This document provides an overview of diabetes, including: - The types of diabetes are type 1 (insulin dependent) and type 2 (non-insulin dependent). Type 2 diabetes is becoming more common. - Diabetic emergencies include hypoglycemia, hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state. Proper management is outlined. - Diabetes complications involve both microvascular complications that damage small blood vessels and macrovascular complications like heart disease. Risk factors for complications are discussed.

1. An Overview of Diabetes
Sid McNulty
Consultant Physician &
Endocrinologist

2. Constructivism and Experiential
learning and the brain
Sensory
Integrative
Making sense
Integrative
Planning
‘Motor’
(plus verbal)
Concrete experience
Active reflection
Abstract
conceptualisation
Active experimentation

3. Neuronal networks
Tap into and build on what the learner already
knows
ACEi actions
K+ sparing
Diuretic
Antihypertensive
Postural hypotension
Insulin action Hypoglycaemia
Addison’s
Lack of RAAS drive
Lack of insulin antagonism
Cushing’s opposite of
Addison’s
and therefore opposite of:
Insulin and diuretics, and
therefore….
Blockage of RAAS

4. Diagnosis of Diabetes
WHO (adopted in UK 6/00):
Symptoms of hyperglycaemia plus 1 blood
Random/2 hr plasma gluc > 11.1 mmol/l, or
Fasting plasma glucose > 7.0 mmol/l
In the absence of symptoms, there must be 2
plasma glucose results in the diabetic range on
separate days.

5. Diagnostic dilemma
Sensitivity: positives identified as positive
Specificity: negatives identified as negative
100% specific
Over 10m long
Over 15,000 mph
Over 6,000 Km high
No false alarms
Lots of false -ve
100% sensitive
Over 1m long
Over 10mph
Off the ground
Don’t miss a strike
Lots of false +ve

6. Lethal Disease X
Affects 1 in 10,000
100% fatal – horrible and painful death
Fantastic test for it 99% (99% sensitive ie picks
up disease as disease, and 99% specific ie
picks up normal as normal)
You have the test
1 week later the results
You are positive
What is your probability you have disease?
What do you do?

7. Please stand up

8. Condition
Positive Negative
Test
Result
Positive True +ve False +ve +ve predictive
value
TP/TP+FP
Negative False -ve True –ve -ve predictive
value
TN/TN+FN
Sensitivity 99%
TP/TP+FN x100
Specificity 99%
TN/TN+FP x
100
A ‘Good’ Test

9. A ‘Good’ Test?

10. The Devil is in the detail!

11. Condition
Positive Negative
Test
Result
Positive True +ve False +ve +ve predictive
value
TP/TP+FP
Negative False -ve True –ve -ve predictive
value
TN/TN+FN
Sensitivity 99%
TP/TP+FN x100
Specificity 99%
TN/TN+FP x
100
A ‘Good’ Test

12. What tests means
Sensitivity: about the disease…the people you identify
with the disease/total number with the disease
(TP/TP+FN)…if you have disease, you test positive
Specificity: about the disease…the people you identify
without the disease/total number without the disease
(TN/TN+FP)… if you don’t have disease you test
negative
Positive predictive value: about the test…the number of
people you test positive with the disease/total number
you test positive (TP/TP+FP)… if you test positive,
likelihood you have disease
Negative predictive value: about the test…the number of
people you test negative without the disease/total
number you test negative (TN/TN+FN)… if you test
negative, likelihood you don’t have the disease

13. Gedankenversuch

14. Test: being called mags to diagnose
being a woman
Male Female
True positive
False
negative
False positive
True
negative

15. What being called mags means
Sensitivity (disease): if you’re a woman, how likely
is it you’ll be called mags (low 1%)
Specificity (disease): if you’re not a woman, how
likely is it you’ll not be called mags (v high
99.99%)
Positive predictive value (test): if you’re called
mags, how likely are you to be a woman (high
99%)
Negative predictive value (test): if you’re not
called mags, how likely you’re not a woman
(poor 50%)

16. Lethal Disease X
Affects 1 in 10,000
100% fatal – horrible and painful death
Fantastic test for it 99% (99% sensitive ie picks
up disease as disease, and 99% specific ie
picks up normal as normal)
You have the test
1 week later the results
You are positive
What is your probability you have disease?
What do you do?

