Diabetes Mellitus

Dr. Yafet Solomon

Introduction
Diabetes mellitus is the most common endocrine disease
and one of the most common chronic conditions in children
Type 2 diabetes and other types of diabetes, including
genetic defects of beta cell function, such as maturity-onset
diabetes of the young, are being increasingly recognized in
children and should be considered when clinical
presentation is atypical for type 1 diabetes.
 Diabetes Mellitus
Definition -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).
 WHO CLASSIFICATION 2000
-Is based on etiology not on type of treatment
or age of the patient.
-Type 1 Diabetes

-Type 2 Diabetes

-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.
Other genetic syndromes sometimes associated with
diabetes
Down syndrome
Klinefelter syndrome
Turner syndrome
Wolfram syndrome
Friedreich ataxia
Huntington chorea
Laurence-Moon-Biedl syndrome
Myotonic dystrophy
Porphyria
Prader-Willi syndrome
Others
 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 -random plasma glucose concentration ≥ 11.1
mmol/L ( ≥200mg/dl).
Random is defined as at any time of the day without regard
to time since the last meal.
-Fasting plasma glucose ≥ 7.0 mmol/L (≥126mg/dl).
Fasting is defined as no caloric intake for at least 8h.
-2h post load glucose ≥ 11.mmol/L (≥200mg/dl) during
an OGTT.
 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
-Symptoms of DKA
-Accidental diagnosis
 Type 1 Diabetes Mellitus
Type 1 DM -is characterized by low or absent levels
of endogenously produced insulin and
dependence on exogenous insulin to
prevent development of ketoacidosis,
an acute life-threatening complication
of T1DM
The natural history includes 4 distinct stages:
1-preclinical β-cell autoimmunity with progressive
defect of insulin secretion,
2-onset of clinical diabetes,
3-transient remission “honeymoon period,”
4-established diabetes associated with acute and
 Type I DM Continued …

-The onset occurs predominantly in childhood

- median age of 7-15 yr, may present at any age
- incidence steadily increasing
- is characterized by autoimmune destruction of
pancreatic islet β cells
-Both genetic susceptibility and environmental
factors contribute to the pathogenesis
DIAGNOSTIC CRITERIA FOR IMPAIRED GLUCOSE
TOLERANCE AND DIABETES MELLITUS
IMPAIRED GLUCOSE TOLERANCE (IGT) DIABETES MELLITUS (DM)
Fasting glucose 100-125 mg/dL (5.6-7.0 mmol/L) Symptoms* of DM plus
random
plasma glucose
≥ 200 mg/dL
(11.1 mmol/L)
2-hr plasma glucose during the OGTT or
≥140 mg/dL, but <200 mg/dL 11.1 mmol/L) Fasting plasma glucose
≥ 126 mg/dL
(7.0 mmol/L)
or
2-hr plasma glucose during
the
OGTT ≥200 mg/dL

