2. DIABETES MELLITUS
Diagnosis & Distinguishing
Various Types

3. Classification
• Type 1
– Panceatic Islet cell deficiency
– Autoimmune / Idiopathic
– Genetic markers HLA DR, HLA DR3, HLA DQ
– Autoantibodies to islet auto antigens (GAD , IA-
2, insulin )
– 5-25% cases
– 25% of people will first present in diabetic
ketoacidosis

4. • Type 2
– Defective insulin secretion or action
– Insulin resistance
– Insulin secretory defect
– 75-95% cases
– Patients typically overweight adults

5. MODY
HNF 4α Glucokinase HNF 1α IPF-1 HNF 1b
MODY 1 MODY 2 MODY 3 MODY 4 MODY 5
Chromosome 20q 7p 12q 13q 17q
Proportion of 5% 15% 70% <1% 2%
Cases
Progression Progressive Little Progressive uncertain uncertain
hyperglycaemia deterioration with hyperglycaemia
age
Microvascular Frequent Rare Frequent Inadequate Frequent
complications data
Others None Reduced birth Sensitive to Pancreatic Renal cysts
weight sulphonylureas agenesis Proteinuria,
Renal
failure

6. • TYPE 1.5 / LADA
– Latent autoimmune diabetes in adults
– Autoantibodies
– Progress within months/yrs to insulin
dependence
– May initially be treated with OHA
initially

7. • Diseases of exocrine pancreas
– Pancreatitis
– Trauma/surgery
– Pancreatic destruction ( cystic fibrosis,
haemochromatosis)
– Neoplasia
• Endocrinopathies
– Cushing’s
– Acromegaly
– Pheochromocytoma
– Glucagonoma
– Hyperthyroidism
– Somatostatinoma

8. • Genetic syndromes
– Down’s
– Klinefelter
– Lawrence – Moon-Biedl Syndrome
– Myotonic Dystrophy
– Prader-Willi
– Turner
– Wolfram (DIDMOAD)
• Drug induced
• Gestational Diabetes
• Genetic defects of insulin action

9. Diagnosis
VENOUS PLASMA FASTING RANDOM
GLUCOSE ≥ 7.0 mmol/L ≥11.1 mmol/L
OGTT plasma glucose levels (mmol/L)
Category 0 hour 2 hours
Normal ≤ 6.1 < 7.8
IFG 6.2 – 6.9 -
IGT - 7.8 – 11.0
DM ≥ 7.0 ≥11.1

10. Patient 1
• 14 year old male, Indian ethnicity
• Presented to A&E with altered mental status,
high anion gap metabolic acidosis
• BMI –18 kg/m2
• 2 months history of generalized lethargy
• Father and 1 other sibling diagnosed with
type 1 DM
• Signs of volume depletion, no acanthosis
nigricans, no hyperpigmentation no vitiligo
/ goitre

11. INVESTIGATIONS
• RBS – 29 mmol/l
• RP & LFT normal
• ABG – metabolic acidosis
– pH was 7.1
– anion gap 26 serum
– Bicarbonate 8 mmol/liter and urine was
• Urine ketones 4+

12. Diagnosis
Diabetic ketoacidosis with
underlying IDDM
–presentation at young age
–Rapid onset ( within weeks )
–BMI low/normal

13. MANAGEMENT
• Admitted to the hospital and received
• standard treatment for DKA with IV fluids
and insulin
• Recovered uneventfully and was
discharged on the third hospital day on a
regimen of sc actrapid 12 u tds and sc
monotard 10u on
• Counseling of patient and family with
diabetic nurse

14. Diagnostic Investigations
• C-peptide 23 pmol/l (298 – 2350 pmol/l)
• Antibodies
– Anti GAD level ( positive >10 IU/ml)
– Anti Insulin (IgG) level (positive >18 U/ml)
– Anti-Islet Cell (ICA) binding index (positive >1.0)
– Anti IA-2 (positive >10 IU/ml

15. Patient 2
• 17 year old Malay female
• Obese, BMI 31.2
• RBS 14.5, glycosuria - urine glucose 4+
• Asymptomatic
• Father diagnosed with type 2 DM, well
controlled on OHA since age 30
• 4 siblings, 1 elder siblings diagnosed with type 2
DM
• No proximal myopathy / abdominal striae
• BP 130/80mmhg
• Fundus normal

16. DIAGNOSIS
• TYPE 2 DM / ? MODY

17. MODY CHARACTERISTICS
• Weight normal / high sugars in some forms
associated with insulin resistance & weight gain
• Usually not insulin resistant
• No islet autoantibodies
• Respond well to drugs stimulating insulin secretion
(MODY 3) / small doses of insulin
• May have high post prandial sugar, normal FBS &
normal HbA1c or high FBS ( glucokinase mutation )
• History of gestatational DM in mother associated
with younger age of onset
• Glycosuria at low blood levels

