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
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+
Diagnosis Diabetic ketoacidosis with underlying IDDM–presentation at young age–Rapid onset ( within weeks )–BMI low/normal
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
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
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
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
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
• 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
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
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
TYPE 1 LADA TYPE 2 MODYAge Childhood/adult Adult adult Chilhood /young adultProgress to Rapid (weeks – Latent (mths – Slow (yrs) Slow (yrs)insulin days) years)dependanceAutoantibodies yes yes no noInsulin no some yes rareresistanceWeight Low/normal Low/normal overweight normalC-peptide low low normalTreatment Insulin Insulin Diet and Diet, OHA lifestyle, (sulphonylureas) OHA, insulin as disease progresses
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,
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
DIAGNOSIS• Drug ( steroid) induced diabetes mellitus
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
• Under opthalmology follow-up since Oct 2006.• Visual acuity reduced: Rt: 6/60 Lt: 6/60.
Family History5 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.
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
• 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
• The best available diagnostic criteria are juvenile onset diabetes mellitus and optic atrophyA 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.