This document discusses various types of diabetes in young people. It begins by defining diabetes mellitus and describing the worldwide rise in prevalence. It then covers the main etiological types including Type 1, Type 2, other genetic defects, and diabetes resulting from diseases of the exocrine pancreas. Risk factors for Type 2 diabetes in children and adolescents are outlined. Maturity-onset diabetes of the young (MODY) is explained in detail, including the genetic defects involved and treatments. Diagnosis and management of diabetes in youth are also addressed.

1. DIABETES IN YOUNG

2. WHAT IS DIABETES?

3. WHAT IS DIABETES?
•Diabetes mellitus is characterized by chronic
hyperglycemia with disturbances of
carbohydrate, fat, and protein metabolism
resulting from defects in insulin secretion, insulin
action, or both.

4. • The worldwide prevalence of DM has risen dramatically overthe past
two decades, from an estimated 30 million cases in 1985 to 382
million in 2013, India – 65.1 million

5. ETIOLOGIC TYPES
•IDDM AND NIDDM
TO
•TYPE 1 AND TYPE 2

6. Classification
•Type 1 – beta cell destruction - 1A and 1B
•Type 2 (may range from predominantly insulin
resistance with relative insulin deficiency to a
predominantly secretory defect with or without
insulin resistance)

7. Other specific types of diabetes
• Genetic defects of beta cell development or function
characterized by mutations in:
• 1. Hepatocyte nuclear transcription factor (HNF) 4α
(MODY 1)
• 2. Glucokinase (MODY 2)
• 3. HNF-1α (MODY 3)
• 4. Insulin promoter factor-1 (IPF-1; MODY 4)
• 5. HNF-1β (MODY 5)

8. •6. NeuroD1 (MODY 6)
•7. Mitochondrial DNA
•8. Subunits of ATP-sensitive potassium channel
•9. Proinsulin or insulin
•10. Other pancreatic islet regulators/proteins
such as KLF11, PAX4, BLK,GATA4, GATA6, SLC2A2
(GLUT2), RFX6, GLIS3

9. Genetic defects in insulin action
• 1. Type A insulin resistance- triad of
hyperandrogenism, insulin resistance, acanthosis
nigricans(HAIR-AN)
• 2. Leprechaunism- Donohue syndrome- IUGR,
characteristic bird facies, fasting hypoglycaemia and
impaired glucose tolerance despite giving more than
100 times of insulin

11. • RABSON-MENDENHALL SYNDROME - abnormalities in the
teeth and nails and pineal gland hyperplasia
• LIPOATROPHIC ATROPHY -a genetically heterogeneous group
of rare syndromes characterized by insulin-resistant diabetes
associated with a regional or complete absence of
subcutaneous adipose tissue and presence of
hypertriglyceridemia
I. Köbberling-Dunnigan syndrome(dominant)
II. Berardinelli-Seip syndrome(recessive)
III. Lawrence syndrome(total)

12. Diseases of the exocrine pancreas
• Pancreatitis
• Pancreatectomy
• Neoplasia
• Cystic fibrosis
• Hemochromatosis
• Fibrocalculous pancreatopathy
• Mutations in carboxyl ester lipase

13. Pancreatic diabetes
•PANCREATECTOMY:-
i. Loss of beta cells
ii. Decrease in secretion of insulin, glucagon and
epinephrine as well
iii. More prone to hypoglycemia
iv. Recovery from hypoglycemia is more
v. Leaner than type 1 DM

14. Pancreatic diabetes
• PANCREATITIS :-
I. 5% in chronic pancreatitis and 40-50% in chronic relapsing
pancreatitis
II. Glucagon level is markedly increased
• FIBROCALCIFIC PANCREATITIS :-
I. 80-90-% have overt diabetes
Cause – not established, but compromised blood flow to islets
from fibrotic scarring of exocrine pancreas may play a role

15. Pancreatic diabetes
•In a small series of patients with chronic
pancreatitis, a partial hepatic insulin resistance
was shown in the presence of pancreatic
polypeptide (PP) deficiency, which was reversible
by PP infusion

16. Pancreatic diabetes
• CYSTIC FIBROSIS :-
I. 50 %
II. Progressive insulin deficiency develops because of
fibrotic destruction of islets and a marked decrease
in β-cell mass
III. Islet amyloid deposition
IV. Mutations in CFTR gene(cystic fibrosis
transmembrane conductance regulator)

17. Pancreatic diabetes
•PANCREATIC CANCER :-
I. loss of β-cell mass
II. 2 fold rise in diabetes patients
III.Insulin-like growth factor (IGF) axis
IV.Islet amyloid polypeptide (IAPP)

18. Endocrinopathies
•Acromegaly
•Cushing’s syndrome
•Glucagonoma,
•Pheochromocytoma
•Hyperthyroidism
•Somatostatinoma
•Aldosteronoma