OGTT - oral glucose tolerance test

 -The term impaired glucose tolerance (IGT) refers to
a metabolic stage that is intermediate between
normal glucose homeostasis and diabetes.
- A FBS 99 mg/dL (5.5 mmol/L) is the upper limit of
“normal.”
-This shows insulin secretion is lost in response to
intravenous administration of glucose
-It is associated with risk of the development of
microvascular and macrovascular complications.
 Pathogenesis
1 -Initiation of autoimmunity
2 -Preclinical autoimmunity with progressive loss
of β-cell function
3 -Onset of clinical disease
4 -Transient remission
5 -Established disease
6 -Development of complications
 Pathophysiology
-Insulin performs a critical role in the storage and retrieval of
cellular fuel.
- Its secretion in response to feeding is exquisitely modulated by
the interplay of neural, hormonal, and substrate-related
mechanisms
- in normal metabolism
after feeding postprandial -> high-insulin anabolic state
during fasting -> low-insulin catabolic state
-this affect liver, muscle, and adipose tissue
-T1DM is a progressive low-insulin catabolic state in which feeding
does not reverse but rather exaggerates these catabolic processes.
-With moderate insulinopenia, glucose utilization by muscle and fat
decreases and postprandial hyperglycemia appears.
- lower insulin levels  production of excessive
glucose in the liver via glycogenolysis
and gluconeogenesis fasting hyperglycemia
begins  osmotic diuresis (glycosuria) when the
renal threshold is exceeded 180 mg/dL  loss of
calories and electrolytes  persistent dehydration
 physiologic stress  hypersecretion of stress
hormones (epinephrine, cortisol, growth hormone,
and glucagon)  further impairing insulin secretion
(epinephrine)  promoting glycogenolysis,
gluconeogenesis, lipolysis, and ketogenesis
 Clinical Manifestations
- polyuria or nocturia
-nocturnal enuresis
- polydipsia
-Female patients may develop monilial vaginitis due
to the chronic glycosuria
-Hyperphagia
- weight loss and diminished subcutaneous fat stores
- abdominal discomfort
- nausea and emesis
 - Dehydration accelerates, causing weakness or
orthostasis
-Ketoacidosis exacerbates prior symptoms and leads
to Kussmaul respirations
-fruity breath odor (acetone)
-prolonged corrected Q-T interval (QTc)
-diminished neurocognitive function, and possible
coma
-About 20-40% of children with new-onset diabetes
progress to DKA before diagnosis.
 Treatment
New-Onset Diabetes without Ketoacidosis
Insulin Therapy
-Children with long-standing diabetes and no insulin
reserve require about
- 0.7 U/kg/day if prepubertal
- 1.0 U/kg/day at midpuberty
-1.2 U/kg/day by the end of puberty.
-it is 60-70% of the full replacement dose based on
pubertal status
 SUBCUTANEOUS INSULIN DOSING

BOLUS[†] INSULIN
BASAL
TOTAL
TARGET INSULIN, %
DAILY
AGE (yr) GLUCOSE OF TOTAL Units Added
INSULIN Units Added
(mg/dL) DAILY per
(U/kg/day)* per 15 g at
DOSE 100 mg/dL
Meal
Above Target

0-5 100-200 0.6-0.7 25-30 0.50 0.50

5-12 80-150 0.7-1.0 40-50 0.75 0.75

12-18 80-130 1.0-1.2 40-50 1.0-2.0[‡] 1.0-2.0

-Newly diagnosed children in the “honeymoon” may
only need 60-70% of a full replacement dose
- Total daily dose per kg increases with puberty
-Frequent blood glucose monitoring and insulin
adjustment are necessary in the 1st weeks as the
child returns to routine activities and adapts to a
new nutritional schedule, and as the total daily
insulin requirements are determined.
 Basic and Advanced Diabetes Education
- education of the patient and family
- Teaching is most efficiently provided by
experienced diabetes educators and nutritionists
- In the acute phase, the family must learn the
“basics,”
- monitoring the child's blood glucose and urine
ketones
- preparing and injecting the correct insulin
dose subcutaneously at the proper time
- recognizing and treating low blood glucose
reactions
- having a basic meal plan
- Written materials covering these basic topics
help the family during the 1st few days.
 Nutritional Management
-Nutrition plays an essential role in the
management of patients with T1DM
- This is of critical importance during childhood and
adolescence, when appropriate energy intake is
required to meet the needs for energy
expenditure, growth, and pubertal development
-It averts or relieves symptoms of hyperglycemia in
diabetic patients
-It may influence the development of long-term
complications of diabetes (diabetic nephropathy)
- There are no special nutritional requirements for
the diabetic child other than those for optimal
growth and development
-Total recommended caloric intake is based on size
or surface area
- The caloric mixture comprise
-55% carbohydrate
- 30% fat
-15% protein
-Approximately 70% of the carbohydrate content should be
derived from complex carbohydrates such as starch
- intake of sucrose and highly refined sugars should be
limited
- Complex carbohydrates require prolonged
digestion and absorption so that plasma glucose
levels increase slowly
- whereas glucose from refined sugars, including
carbonated beverages, is rapidly absorbed and
may cause wide swings in the metabolic pattern
- Carbohydrate counting has become a mainstay in
the nutrition education and management of
patients with DM
CALORIE NEEDS FOR CHILDREN AND YOUNG ADULTS
AGE kcal REQUIRED/kg BODY WEIGHT
CHILDREN
0-12 mo 120
1-10 yr 100-75
YOUNG WOMEN
11-15 yr 35
≥16 yr 30
YOUNG MEN
11-15 yr 80-55 (65)
16-20 yr
Average activity 40
Very physically active 50
Sedentary 30
From Nutrition guide for professionals: diabetes education and meal
planning, Alexandria, VA, and Chicago, IL, 1988, The American Diabetes
 NUTRIENT RECOMMENDATIONS AND DISTRIBUTION

