Endocrine

Diabetes mellitus

د.ندى العلي

The incidence of diabetes in children has increased steadily over the last 20 years and now affects around 2 per 1000 children by 16 years of age. This is most likely to be a result of changes in environmental risk factors. There is considerable racial and geographical variation - Almost all children are insulin-dependent (type 1 diabetes). Type 2 non-insulin-dependent diabetes due to insulin resistance is starting to occur in childhood as severe obesity becomes more common..


Classification of diabetes according to aetiology (adapted from American Diabetes Association,
Type 1. Insulin-dependent
Most childhood diabetes

Type 2. Non-insulin-dependent

Usually older children obesity-related positive family history not prone to ketosis commoner in some ethnic groups

Type 3. Other specific types

Drugs, e.g. corticosteroids Pancreatic exocrine insufficiency, e.g. cystic fibrosis Genetic defects in insulin action Congenital infection e.g. congenital rubella Endocrine diseases, e.g. Cushing's syndrome Genetic/chromosomal syndromes, e.g. Down's and Turner's

Both genetic predisposition and environmental precipitants play a role. Inherited susceptibility is demonstrated by an identical twin of a diabetic having a 30-50% chance of developing the disease


Pathogenesis &Etiology


the increased risk of diabetes amongst those who are HLA-DR3 or HLA-DR4 and a reduced risk with DR2 and DR5
the increased risk of a child developing diabetes if a parent has insulin-dependent diabetes (1 in 20-40 if the father is affected, 1 in 40-80 if it is the mother


Interaction probably occurs between an environmental trigger and an antigen on the surface of β-cells of the pancreas. Triggers which may contribute are viral infections, accounting for the more frequent presentation in spring and autumn, and diet, possibly cow's milk This results in an autoimmune process which damages the pancreatic β-cells and leads to an absolute insulin deficiency. Markers of β-cell destruction include islet cell antibodies and antibodies to glutamic acid decarboxylase (GAD). There is an association with other autoimmune disorders such as hypothyroidism

Clinical picture

The age at presentation It is uncommon before the age of 1 year, but the incidence rises steadily during the early school years Peaks of presentation occur at 5 - 7 years of age and at adolescence 12-13 years of age. In contrast to adults, children usually present with only a few weeks of polyuria, excessive thirst (polydipsia) and weight loss; young children may also develop secondary nocturnal enuresis. Most children are diagnosed at this early stage of the illness . Advanced diabetic ketoacidosis has become an uncommon presentation, but requires urgent recognition and treatment. Diabetic ketoacidosis may be misdiagnosed if the hyperventilation is mistaken for pneumonia or the abdominal pain for appendicitis.

Symptoms and signs of diabetes

Early Most common - the 'classical triad
Excessive drinking polydipsia
Polyuria
Weight loss


Less common
Enuresis (secondary)
Skin sepsis
Candida and other infections

Late - diabetic ketoacidosis

Smell of acetone on breath
Vomiting
Dehydration
Abdominal pain
Hyperventilation due to acidosis (Kussmaul breathing)
Hypovolaemic shock
Drowsiness
Coma

The diagnosis is usually confirmed in asymptomatic child by finding a markedly raised random blood glucose >11.1mmol/L or >200 mg/dl Urine exam: glycosuria and ketonuria


Type 2 diabetes should be suspected if there is a family history, and in severely obese children

Initial management of type 1 diabetes

The initial management will depend on the child's clinical condition. Those in advanced diabetic ketoacidosis require urgent hospital admission and treatment 'Most newly presenting children are alert and able to eat and drink and can be managed with subcutaneous insulin alone. In some centres, children newly presenting with diabetes who do not require intravenous therapy are not admitted to hospital but are managed entirely at home

Insulin

Insulin is made chemically identical to human insulin by recombinant DNA technology or by chemical modification of pork insulin. All insulin that is used in the UK in children is human and in concentrations of 100 U/ml (U-100). The types of insulin include:

3.Intermediate-acting insulin. Onset 1-2 hours, peak 4-12 hours. Isophane insulin is insulin with protamine, 4.Predetermined preparations of mixed short- and intermediate-acting isophane insulins. Examples are Mixtard 30/70 and Humulin M3 (contain 30% soluble and 70% isophane insulin).

Insulin can be given by injections using a variety of syringe and needle sizes, pen-like devices


In young children, insulin is usually given twice a day, before breakfast and evening meals, as a mixture of short-acting (approximately 30% and medium- or long-acting insulin pproximately 70%) In general, about two-thirds of the daily dose is given before breakfast and one-third before the evening meal.