17. Please stand up, again

18. One million people
1 in 10,000 with disease 1 in 100 with false +ve
1 in 10,000 with
disease and +ve
test
ie 100 people
1 in 100 with +ve
test and no disease
ie 10,000 people

19. One million people
How many have disease?
1 in 10,000
100 people
How many would test positive?
1 in 100
10,000
If positive do you have disease?
What is the positive predictive value
TP/TP+FP: 100/10,100
ie 1 in 100 chance!
Therefore – even the best test should be interpreted with
clinical data, and should only be asked for in the right
people (ETT ECGs, VQs etc etc)

20. What tests means
Sensitivity: about the disease…the people you identify
with the disease/total number with the disease
(TP/TP+FN)…if you have disease, you test positive
Specificity: about the disease…the people you identify
without the disease/total number without the disease
(TN/TN+FP)… if you don’t have disease you test
negative
Positive predictive value: about the test…the number of
people you test positive with the disease/total number
you test positive (TP/TP+FP)… if you test positive,
likelihood you have disease
Negative predictive value: about the test…the number of
people you test negative without the disease/total
number you test negative (TN/TN+FN)… if you test
negative, likelihood you don’t have the disease

21. Incidence of Diabetes
The incidence is increasing steeply
World diabetic population is estimated to
reach 221 million people by 2010 (double
the number in 1994).
Over 1.4 million people in the United
Kingdom (3% of the pop) have diagnosed
diabetes mellitus, with perhaps another
million as yet undiagnosed.
Amos AF et al.The rising global burden of diabetes...Diabetic
Med 1997;14(suppl 5):S1-85.

22. Types of diabetes
Type 1 (IDDM)
Absolute insulin
deficiency
ß-cell failure
Young, thin
Prone to DKA
Type 2 (NIDDM)
Relative insulin
deficiency
Insulin resistance
Old, ↑BMI (kg/m2
)
Usually on tablets or diet
(can be on insulin)
No DKA : instead HONK

23. Insulin balance with age T1DM
0
20
40
60
80
100
120
insulin req
insulin T1
‘Event’

24. Obesity and T2DM
Obesity
Inactivity
Insulin resistance
Hyperglycaemia
Micro- and macro-vascular
complications
Hypertension
Dyslipidaemia
Endothelial dysfunction
Prothombotic state

25. The Progress to T2DM
Wt 70 kg
Requires 60 U
Panc Res 200 U
Level: 60 U
Normal
Wt 100 kg
Requires 150 U
PR 200 U
Level: 150 U
‘Normal’
Wt 70 kg
Requires 60 U
Panc Res 100 U
Level: 60 U
Normal
Wt 100 kg
Requires 150 U
Panc Res 100 U
Level: 100 U
DM & Hyperinsulin
NORMAL T2DM

26. 12 v 121 v 1210 units?
8 v 81 v 810 units/hr?
50 v 501 v 5010 units/50ml?
1010 units Actrapid at 100 mls/hr?

27. Insulin balance with age T2DM
0
20
40
60
80
100
120
insulin T1
insulin T2

28. Insulin balance with age T2DM
0
20
40
60
80
100
120
insulin req0
insulin T1
insulin T2

29. Why worry with diabetic in-patients
Avoid emergencies:
Main aim of your Mx
Plus tighten peri-operative glucose control

30. Diabetic emergencies
Hypoglycaemia
Hyperglycaemia
DKA: Type 1
HHS/HONK: Type 2

31. Hypoglycaemia
BMs 2-4
Autonomic symptoms: Sympathetic
Sweaty, agitated, nausea, shaky, pale, hungry
BMs 0-2
Neuroglycopenic:
Confusion, aggression, agitation, coma,
hemiparesis etc

