Diabetes Mellitus in Children
By: Abiye Zeleke (MD, Pediatrician)
July-2019
Out line
Introduction
Classification of diabetes mellitus
Type I diabetes mellitus
Epidemiology
Risk factors
Pathogenesis and Natural History
Clinical manifestation
Diagnosis
Complications
Introduction
Diabetes mellitus (DM) is a common, chronic, metabolic syndrome characterized by
hyperglycemia as a cardinal biochemical feature
DM is not a single entity but rather a heterogeneous group of disorders in which there
are distinct genetic patterns as well as other etiologic and pathophysiologic
mechanisms that lead to impairment of glucose tolerance
The major forms of diabetes are classified according to those caused by deficiency of
insulin secretion due to pancreatic β-cell damage
and those that are a consequence of insulin resistance occurring at the level of
skeletal muscle, liver, and adipose tissue, with various degrees of β-cell impairment
Classification
Three major forms of diabetes and several forms of carbohydrate intolerance
are identified
Type I diabetes (β-cell destruction, usually leading to absolute insulin deficiency)
Immune mediated
Idiopathic
Type 2 diabetes (may range from predominantly insulin resistance with relative
insulin deficiency to a predominantly secretory defect with insulin resistance)
Neonatal diabetes mellitus
Transient—without recurrence
Transient—recurrence 7-20 yr. later
Permanent from onset
Gestational diabetes mellitus
Type 1 Diabetes Mellitus
Formerly called insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes, is
characterized by low or absent levels of endogenously produced insulin and
dependence on exogenous insulin to prevent development of ketoacidosis
is the most common endocrine-metabolic disorder of childhood and adolescence,
with important consequences for physical and emotional development
Patients with any form of diabetes may require insulin treatment at some stage of the
disease. Such use of insulin does not, of itself, classify the patient to T1DM
Epidemiology
T1DM accounts for about 10% of all diabetes, affecting 1.4 million in the USA and over 15
million in the world.
While it accounts for most cases of diabetes in childhood, it is not limited to this age group
new cases continue to occur in adult life and approximately 50% of individuals with T1DM
present as adults
it is estimated that of the 400,000 total new cases of type 1 diabetes occurring annually in all
children under age 14 yr. in the world, about half are in Asia
Girls and boys are almost equally affected but there is a modest female preponderance in
some low-risk populations
there is no apparent correlation with socioeconomic status
Predisposing factors
Genetics(host factor)
There is a clear familial clustering of T1DM, with prevalence in siblings
approaching 6% while the prevalence in the general population in the USA is
only 0.4%.
Risk of diabetes is also increased when a parent has diabetes and this risk differs
between the 2 parents; the risk is 2% if the mother has diabetes, but 7% when
the father has diabetes
In monozygotic twins, the concordance rate ranges from 30-65%, whereas
dizygotic twins have a concordance rate of 6-10%
Genetic cont.
Since the concordance rate of dizygotic twins is higher than the sibling risk, factors
other than the shared genotypes (for example the shared intrauterine environment)
may play a role in increasing the risk in dizygotic twins.
Furthermore, the genetic susceptibility for T1DM in the parents of a child with diabetes
is estimated at 3%.
although there is a large genetic component in T1DM, 85% of newly diagnosed type 1
diabetic patients do not have a family member with T1DM.
Thus, we cannot rely on family history to identify patients who may be at risk for the
future development of T1DM as most cases will develop in individuals with no such
family history environmental factors
Environmental Factors
Viral Infections
Congenital Rubella Syndrome
Enteroviruses
Mumps Virus
Role of Childhood Immunizations
The Hygiene Hypothesis: Possible Protective Role of Infections
Diet
Breast-milk
early introduction of cow's milk protein
early exposure to gluten protein
Psychologic Stress
Whether these stresses only aggravate pre-existing autoimmunity or whether they can
actually trigger autoimmunity, remains unknown.
Role of Insulin Resistance: The Accelerator Hypothesis
Pathogenesis and Natural History of Type 1 Diabetes Mellitus
The pathogenesis and natural history of T1DM involves some or all of the following stages
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
Pathogenesis cont.
Initiation of Autoimmunity
Preclinical Autoimmunity with Progressive Loss of β-Cell Function
In some, but not all patients, the appearance of autoimmunity is followed by
progressive destruction of β cells.