AM 2/3

PM 1/3
2/3 NPH 1/3 Regular
NPH (2/3) Regular (1/3)
NPH and Regular


Continuous subcutaneous insulin infusion (CSII) delivered by a micro-processor controlled pump can approximate insulin delivery to physiological requirements but requires the use of an indwelling plastic needle and multiple tests to achieve optimum control and so is not suitable for all patients.


Shortly after presentation, when some pancreatic function is preserved, insulin requirements often become minimal, the so-called 'honeymoon period'. Requirements subsequently increase to 0.5-1 or even up to 2 units/kg per day during puberty.

The diet and insulin regimen need to be matched ( The aim is to optimise metabolic control whilst maintaining normal growth. On the standard twice-daily regimen, food intake is divided into three main meals with snacks between meals and before going to bed

Blood glucose monitoring

Regular blood glucose measurements: (when a low or high level is suspected) are required to adjust the insulin regimen and learn how changes in lifestyle, food and exercise affect control. A record should be kept in a diary or transferred from the memory of the blood glucose meter. The aim is to maintain blood glucose as near to normal (4-6 mmol/L) as possible. In practice, in order also to avoid hypoglycaemic episodes, this means levels of 4-10 mmol/L in children80-180mg/dl


The measurement of glycosylated haemoglobin (HbA1\C) is particularly helpful as a guide of overall control over the previous 6 weeks and should be checked regularly. The level is directly related to the risk of later complications, but may be misleading if the red blood cell lifespan is reduced, such as in sickle cell trait or if the HbA molecule is abnormal, as in thalassaemia. A level of less than 7% is an often stated but rarely achievable target

Diabetic ketoacidosis

Keotacidosis is responsible for the initial presentation of IDDM in up to 25% of children. early manifestations are mild and include vomiting, polyuria, and dehydration. More severe cases include Kussmaul respirations, odor of acetone on the breath. abdominal pain or rigidity may be present and mimic acute appendicitis or pancreatitis. cerebral obtundation and coma ultimately ensue.
Clinical picture

Essential early investigations

Blood glucose(11.1mmol/L) or (>300mg/dl) Urea and electrolytes, creatinine (dehydration) Blood gas analysis (severe metabolic acidosis) Urinary glucose and ketones (both are present ( Evidence of a precipitating cause, e.g. infection (blood and urine cultures performed( Cardiac monitor for T-wave changes of hypokalaemia


Treatment
Treatment is divided into 3 phases treatment of ketoacidosis transition period continuing phase and guidance

Goals of treatment of DKA intravascular volume expansion correction of deficits in fluids, electrolytes, and acid-base status initiation of insulin therapy to correct catabolism, acidosis


Intravascular volume expansion dehydration is most commonly in the order of 10% initial hydrating fluid should be isotonic saline this alone will often slightly lower the blood glucose rarely is more than 20 cc/kg fluid required to restore hemodynamics
Treatment of electrolyte abnormalities serum K+ is often elevated, though total body K+ is depleted K+ is started early as resolution of acidosis and the administration of insulin will cause a decrease in serum K+


Insulin Therapy continuous infusion of low-dose insulin IV (~ 0.1 U/kg/hr) is effective, simple, and physiologically sound or 0.5-1u/kg then o.2-o.4 every 6hr goal is to slowly decrease serum glucose, frequent laboratory and blood gas analyses are obtained to ensure ongoing resolution of metabolic acidosis

Hypoglycaemia in diabetes

symptoms and signs include pallor, sweating, apprehension,trembling,tachycardia, hunger, drowsiness, mental confusion, seizures and coma management includes administration (if conscious) of carbohydrate-containing snack or drink glucagon 0.5 mg is administered to an unconscious or vomiting child
Hypoglycemic Reactions (Insulin Shock)

Short term Home blood glucose monitoring: technique and methods of analysis and interpretation Urine testing Long term Glycosylated hemoglobin levels Clinical complications
Monitoring



Careful monitoring of blood pressures is an important part of monitoring procedures. Monitoring quantitative urinary albumin excretion also appears to be significant because microalbuminuria exhibits a relationship to the development of significant nephropathy. Yearly monitoring of thyroid function blood cholesterol/triglyceride levels is recommended. Complete ophthalmological examination and urinalysis must become regular components of ongoing management, beginning approximately 5 years after the clinical onset of type I or type II diabetes.
MONITORING COMPLICATIONS