Diabetes in young patients

1. DIABETES CLASSIFCATION &
DIABETES IN YOUNG
- DR.KISHORE KUMAR
(POSTGRADUATE GENERAL MEDICINE )

2. DIABETES CLASSIFICATION
• Etiologic Classification of Diabetes Mellitus
• I. Type 1 diabetes
• (immune-mediated beta cell destruction, usually leading to absolute insulin
deficiency)
• II. Type 2 diabetes
• (may range from predominantly insulin resistance with relative insulin
deficiency to a predominant insulin secretory defect with insulin resistance)

3. III. Specific types of diabetes (MONOGENIC)
• III-A. Genetic defects of beta cell development or function characterized by
mutations in: ( MODY )
• MODY 1- (HNF) 4α
• MODY 2- Glucokinase
• MODY 3- HNF-1α
• MODY 4- Insulin promoter factor-1, HNF-1β, NeuroD1, and other pancreatic islet
regulators/proteins such as KLF11, PAX4, BLK, GATA4, GATA6, SLC2A2 (GLUT2),
RFX6, GLIS3
• MODY 5- Insulin secretory gene , leading to permanent neonatal diabetes
• MODY 6- Subunits of ATP-sensitive potassium channel, leading to permanent
• neonatal diabetes
• MODY 7 - Mitochondrial DNA

4. MODY

5. III. Specific types of diabetes
• III-B. TRANSIENT NEONATAL DIABETES
• III-C. DISEASES OF THE EXOCRINE PANCREAS—
• pancreatitis, pancreatectomy,
• neoplasia, cystic fibrosis, hemochromatosis,
• fibrocalculous pancreatopathy, mutations in carboxyl ester lipase

6. III. Specific types of diabetes
• 3D. Genetic defects in insulin action, including
• TYPE A INSULIN RESISTANCE
• Triad of hyperandrogenism , insulin resistance , Acanthosis nigricans
• HAIR-AN
• LEPRECHAUNISM
• DONOHUE SYNDROME – IUGR
• Bird facies , fasting hypoglycemia & IGT despite giving more than 100 x insulin
• RABSON-MENDENHALL SYNDROME
• Pineal gland hyperplasia with abnormalities in Teeth & nail
• LIPODYSTROPHY SYNDROMES
• Rare syndrome characterised by insulin-resistant diabetes associated with a regional or
complete absence of subcutaneous adipose tissue & presence of Hypertriglyceridemia

7. III. TYPE 3 D DIABETES
Triad of hyperandrogenism , insulin
resistance , Acanthosis nigricans
TYPE A INSULIN RESISTANCE

8. III. TYPE 3 D DIABETES

9. RABSON-MENDENHALL
SYNDROME

10. III. TYPE 3 D DIABETES
LIPODYSTROPHY
SYNDROMES

11. III. Specific types of diabetes
• 3E. Endocrinopathies—
• Acromegaly, Cushing’s syndrome, glucagonoma, pheochromocytoma,
hyperthyroidism, somatostatinoma, aldosteronoma
• 3F. Drug- or chemical-induced—
• glucocorticoids, calcineurin and mTOR inhibitors (after organ transplantation),
• vacor (a rodenticide), pentamidine,
• nicotinic acid, diazoxide, β-adrenergic agonists, thiazides, hydantoins,
• asparaginase, α-interferon, protease inhibitors, antipsychotics (atypicals
• and others), epinephrine

12. • 3G. Infections—congenital rubella, cytomegalovirus, coxsackievirus
• 3H. Uncommon forms of immune-mediated diabetes—
• “stiff-person”syndrome, anti-insulin receptor antibodies
• Has neurological problems of paroxysmal episodes of stiffness at night
• 3I. Other genetic syndromes sometimes associated with diabetes
• Wolfram 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
• IV. Gestational diabetes mellitus (GDM)

14. DIABETES IN YOUNG ADULTS
•It comprises of
•Type 1 DIABETES
•TYPE 2 DIABETES
•TYPE 1.5
• LADA ( LATENT AUTOIMMUNE DIABETES IN ADULT)
• KPD ( KETOSIS PRONE DIABETES )
•MODY

15. T1DM & T2 DM
• TYPE 1 DM
• Immune dysregulation –
autoimmune attack of beta cells
• Disease can develop at any age
• Family history : not significant
• Auto antibodies :
• Anti GAD – most persistent
• Anti IAA
• Anti ICA – most specific
• Anti ZnTB
• TYPE 2 DM
• Polygenic and multifactorial
• Family history more significant
• Insulin resistance +

