Lets know about this killer, non-communicable diseases voluntarily before they demand that we should.

1. DSB 202: General and Systemic Pathology
(Endocrine disorders)
Obesity, Metabolic Syndrome, Diabetes Mellitus
1GKM/MLS3202/LECT 02/2014
Lecturer: Dr. G. Kattam Maiyoh

2. Obesity: definition
• Chronic disease characterized by
accumulation of fat. Obesity is defined as a
condition when ideal body weight is exceeded
by 20%
• Medical condition responsible for serious co-
morbidity and mortality.

3. Psychosocial consequence
• Economical impact of obesity
• Prejudice and Discrimination (pay double fare
in matatus)
• Considered lazy, incompetent and more often
absent due to illness
• Confronted with more problems at job
application :
–Very few executive managers with overweight in
the US

4. Epidemiology
0
10
20
30
40
50
1960
1970
1980
1990
2000
2010
2020
2030
USA
England
Mauritius
Australia
Brazil
Population
percentage
with BMI >
30kg/m2
Obesity rates:
current and projected

6. What causes Obesity?
• Genetic predisposition
• Disruption in energy balance
• Environmental and social factors

7. • An individual may have a genetic
predisposition to become obese, but will only
become obese given the right environmental
influences.
• It has been suggested that up to 50% of the
variability in body weight is governed by
genetic factors.
• Some 360 genes have now been identified
and related to the development of obesity
although some of them may have a very small
role.
Interplay between Genes and Environment

8. Reduced physical activity as computer/ communication
technology advances penetrate the masses.
Leisure activity
Increased participation in computer games
Increased use of computer as a communication
device for recreational purposes (chat rooms, etc.)
Increased use of home-based video - including
video access on the internet
Continued watching of television - cable, satellite

9. New Remote Control
Can Be Operated by
Remote
No more leaning forward to
get remote from coffee
table
means greater convenience
for TV viewers.Television watching
became
even more convenient
with Sony’s introduction
of a new remote-controlled
remote control.

11. ““EAT TO LIVE”EAT TO LIVE”
Intake = ExpenditureIntake = Expenditure
Weight StableWeight Stable
““LIVE TO EAT”LIVE TO EAT”
Intake > ExpenditureIntake > Expenditure
ObeseObese
Disruption in energy balance

12. Ageing and Energy Expenditure
James, Ralph and Ferro-Luzzi, 1989
Kcals/d
Intense
exercise
OccupationalDiscretionary
Sitting, coffee,
smoking
Basal metabolic
rate
Dietary induced
thermogenesis
70 kg, Aged 25 years 70 kg, Aged 70 years
4000
2000
0
3000
1000

13. Fat as the Macronutrient Culprit
Adapted from WHO Consultation 1998Adapted from WHO Consultation 1998
ProteinProtein CarbohydratCarbohydrat
ee
FatFat
Energy content per gEnergy content per g
Ability to end eatingAbility to end eating
Ability to suppress hungerAbility to suppress hunger
Storage capacityStorage capacity
Pathway to transfer excessPathway to transfer excess
to alternative compartmentto alternative compartment
Ability to stimulate ownAbility to stimulate own
oxidationoxidation
44
HighHigh
HighHigh
LowLow
YesYes
ExcellentExcellent
44
ModerateModerate
HighHigh
LowLow
YesYes
ExcellentExcellent
99
LowLow
LowLow
HighHigh
NoNo
PoorPoor

14. Consequences of obesity
Cardiovascular risk
factors
Respiratory disease
Heart disease
Gallbladder disease
Hormonal abnormalities
Hyperuricaemia
and gout
Stroke
Diabetes
Osteoarthritis
Cancer

15. ……because of fat infiltrationbecause of fat infiltration
in eyelids...in eyelids...
Blindness in a child...

16. The Metabolic Syndrome (MS)
•Is a multiplex risk factor for cardiovascular disease
and type 2 diabetes’
• Reflects the clustering of individual risk factors due to
abdominal obesity and insulin resistance.
•This multiplex comprises the following interrelated
metabolic risk conditions:
Atherogenic dyslipidemia, glucose intolerance, elevated
blood pressure, proinflammatory state, and prothrombotic
state.
•Atherogenic dyslipidemia is itself an aggregate term comprised
of elevated fasting and nonfasting triglycerides, elevated VLDL,
reduced HDL, and an atherogenic small dense LDL phenotype

17. • Over-represented
among
populations with CVD
• Often occurs in
individuals with a
distinctive body-type
including an increased
abdominal
circumference
The Metabolic Syndrome (MS)