32. Mechanism of Normoglycaemia
β cell
Proinsulin
Insulin C Peptide
↓ Glucose
Pancreas
Pancreas
Glucagon Glycogen Liver
↑ Glucose

33. Mechanism of Hypoglycaemia
β cell
Proinsulin
Insulin C Peptide
↓ Glucose
Pancreas
Pancreas
Glucagon Glycogen Liver
↑ Glucose
1.Sulphonylureas
3.Exogenous
4.Lack of antagonist
(cortisol etc)
5.IGF 2
6.Excess use
2.Excess
7.Lack of
8.Lack of

34. Treatment of Hypo
Treatment:
IV glucose 50ml 50%
IM glucagon 1 mg
?Treat cause
steroids (Addison’s, NICTH)
surgery (Insulinoma, NICTH)
Diazoxide & high dose BFZ (Paliative Insulinoma)
DSN review/ Psych review

35. Presentation & definition of DKA
Young, thin, T1DM
Poly-uria, -dypsia, weight loss (passing sugar water)
SOB (kussmal - blowing off CO2 to ↓pH),
dehydrated, ↓ BP, vasodilated, drowsy
Raised blood glucose (>15 mmol/L)
Metabolic acidosis:
pH <7.3, Bicarb <15 mmol/L
Ketosis: ketostix > ++

36. Mechanism of DKA
Intercurrent illness
Increased counter-regulatory
hormones (Cats and cortisol)
Severe insulin deficiency
Hyperglycaemia

37. Mechanism of DKA
Hormone-sensitive lipase
TriglycerideNon-esterified fatty acids
Acetoacetate
3-HydroxybutyrateAcetone
Glycerol
+
Insulin
-

38. Mechanism of DKA
Intercurrent illness
Increased counter-regulatory
hormones (Cats and cortisol)
Severe insulin deficiency
Hormone-sensitive lipase
TriglycerideNon-esterified fatty acids
Acetoacetate
3-HydroxybutyrateAcetone
Glycerol
+ +
+
Hyperglycaemia

39. Mechanism of DKA
Hyperglycaemia Ketone bodies
Osmotic
diuresis Vomiting Acidosis
Electrolyte
depletion
Dehydration Vasodilatation
Hypotension Hypothermia

40. Management of DKA General
NG tube
Reduced consciousness
Gastroparesis
IV access
? Central line only if indicated
Catheter
?UTI may have precipitated DKA
Dehydrated and immunosuppressed
Serious risk of introducing ascending infection
Therefore only if not PU’d in 3 hours
Remove / treat precipitator (low threshold for Abs)
?Heparin (coma or Osmolality >350 mOsm/L)

41. Management DKA Specific
T1DM
Acute decompensation
pH <7.3, Bicarb <15, Ketosis, Gluc >15
IV insulin 0.1 unit/kg/hr = 6-8 units/hr
IV fluids 5 Ltr/24hr
? Abs (WCC/Temp mean little)
No Bicarb
Inform your senior

42. 13th
May 2010
Died July 1997
Retired last year and
still facing 12 charges!

43. HyperOsmotic NonKetotic Coma (AKA)
Hyperglycaemic HyperOsmolar Syndrome
Presentation & Definition
In Type 2 DM
Longer Hx -poly-uria/dypsia
Dehydration, ↓BP, unwell
High RBG (usually >>30 mmol/L)
Osmolality >350
(Na+
+ K+
) x2 + Urea + Glucose = Osmol

44. Management of HHS Summary
T2DM, older, co-morbidity, more sick
Osmol > 350 mmol/Ltr
Gluc usually >>30 mmol/Ltr
Same general management as DKA
IV insulin 0.1 units/kg/hr = 6-8 units/hour
IV fluids 3-5 Ltr/24hr
Go more gentle!
?Full heparin dose
Abs, MI screen etc
Inform your senior

