DIABETES MELLITUS D.

M is a heterogenous group of genetically determined, chronic metabolic disorders with one common denominator hyperglycaemia, due to either absolute or relative insulin deficiency. It is the most common of the Paediatric endocrine diseases, with a prevalence of 2:1000 children and an annual incidence of 16 new cases per 100,000 children. Prevalence for Africa is not known. Classification: This is unsatisfactory at present because of the incomplete knowledge of their Pathophysiology. Generally, classified as Primary or Secondary. In secondary there is diminished pancreatic tissue or when other endocrine diseases interfere with insulin action. 1. Primary

A. Type 1 DM (formerly IDDM or Juvenile form): This is the major form of diabetes among children. It is an autoimmune disease that results in absolute insulin deficiency: that is these patients must rely on insulin to control hyperglycaema and prevent keto acidosis. Epidermology and aetiology Incidence varies by age, race, geographic region and season, its onset has a bimodal age pattern, with one peak occurring between 10 and 14 years and another occurring in the fifth decade. It is most common in whites. The highest incidence occurs in scandinava. It is less common in blacks, Hispanics, and Asian. It has a genetic

component with Approximately 50% concordance among monozygotic twins. However it is clearly dependent upon environmental factors for its expression. It is more common in individuals who are HLADR3, -DR4 or both in whites (in Japanese it is seen in individuals with HLA DRH and DR9) for Africans Not known. Environmental factors that may trigger diabetes in genetically susceptible persons are even less well understood. Viruses have been suggested as a possibility Congental rubella syndrome and coxsackievirus have been suggested. Autoimmune damage has also been implicated. 70 to 80% have measurable islet cell antibodies. B. Type 2 (NIDDM) This is a group of disorders with carbohydrate intolerance due to relative or functional insulin deficiency. These patients are usually not insulin dependent nor prone to ketosis. They are characterized by insulin resistance with relative but progressive insulin deficiency. It also has a strong genetic disposition and certain ethnic groups such as Pima Indians, Pacific Islanders and African American. Majority of individuals with type 2 diabetes are obese. C.Maturity onset diabetes of youth (MODY) This is a genetically and clinically heterogenous subtype of NIDDM characterized by early onset between the ages of 9 and 25 years, autosomal dominant inheritance and a primary defect in insulin secretion. Criteria for the diagnosis of MODY include NIDDM in at least 3 generations with autosomal dominant transmission and diagnosis before age 25 years in at least one affected subject.

2.Secondary: This type of DM occurs in patients with diminished pancreatic tissue or with other endocrime diseases that interfere with insulin action. These endocrine disorders include (1) (2) (3) (4) Hyperadrenocortism (10 or 20 to medication) Hyperthyrodism, Excessive secretion of growth hormone, and Phaeochromocytomas.

J Diabetes due to Pancreatic calcification

CLINICAL FEATURES /PATHOPHYSIOLOGY Insulin is an anabolic hormone released in bursts in response to food intake to promote glucose entry in to cells and the synthesis of glycogen, lipid and protein. During periods of fasting, insulin release decreases to a basal level. Counterregulatory hormones such as epinephrine, glucagons, growth hormone and cortisol are released to maintain blood glucoses level by increasing glucose production through glycogenolysis, and gluconeogenesis, while enhancing fat breakdown to fatty acids and ketones for additional energy needs.

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Hyperglycaema (Renal threshold > 160mg/dl) FPS126Mg/dl(7.0mmol/l) RPS200mg/dl(11.1mmol/l) 2HPP200MG/dl(11.1mmol/l)

Impaired FPS>110MG/DL BUT<126mg/dl 2. 3. 4. 5. 6. 2HPP >140 mg/dl but<200mg/dl

Polyuria may present as enuresis Polydipsia Weight loss Ketoacidosis Glycosuria They may also present in coma DKA symptoms; polyuria, polydipsia weight

loss, abdominal pan, weakness, vomiting, confusion. Signs dehydration, lethargy, deep sighing respiration (kussmaul), smell of ketones. Biochemical ketonuria, acidaemia, glucosuria hyponatraemia/ hypernatraemia, hypokalaemia. Reasons for coma unknown but probably combinations of the ketosis, acidosis, hyperosmolality and dehydration.