18. Android obesity
or
• APPLE TYPE
Central or
abdominal
adiposity
(ANDROID) →
increased WHR
& associated
with higher
morbidity risk. ♂
> ♀

19. Gynoid obesity
or
• PEAR TYPE : GYNOID or
typical female distribution
of fat : less health risks

20. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.
JAMA 2001;285:2486-2497
Risk Factor Defining Level
Waist circumference (abdominal
obesity)
>40 in (>102 cm) in men
>35 in (>88 cm) in women
Triglyceride level >150 mg/dl
HDL-C level <40 mg/dl in men
<50 mg/dl in women
Blood pressure >130/>85 mmHg
Fasting glucose >100 mg/dl
Definition of the Metabolic Syndrome
Defined by the presence of >3 risk factors
HDL-C=High-density lipoprotein cholesterol

21. Metabolic Syndrome: CHD
Prevalence and assoc. with Diabetes
• The metabolic syndrome is associated
with an increased prevalence of coronary
heart disease.
• Among individuals with the metabolic
syndrome and diabetes, there is an even
greater prevalence of coronary heart
disease.

22. CHDPrevalence
No MS/No DM
54%
MS/No DM
29%
DM/No MS
2%
DM/MS
15%
8.7%
13.9%
7.5%
19.2%
0%
5%
10%
15%
20%
25%
Metabolic Syndrome: CHD Prevalence*
National Health and Nutrition Examination Survey (NHANES)
% of Population =
Alexander CM et al. Diabetes 2003;52:1210-1214
*Among individual >50 years
CHD=Coronary heart disease, DM=Diabetes
mellitus, MS=Metabolic syndrome

23. 0
1
2
3
4
CVD*
CHD†
0 1 2 3 4 5
Mortalityhazardratio
Number of Metabolic Syndrome Criteria
*
Adjusted for age, sex, race or ethnicity, education, smoking status, non–HDL-C level,
recreational and non-recreational activity, white blood cell count, alcohol use, prevalent
heart disease, and stroke
†
Similar adjustments except for prevalent stroke
Ford ES et al. Atherosclerosis 2004;173:309-314
Metabolic Syndrome: Risk of Death
CHD=Coronary heart disease, CVD=Cardiovascular disease
Risk is Proportional to the Number of ATP III Criteria

24. Tuomilehto J et al. NEJM 2001;344:1343-1350
0
0.05
0.1
0.15
0.2
0.25
Intervention
Control
11%
23%
% with Diabetes Mellitus
Metabolic Syndrome: Risk of Developing DMMetabolic Syndrome: Risk of Developing DM
Finnish Diabetes Prevention Study
†
Defined as a glucose >140 mg/dl 2 hours after an oral glucose challenge
522 overweight (mean BMI=31 kg/m2
) patients with impaired fasting glucose†
randomized to intervention‡
or usual care for 3 years
Lifestyle modification reduces the risk of developing DM
‡
Aimed at reducing weight (>5%), total intake of fat (<30% total calories) and
saturated fat (<10% total calories); increasing uptake of fiber (>15 g/1000
cal); and physical activity (moderate at least 30 min/day)

25. Metabolic Syndrome: Risk of Developing DM
Diabetes Prevention Program (DPP)
Knowler WC et al. NEJM 2002;346:393-403
0 1 2 3 4
0
10
20
30
40
Placebo (n=1082)
Metformin (n=1073, p<0.001 vs. Plac)
Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
Percent developing diabetes
All participantsAll participants
Years from randomization
Cumulativeincidence(%)
*Includes 7% weight loss and at least 150 minutes of physical activity per week
Placebo
Metformin
Lifestyle modification
IncidenceofDM(%)
0
20
30
10
40
00 1 42 3
Years
3,234 patients with elevated fasting and post-load glucose levels randomized to
placebo, metformin (850 mg bid), or lifestyle modification* for 3 years
Lifestyle modification reduces the risk of developing DM

26. Diabetes Mellitus
Type 1 diabetes
 Most frequently affects children and adolescents.
 Symptoms include excessive thirst, excessive urination,
weight loss and lack of energy.
 Daily insulin injections required for survival.
Type 2 diabetes
 Occurs mainly in adults.
 Usually people have no early symptoms.
 People may require oral hypoglycaemic drugs and may also
need insulin injections at later stages.
26GKM/MLS3202/LECT 02/2014

