Transcript PowerPoint Presentation - Insulin Past, Present, and Future
Diabetes Mellitus in Children
Dr Nadeem Zubairi
D.M.
Diabetes mellitus is a group of metabolic diseases in which a person has
high blood sugar
, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).
Before Insulin
JL on 12/15/22 and 2 mos later
Before insulin was discovered in 1921, everyone with type 1 diabetes died within weeks to years of its onset
© 2004, John Walsh, P.A., C.D.E.
1923 Banting and Best Awarded Nobel Prize for Discovery And Use of Insulin in the Treatment of IDDM
OLD CLASSIFICATION (1985)
Type 1, Insulin-dependent (IDDM) Type 2, Non Insulin-dependent (NIDDM) obese non-obese MODY IGT Gestational Diabetes
© 2004, John Walsh, P.A., C.D.E.
WHO CLASSIFICATION 2000
Is based on etiology not on type of treatment or age of the patient.
Type 1 Diabetes ( autoimmune
b
-cell destruction) Type 2 Diabetes (defects in insulin secretion or action) Other specific types
Types of Diabetes in Children
Type 1 diabetes mellitus accounts for >90% of cases.
Type 2 diabetes is increasingly recognized in children with presentation like in adults.
Permanent neonatal diabetes Transient neonatal diabetes Secondary diabetes e.g. in cystic fibrosis or Cushing syndrome.
EPIDEMIOLOGY Type 1 DM
– – – – – – – Most common metabolic disease in childhood Annual incidence 15 new cases per 100,000 in children < 18 yrs Frequency increases with increasing age.
1: 1400 at age 5 yrs 1: 400 at age 16 yrs Males and females equally affected No correlation with socioeconomic status
Etiology
Type 1 DM usually results from
both
an inherited risk and external triggers, Infection, diet .
Type 1 diabetes is an autoimmune disorder in which the body attacks its pancreatic beta cells.
Genetic issues Clear evidence suggests a genetic component in type 1 diabetes mellitus.
Monozygotic twins have a 60% lifetime concordance for developing type 1 diabetes mellitus, although only 30% do so within 10 years after the first twin is diagnosed. In contrast, dizygotic twins have only an 8% risk of concordance, which is similar to the risk among other siblings.
The frequency of diabetes developing in children with a diabetic mother is 2-3% and 5 6% if the father has type 1 diabetes mellitus. The risk to children rises to almost 30% if both parents are diabetic.
Type I – IDDM
Two shared HLA haplotypes (DR3 + DR4) 12-20% risk One shared HLA haplotype (DR3 or DR4) 5-7% risk No shared HLA haplotypes 1-2% risk HLA DQ(beta) Asp 57 virtual protection HLA DQ(beta) non-Asp 57 100 X increased risk
Environmental factors Viral infections (most important) probably by initiating or modifying an autoimmune process.( Mumps, coxsackie virus, CMV, congenital rubella) Dietary factors are also relevant Breastfed infants have a lower risk for Type 1 DM. Some cow's milk proteins (e.g., bovine serum albumin) have antigenic similarities to an islet cell antigen.
Diagnosis
Symptoms of diabetes + casual plasma glucose concentration ≽ 11.1 mmol/L ( ≽ 200mg/dl).
¹ Casual is defined as at any time of the day without regard to time since the last meal.
Or Fasting plasma glucose ≽ 7.0 mmol/L ( ≽ 126mg/dl).
² Fasting is defined as no caloric intake for at least 8h.
Or 2h post load glucose ≽ 11.mmol/L ( ≽ 200mg/dl) during an OGTT.
Progression to Type 1 DM
Autoimmune markers (ICA, IAA, GAD Autoimmune destruction Honeymoon “Diabetes threshold” 100% Islet loss
Honeymoon Period
In patients with new onset of DM1 who do not have DKA, the beta cell mass has not been completely destroyed.
The remaining functional beta cells seem to recover with insulin treatment, and they are again able to produce insulin. When this occurs, insulin requirements decrease, and there is a period of stable blood glucose control, often with nearly normal glucose concentrations. This phase of the disease, known as the honeymoon period , usually starts in the first weeks of therapy and usually continues for a few months at most, but can last 2 years
CLINICAL PRESENTATIONS Classical symptom triad:
polyuria, polydipsia and weight loss
DKA Accidental diagnosis
COMPLICATIONS OF DIABETES
Acute:
DKA
Hypoglycemia Late-onset:
Retinopathy
Neuropathy
Nephropathy
Ischemic heart disease & stroke
DCCT And Other Studies
Research studies between 1970 and 2000 showed that complications could be prevented by lowering high glucose levels
Studies
DCCT 1984-1992 EDIC 1996 UKPDS 1978-1998 Kumamoto 1992-2000
Results
Better health Fewer complications Improved sense of well-being More flexible lifestyle © 2004, John Walsh, P.A., C.D.E.
