Type 2 Diabetes in Children

Dr. Abdulmoein Al-Agha, MBBS,DCH,CABP, MRCP(UK)

Consultant, Pediatric Endocrinologist, King
AbdulAziz University Hospital, Jeddah.


Diabetes mellitus type 2
Is a metabolic disorder that is primarily
characterized by insulin resistance, relative
insulin deficiency & hyperglycemia
It is rapidly increasing in the developed world
Has characterized the increase as an epidemic
Unlike type 1 diabetes, there is little tendency
toward ketoacidosis in Type 2 diabetes, though
it is not unknown
Complex and multi-factorial metabolic changes
lead to damage & function impairment of many
organs, most importantly the cardiovascular
system
Criteria for the Diagnosis of Diabetes
Symptoms of diabetes plus random plasma
glucose concentration 200 mg/dl (11.1 mmol/l).
The classic symptoms of diabetes include:
polyuria, polydepsia, and unexplained weight loss.
OR
FPG 126 mg/dl (7.0 mmol/l).
Fasting is defined as no caloric intake for at least 8 h.
OR
2-h PG 200 mg/dl (11.1 mmol/l) during OGTT
The test should be performed as described by W HO
using a glucose load containing equivalent of 75-g
anhydrous glucose dissolved in water.
Pathophysiology
Insulin resistance means that body cells do not
respond appropriately when insulin is present
Other important contributing factors:
increased hepatic glucose production (e.g., from
glycogen degradation), especially at inappropriate
times
decreased insulin-mediated glucose transport in
(primarily) muscles & adipose tissues (receptor and
post-receptor defects)
impaired beta-cell functionloss of early phase of
insulin release in response to hyperglycemic stimuli
Underlying causes of type 2 diabetes
Obesity
Insulin
resistance
-cell
defect
Impaired
glucose
tolerance
Early
diabetes
Late
diabetes
Hyperinsulinaemia
Decreased insulin
secretion
-cell failure
Adapted from Saltiel AR. J Clin Invest 2000;106:163164.
Obesity & Type 2 Diabetes

Too large meals !
Too high Calories !
Sedentary life style!!




Normal
The progressive nature of
type 2 diabetes
Impaired
glucose
tolerance
Type 2
diabetes
Fasting plasma glucose
Insulin sensitivity
Insulin secretion
Insulin
sensitive
Normal insulin
secretion
Normoglycaemia
Hyperglycaemia
-cell
exhaustion
Insulin
resistance
Late type 2
diabetes
complications
Adapted from Bailey CJ et al. Int J Clin Pract 2004;58:867876.
Groop LC. Diabetes Obes Metab 1999;1 (Suppl. 1):S1S7.
Insulin resistance
Type 2
Obesity&
Insulin
resistance
Genetic
susceptibility
Type 2 Diabetes in Children
Clinical presentation
Children with type 2 diabetes are usually
diagnosed over age of 10 years
Middle to late puberty
Milder symptoms than type 1 with mild
polydepsia, polyuria, little or no weight loss
Glucosuria with / without ketonuria
Up to 33% have ketonuria at diagnosis
525% of patients with type 2 diabetes have
ketoacidosis at presentation
Associated problems with type 2 DM
Obesity
Insulin resistance
Hyperinsulinism
Arterial hypertension
Hyperlipidemia
Acanthosis Nigerians
Macro & microangiopathy
PCOS


Acanthosis Nigricans
Acanthosis nigricans is
a cutaneous finding
frequently in darker-
skinned obese
individuals
Characterized by
velvety hyperpigmented
patches most prominent
in intertriginous areas
and is present in as
many as 90% of
children with type II
diabetes
Screening for type 2 DM in Children
& Adolescents

Why to screen for type 2 DM?


As in adults, a substantantial number of
children with type 2 can be detected in
A symptomatic state
In type 2, there is a prolonged latency period
without symptoms during which abnormality
can be detected
Only children at risk for the presence or
development of type 2 should be screened

Criteria of screening for Type 2 DM in Children
& Adolescents

1. overweight which is defined as (WHO)
body mass index (BMI) > 85
th
percentile
for age and sex
weight for height > 85
th
% ile
weight >120
th
% ile of ideal (50%) for
height
Plus two of the following risk factors:
2. Family history of type 2 DM in first or
second-degree relative