45. GKI/Alberti (to give insulin to T1DM)
15 units Actrapid
500 ml 10% Dextrose
10 mmol KCl
80-100ml/hour
If BMs high add another 5 units (and on)
If BMs low add 5 units less (and on)
Check K 1 hour before bag change
Restart sc insulin 1/2 hour before eating

46. Complications & Diabetes
Microvascular v Macrovascular
‘KNIVES’
K - kidneys
N - nerves
I - impotence, infection
V – vascular (IHD, CVA, PVD)
E - eyes
S - skin infections

47. Macrovascular risk factors
Male
Age
Family History
Other Vascular Disease:
CVA, TIA
LVH
Diabetes
Hypertension
Lipids:
↑Chol, ↑LDL, ↓HDL, ↑ TGs
Smoking
Obesity
Exercise

48. Diabetic complications
Prevention of complications
Risk reduction – relative versus absolute
Risk elimination
Residual risk

49. Intervention studies - Drug X
Reduces total chol 70%
Reduces LDL 50%
Increases HDL 10%
Would you take it?
Surrogate markers
Losing weight reduces chol
Losing weight by losing legs
Reduces relative risk of MI 50%
Would you take it?

50. Relative risk reduction
RR↓ 50%
RR↓ 50%
RR↓ 50%

51. Risk of AE Relative versus absolute risk
RR↓ 50%
Absolute risk reduction
Absolute risk reduction
Absolute risk reduction

52. Lies, damn lies and statistics
6/49 x 5/48 x 4/47 x 3/46 x 2/45 x 1/44 =
720/10,068,347,520 =
1 in 13,983,816
Increase your relative risk by 100%
To 1 in 6,991,908
Absolute risk increase 1 in 13 million
Reduce your relative risk by 50%
1 in 27,967,632
Absolute risk reduction 1 in 13 million

53. Numbers Needed to Treat….
100 patients
10 events
100 patients
5 events
Relative risk reduction 50%
Treat 100 people, 5 events prevented, therefore treat 20 to prevent 1

54. This maybe all that we can offer you
1000 patients
10 events
1000 patients
5 events
Relative risk reduction 50%
Treat 1000 people, 5 events prevented, therefore treat 200 to prevent 1

55. Intervention studies - Drug X
Reduces total chol 70%
Reduces LDL 50%
Increases HDL 10%
Would you take it?
Surrogate markers
Losing weight reduces chol
Losing weight by losing legs
Reduces relative risk of MI 50%
Would you take it?
Serious adverse event 1% per year
Would you take it?

56. What does risk reduction mean?
What was not going
to happen
When does this not
happen
What did happen
in spite of
intervention..
When did you
cause this?
What didn’t happen
with
intervention…
When does this not
happen
When did you
prevent this?

57. RR reduction 50% with 20% side effects
What was not going
to happen
Plus SE
Primum non nocere
First do no harm!
What did happen
in spite of
intervention..
When did you
cause this?
Plus SE
What didn’t
happen with
intervention…
When did you
prevent this?
Plus SE

58. Maximilien François Marie Isidore de Ro
(May 6, 1758–July 28, 1794),
On ne peut pas faire
d'omelette sans casser des
oeufs
You can't make an omelette
without breaking eggs
Primum non nocere

59. Risk of crossing the road
Park cars
Eyes closed
Heavy traffic
Run out
Pedestrian crossing
Wait for green man
Look both ways
Walk briskly don’t
run
No guarantee to be or not be run over
NB you do get to the other side.
The prevention of accident happens in
definite time frame

60. Prevention of macrovascular
complications
Primary prevention
All T2DM & most T1DM (10y risk <15%)
Tight glycaemic control (~UKPDS & DCCT)
Tight BP control (UKPDS)
Tight lipid management
Aspirin, ACE I/AT2A, smoking, BMI
Secondary prevention
Hx of CVA, MI, IHD, PVD, Amputation

