insulin should be initiated. If glycemic targets are no longer met with metformin (with or without basal insulin), liraglutide (a glucagon-like peptide 1 receptor agonist) therapy should be considered in children 10 years of age or older if they have no past medical history or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2.[50]

    In addition to the T2DM management recommendations, the ADA position statement also provides guidance on the management of complications in youth-onset T2DM. In patients at risk of nephropathy, blood pressure should be measured at every visit. It should be optimized to lower the risk of progression of diabetic kidney disease. However, if blood pressure is >95th percentile for age, sex, and height, emphasis should be placed on lifestyle changes to promote weight loss, and antihypertensive therapy may be initiated in case of persistent blood pressure. Urine albumin/creatinine ratio and estimated glomerular filtration rate should be obtained at the time of diagnosis and annually thereafter. Youth with T2DM should be screened for neuropathy by examining the foot and screening of retinopathy by dilated fundoscopy or retinal photography at or soon after diagnosis and every year. Female adolescents with T2DM should be evaluated for PCOS, with laboratory investigations, when indicated.

    According to the ISPAD 2018, if the patient is mildly symptomatic without ketoacidosis, basal insulin should be considered. However, if the target is not attained on basal insulin (up to 1.5 U/kg/day), then prandial therapy should be initiated. If the patient is metabolically stable or has a HbA1c<8.5% and is asymptomatic, metformin is the treatment of choice together with healthy lifestyle changes. If the patient fails to reach target HbA1c of <7.0% (53 mmol/mol) within 4 months on metformin monotherapy, addition of basal insulin should be considered. However, if target is not attained on combination of metformin and basal insulin (up to 1.5 U/kg/day), initiation of prandial insulin should be considered, with titration to reach target HbA1c <7.0% (53 mmol/mol). Furthermore, if the patient is not metabolically stable with HbA1c>8.5% or there are symptoms with ketosis/ketoacidosis, insulin, lifestyle changes, and metformin should be initiated. However, if the patient has ketoacidosis, then metformin should not be started. Transition to metformin can usually be achieved over 2–6 weeks by decreasing the insulin dose 30–50% each time the metformin dose is increased, with a goal of eliminating insulin therapy if this can be achieved without loss of glycemic control.[1]

      Future Therapies Top

    Several therapies are currently under investigation for pediatric patients with T2DM (dulaglutide; colesevelam; exenatide; saxagliptin; exenatide; sitagliptin+metformin XR; sitagliptin; dapagliflozin; albiglutide; canagliflozin; liraglutide; dapagliflozin and saxagliptin; empagliflozin and linagliptin; and alogliptin) [Table 4].[55]
    Table 4: Status of future therapies for use in pediatric patients with T2DM (as on January 2020)[54]

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    The Evaluation of Liraglutide in Pediatrics with Diabetes (ELLIPSE) trial compares liraglutide in combination with metformin versus metformin monotherapy. The key objective was to assess the efficacy and safety of liraglutide in the pediatric population in order to potentially address the unmet need for treatment of children and adolescents with T2DM.

    This was a 26-week, randomized, double-blind study in which eligible patients between 10 and 17 years of age received either subcutaneous liraglutide (up to 1.8 mg per day) or placebo in a 1:1 ratio. This was followed by another 26-week open-label extension period. The key inclusion criteria were a BMI greater than the 85th percentile and a HbA1c level between 7.0% and 11.0% if the patients were being treated with diet and exercise alone or between 6.5% and 11.0% if they were being treated with metformin (with or without insulin). All patients received metformin during the trial. Change from baseline in the HbA1c level after 26 weeks was the primary endpoint of this study, whereas change in the FPG level was the secondary endpoint. Safety was assessed throughout the course of the trial. Of the 135 patients who underwent randomization, 134 received at least one dose of liraglutide (66 patients) or placebo (68 patients). Demographic characteristics were similar in both the treatment groups (mean age, 14.6 years). At 26-week analysis of the primary efficacy endpoint, the mean HbA1c decreased by 0.64% in the liraglutide group, whereas there was a 0.42% increase in the placebo group with an estimated treatment difference of −1.06% (P < 0.001); however this difference increased to −1.30% at the end of 52 weeks of treatment. The FPG level decreased in the liraglutide group at both time points, whereas it increased in the placebo group for the same timepoints.[51]