Differential Diagnosis. 1. Glycosuria without hyperglycaemia occurs in benign renal glycosuria or in renal tubular disease. 2. Polyuria and polydypsia without hyperglycaema occurs in diabetes insipidus or psychogenic polydipsia. 3. hyperglyceama and glycosuria may occurs in cushings syndrome,

phaechomocytoma.

MANAGEMENT 1. Insulin mainstay of treatment Insulin is a polypeptide with 51 amino acid residue. The key characteristics of most frequently used insulin. INSULIN NAME SHORT ACTING Regular INTERMEDIATE NPH Lente LATE ACTING Ultralente Daily requirement. Insulin 0.51.u 1.0 1.u/ kg/ day But for adolescent 1.51.u 201.u/ kg/ day This is divided to give 2/3 AM and 1/3rd PM and each dose to be made up of 2/3rd intermediate acting and 1/3rd short acting. This is to approximate the physiologic insulin release in nondiabetic state. Human insulin is recommended because of its lower incidence of insulin allergy, resistance and lypoatrophy. The insulin is injected subcutaneously, rotating sites on the upper arms, thighs, buttocks, and abdomen to minimize lipohypertrophy INSULIN ACTIVITIES ( IN HOUR ) ONSET PEAK 2 2 6 2-4 4-12 8-10 14-32 DURATION 6-8 24 24 32-36

Factors affecting insulin absorption Increased rapidity of absorption Human NPH insulin Decreased rapidity of absorption Injection with hypertrophied area

I.M injection Abdomen and arms vs legs and buttocks Exercise Massage of site Jet injector Regular vs NPH or lente insulator Increased room and body temperature

Intradermal injection Large insulin volume

insulin antibodies premixing regular with NPH or lente insulin

MANAGEMENT OF DKA. A. I.V fluid 1 Requirement = maintenance + deficit Give antishock 20ml/ kg over 30min 1hour. Start with normal saline then change to 5% Dextrose 10.45N. saline when blood glucose has fallen to 14 17mmol/L. B. Insulin Start with 0.1U/kg stat then 0.1UIkg/hour continue this until blood glucose has fallen to about 14 -17mmol/L then reduce to 0.05unit/kg/hour. Once a good control is attained I.V is changed to subcutaneous (drinking and eating well). C. Potassium this must also be given. Must be commenced after the initial resuscitation fluid Add 20mmol Kcl to every 500ml bag of fluid

D. E.

Acidosis usually will correct itself. Give HCO3 only if PH < 7.1 Treat infection if present or suspected.

MONITORING /CONTINUING MANAGEMENT OF DKA 1) 2) Regular blood glucose monitoring Target blood glucose range School aged child 80 -120mg/dl (4.46.6) in the prepandial and -80 -180mg/dl at other time (4.4 10mmol/l) * Preschool aged 90 140mg/dl in the prepadical (5-7.7) and 90 200mg/dl at other times (5-11) * 3. To avoid hypoglycaemia

Counseling and Education long term nature of disease, insulin administration,

hypoglycaemia awareness and management. 4. Nutrition Balanced Nutrition and a consistent eating schedule are crucial for the

management of diabetes. Children required approximately 1000 calories plus 100 per year of age daily. CHO 50 60% Fats 30% Protein 20 % 5. 6. Exercise of benefit Monitoring of good control Use of glycosylated hb done 3 monthly assess control normal range is 6% 9.5%.

Excellent control < 8% Good control 8 -10% Fair Poor 10-12% >12%

Long Term Complications (1) Retinopathy (2) Cataracts (3) Glomerulosclerosis, (4) Hypertension (5) Vessel Calcification (6) Neuropathy These complications results from the effect of the persistent hyperglycaema on the microvasculature through glycosylation of vascular and basement membrane protein. Sorbitol -a sugar alcohol also accumulates to cause cataract and neuropathy Good control only delays the onset of these complications MORTALITY Cause of death Renal microangiopathy/Leading cause of death Cardiac Lesion DKA Hypoglycaemia/ if not well managed

HYPOGLYCAEMIA Blood, glucose level below normal

It may be asymptomatic. Diagnosis Plasma glucose < 45mg/dl (2.5mml/L) Blood glucose < 40mg/dl (2.2mml/L