RECOMMENDED DAILY
NUTRIENT (%) of CALORIES
INTAKE
High fiber, especially soluble
Carbohydrate Will vary fiber; optimal amount
unknown
Fiber >20g per day

Protein 12-20

Fat <30

Saturated <10

Polyunsaturated 6-8

Monounsaturated Remainder of fat allowance

Cholesterol 300 mg
Avoid excessive; limit to
Sodium 3,000-4,000 mg if
hypertensive
 ADDITIONAL RECOMMENDATIONS
Energy: If using measured diet, reevaluate prescribed
energy level at least every 3 mo.
Protein:- High-protein intakes may contribute to
diabetic nephropathy
-Low intakes may reverse preclinical
nephropathy
-Therefore, 12-20% of energy is
recommended
Alcohol: Safe use of moderate alcohol
Snacks: Snacks vary according to individual needs
Alternative sweeteners: Use of a variety of sweeteners is
suggested.
Educational techniques: No single technique is superior
Follow-up education and
support are required.
Eating disorders: Best treatment is prevention
Unexplained poor control or severe
hypoglycemia may
indicate a potential eating disorder.
Exercise: Education is vital to prevent delayed or
immediate hypoglycemia and to prevent
worsened hyperglycemia and ketosis.
 Hypoglycemic Reactions
- pallor
- sweating
- apprehension or fussiness
- hunger
- tremor
-tachycardia
- Behavioral changes such as tearfulness
- irritability
- aggression
-naughtiness are more prevalent in children
- As glucose levels decline further, cerebral glucopenia
occurs
 - drowsiness
-personality changes
- mental confusion
-impaired judgment (moderate hypoglycemia)
-seizures or coma (severe hypoglycemia)
- Prolonged severe hypoglycemia can result in a
depressed sensorium or strokelike focal motor
deficits that persist after the hypoglycemia has
resolved
- permanent sequelae are rare, but is frightening for
the child and family
 Somogyi Phenomenon, Dawn Phenomenon, and
Brittle Diabetes
-Dawn phenomenon- is thought to be due mainly to
overnight growth hormone secretion and increased
insulin clearance.
-It is a normal in most non diabetic adolescents, who
compensate with more insulin output
- A child with T1DM cannot compensate
- The dawn phenomenon is usually recurrent and
modestly elevates most morning glucose levels
-Somogyi phenomenon- a theoretical rebound from
late night or early morning hypoglycemia, thought
to be due to an exaggerated counter-regulatory
response
-The term brittle diabetes has been used to describe
the child usually an adolescent female
- with unexplained wide fluctuations in blood
glucose
- often with recurrent DKA
- who is taking large doses of insulin
-This children shows normal responsiveness when
in the hospital environment
- Psychosocial
- psychiatric problems
- including eating disorders
-dysfunctional family dynamics are usually present
- aggressive psychosocial or psychiatric evaluation is
essential
Long-Term Complications
-Complications of DM divided into 3 major
categories
-1) microvascular complications, specifically,
retinopathy and nephropathy
-2) macrovascular complications, particularly
accelerated coronary artery disease,
cerebrovascular disease, and peripheral vascular
disease
-3) neuropathies, both peripheral and autonomic,
affecting a variety of organs and systems
 SCREENING GUIDELINES
WHEN TO PREFERRED OTHER POTENTIAL
COMMENCE FREQUENCY METHOD OF SCREENING INTERVENTI
SCREENING SCREENING METHODS ON