16. TYPE 1.5 DIABETES
• What is 1.5 diabetes ?
• LADA
• KPD
• TYPE 1 diabetes which presents late and mimics like T2DM at initial
presentation
• It is TYPE 1.5 LADA ( LATENT AUTOIMMUNE DIABETES OF ADULTS )
• TYPE 2 diabetes which presents like a T1DM at initial presentation
• It is TYPE 1.5 KPD ( ketosis Prone diabetes ) which presents with DKA as initial
presentation
T2DM
T1DM
LADA
KPD

17. LADA TYPE 1.5 DIABETES
•Late – onset autoimmune diabetes of
adulthood
•It’s a Slow onset Type 1 diabetes
•When this Type 1 diabetes develops in
adults usually mistakenly diagnosed as
T2DM
T1DM
LADA

18. CHARACTERISTICS OF LADA
• Adult age usually around 30 yrs at the time of diagnosis
• Phenotypy & history
• Initially appear to be non-obese Type 2 diabetes
• Initially controlled with nutrition and exercise
• As there is some amount of insulin left at presentation
• Patient gradually dependent on insulin
• Positive for auto antibodies
• Low c peptide levels in the body
• Often no family history of type 2 diabetes
T1DM
LADA

19. DEFINITION OF LADA
• The Immunology for Diabetes Society (IDS) has
specified three criteria for the diagnosis of LADA:
1. Age greater than 35 years
2. Positive autoantibodies to islet beta cells
3. Insulin independence for at least the initial 6 months after
initial diagnosis
T1DM
LADA

20. TYPE 1.5 KPD
• Ketosis prone diabetes
• Also called as Flatbush diabetes
• Stigmata of insulin resistance ( acanthosis nigricans , balnophosthitis)
• Dark , hirsute , obese male
• Initially treated with insulin then with OHAs
• Patients with KPD present in DKA , but once DKA resolves
some are able to discontinue insulin and maintain adequate
glycemic control with oral agents.
T2DM
KPD

21. T2DM
T1DM
LADA
KPD
INSULIN OHA

22. DIFFERENCES
TYPE I DM WITH
KETOSIS
TYPE 1.5 KPD
Auo antibodies present No auto antibodies
No stigmata of Insulin
resistance
Insulin resistance present
Lean, tall , fair boys Obese, hirsuite, acanthosis
nigricans ,
balanophoshthis
TYPE 2 DM TYPE 1.5 LADA
No auto antibodies Auto antibodies +
Insulin resistance + No features of insulin
resistance
obese Lean , tall , fair
Young adult presenting with DKA the two
DDs are
Young adult presenting with high
blood sugar

23. MODY – TYPE 3A
• Heterozygous monogenic mutations in
• Enzymes – glucokinase
• Transcription factors – HNF 1aplha, beta, 4 alpha etc
• Autosomal dominant inheritance
• Primary defect in insulin secretion
• PHENOTYPY AND NATURAL HISTORY OF MODY
1. Recognition at young age
• Mild asymptomatic increase in blood glucose in child, adolescent or young adult
• Prominent family history of diabetes in 2-3 generations
• Usually not associated with obesity
2. Not progressive or slowly progressive
• Very good response to OHAs

24. MODY

25. When to suspect MODY
• A supposedly type 1" diabetes patient who has negative blood testing
for autoantibodies.
• A supposedly "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 supposedly "type 2" diabetes patient who is normal weight and
shows no signs of insulin resistance.
• A diabetic with family history of early onset diabetes for 2-3
generations.

26. Genetic testing
• Only definitive way to confirm MODY
• 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
• Then they have a >95% chance of developing MODY at some time in
their life
TREATMENT
very good respone to sulphonylureas

27. APPROACH TO DIABETES IN YOUNG
1. PHYSICAL APPEARANCE
2. Fasting c peptides level
• Normal level : 0.3 – 0.6 nmol/L
• Low : T1DM, LADA
• Normal : KPD,T2DM ,MODY
• Confirmatory test for low c peptide : glucagon stimulated C peptide levels
3. AUTOANTIBODIES
• Anti GAD , anti ICA , IAA & zn TBA
• Anti Gad – most persistent
• Postive – T1DM, LADA

29. DIABETES IN YOUNG – SUMMARY
TYPE I DM TYPE 1.5 LADA Type 2 DM TYPE 1.5 KPD MODY
Phenotype Lean , tall, fair Lean , tall Obese , non
obese
Obese + Normal , lean
Stigmata of
insulin
resistance
Negative Negative + +++ Negative
Family h/o Not significant Not significant + ++++++
Fasting c
peptides
Low Low/ varable Normal Normal normal
Anitbodies ++ ++ - - -

30. • THANK YOU