Diabetes, Obesity and

Insulin Resistance in
Children & Adolescents
Diego Botero, MD
UdeA
2023
 Overview

• Obesity
-epidemiology
-clinical implications

• Insulin resistance & metabolic syndrome

-definition

• Type 2 diabetes in children

-epidemiology
-diagnosis & treatment
ProCon.org, Global Obesity Levels, 2020
The prevalence of obesity and severe obesity among US children
2 to 19 years of age, from 1999 to 2016.

Asheley Cockrell Skinner et al. Pediatrics 2018;141:e20173459

 Prevalencia Obesidad/Sobrepeso,
Colombia
Ensin 2010 Ensin 2015
Edad (años) Prevalencia Edad (años) Prevalencia
Obesidad/Sobrepeso Obesidad/Sobrepeso
(%) (%)
0-4 5.2 0-4 6.3
5-12 18.8 5-12 24.2
13-18 15.5 13-18 17.9
18-64 51.2 18-64
56.4

_____________________________________________________________________
https://www.fsfb.org.co/wps/portal/fsfb/inicio/saludpublica/programas/sectionItem/
___________________
ensin
•. 2016 Aug;87:190-7.
•. •2016 Aug;87:190-7.

Economic Burden
• Annual cost of obesity in the USA (2014): 149.4 dollar billions.
Value in Health 19(5) · April 2016

• Obesity: risk factor of CV (advanced vascular age).

https://www.contemporaryobgyn.net/view/vascular-age-obese-children-similar-middle-aged-men-1
Circ Cardiovasc Imaging, 3 (2010)

• Sleep apnea and gallbladder stones have tripled in the last 3 decades in children & adolescents.
2021: https://emedicine.medscape.com/article/927522-overview#a5
Int J Pediatr Otorhynolaringol, 2016

• 8-45% of new cases of DM in children & adolescents are type 2.

http://www.diabetes.org/assets/pdfs/basics/cdc-statistics-report-2017.pdf
2021: www.uptodate.com/contents/epidemiology-presentation-and-diagnosis-of-type-2-diabetes-mellitus-in-children-and-adolescents#H3
Obesidad y Diabetes
 Childhood obesity is polygenic

• >430 genes associated with human obesity

• Rare monogenic forms: leptin deficiency &

resistance, pro-opiomelanocortin, MC4R
Prader-Willi síndrome.

• Endocrine disorders: hypothyroidism, Cushing

syndrome.
En Colombia el 81,2% de la población consume
gaseosas y el 76,6% golosinas y dulces.
http://www.icbf.gov.co/portal/page/portal/PortalICBF/NormatividadC/E
NSIN1/ENSIN2010/LibroENSIN2010.pdf. 978-958-623-112-1.

ETIOLOGY OF OBESITY

CHO intake

 Consumption of vegetables

 Dietary fiber intake

Burger King Double
cheeseburger

Total calories 610

Fat calories 330
Total fat (g) 37
Saturated fat (g) 18
Cholest (mg) 120
Sodium (mg) 1170
Carbs (g) 32
Protein (g) 38
 Physical inactivity and
Obesity Risk

Physical Activity has decreased

- Screen time: Internet/TV/cellular/computer games
- Decrease in required PE in schools
- Fear of outside play
Obesity Risk

Moderate-to-Vigorous
10% for each hour per day
Physical Activity

Television Viewing 12% for each hour per day

Hernandez et al.
Int J Obesity 1999;23:845
Complications of Pediatric Obesity

Ebbeling, Pawlak, Ludwig

Lancet 2002; 360:473
Adult and Proposed Pediatric Definitions of the
Metabolic Syndrome
Adult Definition * Percentiles Proposed Pediatric
(ATP III) Definition*
Hypertriglyceridemia > 150 mg/dL 75th (male) > 100 mg/dL
85th (female)
Low HDL <40 mg/dL (men) 40th <50 mg/dL
<50 mg/dL (women) (boys age 15-19 years,
<45)
High fasting glucose > 100 mg/dL NA > 100 mg/dL

