aetiopathogenesis, diagnosis, features, management acute complications

1. Diabetes Mellitus
Brig(DR) A B Khare (retd)
Associate professor (med)

2. Investigations
1. Urine glucose : Glycosuria – low threshold , drugs
2. Blood glucose : Venous plasma glucose
Diabetes :- fasting > 126mg% , 2 hrs after 75 gm glucose or
random sample >200 mg% , Or
Pre diabetes :- IFG > 110 - < 126 mg% , IGT 2 hrs after 75
gm glucose 140 - 200 mg% , Or
Hba1c > 6.55%
In asymptomatic patients two diagnostic tests(same) are required to confirm
diabetes

4. Inv contd…
OGTT
 Preparation before the test
 Unrestricted carbohydrate diet for 3 days
 Fasted overnight for at least 8 hours
 Rest for 30 minutes
 Remain seated for the duration of test with no smoking
 Sampling
 Measure plasma glucose before and 2 hours after a 75 gm glucose drink

5. inv contd…
 Blood test :
 Enzymatic reaction (glucose oxidase) , cheap , automated , reliable
depends on timing of meal.
 Testing sticks read with portable electronic meter (capillary/finger prick)
 Testing for control only for those on sulphonylureas /insulin
 For diagnosis: accurate lab method
 Venous plasma values are most reliable for diagnostic purposes

6.  Interstitial glucose :- CGM systems – tiny sensor under skin (measures
every 1-5 min) , life : 2 weeks . Night time glucose level.
 Ketones(Urine & blood ) :- acetoacetate identified by nitroprusside
reaction in urine. Do not measure major ketone found in blood. Also
found in fasting , strenuous exercise , repeated vomiting , diet high fat
low carb.
 Major ketone beta(OH)butyric acid found in blood during DKA
detected by stick/electronic meter . useful for management , detection
& prevention in DKA

7. Inv(ketones) Contd…
measurement
 <0.6mmol/l
(10mg%)
 0.6-1.5mmol/l
(10-27mg%)
 1.5-3mmol/l
(27-54mg%)
 >3.0mmol/l
(>54mg%)
Interpretation
 Normal: no action
 Suggest metabolic going down
 Risk of DKA with high blood glucose
 Severe ketosis : seek urgent medical help

8. Inv contd…
 Glycated Hb : accurate & objective measure of glycaemic control over
weeks – months. Non enzymatic covalent attachment of glucose to Hb
 Islet antibodies :- high titre islet antibodies suggest type 1 DM.
antibodies against components of islets – insulin , glutamic acid
decarboxylase(GAD) , protein tyrosine phosphatase – related proteins (ia-
2) and Zn transporter ZnT8.
 C-peptide :- marker for endogenous insulin. Very low in long standing
type 1DM & very high in severe insulin resistance.
 Urine proteins :- micro albuminuria - indicator of diabetic nephropathy
/ risk of macrovascular disease.

9. Aetiology & Pathogenesis
In both types interplay of environmental factors with genetics decide who &
when.
Type 1 DM :- autoimmune destruction of β cells based on model by Eisenbarth
genetically susceptible individual  exposed to environmental trigger
β cell autoimmunity  progressive loss of β cells.
initially fast first phase insulin secretion loss  IGT & undiagnosed DM
 Pathology– inflammatory lesion ‘insulitis’-β cell specific.
molecular mimicry, oxidative stress, viral infection
auto-ab : 20-25%-single type,50-60% double , 70% three type.

10. Pathogenesis of Type1 DM

11. Contd…
 Genetic predisposition: –
strong but complex multifactorial ,
monozygotic twins 30-50% concordance ,
dizygotic 6-10%
1:20 in 1st degree relative, 1:300 in general
1-4% (mother), 10% (father) still 80-85% in general
inheritance polygenic -20 regions in human genome
HLA region – MHC short arm chromosome 6

12. Contd…
 Environmental predisposition –
Wide geographical & seasonal variation & rapid acquisition in migrants.
Environmental factor : 1-viruses 2- food 3- bovine serum albumin 4 - vit D.
‘hygiene hypothesis’
 Metabolic disturbance – type1 DM present on crossing a threshold β cell
destruction. Resulting high glucose may be toxic to ↑β cell.
Hyperglycaemia  glycosuria & dehydration fatigue, polyuria , nocturia ,
thirst , polydipsia , infection (UTI) , tachycardia , hypotension , unrestricted
lipolysis & proteolysis  weight loss

13. Acute metabolic complications of insulin deficiency

14. Contd…
Ketoacidosis –
When generation exceeds metabolic capacity
Duration of symptoms : short (few weeks).
 Type 1 DM in adults : slow onset type1 diabetes or latent
autoimmune diabetes of adulthood (LADA). Presence of islet ab in
high titre(usually GAD antibody) without rapid progression to insulin
therapy.
 Initially managed as type 2 DM but eventually require insulin.