    Pediatric studies in T2DM have brought about some challenges, such as (1) difficulties in recruiting patients, (2) difficulties in recruiting study sites, and (3) the majority of patients being adolescents are difficult to be retained in clinical studies and have frequently lost to follow-ups.[55] Apart from the challenges, several barriers to participating in these trials have been noted. These include socioeconomic factors such as parents missing work for visits; transportation issues; inadequate compensation; lack of interest in participating by patients and/or their families; restrictive inclusion criteria; and restrictive exclusion criteria due to past or current use of glucose-lowering agents other than metformin therapy.[56],[57]

      Summary Top

    Early development of T2DM is an alarming and important health concern among children and adolescents. Because of a gradual rise in the incidence and prevalence of T2DM in the pediatric population in recent years, it is important to appropriately manage these children, in order to avoid chronic complications and premature death. Hence, new strategies should be implemented to bring about changes in their lifestyle or to cope with societal aspect of living with a long-term condition.

    The key messages highlighted in this article are primarily focussed on optimizing the diagnosis and management of T2DM in children and adolescents. Early initiation of insulin therapy, along with lifestyle changes, helps in delaying the chronic complications associated with T2DM. Furthermore, among the future therapies, SGLT2I and GLP1RA are being evaluated and seem promising, of which liraglutide has been approved and recommended in age greater than 10 years who fail both on metformin and insulins.

    The strength of the current review is that it has been developed with the opinion from the expert panel and the current clinical and therapeutic practices, while drawing recommendations from global guidelines and clinically relevant published literature.

    Financial support and sponsorship

    No funding or medical writing support has been received for this study or publication of this article.

    Conflicts of interest

    There are no conflicts of interest.


    We also acknowledge the consensus expert group members Dr Shanthi, Dr Vamsie Mohan, Dr Achama Mathapan, Dr Prince Sanjeevi Yoganandh, Dr N. Madhu, Dr C. Ambrish, Dr K. Shariff, Dr Madhukar Parikh, Dr Kalyan Das, Dr Anil Chelani, Dr J. Lamba, Dr Supriya Bali, Dr Madhu Pandey, Dr Vinod Kumar Kapil, Dr Rajul Mesvani, Dr Anita Joshi, Dr Sourabh Singh Dudve, Dr Manish Jain, Dr Vimal Garg, Dr Ajoy Biswas, Dr Sudhir Verma, Dr Hiranmoy Pal, Dr Upakul Bora, Dr Tauseef Nabi, Dr A. Rajashekar, Dr Lakhan Das, Dr Sunil Gayad, Dr J. V. Srujan, Dr Thangam, Dr Neeraj Kumar, Dr P. Pramod, Dr Sumora Rai, Dr Monish Gupta, Dr Moomin, Dr Shaibal Chakraborty, Dr Vijaykumar Naik, Dr S. Sengupta, Dr Rajesh Rajput, Dr Sujeet Jha, Dr Sambit Das, Dr Jayanta Panda, Dr K. A. V. Subrahmanyam for their contributions in evolving key message and recommendation. The expert group thanks the organizers of the National Insulin Summit 2018. We would like to thank BioQuest Solutions for providing editorial assistance and APCER Life Sciences Pvt Ltd, India, for submission-related assistance.


    All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. The authors have read and approved the manuscript. The authors believe that the manuscript represents honest work.


    SJ is an Advisory board member for Novo Nordisk. Rest of the authors have no conflict of interest. The details published herein are intended for informational, educational, academic, and/or research purposes and are not intended to substitute for professional medical advice, diagnosis, or treatment.