Central obesity (waist >102 cm (men) 72nd (male) >75th percentile for age
circumference) >88 cm (women) 53rd (female) and gender

Hypertension SBP > 130 mm Hg NA >90th percentile for age,

DBP > 80 mm Hg gender and height

* Three of the five factors are required De Ferranti, Circulation 2004

Plasma Insulin After an Oral Glucose Load
Effects of Obesity and Diabetes
250

200
Normal (obese)
Insulin (U/mL)

DM (obese)
150

100

50 Normal (thin)
DM (thin)
0
0 30 60 90 120 150 180
Time (min)

Bagdade, et al. J Clin Invest. 1967;46:1549-1557

Prevalence of Glycemic Abnormalities
in the United States
US Population: 320 Million in 2015
Undiagnosed
diabetes
7.1 million
Diagnosed Additional
type 1 diabetes 84.1 million
~1.25 million with IGT

Diagnosed
type 2 diabetes
22.9 million

Diabetes Care, 2018.

http://www.diabetes.org/diabetes-basics/statistics/
10
 Estimated lifetime risk of developing T2DM for people born in 2000

• About one of every three Americans born in 2000 will develop DM during their lifetime
• 45% of Hispanic men and 52.5 of Hispanic women are predicted to develop T2DM

Arayan, JAMA 2003;290:1884-1890

Ludwig, JAMA 2001;286:1427-1430
 Diabetes in Youth
• About 193,000 Americans under age 20 are estimated to
have diagnosed diabetes, approximately 0.24% of that
population. (71% T1DM and 29% T2DM)

• In 2011—2012, the annual incidence of diagnosed

diabetes in youth was estimated at 17,900 with T1DM,
5,300 with T2DM.

CDC National Diabetes Statistics Report, 2017.

Prevalence of Diabetes and Impaired Fasting Glucose
Levels Among US Adolescents
National Health and Nutrition Examination Survey, 1999-2002

• Population –based sample weights:

• Prevalence of diabetes in US adolescents 0.5%
• 39.005 US adolescents with T2DM
• 2.769.736 with impaired fasting glucose tolerance
(11%)
• From 8-45% of new pediatric cases are Type 2

Arch Pediatr Adolesc Med, 2006

February 14, 2020, issue of CDC’s Morbidity and Mortality Weekly Report
 T2DM in Children & Adolescents
-screening-
•Overweight/obese children
-BMI >85th percentile or weight >120% of the ideal for height

+ 2 other risk factors:

-Family history of T2DM (1st or 2nd degree relatives)

-Being: African-American, Hispanic, Asian/Pacific Islander,
Native-American
-Signs of insulin resistance: acanthosis nigricans, hypertension
dyslipidemia, PCOS
-------------------------------------------------------------------------------------
• Begin testing at age 10
• Repeat testing every 2 years
❖ Fasting plasma glucose recommended as the preferred test.
Diabetes Care 27:S11-S14, 2004
 Type 1 vs. Type 2 diabetes:
Differential Diagnosis
• In some patients, a clinical differentiation
between T1DM and T2DM is not possible at
diagnosis.
• Family and socio-demographic history
• Presentation
• Physical exam
• Biochemical evaluation
 Type 1 vs. Type 2 diabetes:
Presentation and Physical exam
Type 1 diabetes Type 2 Diabetes
-------------------------------------- -------------------------------
• Polyuria, polydipsia, nocturia • May be detectable in the
common asymptomatic state
• Weight loss common • Weight loss less common
• Symptoms present for days to • Symptoms present for weeks to
weeks months
• Ketosis/ketoacidosis common • Ketosis/ketoacidosis in one third
• Obesity “usually” absent • Obesity present
• Signs of insulin resistance absent • Signs of insulin resistance present
Dermatology Atlas; http://www.DermAtlas.org
 Type 1 vs. Type 2 diabetes:
Family and Socio-demographic History