27. WORLD MAP

29. 29GKM/MLS3202/LECT 02/2014

30. People at high risk of diabetes
Factors associated with increased risk for diabetes include:
 Increasing age
 Metabolic syndrome
 Impaired glucose tolerance
 Polycystic ovary syndrome
 Ethnicity
 History of gestational diabetes
having a baby over 4 kg
 Family history of diabetes
 Physical inactivity
 Increased BMI
 Central obesity
 Hypertension
 Adverse lipid profile
 Elevated LFTs
 Patients taking some drugs e.g.
prednisone or anti-psychotic
drugs (haloperidol,
chlorpromazine, and newer
atypical anti-psychotics).
30GKM/MLS3202/LECT 02/2014

31. Most
important risk
factor !
61% of new
cases DM
result of
overweight
NEJM 2001, 345:790-797

32. People at high risk of diabetes
Risk Factor Defining Level
Waist
circumference*
Men ≥ 100 cm
Women ≥ 90 cm
Triglycerides ≥ 1.7 mmol/L
HDL cholesterol Men < 1.0 mmol/L
Women < 1.3
mmol/L
Blood pressure SBP ≥ 130 or DBP ≥
85
Fasting glucose ≥ 6.1 mmol/L
Three or more of the
following risk factors listed
below are required for a
diagnosis of metabolic
syndrome.
People with the metabolic
syndrome are at increased
risk of diabetes,
cardiovascular disease,
sub-fertility and gout
despite only moderate
elevation in individual risk
factors.
32GKM/MLS3202/LECT 02/2014

33. IGT and IFG are intermediate stages
Both impaired glucose tolerance (IGT) and
impaired fasting glucose (IFG) refer to
metabolic stages intermediate between
normal glucose homeostasis and diabetes,
in which there is an increased risk of
progressing to diabetes.
33GKM/MLS3202/LECT 02/2014

34. Prevention – by early testing
Age to commence
testing
Population group Men Women
Asymptomatic people
without other known
risk factors
45 years 55 years
People with other
known cardiovascular
risk factors or at high
risk of developing
diabetes
35 years 45 years
34GKM/MLS3202/LECT 02/2014

35. How to test
Testing for diabetes
• Fasting morning blood glucose is the best
initial test.
• Urine glucose and HbA1C should not be used
for diagnosis.
35GKM/MLS3202/LECT 02/2014

36. People with symptomatic
hyperglycaemia
•Symptomatic hyperglycaemia may have an acute onset,
usually in younger people with type 1 diabetes, or a more
insidious onset, usually in older people with type 2 diabetes.
•The usual symptoms of hyperglycaemia are thirst, polyuria
and weight loss but hyperglycaemia can also cause fatigue,
lack of energy, blurring of vision or recurrent infections, such
as candida.
For people with symptomatic hyperglycaemia,
a single fasting glucose of ≥ 7.0 mmol/L
OR
a random glucose of ≥ 11.1 mmol/L
is diagnostic of diabetes.
36GKM/MLS3202/LECT 02/2014

37. Action following fasting plasma glucose
Criteria for the diagnosis of diabetes, IGT and IFG.
Normal
Diabetes
Fasting
glucose
result
(mmol/L )
< 5.5 5.5 - 6.0 6.1 - 6.9 ≥ 7.0
Interpretatio
n
Normal
result
Borderline
result
IFG Diabetic
Action
Retest in
3-5 years
or
for those
OGTT for
those at
increased
risk of
diabetes.
Assess
with
OGTT.
Two results
> 7 on two
different
days are
diagnostic of
37

38. OGTT and its Interpretation
•A 75 gram of glucose administered orally (oral glucose tolerance test -
OGTT)
•Is used to follow up people with equivocal results who may have diabetes,
IFG or IGT.
Fasting
mmol/L
2 hours
post load
mmol/L
Normal < 5.5 and < 7.8
IFG 6.1 – 6.9 and < 7.8
IGT < 7.0 and 7.8 – 11.0
Diabetes
mellitus
≥ 7.0 and/or ≥ 11.1
GDM ≥ 5.5 and/or ≥ 9.0
38GKM/MLS3202/LECT 02/2014

39. • Patient 1 = Normal
• Patient 2 = IGT
• Patient 3 = Diabetic
GKM/MLS3202/LECT 02/2014 39

40. Gestational diabetes mellitus
Gestational diabetes mellitus (GDM) increases the risk of many
foetal and maternal complications in pregnancy and the
development of type 2 diabetes later in life (Kjos, 1999).
Screening is recommended for all women between 24 - 28
weeks gestation.
Screening for GDM using 50 gram load (1 hr OGGT)
If the one hour blood glucose is ≥ 7.8 mmol/L, a two hour OGTT
is performed.
OGTT for diagnosis of GDM
A fasting glucose ≥ 5.5 and/or a 2 hour value
≥ 9.0 mmol/L is diagnostic of GDM.
40GKM/MLS3202/LECT 02/2014

