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Type 2 Diabetes in Children
Dr. Abdulmoein Al-Agha, MBBS,DCH,CABP, MRCP(UK) Consultant, Pediatric Endocrinologist, King
AbdulAziz University Hospital, Jeddah.
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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
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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.
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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
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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.
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Obesity & Type 2 Diabetes
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Too large meals ! Too high Calories!
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Sedentary life style!!
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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
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Type 2
Obesity& Insulin resistance
Genetic susceptibility
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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
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Associated problems with type 2 DM
Obesity Insulin resistance Hyperinsulinism Arterial hypertension Hyperlipidemia Acanthosis Nigerians Macro & microangiopathy PCOS
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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
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Screening for type 2 DM in Children & Adolescents
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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
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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
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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
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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.
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Prevention of type 2 DM
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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
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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
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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
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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
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How can insulin resistance be managed?
Improve insulin resistance through: Diet Exercise Pharmacological intervention with
agents that target insulin resistance
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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
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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
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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
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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%
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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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موفقينباذن
الله
تعالى