Type 1 diabetes Type 2 diabetes

----------------------------------- -----------------------------
• Throughout childhood but as • Usually mid-teens and less
great or greater incidence in than 10% are <10yr or
<10 yr prepubertal
• About 5% have a 1st degree • 75% or more have 1st or 2nd
relative affected degree relative affected
• Asians, Native Americans and • African American, Native
African Americans less American, Hispanic, Asian at
frequently affected greater risk
• F=M • F>M
 Type 1 vs. Type 2 Diabetes
Biochemical Evaluation
Type 1 Diabetes Type 2 diabetes
------------------------------ -----------------------------
• 85-95% have positive • Usually not associated
pancreatic antibodies with pancreatic
(insulin, GAD, or IA2) at autoimmunity*
diagnosis
• Low/absent c-peptide • Normal/high c-peptide

* 432 patients with a clinical diagnosis of type 2 diabetes screened

17.4% positive for one or both GAD or IA2 antibodies
ADA 2006, Abstract 289-OR.
 DIET AND EXERCISE:
THE
FIRST-LINE THERAPIES
FOR T2DM
 Glycemic Index
Method for characterizing carbohydrate type based on postprandial
responses to ingestion of carbohydrate-containing foods

The 2 hour blood glucose response of a high

versus low GI food
(2 hour-postprandial AUC) Reference food Test Food

AUC, 50 g carbohydrate, test food X 100

0 2h 0 2h
AUC, 50 g carbohydrate, reference
(glucose) Glucose, GI score 100 Lentils, GI score 40

Jenkins et al.
Am J Clin Nutr 1981;34:362
 LOW GLYCEMIC INDEX DIET
• The glycemic index (GI) is a ranking of carbohydrates on a scale from 0 to 100
according to the extent to which they raise blood sugar levels after eating.

•Basic principle: Carbohydrates that break down rapidly during digestion have the
highest glycemic indices. Carbohydrates that break down slowly, releasing
glucose gradually into the blood stream, have a low glycemic index.

• Recommended by the Study Group of the European Association for the

study of diabetes.

• Recommended by the food and agriculture organization/WHO expert

consultation on carbohydrates.

• Low GI diets promote satiety and facilitate a negative energy balance by

reducing the postprandial glucose and insulin responses
How Much Sugar ( 1 tsp=4.2 gm/sugar)
1 cube:
4 gm
. La “Economía Naranja

.
Houghton Mifflin, 2007

www.endingthefoodfight.com
 Pharmacological Treatment
Major Classes of Medications

1. Drugs that sensitize

the body to insulin Thiazolidinediones
and/or control hepatic → Biguanides
glucose production.

2. Drugs that stimulate Sulfonilureas

the pancreas to make → Meglitinides
more insulin.

3. Drugs that slow the Alpha-glucosidase

absorption of carbs. → inhibitors
Approved medications for T2DM in
children and adolescents

- METFORMIN

- INSULIN

- LIRAGLUTIDE

- EMPLAGLIFOZIN
 T2DM in Children
-Pharmacological Treatment-

• If an oral agent is not tolerated or does not lead to target A1c,

Insulin or a second oral agent must be added.

• For elevated LDL: HMG-CoA reductase inhibitors (statins)

• For hypertension and/or microalbuminuria: ACE inhibitors

 Biguanides*
• Decrease hepatic glucose production
• Decrease fasting plasma glucose 70-80 mg/dL
• Reduce A1C 1.0-2.0%
• GI intolerance
• Lactic acidosis if improperly prescribed
• Small decrease in LDL and TG
• No weight gain
• Contraindicated in impaired renal/liver and cardiac function
• May compromise the absorption of vitamin B12 and folic acid.

