Type 1 diabetes involves the immune system attacking pancreatic cells, reducing insulin & causing high blood sugar. Read about the latest updates in managing diabetes in children & adolescents, including new criteria for diagnosing diabetic ketoacidosis & extensive discussions on T2D in adolescents.

---

Diagnostic criteria

1. A marked elevation of the plasma glucose concentration confirms the diagnosis of diabetes, including random plasma glucose ≥11.1 mmol/L (200 mg/dl) or fasting plasma glucose ≥7.0 mmol/L (≥126 mg/dl) in the presence of overt symptoms.
2. Diagnostic tools, which may assist in confirming the diabetes type if the diagnosis is unclear, include diabetes-associated autoantibodies: glutamic acid decarboxylase 65 autoantibodies (GAD), tyrosine phosphatase-like insulinoma antigen 2 (IA2), insulin autoantibodies (IAA), and β-cell specific zinc transporter 8 autoantibodies (ZnT8). The presence of one or more of these antibodies confirms the diagnosis of T1D in children. Molecular genetic testing may be required to diagnose monogenic diabetes.
3. The possibility of other types of diabetes should be considered in the child who has negative diabetes-associated autoantibodies and: an autosomal dominant family history of diabetes (MODY).
   1. Age < 12 months and especially in the first 6 months of life (neonatal diabetes mellitus [NDM]).
   2. Mild-fasting hyperglycaemia (5.5–8.5 mmol/L [100–150 mg/dl]), especially if young, non-obese, and asymptomatic (MODY).
   3. A prolonged honeymoon period lasting more than 1 year or an unusually low requirement for insulin of ≤0.5 U/kg/day after 1 year of diabetes (MODY).
   4. Associated conditions such as deafness, optic atrophy, or syndromic features (mitochondrial disease).
   5. A history of exposure to drugs known to be toxic to β-cells or cause insulin resistance (e.g., immunosuppressive drugs such as tacrolimus or cyclosporin; glucocorticoids or some antidepressants).

---

Stages of type 1 diabetes in children and adolescents

---

Type 2 diabetes in children and adolescents

Screening of T2 DM

1. Targeted screening to identify cases of T2D can be considered after the onset of puberty or after 10 years of age in youth who have a body mass index (BMI) ≥85th percentile for age and sex and risk factors for T2D.
2. Fasting plasma glucose (FPG), 2-h plasma glucose after a 75-g oral glucose tolerance test (OGTT), or HbA1c can be used to screen for T2D.
3. If tests are normal, repeat screening should occur at a minimum every 3 years. Annual screening may be necessary if (BMI) is increasing, the cardio-metabolic risk profile is worsening, and there is a strong family history of T2D or evidence of pre-diabetes.

Diagnosis of T2D

Symptoms of hyperglycaemia and one of the following laboratory values and negative islet autoantibodies.

• FPG ≥126 mg/dl (7.0 mmol/L)
• 2-h plasma glucose on an OGTT ≥200 mg/dl (11.1 mmol/L)
• Random plasma glucose ≥200 mg/dl (11.1 mmol/L)
• HbA1c ≥ 6.5% (48 mmol/mol) by an NGSP-certified device, standardised to the DCCT assay

Glycaemic monitoring and targets

• FPG targets are 70–110 mg/dl (4–6 mmol/L)
• Postprandial blood glucose targets are 70–140 mg/dl (4–8 mmol/L)
• HbA1c target is <7% and in most cases can be <6.5%

Treatment

1. Lifestyle modification remains the first choice of treatment followed by pharmacotherapy.
2. If HbA1c <8.5% (69 mmol/mol) – Metformin is the treatment of choice together with healthy lifestyle changes.
3. In youth with ketosis/ketonuria/ketoacidosis or HbA1c ≥8.5% (69 mmol/mol), insulin is required initially with once-a-day intermediate-acting or long-acting basal insulin (starting dose 0.25–0.5 units/kg).

Subsequent therapy

1. The goal of initial treatment should be to attain an HbA1c of <7.0% (53 mmol/mol) and in some situations <6.5% (48 mmol/ mol) if this can be attained without hypoglycaemia.
2. If HbA1c of <7.0% (53 mmol/mol) is not attained, consider the addition of a second agent which is approved in adolescents.
3. If HbA1c >10%, initiation or re-initiation of basal insulin is the preferred option. The use of GLP analogues has been approved for the management of type 2 diabetes in adolescents.