61. Glycaemia in T2DM
HbA1c 2/12 marker (area under the curve)
Mean 5.4%, SD 0.4%
i.e. normal <6.2
HbA1c <7.5 <6.5

62. Normality
Mean
1 SD
2 SDs
3 SDs
68%
95%
99%

63. HbA1c: mean 5.4%, SD 0.4%
5.4%
6.2%
68%
95%
99.5%
7.0%4.6%
2.5% ‘normal
population’
0.25%

64. Oral Hypoglycaemics
Metformin (if BMI >24)
500 - 1000mg b.d - t.d.s
Side effects - GI….lactic acidosis
Contraindications - CRF, CCF, hepatic problems
No weight gain, no hypos
Gliclazide (if BMI <22)
40 - 320mg per day (od - bd)
Side effects weight gain & hypos
Glitazones (pioglitazone > rosiglitazone), acarbose
etc

65. Hypoglycaemics
Incretins – Exanatide, gliptins
Insulins:
long v short
free v pre-mixed
human v pork v analogue
?CSII etc
Combination with OHA

66. Normal person
0
2
4
6
8
10
12
14
16
18
1 3 5 7 9 11 13 15 17 19 21 23
Isulin
Glusose

67. BD Mix
0
5
10
15
20
25
30
35
40
short
long
7am 6pm
Breakfast
Lunch
Dinner
Snack

68. Basal Bolus
0
5
10
15
20
25
30
35
1
3
5
7
9
11
13
15
17
19
21
23
Basal
Bolus
am short
Lunch short
Dinner short
Evening background

69. Titrating Insulin-
BD mix
BM reading Insulin
7 am Nocte long
Noon Mane short
6 pm Mane long
10 pm Nocte short

70. Titrating Insulin-
Basal Bolus
BM reading Insulin
7 am Nocte basal
Noon Mane short
6 pm Noon short
10 pm Supper short

71. Lipid lowering
Diet/lifestyle/co-morbid/smoking
CVS equivalent (or CVS risk >15%@10 yr)
LDL/Total Chol (>2.0/4.0) - Statins
HDL/Trigs (<1, >2.2) - ? Fibrates
Statins - Simva 40, Atova 40-80mg nocte
good for total and LDL chol
Fibrates - Fenofibrate micro 267mg mane
good for trigs and HDL
Nicotinic acid - good for trigs and HDL
Ezetimibe - add on therapy, Omacor - post MI

72. ABCD tool

73. Anti-hypertensives
ACE I/AT2A
Ramipril 2.5 - 10mg, Irebesartan 150 - 300mg
Partic if: CCF, IHD, MI, nephropathy, CVA
CI: pregnant, renovascular disease (watch Creat)
Thiazide diuretics (low dose!) - BFZ 2.5 mg o.d
β blockers - atenolol 50mg
Partic if MI, IHD, CCF
CCB - Amolidipine 5-10mg o.d
α blockers - Doxazosin XL 4-16mg (BPH)
Central acting etc

74. Microvascular Complications
Retinopathy
Nephropathy
Neuropathy
Erectile dysfunction

75. Prevention of microvascular
complications
Primary prevention
Tighten control:
Glycaemia, BP, Lipids
Aspirin, ACE I, Anti Obesity
Secondary prevention
Catch & Treat early (as above, laser Rx etc)
Therefore screen for them
Funduscopy, feet inspection, urine & blood tests

76. Annual Screen
HbA1c/Lipids/Creat/BP/Wt
Alb:Creat Ratio
Feet - pulses, sensation (10g MF), ulcers
Eyes - dilated funduscopy, VAs
Kidneys - BP/ACR/Creat
Smoking status

77. Mx T2DM Conclusions
Lifestyle: Smoking, Diet, Exercise & Weight
Annual screen for complications
Glycaemic control (UKPDS Metformin > Glic)
CVS Risk Calculation (>15%) v Equiv
Lipid control
LFD, Statin, ?Fibrates
BP control
ACE I, ATII, Diuretics, β Blocker, CCB, other
Other drug Rx:
Aspirin,?anti obesity,?anti smoking, ?HRT

78. Questions?