TREATMENT ELEMENTS
Education Insulin therapy Diet and meal planning Exercise Monitoring
HbA1c every 2-months
Home regular BG monitoring
Home urine ketones tests when indicated
EDUCATION
Educate child & care givers about:
Diabetes
Insulin Life-saving skills Recognition of Hypo & DKA Meal plan Sick-day management
Management
Principles of insulin therapy Varies between individuals and changes over time The correct dose of insulin is the dose that achieves the best glycemic control without causing obvious hypoglycemia problems and achieving normal growth(height and weight) Dosage depends on, Age, weight, stage of puberty, duration and phase of diabetes, state of injection sites, nutritional intake and distribution, exercise pattern, daily routine
Hyperglycemia:
Microangiopathic complications
Hypoglycemia:
Neuronal loss Poor school performance seizures
TYPES OF INSULIN
Short acting (neutral, soluble, regular)
Peak 2-3 hours & duration up to 8 hours Intermediate acting
Isophane (peak 6-8 h & duration 16-24 h)
Biphasic (peak 4-6 h & duration 12-20 h) Semilente (peak 5-7 h & duration 12-18 h) Long acting (lente, ultralente & PZI)
Peak 8-14 h & duration 20-36 h
INSULIN ANALOGS
Ultra short acting
Insulin Lispro Insulin Aspart Long acting without peak action to simulate normal basal insulin
Glargine
FREQUENTLY USED REGIMES
Twice daily regimes 2 daily injections of a mixture of a short or rapid insulin with an intermediate acting insulin (before meal and before main evening meal).
Approximately 1/3 of the total insulin dose is short acting and 2/3 is intermediate.
2/3 of the total daily insulin is given in the morning and 1/3 in the evening.
Three injections daily Before breakfast – mixture of rapid or short with intermediate Before afternoon snack or evening meal – rapid or short Before bed – intermediate acting
Insulin Dosage
Prepubertal children usually require 0.7-1.0 IU/kg/day During puberty, requirements may rise above 1 and even up to 2 IU/kg/day
INSULIN CONCENTRATIONS
Insulin is available in different concentrations 40, 80 & 100 Unit/ml.
WHO now recommends U 100 to be the only used insulin to prevent confusion.
Special preparation for infusion pumps is soluble insulin 500 U/ml.
ADVERSE EFFECTS OF INSULIN
Hypoglycemia Lipoatrophy Lipohypertrophy Obesity Insulin allergy Insulin antibodies Insulin induced edema
PRACTICAL PROBLEMS
injection sites & technique Insulin storage & transfer Mixing insulin preparations Insulin & school hours Adjusting insulin dose at home Sick-day management Recognition & Rx of hypo at home
TREATMENT MADE EASY
Insulin pens & new delivery products Handy insulin pumps fine micro needles Simple accurate glucometers Free educational material computer programs for comprehensive management & monitoring
Diet On the standard twice daily regime, food intake is divided into 3 main meals with snacks between meals and before going to bed. Diet should be high in fibre which will provide a sustained release of carbs.
Type of Food
The following are among the most recent consensus recommendations: Carbohydrates should provide 50-55% of daily energy intake. (No more than 10% of carbohydrates should be from sucrose or other refined carbohydrates.) Fat should provide 30-35% of daily energy intake.
Protein should provide 10-15% of daily energy intake.
Activity
Type 1 diabetes mellitus requires no restrictions on activity; exercise has real benefits for a child with diabetes.
Most children can adjust their insulin dosage and diet to cope with all forms of exercise.
The current guidelines are increasingly sophisticated and allow children to compete at the highest levels in sport.
Dreams are the seedlings of realities
FUTURE PROMISES
The cure for IDDM is successful islet cell transplantation , which will be available in the near future.
Primary prevention by a vaccine or drug will be offered to at risk subjects identified by genetic studies. Gene modulation therapy for susceptible subjects is a promising preventive measure.
DIABETES MELLITUS - TYPE 1 MONITORING STRATEGIES
• Self Blood Glucose Monitoring – 2 to 4 / day • Urine Testing – Ketones • Glycosylated Hemoglobin - HbA1 C - quarterly • Blood lipids - annually • Thyroid function – annually • Urine micro albumin – quarterly after 5 yr • Dilated fundoscopy – age 10 yr + 3-5 yr
Diabetic ketoacidosis
Ketoacidosis is a state of uncontrolled catabolism associated with insulin deficiency Diabetic ketoacidosis tends to occur in individuals younger than 19 years, but it may occur in patients with diabetes at any age.
Criteria Hyperglycemia: blood glucose >11mmol/L(200mg/dL) Venous pH<7.3 or bicarbonate <15 mmol/L Ketonemia and ketonuria
Diabetic ketoacidosis
In the absence of insulin, hepatic glucose production accelerates, and peripheral uptake by tissues such as muscle is reduced.
Rising glucose levels lead to an osmotic diuresis, loss of fluid and electrolytes, and dehydration.
