DIABETES MELLITUS TYPE 1

Dr Faten Zaidan

Pathophysiology

Immune or non-immune destruction (autoantibodies) of insulin secreting beta cells of pancreas leading to severe or absolute deficiency of insulin and required exogenous insulin
First there will be partial deficiency of insulin:
- decreased lipogenesis, energy expenditure, weight loss, fatigability, classic triad
As more insulin is getting deficient reaching into absolute insulin deficiency: there will be increased lipolysis and production of ketone bodies resulting in DKA

DM type I may also be idiopathic, syndromic or due to infections

”Stages” in Development of Type 1A Diabetes

Secondary Causes of DM

Cystic fibrosis – related diabetes
Trauma – pancreatectomy
Pancreatitis
Congenital rubella
Cytomegalovirus
Endocrine tumors
Neonatal diabetes
Genetic syndrome such as Down Syndrome, Prader Willi, Turner, Klinefelter
Medications such as l-asparaginase, phenytoin, diazoxide, nicotinic acid, etc

Initial Clinical and Laboratory Findings in New-Onset Type 1 Diabetes

Table 1 – Initial clinical and laboratory findings in new-onset type 1 diabetes in children and adolescents

Clinical findings
Fatigue
Weight loss
Polyuria
Polydipsia
Secondary nocturnal enuresis
Blurred vision
Urinary tract infection
Vaginal candidiasis
Abdominal pain
Vomiting
Ketone breath
Kussmaul respiration
Laboratory findings
Hyperglycemia
Glucosuria
Ketonuria
Metabolic acidosis
Elevated blood urea nitrogen level
Elevated serum β-hydroxybutyrate level
Low C-peptide level
Elevated antibody levels (anti-glutamic acid decarboxylase, anti-islet cell, anti-insulin)

Diagnostic Criteria

Symptoms of diabetes
Blood test:
1. Random plasma glucose 200 mg/dl (11.1 mmol/l), OR
2. Fasting plasma glucose 126 mg/dl (7 mmol/l), OR
3. 2-hour plasma glucose 200 mg/dl during an oral glucose tolerance test.

HbA1c >= 6.5%

For monitoring therapy
For diagnosing DM

Impaired Glucose Tolerance Test

Blood Test Levels for Diagnosis of Diabetes and Prediabetes

Definitions: mg = milligram, dL = deciliter

For all three tests, within the prediabetes range, the higher the test result, the greater the risk of diabetes.

Conversion:

To convert mmol/l into mg/dl, multiply by 18
7 mmol/l × 18 = 126 mg/dl
11.1 mmol/l × 18 = 200 mg/dl

Approach for Newly Diagnosed DM I

Blood investigations:

Random blood glucose
Blood ketones
Urea and electrolytes (to assess dehydration and electrolyte disturbance)
Blood gas (to assess for acidosis)
Thyroid function test
Celiac screen
Diabetes related autoantibodies: GAD autoantibodies and islet cell antibodies

Physiological Serum Insulin Secretion Profile

Types of Insulin Injections

Several Methods for Insulin Injections

Method A: once-daily glargine
Method B: twice-daily detemir
Method C: twice-daily NPH along with a short-acting analogue insulin before each meal

Insulin Pump

Insulin pumps are programmed to automatically deliver certain amounts of fast-acting insulin that is stored in the pump’s reservoir. Insulin is delivered to the body through a tube attached to a small plastic needle, which is inserted under the skin

Insulin doses administered by an insulin pump are separated into:

Basal rates: Basal insulin is delivered continuously throughout the day. It keeps blood glucose levels in range between meals and overnight.
Bolus Doses to Cover Carbohydrate in Meals: When the patient eats a meal, an additional insulin dose called a bolus is required to cover the carbohydrates in each meal. The patient should insert the amount of carbohydrates in the meal by using the buttons on the insulin pump, as well as measure their blood sugar levels. The pump responds by providing options of insulin doses that are proportional to the amount of carbohydrates in the meal and the patient’s current blood sugar levels. It is then up to the patient to give the pumping order.
Correction or Supplemental Doses: The patient inserts their current blood sugar levels, then chooses the appropriate dose by giving the pumping order.