19. Drug- or chemical-induced
• Glucocorticoids
• Vacor (a rodenticide)
• Pentamidine
• Nicotinic acid
• Diazoxide
• β-adrenergic agonists
• Thiazides
• calcineurin and mTOR
inhibitors
•Hydantoins
•Asparaginase
•α-interferon
•Protease inhibitors
•Antipsychotics (atypicals
and others)
•Epinephrine

20. Infections
•Congenital rubella
•Cytomegalovirus
•Coxsackievirus

21. Uncommon forms of immune-mediated diabetes
•”stiff-person”syndrome
•Anti-insulin receptor antibodies

22. Other genetic syndromes sometimes
associated with diabetes
•Wolfram’s syndrome
•Down’s syndrome
•Klinefelter’s syndrome
•Turner’s syndrome
•Friedreich’s ataxia,
•Huntington’s chorea
•Laurence-Moon-Biedl
syndrome
•Myotonic dystrophy
•Porphyria
•Prader-Willi syndrome

23. • Gestational diabetes mellitus (GDM)
• LADA latent autoimmune diabetes in adults type 1.5

24. WHY DIABETES IN YOUNG?

25. WHY DIABETES IN YOUNG?
• Increase in the incidence and prevalence of diabetes mellitus type
1– In US the incidence is approximately 18 per 100,000 and incidence
is 1.7 per 1000 in children and adolescents.
• High fat diet
• Decrease in exercise
• Obesity
• Gene mutations

26. CLINCAL STAGES
• Normal glucose level
• Only on OGTT
• IFG/IGT
• Honeymoon period »Intensification»Total diabetes
• Gestational

27. Type 1 diabetes mellitus
• Presence of circulating antibodies like
1. Cytoplasmic circulating antibodies (ICAs)
2. Insulin antibodies (IAAs)
3. Glutamic acid decarboxylase (GAD)antibodies
4. 64-kilodalton (IA-2) autoantibodies to tyrosine
phosphatases ( IS-2 and IA-β)
5. Beta cell–specific zinc transporter(ZnT-8) antibody

28. • Environmental factors, including foods , toxins, and
viruses, have been suggested as triggers of the
autoimmune process in genetically susceptible
persons
• No strong family history.
• The concordance rate in identical twins is only 30% to
50%

29. • Type 1A diabetes shows strong associations with specific haplotypes
or alleles at the DQ-A and DQ-B loci of the human leukocyte antigen
(HLA) complex
• The rate of β-cell destruction is quite variable, being rapid in some
individuals, especially in infants and children, and slower in adults
• Some have modest fasting hyperglycemia that can rapidly change to
severe hyperglycemia or ketoacidosis, and others, particularly adults,
may retain some residual β-cell function for many years and have
sometimes been termed as having “latent autoimmune diabetes”

30. Type 1A
• Type 1 diabetes have low or undetectable levels of
insulin and plasma C-peptide. They are also more
likely to have other concomitant autoimmune
disorders, such as Graves disease, Hashimoto
thyroiditis, Addison disease, vitiligo, or pernicious
anemia.

31. Type 1B
• Idiopathic
• is characterized by low insulin and C-peptide levels similar to those in type 1A
• Prone to ketoacidosis, although they have no clinical evidence of autoimmune
antibodies
• African or Asian origin.
• They may suffer from episodic ketoacidosis, but the pathogenetic basis for their
insulinopenia remains obscure.

32. Type 2
• Most common form of Diabetes
• Specific etiology for this Diabetes is not known
• It is characterized by disorders of insulin action and insulin
secretion, either of which may be predominant feature.
• Ketoacidosis seldom occurs

33. RISK FACTORS FOR DM2 IN CHILDREN AND ADULTS
• Physical inactivity.
• Signs of insulin resistance such as hypertension,
hyperlipidemia, and polycystic ovarian syndrome
• Family history.
• Ethnic background and race

34. • Previous history of gestational diabetes.
• Gender disparity – female:male = 2:1 in type 2 DM in
comparison no gender difference in type 1
• Acanthosis nigricans
• Body mass index ≥27 kg/m2; BMI 85th percentile for age and
gender; weight for height >85th percentile; >120% ideal
body weight

35. • ≥10 y of age (in mid or late puberty)
• African-American, Hispanic, Asian, and American Indian
descent

36. Type 2 DM in young
• First identified in 1970s.
• And now has become a major medical and public health
problem as a result of burgeoning epidemic of childhood
obesity.