18. Diagnostic Investigations
• C peptide – 208 pmol/L ( 298-2350)
• Antibodies
– Anti GAD level <0.01 U/ml
( positive >10 IU/ml)
– Anti Insulin (IgG) level 0.44 U/ml
(positive >18 U/ml)
– Anti-Islet Cell (ICA) binding index 0.62
(positive >1.0)
– Anti IA-2 <0.01U/ml
(positive >10 IU/ml
• Genetic studies

19. Patient 3
• 42 year old Indian male
• History of obesity BM1 30 kg/m2
• Diagnosed with type 2 Diabetes 18 mths ago
with RBS 22.2 mmol/L
• Initial presentation with Polyuria, polydipsia ,
polyphagia
• Obese sibling who has been treated with diet
and oral anti-diabetic agent.
• Given daonil for 18 mths, SMBG initially good,
however 1 year after treatment, sugars difficult to
control, started losing weight
• Presented 18 mths later to hospital with DKA,
commenced on insulin therapy

20. • Clinical examination
– BM1 26 kg/m2
– BP 128/78 mmHg
– No acanthosis nigricans
– No abdominal striae / proximal myopathy
– Fundus normal, monofilament test normal,
– Normal peripheral pulses

21. Investigations
• C peptide – 42 pmol/L ( 298-2350)
• Antibodies
– Anti GAD level 18 IU/ml
( positive >10 IU/ml)
– Anti Insulin (IgG) level 0.62 U/ml
(positive >18 U/ml)
– Anti-Islet Cell (ICA) binding index 0.57
(positive >1.0)
– Anti IA-2 <0.01U/ml
(positive >10 IU/ml

22. DIAGNOSIS
• LADA
– Onset >25 yrs
– Initial control of hyperglycemia with diet
and OHA, evolution to insulin necessity
within mths
– low fasting C-peptide
– positive anti-GAD antibodies

23. TYPE 1 LADA TYPE 2 MODY
Age Childhood/adult Adult adult Chilhood /young
adult
Progress to Rapid (weeks – Latent (mths – Slow (yrs) Slow (yrs)
insulin days) years)
dependance
Autoantibodies yes yes no no
Insulin no some yes rare
resistance
Weight Low/normal Low/normal overweight normal
C-peptide low low normal
Treatment Insulin Insulin Diet and Diet, OHA
lifestyle, (sulphonylureas)
OHA, insulin
as disease
progresses

24. Patient 4
• 73 year old Malay lady
• Underlying hypertension and bilateral knee
osteoarthosis on painkillers
• Presented to A&E with generalized lethargy, polyuria
and polydipsia for past 1 month.
• RBS 35 mmol/L, glycosuria 4+
• On examination BMI 28 kg/m2
• Dehydrated , ABG – no acidosis
• Renal function and liver function – normal
• Initially started on IV insulin sliding scale in the ward
• subsequently discharged 2 days later on
T.Metformin 500mg BD and T. Gliclazide 80 mg BD,

25. Follow up
• 2 weeks later
– History of palpitation and sweating at home
since discharge from hospital
– CBS stat in clinic – 2.1mmol/L
• Further history – taking traditional
medication & painkillers for knee pain
past 2 mths ? steroids

26. DIAGNOSIS
• Drug ( steroid) induced
diabetes mellitus

27. Patient 5
• 27 year old male, Indian ethnicity
• Diagnosed at 5 yrs of age to have IDDM & on sc
insulin injection since childhood
• History of visual impairment under
opthalmological follow-up.
• B/L hearing loss using hearing aid but not on
ENT follow-up.
• CBS on follow-up in nearest clinic noted to be
23mmol/L in August 2007
• Polyphagia and Polydipsia 3 days prior to
presentation

28. • Under opthalmology follow-up since Oct 2006.
• Visual acuity reduced:
Rt: 6/60 Lt: 6/60.

29. Family History
5 siblings. Parents well.
• 2nd brother (30y.o), IDDM since 5 yrs,
bilateral optic atrophy & hearing loss.
• 3rd sister (27y.o), IDDM since 2 yrs,
bilateral optic atrophy & hearing loss.
• 4th brother (25y.o): IDDM since 7 yrs,
visual problem and hearing problems
• No problems in eldest sister and
youngest brother so far.

30. DIAGNOSIS
DIDMOAD (Wolfram’s Syndrome)
(Diabetes Insipidus, Diabetes Mellitus, Optic
Atrophy, and Deafness),

31. Wolfram’s Syndrome
• Autosomal
recessive/dominant/mitochondrial
inheritance
• Early-onset IDDM and optic atrophy
• constriction of visual fields and decline
visual acuity and color vision
• diabetic retinopathy may be rarely
observed

32. • Renal tract abnormalities usually
develop in the 3rd decade
• atonic bladder with a large capacity has
been mostly reported
• In the 4th decade, multiple neurological
abnormalities (cerebellar ataxia,
myoclonus, and psychiatric illness can
occur)
• Death usually due to central respiratory
failure as a result of brain stem atrophy in
their 3rd or 4th decade

33. • The best available diagnostic
criteria are juvenile onset diabetes
mellitus and optic atrophy
A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic
atrophy (Wolfram syndrome) Nat Genet. 1998;20:143–148. doi: 10.1038/2441.

34. Thank you for your attention