Antibodies are a marker for the presence of autoimmunity, but the actual
damage to the β cells is primarily T-cell mediated
Histologic analysis of the pancreas from patients with recent-onset T1DM
reveals insulitis, with an infiltration of the islets of Langerhans by mononuclear
cells, including T and B lymphocytes, monocytes/macrophages, and natural killer
(NK) cells
Pathophysiology
Insulin is considered to be the major factor governing these metabolic processes. Diabetes
mellitus may be viewed as a permanent low-insulin state that, untreated, results in
exaggerated fasting
Diagnosis of DM
DIAGNOSTIC CRITERIA FOR IMPAIRED GLUCOSE TOLERANCE AND DIABETES
MELLITUS
Symptoms include polyuria, polydipsia, and unexplained weight loss with glucosuria and
ketonuria.
Clinical Manifestations
As diabetes develops, symptoms steadily increase, reflecting the decreasing β-
cell mass, worsening insulinopenia, progressive hyperglycemia, and eventual
ketoacidosis
Initially, when only insulin reserve is limited, occasional hyperglycemia occurs.
When the serum glucose increases above the renal threshold, intermittent
polyuria or nocturia begins.
With further β-cell loss, chronic hyperglycemia causes a more persistent
diuresis, often with nocturnal enuresis, and polydipsia becomes more apparent
Clinical….cont.
Peaks of presentation occur in 2 age groups:
at 5-7 yr. of age and at the time of puberty.
The 1st peak may correspond to the time of increased exposure to infectious agents
coincident with the beginning of school;
the 2nd peak may correspond to the pubertal growth spurt induced by gonadal
steroids and the increased pubertal growth hormone secretion (which antagonizes
insulin).
These possible cause-and-effect relationships remain to be proved
A growing number of cases are presenting between 1 and 2 yr of age, especially in
high-risk groups
Complications
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are
acute complications of diabetes.
DKA was formerly considered a hallmark of type 1 DM, but it also occurs in
individuals who lack immunologic features of type 1 DM and who can
subsequently be treated with oral glucose-lowering agents (these obese
individuals with type 2 DM
complication……….. cont.
When extremely low insulin levels are reached, keto acids accumulate.
At this point, the child quickly deteriorates.
Keto acids produce abdominal discomfort, nausea, and emesis, preventing oral
replacement of urinary water losses.
Dehydration accelerates, causing weakness or orthostasis—but polyuria
persists.
As in any hyperosmotic state, the degree of dehydration may be clinically
underestimated because intravascular volume is conserved at the expense of
intracellular volume
About 20-40% of children with new-onset diabetes progress to DKA before
diagnosis.
Diabetic Ketoacidosis
DKA is the end result of the metabolic abnormalities resulting from a severe
deficiency of insulin or insulin effectiveness.
The latter occurs during stress as counter-regulatory hormones block insulin
action.
DKA occurs in 20-40% of children with new-onset diabetes and in children
with known diabetes who omit insulin doses or who do not successfully
manage an intercurrent illness.
DKA may be arbitrarily classified as mild, moderate, or severe
PATHOPHYSIOLOGY
Precipitating factors
Natural course
Inadequate insulin administration
Infection (pneumonia/UTI/gastroenteritis/sepsis)
Infarction (cerebral, coronary, mesenteric, peripheral)
Drugs (cocaine)
Pregnancy
Clinical manifestation of DKA
Symptoms
In addition to poly symptoms
Nausea/vomiting
Thirst/polyuria
Abdominal pain
Physical findings
Tachycardia
Tachypnea / Kussmaul respirations/respiratory distress
Dehydration / hypotension
Shortness of breath
Abdominal tenderness (may resemble acute pancreatitis or surgical abdomen
Lethargy /obtundation / cerebral edema / possibly coma
Classification DKA
Used for management purpose
It can be based on
Clinical criteria
Laboratory findings
Classification cont.
Management principle of DKA
Confirm diagnosis
Admit to hospital
Assess:
Serum electrolytes
Acid-base status
Renal function
Replace fluids
Administer short-acting insulin
Management principle cont.
Replace Electrolyte
Threat the precipitating factor
Follow up
Administer intermediate or long-acting insulin as soon as patient is out of
DKA
Complication of DKA
Cerebral Edema
Cerebral edema complicating DKA remains the major cause of morbidity and
mortality in children and adolescents with T1DM
Hypoglycemia
Electrolyte disorder
Thank you