    Compliance with ethics guidelines

    This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

      References Top

    Zeitler P, Arslanian S, Fu J, Pinhas-Hamiel O, Reinehr T, Tandon N, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Type 2 diabetes mellitus in youth. Pediatr Diabetes 2018;19(Suppl. 27):28-46.  Back to cited text no. 1
    Imperatore G, Boyle JP, Thompson TJ, Case D, Dabelea D, Hamman RF, et al; SEARCH for Diabetes in Youth Study Group. Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: Dynamic modeling of incidence, mortality, and population growth. Diabetes Care 2012;35:2515-20.  Back to cited text no. 2
    Vikram NK, Tandon N, Misra A, Srivastava MC, Pandey RM, Mithal A, et al. Correlates of type 2 diabetes mellitus in children, adolescents and young adults in North India: A multisite collaborative case–control study. Diabet Med 2006;23:293-8.  Back to cited text no. 3
    Amutha A, Unnikrishnan R, Anjana RM, Mohan V. Prepubertal childhood onset type 2 diabetes mellitus: Four case reports. J Assoc Physicians India 2017;65:43-6.  Back to cited text no. 4
    Amutha A, Pradeepa R, Chella KS, Anjana RM, Unnikrishnan R, Mohan V. Lipid profile in childhood- and youth-onset type 2 diabetes and their association with microvascular complications. J Assoc Physicians India 2017;65:42-7.  Back to cited text no. 5
    Alberti G, Zimmet P, Shaw J, Bloomgarden Z, Kaufman F, Silink M; Consensus Workshop Group. Type 2 diabetes in the young: The evolving epidemic: The International Diabetes Federation Consensus Workshop. Diabetes Care 2004;27:1798-811.  Back to cited text no. 6
    Ranjani H, Sonya J, Anjana RM, Mohan V. Prevalence of glucose intolerance among children and adolescents in urban South India (ORANGE-2). Diabetes Technol Ther 2013;15:13-9.  Back to cited text no. 7
    Reinehr T. Type 2 diabetes mellitus in children and adolescents. World J Diabetes 2013;4:270-81.  Back to cited text no. 8
    Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-74.  Back to cited text no. 9
    Roth CL, Reinehr T. Roles of gastrointestinal and adipose tissue peptides in childhood obesity and changes after weight loss due to lifestyle intervention. Arch Pediatr Adolesc Med 2010;164:131-8.  Back to cited text no. 10
    Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA. Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care 2002;25:2081-7.  Back to cited text no. 11
    Hagman E, Reinehr T, Kowalski J, Ekbom A, Marcus C, Holl RW. Impaired fasting glucose prevalence in two nationwide cohorts of obese children and adolescents. Int J Obes (Lond) 2014;38:40-5.  Back to cited text no. 12
    Srinivasan SR, Frontini MG, Berenson GS; Bogalusa Heart Study. Longitudinal changes in risk variables of insulin resistance syndrome from childhood to young adulthood in offspring of parents with type 2 diabetes: The Bogalusa Heart Study. Metabolism 2003;52:443-50; discussion 451-3.  Back to cited text no. 13
    Caprio S, Plewe G, Diamond MP, Simonson DC, Boulware SD, Sherwin RS, et al. Increased insulin secretion in puberty: A compensatory response to reductions in insulin sensitivity. J Pediatr 1989;114:963-7.  Back to cited text no. 14
    Pettitt DJ, Nelson RG, Saad MF, Bennett PH, Knowler WC. Diabetes and obesity in the offspring of Pima Indian Women with diabetes during pregnancy. Diabetes Care 1993;16:310-4.  Back to cited text no. 15
    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010;33(Suppl. 1): S62-9. Available from: https://doi.org/10.2337/dc10-S062. Accessed on: November 5, 2018.  Back to cited text no. 16
    Reinehr T. Clinical presentation of type 2 diabetes mellitus in children and adolescents. Int J Obes (Lond) 2005;29(Suppl. 2):S105-10.  Back to cited text no. 17
    Dabelea D, Rewers A, Stafford JM, Standiford DA, Lawrence JM, Saydah S, et al; SEARCH for Diabetes in Youth Study Group. Trends in the prevalence of ketoacidosis at diabetes diagnosis: The SEARCH for diabetes in youth study. Pediatrics 2014;133:e938-45.  Back to cited text no. 18
    Kahn SE, Lachin JM, Zinman B, Haffner SM, Aftring RP, Paul G, et al; ADOPT Study Group. Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT. Diabetes 2011;60:1552-60.  Back to cited text no. 19
    Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC. UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) group. Diabet Med 1998;15:297-303.  Back to cited text no. 20
    Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR; UKPDS Study Group. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes study 74. Diabetes 2006;55:1832-9.  Back to cited text no. 21
    Centres for Disease Control and Prevention. National Diabetes Fact Sheet. Fast Facts on Diabetes. 2011. Available from: https://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. Accessed on November 5, 2018.  Back to cited text no. 22
    TODAY Study Group. Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: The TODAY clinical trial. Diabetes Care 2013;36:1735-41.  Back to cited text no. 23
    Jacobs MJ, Kleisli T, Pio JR, Malik S, L’Italien GJ, Chen RS, et al. Prevalence and control of dyslipidemia among persons with diabetes in the United States. Diabetes Res Clin Pract 2005;70:263-9.  Back to cited text no. 24
    TODAY Study Group. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes: The TODAY clinical trial. Diabetes Care 2013;36:1758-64.   Back to cited text no. 25
    TODAY Study Group. Retinopathy in youth with type 2 diabetes participating in the TODAY clinical trial. Diabetes Care 2013;36:1772-74.   Back to cited text no. 26
    Diabetes Prevention Program Research Group. The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet Med 2007;24: 137-44.  Back to cited text no. 27
    Anderson BJ, Edelstein S, Abramson NW, Katz LE, Yasuda PM, Lavietes SJ, et al. Depressive symptoms and quality of life in adolescents with type 2 diabetes: Baseline data from the TODAY study. Diabetes Care 2011;34:2205-7.  Back to cited text no. 28
    Ali S, Stone MA, Peters JL, Davies MJ, Khunti K. The prevalence of co-morbid depression in adults with type 2 diabetes: A systematic review and meta-analysis. Diabet Med 2006;23:1165-73.  Back to cited text no. 29
    Zeitler P, Hirst K, Pyle L, Linder B, Copeland K, Arslanian S, et al; TODAY Study Group. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 2012;366:2247-56.  Back to cited text no. 30
    Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2020 Executive Summary. Endocr Pract 2020;26:107-39.  Back to cited text no. 31
    Panagiotopoulos C, Hadjiyannakis S, Henderson M. Type 2 diabetes in children and adolescents. Diabetes Canada Clinical Practice Guidelines Expert Committee. Can J Diabetes 2018;42:S247-54.  Back to cited text no. 32
    Bhatia V; IAP National Task Force for Childhood Prevention of Adult Diseases. IAP National Task Force for childhood prevention of adult diseases: Insulin resistance and type 2 diabetes mellitus in childhood. Indian Pediatr 2004;41:443-57.  Back to cited text no. 33
    Unnikrishnan R, Shah VN, Mohan V. Challenges in diagnosis and management of diabetes in the young. Clin Diabetes Endocrinol 2016;2:18.  Back to cited text no. 34
    Global International Diabetes Federation/International Society for Pediatric and Adolescent Diabetes Guideline for Diabetes in Childhood and Adolescence. 2011. Available from: https://c.ymcdn.com/sites/ispad.site-ym.com/resource/resmgr/Docs/idf-ispad_guidelines_2011_0.pdf. Accessed on: November 5, 2018.  Back to cited text no. 35
    Lawrence JM, Mayer-Davis EJ, Reynolds K, Beyer J, Pettitt DJ, D’Agostino RB, et al. Diabetes in Hispanic American youth: Prevalence, incidence, demographics, and clinical characteristics: The SEARCH for Diabetes in Youth Study. Diabetes Care2009;32(Suppl. 2):S123-32.  Back to cited text no. 36
    Mayer-Davis EJ, Beyer J, Bell RA, Dabelea D, D’Agostino R Jr, Imperatore G, et al; SEARCH for Diabetes in Youth Study Group. Diabetes in African American Youth: Prevalence, incidence, and clinical characteristics: The SEARCH for diabetes in youth study. Diabetes Care 2009;32(Suppl. 2):S112-22.  Back to cited text no. 37
    ICMR guidelines for management of type 2 diabetes 2018, as accessed on 14/07/2021 at ICMR_GuidelinesType2diabetes2018_0.pdf.  Back to cited text no. 38
    Naranjo D, Hood K. Psychological challenges for children living with diabetes. Diabetes Voice 2013;58:38-40.  Back to cited text no. 39
    Cameron FJ, Wherrett DK. Care of diabetes in children and adolescents: Controversies, changes, and consensus. Lancet 2015;385:2096-106.  Back to cited text no. 40
