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 function—loss of early phase of insulin release in response to hyperglycemic stimuli

Underlying causes of type 2 diabetes

Obesity

Insulinresistance

-celldefect

Impairedglucose tolerance

Earlydiabetes

Latediabetes

Hyperinsulinaemia

Decreased insulinsecretion

-cell failure

Adapted from Saltiel AR. J Clin Invest 2000;106:163–164.

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 glucoseInsulin sensitivityInsulin secretion

Insulin sensitive

Normal insulin secretion

Normoglycaemia

Hyperglycaemia

β-cell exhaustion

Insulin resistance

Late type 2 diabetes

complications

Adapted from Bailey CJ et al. Int J Clin Pract 2004;58:867–876. Groop LC. Diabetes Obes Metab 1999;1 (Suppl. 1):S1–S7.

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 5–25% 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) > 85th percentile

for age and sex weight for height > 85th % ile weight >120th % 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

DiabeticretinopathyLeading causeof blindnessin working-ageadults1

DiabeticnephropathyLeading cause of end-stage renal disease2

Cardiovasculardisease

Stroke1.2- to 1.8-fold increase in stroke3

DiabeticneuropathyLeading cause of non-traumatic lower extremity amputations5

75% diabetic patients die from CV events4

Type 2 diabetes is NOT a mild disease

1Fong DS, et al. Diabetes Care 2003;26 (Suppl. 1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003;26 (Suppl. 1):S94–S98. 3Kannel WB, et al. Am Heart J 1990;120:672–676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.

5Mayfield JA, et al. Diabetes Care 2003;26 (Suppl. 1):S78–S79.

Prevention of type 2 DM

Prevention of obesity

شرا ( وعاء آدمي مأل ما وسلم عليه الله صلى قالفان صلبه، يقمن لقيمات آدم ابن بحسب بطنه، من

وثلث لشرابه وثلث لطعامه فثلث فاعال البد كانوالترمذي). أحمد رواه لنفسه

Prevention of type 2 DM

Public health measures 1. Media2. School3. Community 4. Family

Increase physical activity Reduce caloric intake/obesity Decrease sedentary life style

I. Computer 2. Video games3. 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• HbA1c < 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 (3–6 months), Some clinicians would add a sulfonylurea, whereas others might add insulin

Sulfonylureas stimulate insulin secretion and reduce HbA1c levels by 1–2%

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 HbA1c by 0.5–0.9%

The thiazolidinediones improve peripheral

insulin sensitivity & reduce HbA1c by 0.5–1.5% 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

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