Advantages of Using an Insulin Pump:

It improves the patient’s quality of life and makes it easier for them to live with the disease
Fewer injections and needles
Tighter control over blood sugar levels (it reduces the risk of low blood sugar and improves average blood sugar levels)
Easier and more efficient insulin delivery (with the press of a button)

Disadvantages of Using an Insulin Pump:

Higher risk of skin infections and skin irritation
It requires the patient to check their blood sugar level at least four times a day
It can cause diabetic ketoacidosis due to pump malfunction if the tube gets blocked

Insulin pumps

Blood Glucose Target in DM Patients

Blood glucose targets are:

On waking: 4-7 mmol/l
Before meals: 4-7 mmol/l Z
After meals: 5-9 mmol/l

Injection Technique

Complications to Insulin Injections

Lipoatrophy (adverse immunological side effect of insulin)
Lipohypertrophy (benign tumour-like swelling of fatty tissue at injection site secondary to lipogenic effect of insulin)
Local Allergic reaction (erythema and pruritis)

Education and Counselling

Children with new-onset type 1 diabetes and their families require intensive diabetes education by a multidisciplinary pediatric diabetes healthcare team (endocrinologist, nutritionist, general pediatrician):

Insulin Action and Administration, Dosage Adjustment

Fasting blood glucose reflects the action of the basal insulin and if patient has a pattern of high fasting blood glucose, then the basal insulin dose will need to be increased to bring the glucose level into target range
The premeal blood glucose reflects the action of the insulin analogue injected in the preceding meal
Start insulin as multiple daily insulin injections or as a continuous subcutaneous insulin infusion 0.5-0.78 units/kg/day

Patient and Family Education:

Patients and their families should be taught to monitor glucose and blood ketones levels, assess carbohydrates content of food and use insulin:carbohydrate ratio to decide the premeal insulin dosage
Patients and their families should learn how to manage both hypo and hyperglycemia, prevent development of DKA and manage days when other illnesses develop (sick day rules)
If hypoglycemic, give oral sugar containing fluids. If unconscious, give glucagon 30 mcg/kg
If hyperglycemic and ketones present in urine, give extra regular insulin 0.1 units/kg/dose every 4-6 hours Z
All children and their families should be taught about the need for healthy eating and carbohydrate counting skills at diagnosis. Healthy, balanced diet consist of: z
- 50-60% of total calories from carbohydrate
- <30% from fat
- 10-20% from protein
Families should be taught on how to use the information to adjust insulin dosages to achieve the glycemic target
Exercise is essential for all and is to be encouraged and supported z

Sick Day Rules

Illness affects diabetes by two ways:

Lack of appetite: Frequent monitoring and sugar-containing oral fluids to avoid hypoglycemia is required. Insulin may be decreased but NEVER STOPPED
hyperglycemia and ketosis may be developed: Supplement with extra rapid or regular insulin 0.1 unit/kg/dose every 4-6 hours

Guidelines:

Follow local guidelines given to patient and family by diabetes team
Ensure drinking enough fluids to avoid dehydration
Never stop or omit insulin—though dose may need adjusting
Check blood glucose every 2 hours
Check blood ketones regularly
Administer correction doses of insulin to bring any high blood glucose in target
If blood glucose and blood ketones are high and the child is vomiting, they need urgent admission to hospital as the child is in DKA

Autoimmune Disease

There is higher risk in developing other autoimmune diseases in DM I patients compared to general population:

Autoimmune cond. inc. z	Indications for screening	Screening test	Frequency
Autoimmune thyroid disease - most common	All children with type 1 diabetes	Serum TSH level + thyroperoxidase antibodies	After diagnosis and every 2 years thereafter
	Positive thyroid antibodies, thyroid symptoms or goiter	Serum TSH level + thyroperoxidase antibodies	Every 6–12 months
Addison’s disease - uncommon	Unexplained recurrent hypoglycemia and decreasing insulin requirements	8 AM serum cortisol + serum sodium and potassium	As clinically indicated
Celiac disease - 2nd	Recurrent gastrointestinal symptoms, poor linear growth, poor weight gain, fatigue, anemia, unexplained frequent hypoglycemia or poor metabolic control	Tissue transglutaminase + immunoglobulin A levels	As clinically indicated

Others:

Autoimmune liver disease
Thyrotoxicosis

Complications

Risk of long-term complications is reduced by improved glycemic control:

Diabetic nephropathy
Diabetic retinopathy
Diabetic neuropathy
Ischemic heart disease
Hypertension
Peripheral and cerebrovascular disease

Outpatient Care:

Visiting every 3 – 4 months
HbA1C every 3 – 4 months
Check clinically and biochemically for the associated condition eg. hypothyroidism once every 1 – 2 years
Provide free access to service
Continuous teaching
Group activities

Screening for Complications: Z

Complication	Indications & intervals for screening	Screening method
Nephropathy	• Yearly screening commencing at 12 years of age in those with duration of type 1 diabetes ≥ 5 years	• First morning (preferred) or random ACR • Abnormal ACR requires confirmation at least 1 month later with a first morning ACR, and if abnormal, followed by timed, overnight or 24-hour split urine collections for albumin excretion rate • Repeated sampling should be done every 3–4 months over a 12-month period to demonstrate persistence
Retinopathy	• Yearly screening commencing at 15 yrs of age with duration of DM ≥ 5 yrs • Screening interval can increase to 2 yrs if good glycemic control, duration of diabetes < 10 yrs, and no retinopathy at initial assessment	• 7-standard field, stereoscopic-colour fundus photography with interpretation by a trained reader (gold standard); or • Direct ophthalmoscopy or indirect slit-lamp fundoscopy through dilated pupil; or • Digital fundus photography
Neuropathy	• Postpubertal adolescents with poor metabolic control should be screened yearly after 5 years’ duration of DM - clinical	• Question and examine for symptoms of numbness, pain, cramps and paresthesia, as well as sensation, vibration sense, light touch & ankle reflexes
Dyslipidemia	• Delay screening post-diabetes diagnosis until metabolic control has stabilized • Screen at ≥12 years of age or <12 years of age with BMI > 95th percentile, family history of hyperlipidemia or premature CVD	• Fasting total cholesterol, high-density lipoprotein cholesterol, triglycerides, calculated low-density lipoprotein cholesterol
Hypertension	• Screen all children with type 1 diabetes at least twice a year	• Use appropriate cuff size

DKA (Diabetic Ketoacidosis) Management

Confirm DKA:

Ketonuria
Glucose >11 mmol/L
pH <7.3
Serum Bicarbonate <18 mmol/L
Consult Pediatrician immediately

Algorithm of DKA Management

Resuscitation:

Assess airway and breathing
Apply 100% oxygen by mask
Normal Saline 10 ml/kg to expand vascular space

THEN:

Decrease to 5-7 ml/kg/hr with Potassium Chloride as noted below

After 1st Hour of IV Fluids:

If history of voiding within last hour and Potassium <5.5 mmol/L, add 40 mEq/L of Potassium Chloride to IV fluid
Aim to keep Potassium between 4-5 mEq/L
Continuous insulin infusion 0.1 units/kg/hr = 1 ml/kg/hr Z (of solution of 25 units of Regular Insulin in 250 ml Normal Saline). Include this amount in total fluid intake.
DO NOT GIVE BOLUS OF INSULIN
Continuous cardio-respiratory monitoring (with EKG tracing)

NOTE: Acidosis improving

Acidosis Improving Criteria:

Blood glucose <15 mmol/L

Blood glucose falls >5 mmol/L/h after 1st hour of fluids
- Change IV to D5/Normal Saline with Potassium as above
- Decrease insulin to 0.04 - 0.05 U/kg/hr = 0.4 - 0.5 ml/kg/hr of standard solution as above
Blood glucose <10 mmol/L change to D10/Normal Saline with Potassium as above

Improvement Criteria:

Clinically well
Tolerating oral fluids
pH >7.3
Bicarbonate >18 mmol/L
Start S/C insulin
Stop IV insulin ½ hour after S/C dose of rapid-acting or 1 hour after S/C dose of regular insulin
Determine cause of DKA
Contact regional Pediatric Diabetes Education Centre

lastly admit to endocrinology team

Neurological Deterioration:

Symptoms: Headache, irritability, decreased level of consciousness, decreased HR

First rapidly exclude hypoglycemia by capillary blood glucose measurement

THEN:

Treat for cerebral edema:

20% Mannitol 5 ml/kg over 20 minutes
If Sodium has declined, administer 2 - 4 ml/kg of 3% saline over 10 - 20 min