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
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
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
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
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
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.
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.