Expert’s Opinion

Diabetes mellitus (DM) is a new challenge in young adults as it is becoming increasingly prevalent in this cohort.¹Obesity,signs of insulin resistance and prevalence of cardiovascular (CVD) risk factors such as hypertension and dyslipidemia arevery commonly associated with type 2 diabetes mellitus (T2DM) patients. The young age group with such type of high-riskconditions requires urgent attention to avoid macro and microvascular complications.¹Globally, 463 million population isliving with diabetes mellitus, wherein china has the highest number of DM population, followed by India with 77 million.From the current scenario, with the growth of 51%, it is anticipated that by 2045, the DM population will be 629 millionglobally; wherein currently, 75% are from working-age between 30-55 years. It is an estimation that 5.8-6.4 years of life arelost in diabetes at the age of 50 years.1,2 T2DM is not only highly prevalent in adults, but also increasing in youth.¹In theUSA, its incidence is increased by 7.1% annually in the young population of less than 19 years. Even in Asian countries likeJapan, its incidence is continuously increasing in children in the age group of 13-15 years and T2DM is dominating type1 diabetes mellitus (T1DM) even in this age group.3-5 The early onset DM develops fast and remains more cumbersomethan a late onset of the disease, leading to early morbidity and reduced quality of life. When compared to type 1 diabetesor T2DM in adults, T2DM in the young population are at a higher risk of developing early and severe microvascular andcardiovascular complications. Some risk factors in young adults like obesity, family history, and ethnicity are similar to adultDM. Additionally, metabolic risk factors for T2DM like high blood pressure, high cholesterol, impaired glucose tolerance,and metabolic syndrome, are also associated with obesity.⁶

Insulin resistance is a pathological hallmark for T2DM and its development at an early age will harbinger the onset of diabetesin the young population. Other metabolic consequences of insulin resistance can result in hyperglycaemia, hypertension,dyslipidaemia, visceral adiposity, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, and prothrombicstate and may be associated with metabolic conditions like Obesity, acanthosis nigricans, polycystic ovarian syndrome(PCOS), non-alcoholic fatty liver disease (NAFLD); which are considered as significant risk factors for the development of cardiovascular diseases. Some of these complications may appear before the detection of T2DM and probably suggestimpaired glucose metabolism in the body.7,8 Low level of suspicion of DM at that age leads to missing the diagnosis bythe clinician. Though patients with T1DM typically present with profound and rapid onset hyperglycaemia related osmoticsymptoms or even ketoacidosis, sometimes it is very challenging to differentiate between type 1 DM and type 2 DM in youngadults. Incorrect diagnosis leads to life-threatening complications; especially when T1DM patient is treated with oral diabetesmedication rather than insulin. Similarly, misdiagnosing T2DM as T1DM can result in mental trauma, agony to the family,avoiding the benefit of insulin sensitizers and unnecessary insulin therapy which may be prolonged resulting in metaboliccomplications like hypoglycaemia and weight gain.¹Sometimes special biochemical tests may be required to diagnose andguide the clinical management. In T2DM, serum insulin and C peptide concentration will remain persistently normal orhigh which is very unusual in T1DM. But sometimes there may be an overlap of insulin and c peptide levels betweenT1DM and T2DM initially, making the differentiation difficult.⁹Other types of diabetes like MODY can also occur at thisage. Transcription factor diabetes (HNF4A, HNF1A), MIDD (maternal inherited diabetes and deafness), calcific pancreaticdiabetes (type 3c) and permanent neonatal diabetes (PNDM) can also present at this age and these possibilities should be keptin mind while dealing with hyperglycaemia in the young. A careful history of the age of onset of hyperglycaemia can give clue.The age of onset is in early childhood and adolescence in type 1 DM and before the age of 6 months in PNDM. Family historyof DM will be common in type 2DM, MODY and history of diabetes in mother is present in MIDD. Acanthosis nigricans isseen in patients with type 2 DM whereas MIDD patients are lean. The diagnostic evaluation for young adults even for childrenand adolescents is based on common symptoms of diabetes mellitus such as polydipsia, polyuria, and unexplained weight lossplus routine laboratory blood glucose measurement like fasting blood glucose, postprandial blood glucose level and HbA1c.¹⁰High glucose levels are seen in patients with type 1 DM, HNF1A MODY, PNDM. C peptide levels are low in type 1 DM,MODY, PNDM and type 3c DM. Presence of beta cell autoantibodies like glutamic acid decarboxylase (GAD) autoantibodieswill confirm the diagnosis of T1DM. Ultrasound (US) scan of the abdomen showing ductal calcification and stones is seen intype 3c DM. Genetic analysis for HNF1A, HNF4A and HNF1B mutations can confirm maturity-onset diabetes of the young(MODY). So, careful evaluation of the patient with a good history, examination and investigations will clinch the diagnosis.

Appropriate education and life-style modification certainly delays the new onset of DM and helps in reaching the targets andalso reduces the severity of complications. But following lifestyle measures is difficult and much more problematic for theyoung diabetics to follow the regular guideline recommendations due to age, puberty and peer group influences.Compared to the elderly population, controlling glycaemic level in young adults is a major challenge. It is observedthat control remains poor both within and beyond 5 years of diagnosis in young adults.⁶ In the management of T2DM,glycaemic control with HbA1c level <6.5% is an utmost important goal in most of the patients. Along with appropriatelifestyle modification, optimum weight control will help to reach the desired target with medication.¹¹ Physical exercise likeaerobic activity, sports alone or in combination with diet can reduce weight, blood lipid level, elevated blood pressure andalso helps to maintain mental health as well.¹² For pharmacological management approach, most of the drugs are investigatedin adults with less number of research studies in young. Metformin is the most appropriate starting point for any age groupwith T2DM. The results of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study suggest thatmonotherapy with metformin was associated with durable glycaemic control in children and adolescents.¹³ Apart from this inyoung age group patients, currently, many newer oral antidiabetic agents are introduced which not only control glucose levelbut also reduces cardiovascular mortality like sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide 1(GLP-1) analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors. Metformin is always considered as first-line therapy if thereare no contraindications, but after metformin or along with metformin if the patient has any marked CV risk factor, thenSGLT2 inhibitors, GLP-1 analogues are preferred agents. Treatment with these agents may increase the cost of therapy butproper counselling of patient may improve adherence to this therapy. Alternatively, along with metformin other agents likesulfonylureas, meglitinides, thiazolidinediones, α-Glucosidase inhibitors, DPP-4 inhibitors are preferred options. In case ofuncontrolled glucose with adequate antidiabetic drugs and HbA1c level more than 9%, treatment with insulin or its analoguesare preferred to manage DM.¹⁴ Bariatric surgery is emerging as a viable treatment option in young individuals with type 2diabetes and evidence has been accumulating that it is safe and effective in obese adolescents.¹⁵