Type 2 diabetes is increasingly common in youth, especially overweight and obese adolescents. Guidelines recommend lifestyle changes and metformin as first-line treatment, with insulin as needed for glycemic control. Treatment goals include an HbA1c under 7% to reduce complications, though pediatric diabetes may be more aggressive than adult-onset disease given earlier presentation and longer disease duration. Management poses challenges due to developmental factors, requiring sensitivity to achieve adherence.

1. Type 2 Diabetes in Young
& its Management
Dr. Sushama Jotkar
M.D. (Medicine)
Professor
D.Y.Patil Medical College, Kolhapur

2. Emergence of Type 2 Diabetes in Youth
T2DM was traditionally thought of as a disorder of middle-aged &
elderly adults.
However, diabetes has become more common, not only in young
adults, but also in adolescents & children.
Overweight or obese children & adolescents are presenting with
Type 2 diabetes associated insulin resistance
Earlier age of onset will affect the future global burden of diabetes
and prevention activities
Lancet Diabetes Endocrinol. 2014 Jan_2(1)56-64.

3. Emergence of Type 2 Diabetes & Prediabetes in Youth
As obesity in young people increases in Asian countries like India, without
effective intervention strategies to reduce obesity, more people will develop
T2DM at younger ages
Lancet Diabetes Endocrinol. 2014 Jan_2(1)56-64.

4. Emergence of Type 2 Diabetes & Prediabetes in Youth
Microalbuminuria of
close to 100%
Blindness of 20% 15 years of
life lost
Lancet Diabetes Endocrinol. 2014 Jan_2(1)56-64.
T2DM that develops between the ages of 15 and 24 years will result in
a lifetime risk of

5. Type 2 Diabetes in Children
In India, type 2 diabetes is reaching epidemic proportions
Type 2 diabetes mellitus in children is becoming common in
many countries, especially among the Asian-Indian
population
In India, the age at onset of T2DM is generally low and this
form of diabetes in children is being detected more
frequently now
Diabetes Care 26:1022–1025, 2003

6. Diabetes in Young - The Scenario is changing
Population-based estimates of T2DM in the young are lacking as
screening for diabetes is not recommended in children and
adolescents.
Clinic-based data suggest that T2DM is increasing in the young,
although this could be due to increased awareness and/ or referral
bias.
The ICMR-INDIAB study also showed that there is a shift of T2DM
to younger age groups and that the takeoff point of prevalence of
diabetes occurs at ages 25–34 years in India
ICMR INDIAB) study. Diabetologia. 2011;54(12):3022-7.

7. The Dutch Famine Birth Cohort Study
Diabetes Risk in Adulthood
Decreased Fetal
Nutrition
It is defined as heritable changes in gene expression that are not associated with
changes in DNA sequence, but rather through DNA methylation and histone
modification
An Important Mechanism for this Involves Epigenetic Modification
Lancet 1998; 351: 173–77.
Lancet Diabetes Endocrinol. 2014 Jan_2(1)56-64.

8. Dabalea D, Hanson RL, Bennett PH, et al. Increasing prevalence of Type II diabetes in American Indian children. Diabetologia. 1998;41(8):904–910
Diabetes in pregnancy can lead to a cycle of diabetes affecting future
generations
Gestational Diabetes as a Driver of T2

9. Is Pediatric T2DM a global epidemic?
• Cohort of 535 obese Italian children
IFG (7.6%), IGT (3.2%), T2DM (0.18%)
Cambuli, VM, et.al. Diab Metab Res Rev, 2009
• Prevalence of T2DM among 0-20 year old German children
estimated at 2.3 cases per 100,000.
Neu A, et.al. Pediatric Diabetes, 2009
• Highest risk populations (obese, Latino, positive fam hx) from
Los Angeles from 2000-2007 showed prevalence of 1.3% on OGTT
Goran MI, et.al. J Pediatr, 2008
• Taiwanese children aged 6-18 taking part in screening program
found diabetes prevalence of 9 (♂) and 15.3 (♀) per 100,000
children. After 3 years, 54% of cases identified as type 2.
Wei JN, et.al. JAMA, 2003

10. Known and diagnosed cases of
pediatric T2D
Undiagnosed cases of pediatric pre-T2D
(IGT/metabolic syndrome)
“Pre-pre” T2D: insulin resistance
with risk factors

11. How did we get here?

12. Obesity rates are highest among adolescents of
ethnic backgrounds
Prevalence of obesity among boys
aged 12-19 years
Prevalence of obesity among girls
aged 12-19 years
Source: CDC (NHANES data)