37. • Like type 2 diabetes in adults, the increase in youth is the direct result
of greater caloric intake with decreased caloric expenditure.
• Poor eating habits, eating high-calorie, high-fat, “super-sized” fast
foods
• Spend an increased amount of time watching television or using
computers or playing video games
• Almost all youths with type 2 diabetes are overweight and have a
positive family history of type 2 diabetes

38. Prevalence of DM 2 in children and
adolescents
• The first data on type 2 diabetes in youth are from the Pima Indians,
the group with the world's highest prevalence of type 2 diabetes
• In 1979, the prevalence of type 2 diabetes was 1 in 1,000 children 5
to 14 years of age and 9 in 1,000 youths 15 to 24 years of age
• By 1996, the prevalence had increased to 22.3 per 1,000 in the 10- to
14-year-old age group and 50.9 per 1,000 in the 15- to 19-year-old
group

40. THREFTY GENES

41. Differential Diagnosis of Type 1 and Type 2 Diabetes in Children
and Adolescents
Type 1: immune-mediated diabetes Type 2: non-immune-mediated diabetes
Not generally overweight Overweight/obese (85%)
Low endogenous insulin Signs of insulin resistance
Low C-peptide High endogenous insulina
Positive insulin and pancreatic autoantibodies High C-peptide levelsa
High ketone levels (30%–40% have ketoacidosis) Low ketone levels (<33% have ketonuria; 5%–
25% have ketoacidosis)
aCan be suppressed for 2 to 3 months after diagnosis

42. When to test for Diabetes in youth??
• As recommended by NIDDK,CDC,ADA and AAP testing for
Diabetes should begin at 10 years of age or at the onset of
puberty if earlier, in overweight, any of the following 2 :
1. f/h/o of 1st or 2nd degree relative
2. Race/ethnicity: African, Hispanic, Asian/South Pacific, and
Native-American descent.
3. Signs of insulin resistance such as hypertension,
hyperlipidemia, or polycystic ovary syndrome (PCOS)

43. DIAGNOSIS
•FBS 126 mg/dl or higher.
•Testing should be repeated every 2 years.

44. Treatment
• In DKA and NKHHS insulin is the main line of treatment.
• Initially tried with medical nutritional therapy, weight loss and increased physical
activity.
• FDA has approved insulin and now metformin for children more than 12 years
• There are currently NIH-funded multicenter clinical trials under way to examine
treatment and prevention strategies of type 2 diabetes in youth.

45. MODY

46. Maturity-Onset Diabetes of the Young
• MODY is a monogenic autosomal dominant, heterogeneous form of
diabetes.
• It is related to a defect in insulin secretion by the β-cells in the
pancreas rather than to an impairment of insulin sensitivity.
• 1% to 3% of people with diabetes have MODY
• 10–30 years of age, although it can be as early as 2 to 3 years of age

47. • The majority of individuals with MODY are not overweight.
• This diagnosis should be entertained in children and
adolescents with a strong family history of diabetes in
multiple generations

48. Genetic defects of β-cell function-MODY
• Chromosome 20, HNF4α (MODY1)
• Chromosome 7, glucokinase (MODY2)
• Chromosome 12, HNF1α (MODY3)
• Chromosome 13, IPF1 (MODY4)
• Chromosome 17, HNF1β (MODY5)
• NeuroD1 (MODY6)
HNF-hepatic nuclear factor
IPF- insulin promoting factor

50. Glucokinase (MODY2)
Expressed in b-cells and liver
It catalyzes the formation of glucose-6-phosphate from glucose.
Beta cells - “Glucose sensor” Control rate of Glucose phosphorylation
Liver – Helps in storage of glucose as glycogen
Mild stable hyperglycemia
Does not respond to Sulfonylureas

51. Liver-enriched transcription factors
HNF-1a, HNF-1b, and HNF-4a(3,5,1)
Expressed in liver, pancreatic islets, kidneys and genitalia.
In Beta cells they regulate the expression of the insulin gene
Proteins involved in glucose transport and metabolism.
Mutations results in defect of insulin secretion response to
glucose, leading to progressive decline in glycemic control.
MODY 1 &3 responds to sulfonylurea initially.

52. MODY 4
Transcription factor IPF-1
Expressed in pancreatic islets
Central role in development of pancreas.
Mediates glucose-induced stimulation of insulin-
gene transcription
Exocrine pancreatic insufficiency may occur.

53. MODY 6
• Transcription factor Neuro-D1 (BETA2)
Rare
Expressed in pancreatic islets
Activates the transcription of the insulin gene
Required for normal development of the pancreatic islets

54. Phenotypic Expression and Natural History of
MODY
Recognition at young age
1.Mild, asymptomatic increase in blood glucose in a child,
adolescent or young adult(<25 years)
2. Prominent family history of diabetes in 2-3 generations
3. Usually not associated with obesity
Not progressive, or slowly progressive hyperglycemia
Hyperglycemia responsive to diet and/or oral
anti-hyperglycemic agents for years to decades