After 5 yr duration in Fluorescein

prepubertal children, angiography, Improved glycemic
Retinopathy 1-2 yearly Fundal photography
after 2 yr in pubertal mydriatic control, laser therapy
children ophthalmoscopy

After 5 yr duration in 24-hr excretion of Improved glycemic

Overnight timed
prepubertal children, albumin, urinary control, blood
Nephropathy Annually urine excretion of
after 2 yr in pubertal albumin/creatinine pressure control, ACE
albumin
children ratio inhibitors

Nerve conduction,
thermal and
vibration threshold, Improved glycemic
Neuropathy Unclear Unclear Physical examination
pupillometry, control
cardiovascular
reflexes
Statins for
Macrovascular hyperlipidemia
After age 2 yr Every 5 yr Lipids Blood pressure
disease Blood pressure
control
Thyroid peroxidase
Thyroid disease At diagnosis Every 2-3 yr TSH Thyroxine
antibody
Tissue
Antigliadin
Celiac disease At diagnosis Every 2-3 yr transglutaminase, Gluten-free diet
antibodies
endomysial antibody
Diabetic retinopathy
- is the leading cause of blindness in adults aged 20-65 yr
- The risk of diabetic retinopathy after 15 yr duration of
diabetes is 98% for individuals with T1DM
- 78% for those with T2DM
- The earliest clinically apparent manifestations of diabetic
retinopathy are classified as nonproliferative or background
diabetic retinopathy
-microaneurysms
- dot and blot hemorrhages
- hard and soft exudates
-venous dilation and beading
-intraretinal microvascular abnormalities
 - These changes do not impair vision
- The more severe form is proliferative diabetic
retinopathy
-manifested by neovascularization
- fibrous proliferation
- and preretinal and vitreous hemorrhages
- Proliferative retinopathy, if not treated, is
relentlessly progressive and impairs vision, leading
to blindness.
-The mainstay of treatment is panretinal laser
photocoagulation
 Diabetic nephropathy
-is the leading known cause of end-stage renal disease
(ESRD)
- Most ESRD from diabetic nephropathy is preventable
- Diabetic nephropathy affects 20-30% of patients with
T1DM
- 15-20% of T2DM patients 20 yr after onset
- The mean 5-yr life expectancy with diabetes-related
ESRD is less than 20%
- The glycation of tissue proteins results in glomerular
basement membrane thickening
- The course of diabetic nephropathy is slow
- An increased urinary albumin excretion rate (AER)
-microalbuminuria
- glomerular hyperfiltration
- blood pressure elevation
- proteinuria
- hypertension
- Advanced stage
- decline in renal function
-declining glomerular filtration rate
- elevation of serum blood urea and creatinine
- progressive proteinuria
- hypertension
- Progression to ESRD is recognized by the appearance
 Diabetic Neuropathy
- Both the peripheral and autonomic nervous systems
can be involved, and adolescents with diabetes can
show early evidence of neuropathy
-Subclinical motor nerve impairment
- An early sign of autonomic neuropathy such as
decreased heart rate variability may present in
adolescents with a history of long-standing disease
and poor metabolic control
-There are different treatment modalities , among them
use of anticonvulsants (e.g., lorazepam, valproate,
carbamazepine, tiagabine, and topiramate) for
treatment of neuropathic pain.
 Prognosis
-T1DM is a serious, chronic disease
- average life span 10 yr shorter than that of the
non diabetic population
- puberty may be delayed
- the final height may be less than the genetic
potential
THANK YOU!