obesity diabetes and metabolic syndrome
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Lets know about this killer, non-communicable diseases voluntarily before they demand that we should.TRANSCRIPT
DSB 202: General and Systemic Pathology (Endocrine disorders)
Obesity, Metabolic Syndrome, Diabetes Mellitus
1GKM/MLS3202/LECT 02/2014
Lecturer: Dr. G. Kattam Maiyoh
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.
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
Epidemiology
0
102030
4050
19601970
19801990
20002010
20202030
USAEngland
MauritiusAustralia
BrazilPopulation percentage with BMI > 30kg/m2
Obesity rates:
current and projected
What causes Obesity?
• Genetic predisposition
• Disruption in energy balance
• Environmental and social factors
• 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
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 internetContinued watching of television - cable, satellite
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.
““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
Ageing and Energy Expenditure
James, Ralph and Ferro-Luzzi, 1989
Kca
ls/d
Intenseexercise OccupationalDiscretionary
Sitting, coffee,smoking
Basal metabolicrate
Dietary induced thermogenesis
70 kg, Aged 25 years 70 kg, Aged 70 years
4000
2000
0
3000
1000
Fat as the Macronutrient Culprit
Adapted from WHO Consultation 1998Adapted from WHO Consultation 1998
ProteinProtein CarbohydraCarbohydratete FatFat
Energy content per gEnergy content per g
Ability to end eatingAbility to end eating
Ability to suppress Ability to suppress hungerhunger
Storage capacityStorage capacityPathway to transfer Pathway to transfer
excessexcess to alternative to alternative compartmentcompartment
Ability to stimulate own Ability to stimulate own oxidationoxidation
44
HighHigh
HighHigh
LowLow
YesYes
ExcellentExcellent
44
ModerateModerate
HighHigh
LowLow
YesYes
ExcellentExcellent
99
LowLow
LowLow
HighHigh
NoNo
PoorPoor
Consequences of obesity
Cardiovascular risk factors
Respiratory diseaseHeart disease
Gallbladder disease
Hormonal abnormalities
Hyperuricaemiaand gout
Stroke
Diabetes
OsteoarthritisCancer
……because of fat infiltrationbecause of fat infiltrationin eyelids...in eyelids...
Blindness in a child...
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
• Over-represented among populations with CVD
• Often occurs in individuals with a distinctive body-type including an increased abdominal circumference
The Metabolic Syndrome (MS)
Android obesity
or
• APPLE TYPE Central or abdominal adiposity (ANDROID) increased WHR & associated with higher morbidity risk.
> ♂ ♀
Gynoid obesity
or
• PEAR TYPE : GYNOID or typical female distribution of fat : less health risks
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
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.
CHD
Pre
vale
nce
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
0
1
2
3
4CVD*
CHD†
0 1 2 3 4 5
Mor
talit
y ha
zard
ratio
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
Tuomilehto J et al. NEJM 2001;344:1343-1350
0
0.05
0.1
0.15
0.2
0.25
InterventionControl
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)
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
40Placebo (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 participants
All participants
Years from randomization
Cum
ula
tive in
cidence
(%
)
*Includes 7% weight loss and at least 150 minutes of physical activity per week
PlaceboMetforminLifestyle modification
Inci
denc
e of
DM
(%)
0
20
30
10
40
00 1 42 3Years
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
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.
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WORLD MAP
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People at high risk of diabetesFactors 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
Most important risk
factor !
61% of new cases DM result of
overweight
NEJM 2001, 345:790-797
People at high risk of diabetesRisk Factor
Defining Level
Waist circumference*
Men ≥ 100 cmWomen ≥ 90 cm
Triglycerides ≥ 1.7 mmol/L
HDL cholesterol
Men < 1.0 mmol/LWomen < 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
IGT and IFG are intermediate stagesBoth 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
Prevention – by early testing Age to commence testing
Population group Men WomenAsymptomatic 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
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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.
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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 ORa random glucose of ≥ 11.1 mmol/L is diagnostic of diabetes.
36GKM/MLS3202/LECT 02/2014
Action following fasting plasma glucoseCriteria 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
Interpretation
Normal result
Borderline result
IFG Diabetic
Action
Retest in 3-5 years orfor those at risk.
OGTT for those at increased risk of diabetes.Re-test annually those with IFG or IGT.
Assess with OGTT.Re-test annually
Two results > 7 on two different days are diagnostic of diabetes. OGTT is not required.
37
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.
Fastingmmol/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
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• Patient 1 = Normal
• Patient 2 = IGT
• Patient 3 = Diabetic
GKM/MLS3202/LECT 02/2014 39
Gestational diabetes mellitusGestational 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.
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GDM
GKM/MLS3202/LECT 02/2014 41
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
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
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 treatmentTest no more than three monthly
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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….”
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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
ParameterOptimal 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
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Short-term Complications
47
Long-term Complications
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• 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
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• 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
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• Kidney disease
– diabetic nephrosclerosis– atherosclerosis of renal arteries
• Among the leading causes of renal failure
– infections of bladder & kidney
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• Eye disease
– Important cause of blindness associated with
• cataracts• glaucoma• diabetic
retinopathy
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• 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
Thank you for listening