41. GDM
GKM/MLS3202/LECT 02/2014 41

42. Types of gestational diabetes
Type A1
– Reveals altered finding during oral glucose tolerance test (OGTT),
but with normal blood glucose levels with fasting and after two
hours with meals.
– With this stage of gestational diabetes, diet modification is
enough to manage the increased glucose levels.
• Type A2
– Reveals altered finding during oral glucose tolerance test (OGTT),
it also has elevated glucose levels even during fasting and/ or
during after meals.
– Apart from modification of lifestyle and diet, adjunct therapy with
insulin and other diabetes medications are indicated and
necessary.
GKM/MLS3202/LECT 02/2014 42

43. Hyperglycemia causes
glycosylation
– glucose attaches to proteins
– indicators are
• Haemoglobin A1c(Hgb A1C)
–average of blood glucose over the past 2-3
months
• fructosamine
–average of blood glucose over the past 2-3
weeks
GKM/MLS3202/LECT 02/2014 43

44. HbA1C and Target levels
Any sustained reduction of HbA1C is worthwhile
because there appears to be a direct relationship
between cardiovascular risk and HbA1C.
The goal is to achieve an HbA1C as low as possible,
preferably less than 7.0%, without causing
unacceptable hypoglycaemia.
HbA1C > 8 mmol/L is a sign of inadequate control for
most people.
HbA1C targets need to be indiviadualized, taking into
consideration factors such as the patient’s age .
Stable diabetes Test six monthly
Changes in treatment
Test no more than three
monthly
44GKM/MLS3202/LECT 02/2014

45. Self monitoring blood glucose (SMBG)
People who take insulin should regularly self monitor
blood glucose.
For people with non-insulin treated type 2 diabetes
testing is most useful if patients use the results to learn
and alter behaviour, or medication.
“...SMBG is most useful if patients use the results to learn, as part of an
overall diabetes education package….”
45GKM/MLS3202/LECT 02/2014

46. Laboratory tests to prevent and delay
complications of diabetes
People with diabetes usually die from
macrovascular complications of their
diabetes; namely cardiovascular
disease.
This is influenced by all of the
commonly recognised risk factors for
cardiovascular disease as well as
glycaemic control.
Fasting lipid levels are measured
three monthly until stable and then 6
- 12 monthly thereafter.
It is important that management
should be individualised
Parameter Optimal value
Total
cholesterol
< 4 mmol/L
LDL
cholesterol
< 2.5 mmol/L
HDL
cholesterol
> 1 mmol/L
TC:HDL ratio < 4.5
Triglycerides < 1.7 mmol/L
HbA1C < 7 mmol/L
46GKM/MLS3202/LECT 02/2014

47. Short-term
Complications
47

48. Long-term
Complications
48GKM/MLS3202/LECT 02/2014

49. • Glycosylation damages blood vessels
• Mostly affects blood vessels & nerves
– glycolated proteins in vessel wall makes it stiffer &
less elastic
– in large vessels, accelerates atherosclerosis
– in small vessels, slows blood flow & diffusion
49GKM/MLS3202/LECT 02/2014

50. • Vascular disease
• impairs blood flow causing ischemia (restriction in
blood supply to tissues) & infarction
• high incidence of
– Myocardial infarction (MI)
– stroke
– lower limb gangrene
– microvascular disease
• characterized by hyaline arteriolosclerosis (refers to
thickening of the walls of arterioles)
• leads to diabetic nephropathy & diabetic retinopathy
50GKM/MLS3202/LECT 02/2014

51. • Kidney disease
– diabetic nephrosclerosis
– atherosclerosis of renal arteries
• Among the leading causes of renal
failure
– infections of bladder & kidney
51GKM/MLS3202/LECT 02/2014

52. • Eye disease
– Important cause of
blindness
associated with
• cataracts
• glaucoma
• diabetic
retinopathy
52GKM/MLS3202/LECT 02/2014

53. • Conclusion
–combination of different factors can prevent
Diabetes
• BMI ≤ 25
• Diet : high fibre intake; PUFA, Low SFA; trans
fats and GI
• Regular physiacl activity
• Non Smoker
• Moderate alcohol use
–incidence of diabetes approx. 90 % lower in
this group

54. Thank you for listening