55. When to suspect MODY
When to suspect MODY
a “type 1″ diabetes patient who has negative blood testing for
autoantibodies.
a “type 1″ diabetes patient who generates a significant amount of
insulin for years beyond diagnosis (detectable blood levels of c-
peptide, proinsulin, and/ or insulin)
a “type 2″ diabetes patient who is normal weight and shows no signs
of insulin resistance.
a diabetes with family history of early onset diabetes for 2-3
generations.
Diabetes paired with pancreatic insufficiency
Individual or family history of diabetes paired with developmental
kidney disease or kidney cysts

56. Genetic Testing
Only definitive way to confirm MODY
Blood or saliva
Not all mutations cause diabetes
Each child will have a 50% chance of inheriting the gene
1st degree relatives have a 50% chance of carrying the same
gene mutation

57. Rx for MODY
Rx depends on the involved gene and other factors
 MODY 3 and 1 can be treated initially with sulfonylureas,
prompts the body to produce insulin.
 Usually GCK-MODY requires no treatment at all.
 Other type of MODY Rx is unclear may require multiple
daily Insulin injections.

59. LATENT AUTOIMMUNE DIABETES OF
ADULTHOOD
Late-onset autoimmune diabetes of adulthood
Slow Onset Type 1 diabetes
Type 1.5 diabetes - Type 1 diabetes develops in adults
Mistakenly diagnosed as T2DM

60. Characteristics of LADA
Adult age (usually over 30 years) at time of diagnosis
May initially appear to be non-obese Type 2 diabetes
May initially be controlled with nutrition and exercise
Patient gradually becomes dependent on insulin
Positive for auto-antibodies
Low C-peptide levels in the body
Often does not have a family history of Type 2 diabetes

61. LADA Vs T2DM
C-peptide levels
LADA have low level VS Normal or high in T2DM
Glutamic acid decarboxylase(GAD) autoantibodies – Common in T1DM
Early age of onset
Non obese individuals
No family history of early onset diabetes
Ketosis prone
May requires insulin after initial 6 months

62. DIAGNOSING LADA
• Performing a GAD antibody test is the most common
method of diagnosing LADA.

63. Management of LADA
LADA often does not require insulin at the time of diagnosis and may
be managed with diet and exercise.
 Due to destruction of the β-cells, they become insulin dependent
more rapidly than “classic” type 2 diabetes
May require multiple daily Insulin injections(after 6 months)

64. DIABETES IN PUBERTY

65. PUBERTY

66. • Puberty sets in insulin resistance due to increase in
production of growth hormone and sex hormone.
• Insulin requirements go up by more than 50%
• HBA1c should be monitored.

67. THE TEAM APPROACH

68. Goals for Glycemic Control for Children, Adolescents, and Young Adults with Diabetes
Blood glucose goal range(mg/dl)
Values by age Before meals Bedtime/overnight HBA1c
Toddlers and preschoolers
Whole blood 90-180 100-200 7-9%
Plasma 100-200 110-220
School age
Whole blood 70-80 90-180 ≤8%
Plasma 80-200 100-200
Adolescents and young
aduts
Whole blood 70-150 80-160 ≤7%
plasma 80-170 90-180

69. INSULIN therapy

70. INSULIN therapy
• By insulin syringes, pens, pumps and air injectors
• The small insulin needs of infants and toddlers may require
insulin diluted to U10, U25, or U50 as opposed to the
standard U100 preparations (100 U/mL)
• FDA approved lispro and aspart but glargine not below 6
years
• Premixed insulins are not recommended in the pediatric
population unless all other insulin programs have failed
• Insulin pumps

71. Usual Subcutaneous Daily Dosages of Insulin in Children and
Adolescents with Diabetes
Type Non DKA presentation DKA presentation
Type 1 diabetes
Child, prepubertal 0.25-0.5 U/kg per day 0.5-0.75 U/kg per day
Adolescent, pubertal 0.5-0.75 U/kg per day 0.75-1.0 U/kg per day
Type 2 diabetes
Adolescent 20-40 U/kg per day
Lispro/glargine

72. OTHER SPECIFIC TYPES WITH SECONDARY DM

74. Diabates care
• Optimal and individualized glycemic control
• Self-monitoring of blood glucose
• HbA1c testing (2–4 times/year)
• Patient education in diabetes management (annual);
diabetes-self management education and support
• Medical nutrition therapy and education (annual)
• Eye examination (annual or biannual)
• Foot examination (1–2 times/year by physician; daily by
patient)

75. • Screening for diabetic nephropathy (annual)
• Blood pressure measurement (quarterly)
• Lipid profile and serum creatinine (estimate GFR)
(annual)
• Influenza/pneumococcal/hepatitis B immunizations
• Consider antiplatelet therapy

76. TAKE AWAY MESSAGE
1. Eat healthy food
2. Exercise regularly
3. Avoid fatty/saturated foods
4. Avoid alcohol
5. We are all prone for diabetes

77. THANK YOU