---

Screening for comorbidities and complications

Hypertension

Blood pressure (BP) should be measured starting at diabetes diagnosis and at every subsequent visit with appropriate cuff size.

Dyslipidaemia

In youth with T2D, testing for dyslipidaemia should occur once glycaemic control has been achieved or after 3 months of initiation of medication regardless of HbA1c values, and annually thereafter unless abnormal.

Nephropathy

1. Albuminuria screening using 3 first morning urine collections should occur at diagnosis and annually thereafter.
2. If the urine albumin/creatinine ratio is confirmed to be >30 mg/g (3 mg/mmol) and BP is elevated or the urine albumin/creatinine ratio is >300 mg/g (30 mg/mmol) irrespective of BP, an ACE inhibitor or ARB should be started and BP normalised.

Retinopathy

Screen youth with T2D for retinopathy at the time of initial diagnosis and annually by an ophthalmologist or optometrist by comprehensive eye examination with dilated pupils or retinal photography.

Neuropathy

Foot examination (including sensation, vibration sense, light touch and ankle reflexes) at diagnosis and annually is recommended to detect neuropathy.

Psychosocial health

Youth with T2D should be screened for psychological comorbidities including depression, diabetes distress, and disordered eating at diagnosis and at regular follow-up intervals. Mental health support should be offered to youth with mental health concerns.

---

Diagnosis and management of monogenic diabetes in children and adolescents

Neonatal diabetes

1. All infants diagnosed with diabetes in the first 6 months of life are recommended to have immediate molecular genetic testing.
2. Genetic testing may be considered in infants diagnosed between 6 and 12 months, especially in those without islet autoantibodies or who have other features suggestive of a monogenic cause.
3. Treatment with SU, especially glibenclamide (also known as glyburide), is recommended for NDM due to KCNJ11 and ABCC8 abnormalities.

Maturity onset diabetes of the young (MODY)

The diagnosis of MODY is recommended in the following scenarios:

1. A family history of diabetes in a parent and first-degree relatives of that affected parent in persons with diabetes who lack the characteristics of T1D and T2D.
2. Testing for GCK-MODY, which is the commonest cause of persistent, incidental hyperglycaemia in the paediatric population, is recommended for mild stable fasting hyperglycaemia that does not progress.
3. Some forms of MODY are sensitive to SU, such as HNF1A-MODY and HNF4A-MODY.

---

Glycaemic targets and glucose monitoring for children, adolescents, and young people with diabetes

1. Adoption of a unified fingerstick capillary glucose (SMBG) target of between 4 and 10 mmol/L (70–180 mg/dl), which aligns with the target CGM time in range (TIR), while emphasising a tighter fasting target range of 4–8 mmol/L (70–144 mg/dl).
2. HbA1c assessments are recommended every 3 months, target HbA1c for young people with diabetes should be <53 mmol/mol (<7.0%).
3. An HbA1c target of <48 mmol/mol (6.5%) is recommended for the remission phase or early stage 3 diabetes “honeymoon” period and in populations with access to advanced technology combined with a highly skilled specialised health care professional service adept in diabetes education.
4. SMBG should be assessed at least 6 times a day for a person with diabetes taking insulin.
5. Recommended target glucose values are between 4 and 10 mmol (70–180 mg/dl), with a narrower fasting target range of 4 and 8 mmol/L (70–144 mg/dl).

---

Insulin treatment in children and adolescents with diabetes

1. Prepubertal children (outside the partial remission phase) usually require 0.7 to 1.0 IU/kg/day and during puberty, insulin dose requirements may rise to between 1 and 2 IU/kg/day.
2. Insulin treatment must be started as soon as possible after diagnosis (usually within 6 h if ketonuria is present) to prevent metabolic decompensation and diabetic ketoacidosis (DKA).
3. Intensive insulin regimens delivered by combinations of multiple daily injections or pump therapy with substitution of basal and prandial insulin aiming to have optimal glycaemic levels have become the gold standard for the treatment of diabetes in children across all age groups.

---

Nutritional management in children and adolescents with diabetes

1. As a guide, carbohydrates should approximate 40-50% of energy, fat <35% of energy (saturated fat <10%), and protein 15%-25% of energy.
2. Carbohydrate counting is best introduced at the onset of type 1 diabetes (T1D) along with education about the impact of mixed meals on postprandial glucose profiles.
3. The use of the glycaemic index provides additional benefit to glycaemic management over that observed when total carbohydrate is considered alone.
4. Changes to both the insulin dose and pattern of delivery are needed for meals higher in protein and fat.