13. Caglecartoons.com
Visceral
Adiposity

15. Risks of obesity increases with
sedentary Style
Gortmaker S., et.al. Arch Pediatr Adol Med, 1996; 150: 356-62

16. Energy Excess
Adipocyte Hepatocyteb-cell
Lipogenesis
Steatohepatitis
Insulin Resistance
Oxidative Stress
Impaired Insulin Secreti
on
Hypertrophy & Hyperplasia
Oxidative Stress/ROS
CarbohydratesCarbohydrates Fats
Inflammatory
Mediators
Adipokines Free Fatty
Acids
•Peripheral Insulin Resistance
•Lipid accumulation in peripheral tissues
•Endothelial Dysfunction
Diet & Activity
Genetic Influences
Frohnert B, et.al. Rev Endocr Metab Disord, 2008

17. Is the Presentation the Same as in Adults?
Does not appear to be preceded by long
asymptomatic period
Do not find undiagnosed cases on
screening

18. Years from Clinical Diagnosis
B-cellFunction(%)
UKPDS Data
Type 2 Diabetes
Progressive Pancreatic B-cell Failure
Prevention and Early Treatment
? Curve for Youth

19. Question
Is the Pathophysiology the Same as in Adults?
Associated with significant ß-cell failure as well as
insulin resistance
Occurs at the time of puberty due to intense
insulin resistance

20. Insulin
Resistance
Age
Puberty
Type 2 Diabetes
Prediabetes
Beta Cell Defect
Obesity
BP,
Lipids
Gender – Girls
Polycystic ovary syndrome
Genetics
Ethnicity
Sedentary Lifestyle
Beta Cell Defect

21. Insulin
Resistance
Autoimmunity
Type 2 Diabetes
Prediabetes
Beta Cell DefectGenetic Defect
Intrauterine
IUGR, DM Glucose
toxicity
Beta Cell Defect
Fat cell
toxicity

22. Primary Factors Contributing to
Development of T2DM in Children
INSULIN RESISTANCE
PRENATAL
ENVT.
FEMALE GENDER
ETHNIC BACK
GROUND
FAMILY HISTORY
PUBERTY
T2DM
OTHER GENES
SEDENTARY L
IFESTYLE
OBESITY
• visceral
ACCELERATED
BETA CELL FAI
LURE
IFG/IGT

23. Features to Differentiate T1DM, T2DM and Monogenic Diabetes
in Children and Adolescents
IDF/ ISPAD Guideline For Diabetes In Children And Adolescence 2011: 1-132

24. Differential Diagnosis of Diabetes in Youth
Pediatric Diabetes 2007: 8 (Suppl. 9): 28–34.

26. Diabetes CareJanuary 2017 Volume 40, Supplement 1
ADA 2017 Screening Recommendations

27. Acanthosis Nigricans:
A Sign of Insulin Resistance

28. Challenges in Management
Management of T2DM in a child or adolescent is
entirely different from that of diabetes in adults
Lifestyle change and adherence to medication are
difficult to achieve in this age group
Diabetes onset so early in life usually means many years
of disease and treatment
Children & Adolescents with T2DM are at a higher risk
of both microvascular and macrovascular complications
Lancet Diabetes Endocrinol. 2014 Jan_2(1)56-64.

29. PEDIATRICS Volume 131, Number 2, February 2013
The most recent American Academy of Pediatrics (AAP) clinical practice
guidelines for the management of T2DM in patients 10 to 18 years old
recommend prompt initiation of lifestyle modifications and either insulin
or metformin as first-line pharmacological options
Metformin Dosage Start at a low dose of 500 mg daily, increasing by 500
mg every 1 to 2 weeks, up to an ideal and maximum dose of 2000 mg
daily in divided doses

30. Question
What are the Treatment Regimens for Youth?

31. GLP

32. • Lifestyle change should be initiated at the time of diagnosis
of T2DM
• Initial pharmacologic treatment of youth with T2DM should
include Metformin and insulin alone or in combination.
•Pediatric Diabetes 2014: 15(Suppl. 20): 26–46

33. ISPAD Clinical Practice Consensus Guidelines Approach to Initial
and Subsequent Treatment of Youth with T2DM
Pediatric Diabetes 2014: 15(Suppl. 20): 26–46

34. Diabetes(type 1 and type 2) in children and young people:
Diagnosis and management
NICE Guideline 18
Methods, evidence and recommendations
August 2015

35. NICE Guidelines 2015
Type 2 Diabetes: Specific Recommendations
• Dietary management:
- At each contact with those who are overweight or obese, advise about the
benefits of physical activity and weight loss, and provide support towards
achieving this in accordance with NICE guidance.
- Provide dietary advice in a sensitive manner, taking into account the
difficulties many people encounter with weight reduction, and emphasise
the additional advantages of healthy eating for blood glucose control and
avoiding complications.
• Offer metformin from diagnosis to children and young people with type 2
diabetes. [new 2015]