    American Diabetes Association. Executive Summary: Standards of Medical Care in Diabetes. 2014. Diabetes Care 2014;37:S5-13. Available from: http://care.diabetesjournals.org/content/diacare/37/Supplement_1/S5.full.pdf. Accessed on November 5, 2018.  Back to cited text no. 41
    Silverstein J, Klingensmith G, Copeland K, Plotnick L, Kaufman F, Laffel L, et al; American Diabetes Association. Care of children and adolescents with type 1 diabetes: A statement of the American Diabetes Association. Diabetes Care 2005;28:186-212.  Back to cited text no. 42
    American Diabetes Association. Children and adolescents (Chapter 11). Diabetes Care 2016;39(Suppl. 1):S86-93. Available from: https://doi.org/10.2337/dc16-S014. Accessed on: November 5, 2018.  Back to cited text no. 43
    Huynh E, Rand D, McNeill C, Brown S, Senechal M, Wicklow B, et al. Beating diabetes together: A mixed-methods analysis of a feasibility study of intensive lifestyle intervention for youth with type 2 diabetes. Can J Diabetes 2015;39:484-90.  Back to cited text no. 44
    McGavock J, Dart A, Wicklow B. Lifestyle therapy for the treatment of youth with type 2 diabetes. Curr Diab Rep 2015;15:568.  Back to cited text no. 45
    Vander Wal JS, Mitchell ER. Psychological complications of pediatric obesity. Pediatr Clin North Am 2011;58:1393-401.  Back to cited text no. 46
    Pinhas-Hamiel O, Zeitler P. Barriers to the treatment of adolescent type 2 diabetes—A survey of provider perceptions. Pediatr Diabetes 2003;4:24-8.  Back to cited text no. 47
    Tieh P, Dreimane D. Type 2 diabetes mellitus in children and adolescents. Indian J Pediatr 2014;81:165-9.  Back to cited text no. 48
    Delamater AM. Psychological care of children and adolescents with diabetes. Pediatr Diabetes 2009;10(Suppl. 12):175-84.  Back to cited text no. 49
    American Diabetes Association. Children and adolescents (Chapter 13). Diabetes Care 2020;43(Suppl. 1):S163-82. https://doi.org/10.2337/dc20-S013.  Back to cited text no. 50
    Tamborlane WV, Barrientos-Pérez M, Fainberg U, Frimer-Larsen H, Hafez M, Hale PM, et al; Ellipse Trial Investigators. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med 2019;381:637-46.  Back to cited text no. 51
    Peters A, Laffel L; American Diabetes Association Transitions Working Group. Diabetes care for emerging adults: Recommendations for transition from pediatric to adult diabetes care systems: A position statement of the American Diabetes Association, with representation by the American College of Osteopathic Family Physicians, the American Academy of Pediatrics, the American Association of Clinical Endocrinologists, the American Osteopathic Association, the Centers for Disease Control and Prevention, Children with Diabetes, the Endocrine Society, the International Society for Pediatric and Adolescent Diabetes, Juvenile Diabetes Research Foundation International, the National Diabetes Education Program, and the Pediatric Endocrine Society (formerly Lawson Wilkins Pediatric Endocrine Society). Diabetes Care 2011;34:2477-85.  Back to cited text no. 52
    FDA Approved Drug Products. Available from: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed on March 4, 2019.  Back to cited text no. 53
    List of Approved Drugs. Available from: https://cdsco.gov.in/opencms/opencms/en/Approval_new/. Accessed on March 4, 2019.  Back to cited text no. 54
    Trials in Pediatric Patients with Type 2 Diabetes Mellitus. Available from www.clinicaltrials.gov. Accessed on August 2018.  Back to cited text no. 55
    Tamborlane WV, Haymond MW, Dunger D, Shankar R, Gubitosi-Klug R, Bethin K, et al; NICHD Diabetes Working Group. Expanding treatment options for youth with type 2 diabetes: Current problems and proposed solutions: A white paper from the NICHD Diabetes Working group. Diabetes Care 2016;39:323-9.  Back to cited text no. 56
    Nguyen TT, Jayadeva V, Cizza G, Brown RJ, Nandagopal R, Rodriguez LM, et al. Challenging recruitment of youth with type 2 diabetes into clinical trials. J Adolesc Health2014;54:247-54.  Back to cited text no. 57


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      [Table 1], [Table 2], [Table 3], [Table 4]


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