Criteria of screening for Type 2 DM in Children
& Adolescents

2. Race/ethnicity (Pima Indian, African-
American, Hispanic,
Asian / Pacific Islander)
3. Signs of insulin resistance or conditions
associated with insulin resistance
acanthosis nigricans
polycystic ovary syndrome
hypertension
dyslipidemia
Diabetic
retinopathy
Leading cause
of blindness
in working-age
adults
1
Diabetic
nephropathy
Leading cause of
end-stage renal disease
2
Cardiovascular
disease
Stroke
1.2- to 1.8-fold
increase in stroke
3
Diabetic
neuropathy
Leading cause of
non-traumatic lower
extremity amputations
5
75% diabetic
patients
die from CV events
4

Type 2 diabetes is NOT a mild disease
1
Fong DS, et al. Diabetes Care 2003;26 (Suppl. 1):S99S102.
2
Molitch ME, et al. Diabetes Care 2003;26 (Suppl. 1):S94S98.
3
Kannel WB, et al. Am Heart J 1990;120:672676.
4
Gray RP & Yudkin JS. In Textbook of Diabetes 1997.
5
Mayfield JA, et al. Diabetes Care 2003;26 (Suppl. 1):S78S79.

Prevention of type 2 DM
Prevention of obesity
(

.)
Prevention of type 2 DM
Public health measures
1. Media
2. School
3. Community
4. Family
Increase physical activity
Reduce caloric intake/obesity
Decrease sedentary life style
I. Computer
2. Video games
3. Television

Treatment of type 2 diabetes
There are limited data available regarding
management of type 2 diabetes in children
As a result, the goals of treatment in type 2
diabetes in adults have been applied to children
and adolescents
These goals include:
achieving psychological & physical well-being
long term glycemic control
defined as a fasting plasma glucose < 130mg/dL
HbA
1c
< 7%
preventing microvascular & macrovascular complications

Initial treatment of type 2 DM, will vary
depending on clinical presentation
Wide range from A symptomatic hyperglycemia to
DKA
Children who are not ill at diagnosis can be
managed with diet ,exercise & oral agents
Children who are ill, dehydrated, presence of
ketosis and acidosis need insulin therapy
When stabilized, tapering of insulin gradually
and introduction oral agents
In all patients, identification & treatment of co-
morbid conditions are important

How can insulin resistance be
managed?
Improve insulin resistance through:
Diet
Exercise
Pharmacological intervention with
agents
that target insulin resistance
Oral hypoglycemic agents
Biguanides: Metformin
The first oral agent used should be metformin.
decrease hepatic glucose output
enhance hepatic & muscle insulin sensitivity without
a direct effect on b-cell function
Sulfonylureas: chlorpropamide, gliclazide,
glimepiride, glipizide, tolazamide, & tolbutamide
promote insulin secretion from islet cells
Thiazolidenediones: troglitazone, rosiglitazone
improve peripheral insulin sensitivity
Troglitazone has been associated with fatal hepatic
failure; its use in children is not recommended

Metformin
The first oral agent should be used in type 2
Metformin has advantage over sulfonylureas of
a similar reduction in HbA1c without the risk of
hypoglycemia
Metformin normalizes ovulatory abnormalities in
girls with PCOS
Because of concerns about lactic acidosis,
Metformin is contraindicated in patients with:
impaired renal function
should be discontinued with the administration of
radiocontrast material.
should not be used in patients with known hepatic
disease, hypoxemic conditions, severe infections, or
alcohol abuse
Metformin
The most common side effects of Metformin
Gastrointestinal disturbances
Because proper dosing in children has not
been evaluated & because most patients are
near or at adult weight, it is reasonable to use
the doses recommended for adults
If monotherapy with Metformin is not
successful over a period of time (36 months),
Some clinicians would add a sulfonylurea,
whereas others might add insulin
Sulfonylureas stimulate insulin secretion and reduce
HbA
1c
levels by 12%
Sulfonylureas may cause weight gain and are
associated with the highest incidence of
hypoglycemia among the oral antidiabetic agents.
Glucosidase inhibitors slow the hydrolysis of complex
carbohydrates and carbohydrate absorption
(acarbose and miglitol)
The glucosidase inhibitors reduce HbA
1c
by 0.50.9%

The thiazolidinediones improve peripheral
insulin sensitivity & reduce HbA
1c
by 0.51.5%
The thiazolidinediones do not cause
hypoglycemia when used as monotherapy, but
may cause edema & weight gain
The sulfonylureas, nonsulfonylureas,
glucosidase inhibitors & thiazolidinediones have
not received approval by FDA for use in the
pediatric population