36. • Metformin is the initial pharmacologic treatment of choice,
if metabolically stable
• If insulin was initially required,
transition from insulin to metformin over 2-6 weeks
( beginning when metabolic stability is reached, usually 1-2
weeks after diagnosis).
IDF/ ISPAD Guideline For Diabetes In Children And Adolescence 2011: 1-132

37. Recommended Dosage of Metformin in T2DM in Children
• ISPAD Clinical Practice Consensus Guidelines
Begin with 500 mg daily×7 d. Titrate by 500 mg once a week over 3–4
wk to the maximal dose of 1000 mg twice-daily (BID)
• AAP clinical practice guidelines
Start at a low dose of 500 mg daily, increasing by 500 mg every 1 to 2
weeks, up to an ideal and maximum dose of 2000 mg daily in divided
doses
• IDF/ ISPAD Guideline For Diabetes In Children And Adolescence
Begin with 250 mg daily for 3-4 days, if tolerated, increase to 250 mg
twice a day, titrate in this manner over 3-4 weeks until the maximal
dose of 1,000 mg twice a day is reached.
1.Pediatric Diabetes 2014: 15(Suppl. 20): 26–46 2. PEDIATRICS Volume 131, Number 2, February 2013
3. IDF/ ISPAD Guideline For Diabetes In Children And Adolescence 2011: 1-132

38. Annals of Pharmacotherapy, 2016, 1–10
• Relevant articles and preliminary data from clinical trials on me
tformin, insulin, sulfonylureas, thiazolidinediones (TZDs),
GLP -1 receptor agonists, DPP-4 inhibitors, and α-glucosidase
inhibitors for the treatment of pediatric T2DM were reviewed.
• Data Sources: A search from January 1990 to April 2016 was
conducted using PubMed and clinicaltrials.gov

39. • As per USFDA guidelines Metformin is recommended for the
management of T2DM in children with 10 to 18 years
• Metformin and insulin, either alone or in combination,remain
the safest treatment options for management of pediatric
T2DM.
• Metformin & Insulin remain the mainstay of treatment for
T2DM in pediatric patients.
Annals of Pharmacotherapy, 2016, 1–10

40. Objective :
•To review oral antidiabetic agents that have completed pediatric
drug development programs and undergone FDA review.
•This review summarizes results of 4 pediatric drug development
programs for T2DM
The Journal of Clinical Pharmacology 2015, 55(7) 731–738

41. • Each agent achieved reductions in glycemic parameters; however, 3 of 4
failed to reach the threshold efficacy relative to their control(s) to gain FDA
approval.
• Only 1 drug (metformin) of the first 4 T2DM drugs to complete testing in
children gained FDA approval.
The Journal of Clinical Pharmacology 2015, 55(7) 731–738

42. Expert Opin. Biol. Ther. (2014) 14(3):355-364
• Highlights
• Diabetes management is challenging during childhood and adolescence
due to age-specific characteristics.
• Insulin therapy is the cornerstone of treatment of type 1 diabetes.
• Treatment of type 2 diabetes is based on lifestyle interventions and
metformin as the first-line drug for children older than 10 years.
• Insulin should be implemented in youth with type 2 diabetes and metabo
lic decompensation or in cases of difficult controls with oral agents.

43. Question
What Are Treatment Targets in Youth with Type 2 Diabetes?
Are they the same as in adults?

44. TREATMENT GOALS
• Glucose control, HbA1c <7%
– Eliminate symptoms of hyperglycemia
• Maintenance of reasonable body weight
• Improve cardiovascular risk factors
• Reduce microvascular complications
• Improvement in physical and emotional
well-being
Goals
(Diabetes
Care, 2000)
FG 80-120
PP 100-160
Bed 100-160
A1c <7.0

45. Adolescents during their pubertal growth spurt have higher insulin resistance compared to
other periods in life.
The use of Metformin in many diseases in which insulin resistance constitutes an essential
part of the pathogenesis appears promising with variable rates of success.
These include obesity, prediabetes, polycystic ovary disease, premature pubarche, and non-
alcoholic fatty liver disease.
Metformin is a good insulin sensitizer that proved effective in adults and recently in
adolescents with T2DM.

46. Summary
Type 2 diabetes in Indian youth is rising at an alarming rate.
Early detection and treatment are the cornerstones to reduce
morbidity and mortality due to youth-onset type 2 diabetes.
Lifestyle change and adherence to medication are difficult to
achieve in this age group.
Major Pediatric guidelines recommends use of metfomin in
the management of T2DM in children with 10 to 18 years old.
Metformin & Insulin remain the mainstay of treatment for
T2DM in pediatric patients.

47. Conclusion
• Increased incidence
• Difficult to distinguish from type 1
• Occurs at the time of intense insulin resistance due
to puberty
• Does not appear to be preceded by long
asymptomatic period
• More insulin deficiency and requirement for
exogenous insulin early
• Safety and efficacy of therapeutic agents
• Rapid progression of co-morbidities and
complications