Type 2 diabetes in children and adolescents: Exploring the disease heterogeneity and research gaps to optimum management

Table 1 Screening and management of complications in young-onset type 2 diabetes mellitus

Complication	American diabetes association 2018[87]	International society for paediatric and adolescent diabetes 2022[91]
Cardiovascular disease	Intensive lifestyle interventions focusing on weight loss, dyslipidemia, hypertension, and dysglycemia are important to prevent overt macrovascular disease in early adulthood. Routine ECG, echocardiography, stress tests or other screening tests for cardiovascular disease are not warranted in the absence of cardiac symptoms
Retinopathy	Screening for retinopathy should be performed by dilated fundoscopy or retinal photography as soon as possible after diagnosis and then annually. Less frequent examination (every 2 yr) may be considered for those with adequate glycemic control and a normal eye examination	Screening of youth with T2DM at the time of initial diagnosis and annually by an ophthalmologist or optometrist by a comprehensive eye examination with dilated pupils or retinal photograph. More frequent examinations are required if retinopathy is of higher grade, progressing and if there is suboptimal glycemic control
Neuropathy	Screening for the presence of neuropathy by foot examination at diagnosis and then annually, including inspection, assessment of foot pulses, pinprick and 10-g monofilament tests, testing of vibration perception using a 128-Hz tuning fork, and ankle reflexes	Foot examination (including sensation, vibration sense, light touch and ankle reflexes) at diagnosis and then annually is recommended to detect at risk feet
Nephropathy	UACR to be obtained at diagnosis and then annually thereafter. Elevated UACR (> 30 mg/g creatinine) should be confirmed on two out of three samples. eGFR should be determined at the time of diagnosis and annually thereafter. Those with nephropathy should undergo continued monitoring with yearly UACR, eGFR, and serum potassium. Referral to nephrology is recommended if etiology is uncertain or if there is worsening UACR, or decline in eGFR	Albuminuria screening should occur at diagnosis and annually thereafter using three first morning urine collections. If UACR is > 30 mg/g (3 mg/mmol) and BP is elevated or UACR is > 300 mg/g (30 mg/mmol) irrespective of BP, ACEi, or ARB should be started and BP normalized. If albuminuria is present, serum potassium and renal function should be evaluated annually. Renal function to be evaluated using calculated eGFR from validated formulas cystatin C measurement is currently not recommended as it shows high variability and is affected by age, sex, BMI, and diabetes control. A repeat UACR may be helpful 6 mo after the start of ACEi or ARB to ensure albuminuria is normalized. Non-diabetes-related causes of renal disease should be considered and consultation with a nephrologist obtained if severely increased albuminuria (UACR > 300 mg/g or 30 mg/mmol) or if hypertension is present
Hypertension	BP should be measured at every visit and optimized if necessary. If BP is > 95th percentile for age, sex, and height, increased emphasis should be placed on lifestyle management. Antihypertensive therapy should be initiated if BP is not optimized by 6 mo. ACEi or ARB) should be initial therapeutic agents. Other BP–lowering agents may be added if needed to optimize BP	BP should be measured at diabetes diagnosis and at every subsequent visit, in the seated position. ABPM can be considered if there is suspicion of white coat hypertension or to confirm hypertension. Echocardiographic evaluation is recommended in youth with confirmed hypertension to assess for left ventricular target organ injury
Dyslipidemia	Lipid testing after initial glycemic control has been achieved and repeated annually thereafter. Optimal goals are: LDL-C < 100 mg/dL (2.6 mmol/L), HDL-C > 35 mg/dL (0.905 mmol/L), triglycerides < 150 mg/dL (1.7 mmol/L). Dietary counseling using the AHA Step 2 diet. If LDL-C remains above goal after 6 mo of dietary intervention, to initiate statins with goal of LDL-C < 100 mg/dL. If triglycerides are > 400 mg/dL (4.7 mmol/L) fasting or > 1000 mg/dL (11.6 mmol/L) non-fasting, to optimize glycemia and begin fibrate, with a goal of < 400 mg/dL (4.7 mmol/L) fasting to reduce risk of pancreatitis	Testing for dyslipidemia should occur once glycemic control has been achieved or after 3 mo of initiation of medication, and annually thereafter unless abnormal
NAFLD	Evaluation for NAFLD (by measuring ALT and AST) should be done at diagnosis and annually thereafter. Referral to gastroenterology should be considered for persistently elevated or worsening transaminases	Liver enzymes (ALT, AST, and GGT) should be evaluated at T2DM diagnosis and annually thereafter, preferably sooner if abnormal
Psychosocial	Assessment of social factors, including food and housing stability, financial constraints. Appropriate patient-appropriate validated tools to assess mental health issues including diabetes distress, depression and disordered eating behaviours, and referral to specialty care if needed. At every visit, to check medication adherence. Effects of medication on body weight must be considered. Screening for smoking and alcohol use at diagnosis and at regular intervals	Youth with T2DM should be screened for psychological co-morbidities including depression, diabetes distress, and disordered eating at diagnosis and at regular follow-up intervals. Providers should specifically consider household food security, housing stability, and family financial resources when devising a treatment plan with the youth and family
OSA	OSA screening should be done at each visit, and referral to a pediatric sleep specialist for evaluation and a polysomnogram, if indicated, is recommended. OSA should be treated when documented	Youth with T2DM should be screened for symptoms of OSA at diagnosis and annually thereafter unless there is excessive weight gain, which requires an earlier review of OSA symptoms. OSA can be initially evaluated using general questions about snoring, sleep quality, apnea, morning headaches, daytime sleepiness, nocturia, and enuresis. If symptoms are suggestive of OSA, the diagnosis of OSA is confirmed by a sleep study and referral to a sleep specialist. Nocturnal pulse oximetry can be an initial useful evaluation if there is limited access to a sleep study
PCOS	Adolescents with T2DM should be evaluated for PCOS including laboratory studies when indicated. Metformin in addition to lifestyle modification can be used to improve the menstrual cyclicity and hyperandrogenism in girls with T2DM. Weight loss and metformin may improve the menstrual disorder. If hormonal contraception is commenced, effects on metabolic risk should be considered in agent-selection. Oral contraceptives, if required for treatment of PCOS, are not contraindicated for girls with T2DM	PCOS screening should occur at diagnosis in pubertal girls and yearly after that with an evaluation of menstrual history and evidence of hyperandrogenism (hirsutism and/or moderate to severe acne and/or total testosterone measurement). PCOS is diagnosed based on the presence of oligo- or amenorrhea with clinical or biochemical evidence of hyperandrogenism (total testosterone) after exclusion of other possible causes. Pelvic ultrasound is not recommended for the diagnosis of PCOS within 8 yr post-menarche
Pregnancy	Pre-conception counseling should be incorporated into routine diabetes clinic visits for all females of child-bearing potential, starting from puberty

ABPM: Ambulatory blood pressure monitoring; ACEi: Angiotensin convertase enzyme inhibitors; AHA: American Heart Association; ALT: Alanine transaminase; ARB: Angiotensin receptor blocker; AST: Aspartate transaminase; BP: Blood pressure; ECG: Electrocardiogram; eGFR: Estimated glomerular filtration rate; GGT: Gamma glutamyl transaminase; HDL-C: High-density lipoprotein cholesterol; Hz: Hertz; LDL-C: Low-density lipoprotein cholesterol; NAFLD: Non-alcoholic fatty liver disease; OSA: Obstructive sleep apnea, PCOS: Polycystic ovarian syndrome; T2DM: Type 2 diabetes mellitus; UACR: Urine albumin/creatinine ratio.