Plasma glucose concentration is normally maintained within a relatively normal range of 3.9 8.3 mml/L (70-150mg/dl) despite wide variations in glucose influx and exflux such as those that follows meals and occur during exercise. The balance is maintained by hormone interaction. Insulin is the only hypoglycaemic hormone and it functions to: 1) Stimulate transmembrance movement of glucose into skeletal and cardiac muscle and adipose tissue. 2) 3) It stimulates conversion of glucose to glycogen and triglyceride It stimulates intracellular transport of amino acids in these tissues and their

incorporation into protein. Opposed to insulin actions are the actors of adrenocorticotropic hormone (ACTN), Cortisol, glucagan, epinephrine and growth hormone these hormones function to increase the ambient blood glucose level by i. inhibiting glucose uptake by muscle epinephrine, cortisol and Growth Hormone. ii. increase endogenous gluconeogenic amino acid supply by mobilization from muscle - cortisone iii. activating liypolysis and providing increased FFA as a source of energy and glycerol for gluconeogenesis- epinephrine, glucagons, GH, ACTH and Crtisol iv. v. Inhibiting insulin secretion from the Pancreas- epinephrine Acute activation of glycogenolytic and gluconeogenic enzymes epinephrine and glucagons. vi. Chronic induction of gluconeogenic enzyme synthesis e.g. glucagons and cortisol.

Incidence/Prevalence * * * it is a common problem in children Solomon et al reported a rate of 7.1% in Mozambique. A rate of 6.54% was reported in Birmigham Elusiyan et al reported a rate of 6.4% among Nigerian children.

Clinical Feature are due to: 1. Excessive epinephrine action Pallor, Sweating, weakness, tachycardia, nervousness and hunger. 2. Cerebral hypoglycopeania headache, irritability, mental confusion, psychotic behaviour, visual symptoms, lethargy, impaired performance of routine tasks, vertigo, paresthesia, inco-ordination, slurred speech, seizure and coma may N.B Symptma in neonate may be non- specific jitteriness, cyanosis, excessive sweating, apnoa. Hypoglycaema triad symptoms consistent with hypoglycaemia. 2. A relatively

low blood glucose level and 3 prompt relief of symptoms when the blood glucose level is raised.

Aetiology In Neonates A 1. Transient 0-7 days Hyperinsulism Infant of DM, erythroblastosis, discontinuation of IV glucose.

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2. B. 1.

Exact cause unknown SGA, fetal distress, any sick newborn NNs, NNT etc. Persistent (Neonatal, Infancy and early child hood 0-2yrs) Hyperinsulism Islet cell hyperplasia, Nessidioblastosis, Islet cell adenoma, leucine sensitivity, beckwith wieldeman sydrome

2. 3. 4. 5.

Glycogen Storage disease Defect in gluconeogenesis Hormone deficiency CAH, hypothyondism etc. Miscellaneous Galactosaema, Fructose intolerance, salycylate intoxication,

Reye syndrone, Hepatitis, malnutrition, alcohol intoxication,

Older Children 1-18years 1. Hyperinsulinsm secondary to therapy of diabetes, islet cell adenoma, malicious insulin or oral hypoglycaemic administration. Miscellaneous as above, Cow urine concortion, infection quinine administration etc. Elusiyan et al fond hypoglycaemia to be most commonly seen in severe malaria, Septicaema, Pneumonia and PEM. Two commonest predisposition, unconsciousness and fasting longer than 12 hours. Treatment 1. Give glucose 0.2g/kg bolus either as 2ml/kg of 10% D/W or 0.5ml/kg of 50% D/W in 1:2 dilution then 6-8mg/kg/min of glucose infusion. * * Treat suspected /identified aetiology Monitor blood sugar regular 30m, hrly, 2hrly until you obtain 2 normal readings

on two consecutive occasions.

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* * a. b. c.

Start oral feeding early If hypoglycaema persist give Hydrocortisone 5mg/kg/dose glucagon 1.m 0.mg if <25kg; 1mg if > 25kg diazoxide 8 12 mg/kg

if not controlled suspect hyperinsulinemia and prepare for surgery subtotal pancreatectomy

Complication of Hypoglycaemia 1. 2. Increased morbidity and mortality Neurological sequelae transient, mild to profound, depending or seventy and

duration of hypoglyceamia

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