---

Diabetic ketoacidosis and hyperglycaemic hyperosmolar state

The biochemical criteria for the diagnosis of DKA are:

• Hyperglycaemia (blood glucose >11 mmol/L [≈200 mg/dl])
• Venous pH <7.3 or serum bicarbonate <18 mmol/L(C)
• Ketonemia (blood ß-hydroxybutyrate ≥3 mmol/L) (C) or moderate or large ketonuria

Fluid replacement should begin before starting insulin therapy.

Expand volume using one or more boluses of 0.9% saline infused over 20–30 min to restore peripheral circulation.

Calculate the subsequent rate of fluid administration (0.45% to 0.9% saline), including the provision of maintenance fluid requirements, aiming to replace the estimated fluid deficit over 24 to 48 hours.

1. Insulin therapy: begin with 0.05–0.1 U/kg/h (0.05 U/kg/h can be considered with pH > 7.15) at least 1 hour after starting fluid replacement therapy.
2. Potassium: If the child has hyperkalaemia (potassium >5.5 mmol/L), defer potassium replacement therapy until urine output is documented. Begin potassium infusion when potassium <5.5 mmol/L. In the rare child with hypokalaemia (potassium <3.0 mmol/L), defer insulin treatment and give a bolus of potassium (not to exceed 0.5 mEq/Kg/h), along with cardiac monitoring. Otherwise, begin with 40 mmol potassium/L.
3. Bicarbonate administration is not recommended except for the treatment of life-threatening hyperkalaemia or severe acidosis (venous pH < 6.9) with evidence of compromised cardiac contractility.
4. In children with multiple risk factors for cerebral injury (elevated serum urea nitrogen concentration (>20 mg/dl), severe acidosis (pH < 7.1), severe hypocapnia (pCO2 < 21 mmHg), age < 5 years), have mannitol or hypertonic saline at the bedside and the dose calculated.
5. If neurologic status deteriorates acutely, hyperosmolar therapy with mannitol or hypertonic saline should be given immediately.

---

Criteria for Hyperglycaemic Hyperosmolar State (HHS) include all the following:

• Plasma glucose concentration > 33.3 mmol/L (600 mg/dl)
• Venous pH > 7.25; arterial pH > 7.30
• Serum bicarbonate >15 mmol/L
• Small ketonuria, absent to mild ketonemia
• Effective serum osmolality >320 mOsm/kg

In HHS, begin insulin administration at a dose of 0.025 to 0.05 U/kg/h once plasma glucose is decreasing by less than 3 mmol/L (50 mg/dl) per hour with fluid alone. Rates of fluid administration, both as initial fluid boluses to restore circulation and as ongoing deficit replacement, are substantially higher than for DKA.

---

Assessment and management of hypoglycaemia in children and adolescents with diabetes

1. Glucose value <3.9 mmol/L (70 mg/dl) is used as the clinical alert or threshold value for initiating treatment for hypoglycaemia because of the potential for glucose to fall further and avoid consequences of glucose levels below 3 mmol/L.
2. Glucose value <3.0 mmol/L (54 mg/dl) is defined as clinically important or serious hypoglycaemia as neurogenic symptoms and cognitive dysfunction can occur below this level. Children with T1D should spend less than 1% of their time <3.0 mmol/L (54 mg/dl).
3. Hypoglycaemia should be treated with oral glucose. An immediate source of glucose must always be available to young people with diabetes.
4. Treatment of hypoglycaemia should increase blood glucose level by 3 to 4 mmol/L (54 to 72 mg/dl). This can be accomplished by administering 0.3 g/kg glucose orally, which equates to 9 g of glucose for a 30 kg child and 15 g for children >50 kg.
5. If on standard pump therapy (no suspend or automated insulin delivery) and glucose level <3 mmol/L, suspend insulin delivery until glucose >4 mmol/L.
6. Severe hypoglycaemia requires urgent treatment with glucagon. In the ambulatory setting, SC or IM glucagon should be given (1 mg for children >25 kg and 0.5 mg for children <25 kg. In a hospital setting, intravenous glucose (10% dextrose, 2 ml/kg) can be administered.
7. If unexplained hypoglycaemia is frequent, evaluation for unrecognised celiac and Addison's disease should be considered.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Hitesh Saraogi is a diabetologist, physician and an obesity specialist at Dhanvantari Hospital, Raj Nagar Extension, Ghaziabad.