Plasma osmolality rises and renal perfusion falls. In parallel, rapid lipolysis occurs, leading to elevated circulating free fatty-acid levels.
The free fatty acids are broken down to fatty acyl-CoA within the liver cells, and this in turn is converted to ketonebodies within the mitochondria
Diabetic ketoacidosis
Accumulation of ketone bodies produces a metabolic acidosis . Vomiting leads to further loss of fluid and electrolytes.
The excess ketones are excreted in the urine but also appear in the breath, producing a distinctive smell similar to that of acetone.
Respiratory compensation for the acidosis leads to hyperventilation, graphically described as 'air hunger'. Progressive dehydration impairs renal excretion of hydrogen ions and ketones, aggravating the acidosis
Diabetic ketoacidosis
Mostly the causes are Previous undiagnosed diabetes Interruption of insulin therapy The stress of intercurrent illness Goals of therapy Correct dehydration Correct acidosis and reverse ketosis Restore blood glucose to near normal Avoid complications of therapy Identify and treat precipitating event
History
Classic symptoms of hyperglycemia Thirst Polyuria, polydipsia Nocturia Other symptoms Generalized weakness Malaise/lethargy Nausea/vomiting Decreased perspiration Fatigue Anorexia or increased appetite Confusion Symptoms of associated infections and conditions Fever Dysuria Chills Chest pain Abdominal pain Shortness of breath
Physical
General signs Ill appearance Dry skin Labored respirations Dry mucous membranes Decreased skin turgor Decreased reflexes Vital signs Tachycardia Hypotension Tachypnea Hypothermia Fever, if infection Specific signs Ketotic breath (fruity, with acetone smell) Confusion Coma Abdominal tenderness
Management
1. Fluids If in shock, initial resuscitation with normal saline. Dehydration should then be
corrected gradually over 48 to 72 hour
-
using 0.45% Saline
Monitor : Fluid input and output Electrolytes, creatinine and acid-base status regularly Neurological states 2 .
Insulin insulin infusion is started, titrating the dose according to the blood glucose. Monitor blood glucose regularly.
aim for gradual reduction of blood glucose .
3. Potassium Although the initial plasma concentration may be high, it will fall following treatment with insulin and rehydration High doses (20 to 40 mEq/L) to be added to drips 4. Sodobicarb (used only in selected patients) severe acidemia(arterial pH<6.9)in whom decreased cardiac contractility and peripheral vasodilation can further impair tissue function life threatening hyperkalemia cautiously give 1-2 mmol/kg over 60 min
COMPLICATIONS OF THERAPY
Main complication is
BRAIN EDEMA
© 2004, John Walsh, P.A., C.D.E.
TYPE 2 DM IN CHILDREN
Among 10 – 19 yr olds
T2 DM accounts for 33% of all new cases
African Americans – 42% Caucasians – 10%
Obesity Acanthosis Nigricans
Natural History of Type 2 Diabetes
Complications Disability Genetic susceptibility Environmental factors Onset of diabetes Obesity Insulin resistance P R E Risk for Disease Metabolic Syndrome Ongoing hyperglycemia Atherosclerosis Hyperglycemia Hypertension Retinopathy Nephropathy Neuropathy Death Blindness Renal failure CHD Amputation
Therapy of T2 DM in Children
Reduce calories – weight loss NOT T1 DM diet with high complex CHO No Between meal snacks NOT T1 DM where hypoglycemia is frequent Reduce CHO intake Reduce fat intake Exercise – increase healthy life style x Drug treatment early
BG 250 mg/dL or 12 mmol/L Start with insulin and diet, exercise Diagnosis Asymptomatic
Diet and exercise
< 7% Add metformin Attempt to wean insulin
Monthly review, A1C q3mo
> 7%
Add metformin
> 7%
Add insulin, TZD, sulfonylurea
> 7%
Add 3rd agent
TZD = thiazolidinedione Silverstein JH, Rosenbloom AL.
J Pediatr Endcrinol Metab. 2000;13 Suppl 6:1406-1409.
< 7%
T2 DM vs T1 DM
T2 DM Obesity
+
Family Hx T2 95% > 85%tile 72 – 85% Acanthosis Nigricans Maternal Gestational DM IUGR 60 – 86%
+ +
T1 DM Not Common Not Common 7% all school aged children Not Common Not common
T2 DM vs. T1 DM
Polyuria/dypsia Ketonuria DKA Autoimmunity Initial insulin Honeymoon Worse @ illness T2 - DM
+ + / + / + / -
Often required
+ +
T1 – DM
+ + / + / +
Required
+ +
Amputations Loss of Sensations Heart disease and strokes Blindness Kidney failure
Uncontrolled diabetes can lead to…
Death
By learning you will teach; By teaching you will learn.
Latin Proverb
© 2004, John Walsh, P.A., C.D.E.
Research tells us 14 out of any 10 individuals likes Candy