* metformin (Glucophage), metformin extended release (Glucophage XR), liquid formulation

(Riomet)

American Diabetes Association. WWW.diabetes.org

 Management of T2DM in Children
Symptomatic Mildly symptomatic Asymptomatic
>300 mg/dl (-) ketones (-) ketones
(+) ketones
Diet/exercise
+
Insulin + metformin
Diet/exercise 
Monthly reviews
A1c / 3 months
Attempt to wean >7% <7% Diet/exercise
off insulin  Continue metformin
Start metformin Verify compliance
Add 2nd oral agent or insulin

Monthly reviews
A1c / 3 months
>7% <7% Diet/exercise
 Continue combined therapy
Verify compliance
Start insulin
Botero et al. Arch of Med Res 2005
 Monitoring complications
Test When Normal
________________________________________________________
• BP Every visit Age appropriate or <130/80

• Urine microalbumin Annually, beginning at diagnosis

• Complete dilated eye exam Annually, beginning at diagnosis

• Symptoms of neuropathy Every visit

• Foot exam Annually

• Lipid profile At diagnosis (after control is LDL <100 mg/dL
established), then annually TG <150 mg/dL
HDL >40 mg/dL
 Newer Classes of Medications

1. Drugs that promote Incretin Mimetics (Exenatide)

glucose dependent DPP-IV inhibitors (Sitagliptin)
insulin secretion.

2. Drugs that delay Amylin Receptor Agonist

gastric emptying, (Pramlintide acetate)
inhibit glucagon, and
modulate satiety.
 Lecturas Recomendadas

Diabetes tipo 2
https://www.uptodate.com/contents/epidemiology-presentation-and-diagnosis-of-type-2-diabetes-
mellitus-in-children-and-adolescents

https://www.uptodate.com/contents/management-of-type-2-diabetes-mellitus-in-children-and-
adolescents
Gracias
 Evaluación
De cada uno de estos temas, escribir un corto resumen que incluya los aspectos básicos importantes.

1. Que es la leptina
2. Que es el síndrome de Prader Willi
3. Que son las incretinas
4. Que es la amilina
5. Que es el péptido C

Parágrafo de 6 a 10 líneas de cada tópico. Incluir la(s) ref. bibliográfica.

Enviar las respuestas a: [email protected] Incluir el nombre y la identificación.

* Fecha limite de entrega: Martes 31 de octubre.

The more tests that you order, the more likely it will be that one or more tests will be
outside the reference interval (a.k.a. - "abnormal")..... Then you'll need to do more tests....
and possibly still do more tests.
Because reference intervals are usually defined as the central 95% of the distribution, the
likelihood that any one test is outside the reference interval is 5%.
The formula that can be used to calculate the proportion of tests that all "normal" in a
person undergoing multiple testing is (1 - 0.05) to the power of N (N is the number of tests
performed; "0.05" is the fraction of tests with abnormal values). This formula assumes that
the tests are independent of one another.
Here is a table showing the number of tests performed and the percent of the people
tested that will have all of the test results falling within the reference intervals:

N % all tests "normal"

1 95%
2 90%
3 86%
4 81%
5 77%
10 60%
15 46%
20 36%
If you order 5 tests that are independent of one another, there is almost a 1 in
4 chance (23%) that one of the 4 tests will fall outside of the reference interval.
........ So ..... running tests to appease patients/parents that are not medically
indicated does not properly serve the patient/parent.
I would emphasize to the patient/parent that you are doing something:
history, physical examination, and review of the case. If testing is required,
order the appropriate tests. Hopefully, some patients/parents might care that
you spent 4 years in college, 4 years in medical school, 3 years in residency
training, 3 years in fellowship training and "X" years (you fill in the "X") in
clinical practice.
Another part of the discussion is "Who pays for unjustified tests?" AND ...
being able to pay for unjustified tests does not justify that such tests be
ordered.
William E. Winter, M.D., DABCC, FAACC, FCAP
Professor, Departments of Pathology and Pediatrics
Medical Director, Clinical Laboratory Support Services (CLSC)
Medical Director, Point-of-Care Testing (POCT)