15. Contd…
Type 2 DM : diagnosis of exclusion , highly heterogenous group
initially insulin resistance -- increased insulin secretion – eventual beta cell
failure.
 one group– young – insulin resistance due to obesity ,ethnicity
 second group – old -- nonobese – pronounced beta cell failure
 key feature relative insulin deficiency

16. Natural history of type2 Diabetes

17. Natural history of Type2 Diabetes

18. Contd…
 Insulin resistance & metabolic syndrome
often have hypertension , dyslipidaemia (high LDL , TG, low HDL) , NAFLD ,
PCOD .
much more common in obese people
Cause of insulin resistance –
1- central obesity – active adipocyte – FFA – compete with glucose
adipokine like cytokine – on liver & muscle receptors – insulin resistance

19. Contd …
2-- physical activity
inactivity – downregulation insulin sensitive kinase—FFA accumulation
3– Deposition of fat in liver – NAFLD – NASH – cirrhosis .
 Pancreatic β cell failure
Early stage: modest decrease in beta cell mass.
At diagnosis- 50% decrease and decline thereafter.
Amyloid deposition
Increased FFA & glucose  toxic effect on βcell impaired insulin secretion.

20. Contd…
 Genetic predisposition
monozygotic twins : 100 % concordance
over 70 genes/gene regions are associated in beta cell function / turnover
& regulation of cell cycle.
powerful influence by environmental factors.
 Environmental factors
overeating ,obesity , decreased activity , age (70%>50 yrs) , ethnicity

21. Contd…
 Metabolic disturbances in type 2 DM :
 Slow onset relative insulin deficiency
 In contrast to type 1, lipolysis & proteolysis not unrestrained – wt.
loss & ketoacidosis seldom occurs
 Hyperglycaemia develops over years
 At diagnosis – asymptomatic , fatigue over many months ± osmotic
Sx , some spiral decline –DKA, ketosis prone Flatbush syndrome

24. Presenting problems
in
diabetes mellitus

27. New onset hyperglycaemia
(Confirm Diabetes)

28. New onset hyperglycaemia
(confirm Diabetes)

30. Complications
of
Diabetes Mellitus

31. Acute complications/ Diabetic emergencies
 Diabetic ketoacidosis
 Hyperglycaemic hyperosmolar state
 Hypoglycaemia

32. Chronic Complications
Microvascular :
 Retinopathy / cataract : impaired vision
 Nephropathy : renal failure
 Peripheral neuropathy : sensory loss , motor weakness , pain
 Autonomic neuropathy : GI problems (gastroparesis , altered bowel
habit) , postural hypotension
 Foot disease : ulceration , arthropathy

33. Contd…
Macrovascular :
 Coronary circulation : myocardial ischaemia / infarction
 Cerebral circulation : transient ischaemic attack , stroke
 Peripheral circulation : claudication , ischaemia

34. Diabetic emergencies

35. Diabetic Emergencies
 Diabetic ketoacidosis:
Medical emergency
Features :
Hyperketonaemia > 3.0 mmol/l
or ketonuria > 2 +
hyperglycaemia > 200 mg %
metabolic acidosis ph. < 7.3 or
H+ > 50 nmol / l

36. Contd…
• Profound osmotic diuresis
• Potassium loss
• Ketosis
• Metabolic acidosis
• Loss of fluid & electrolytes

37. Clinical presentation

39. Contd…
 Clinical features ;
Loss of skin turgor ,furred tongue ,cracked lips ,tachycardia ,
hypotension , Decreased IOP, deep sighing breathing ( Kussmaul's
sign) , sweet smell of acetone , mental apathy , delirium , coma
abdominal pain
 Investigations: (without delaying fluid & insulin administration )
venous blood ; urea , electrolytes , glucose , bicarbonate , ABG
urine & blood samples for ketones
infection screen ; CBC , C-reactive protein , blood / urine culture chest x ray
leucocytosis

40. Fluid & electrolyte loss in moderate DKA

42. Contd…
 Management ;
fluids : isotonic saline (.9% Nacl) (correction of ECF )
10 % Glucose when blood Sugar < 200mg % ( correction of ICF )
insulin: Infusion 0.1 u/kg /hr
or
IM loading dose 10-20 u followed by 5 u/hr
or
Subcutaneous 0.3u/kg then 0.1 u/kg
Blood glucose fall 55-110mg% /hr , ketone conc.↓ By 0.5 mmol/hr

43. Contd…
 Potassium
 Bicarbonates
 Phosphates
 Other ongoing treatment

44. Emergency management of DKA

45. DKA management Contd…

46. DKA Management contd…

47. DKA Management contd…

48. Hyperglycaemic hyperosmolar state
 Different from DKA
 Different approach to management
 Hypovolemia , hyperglycaemia (> 600mg % ) , hyperosmolality (> 320
mosm/kg) ketonemia < 3.0 mmol/ L , lactic acidosis , pH > 7.3 , H+ < 50 nmol/L
, bicarbonate > 15mmol /L
 Mortality rate > 20%

49. Poor prognostic signs
 Hypothermia
 Hypotension
 Tachy- or bradycardia
 Serum osmolality > 360 mosm/L
 Other serious comorbidity

50. Emergency management Hyperglycaemic Hyperosmolar
State(HHS)

51. Emergency management HHS contd…

52. Emergency management HHS contd…

53. Emergency management of HHS contd…

54. Hypoglycaemia

55. Hypoglycaemia Symptoms

57. Hypoglycaemia Management

58. Hypoglycaemia : common causes & risk factors

59. Hypoglycaemia cause & risk factors contd…

60.  To be continued……….