nutrition.pptx

Nutrition, metabolic disease and GIT
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Brain storm
What do you think the d/c b/n the f.f disciplines?
Chemistry
Physiology
Medical Biochemistry
What is nutrition, food, diet, nutrient & their roles?
Why do you think learning nutrition is important for health student?
What is healthy diet? What is unhealthy diet?
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Introduction to Medical Biochemistry
Biochemistry is the science concerned with the chemical basis /constituents of life
It deals with the normal and abnormal function of cells at molecular level
It deals with metabolism and its interrelationship, fate of diet, mechanism of action of
drug.
It is a laboratory based science that brings together biology and chemistry concepts.
By using chemical knowledge and techniques, biochemists can understand and solve
biological problems

The aim of Biochemistry
To understand life at the molecular level and all of the chemical processes
associated with living cells
Via isolate the numerous molecules found in cells to determine their structures &
analyze how they function by using techniques likes
Chromatography
Electrophoresis
Ultracentrifugation
Specific sequencing methods

BIOMOLECULES
Human body is composed of about 60% water, 15% proteins, 15% lipids, 2% carbohydrates and
8% minerals.
In living organisms, biomolecules are ordered in to a hierarchy of increasing molecular complexity.
 Proteins
 Polysaccharides
 lipids
 Nucleic acids
Macromolecules associate with each other by non-covalent forces to form supra-molecular
systems. e.g. ribosomes

STABILIZING FORCES IN MOLECULES
Electrostatic attraction between an electronegative atom and a hydrogen atom covalently bonded to a
second electronegative atom called hydrogen bond

NUTRITION AND NUTRITIONAL BIOCHEMISTRY
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When biochemistry is linked with diet, health and disease susceptibility it known
as nutritional biochemistry.
 In living cell there are two molecules
 Macro and Micro molecules
 Metabolites of biological molecules like glucose, glycerol and A.As
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Nutritional Biochemistry

Nutrition
Nutrition: is the science that study the interaction of nutrients and other
substances in food in relation to health and maintenance, growth, reproduction,
and disease of an organism.
It is also deal with the process by which the organism ingests, digests, absorbs,
transports, utilizes and excretes food substances ===>natural science origin
It concerned with social, economical, and cultural implications of food and eating
===>social science origin
Nutritional science studies the relationship between diet with states of health
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protein
Nutrition as a science can study six main categories of food components
vitamins
fat
water
carbohydrate
minerals
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What is food?
o Food is any substance that can be eaten, drunk or taken in order to sustain life,
give energy, growth and etc.
o Food: is defined as anything edible as defined based on specific culture, religion,
etc.
o It includes all foods and drinks acceptable to be ingested by certain society.
o Nutrient: Is an active chemical component in the food that play specific structural
or functional role in the body.
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Food
Nutrients
1-Macronutrients
2-Micronutrients
Other compounds
-Fibers
-Phytochemicals
-Pigments
-Additives
-Alcohols and others
Food composition
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Function of food
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Function of food
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Diet
Diet: Is the total of foods that one consumes in sequence and balance in each day.
It deal with quantity, quality and frequency of food consumption daily by
individual
Diet -The quality of our diet affects the quality of health and the risk of chronic
diseases
Diet: concerned about the eating patterns of individuals or a group
o Some people may eat twice in a day (breakfast and dinner),
o Others may eat four times in a day (breakfast, lunch, snack and Dinner)
o Still others may remain munching all the day round, etc.
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 It is a diversified diet that contains all the essential nutrients in the appropriate
proportion that is required for optimal health.
Your Menu Should be colourful!
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Balanced diet/Healthy diet

Deadly obese( overnutrition)
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Underweight (undernourished)
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Normal weight
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Eat to
Live!
Live to Eat!
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“EAT TO LIVE”
Intake = Expenditure
Weight Stable
“LIVE TO EAT”
Intake > Expenditure
Obese
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Healthy Eating Pyramid
Carbohydrates: take most food
from this group (rice, pasta,
bread, potatoes)
Fruit and vegetables: take 5
portions a day from this group
Meat, fish and dairy: take
something from this group
Foods high in fats and sugars:
take only small amounts from
this group
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Principles of Good Nutrition
1. Adequacy
2. Balance
3. Energy Control
4. Nutrient Density
5. Moderation
6. Variety
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ABCDMV

Elements of a Healthy Diet - ABCMV
Adequacy - get enough of essential nutrients.
Balance - contains a good proportion of nutrients. No
overemphasis of a food group.
Calorie control - choose foods to maintain ideal body weight.
Moderation - eat any food in reasonable-size portions.
Variety - eat different types of food to prevent boredom.
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Diet Health
Linked to each other
If we want to fulfill the dream our country, we will have to educate our
people regarding what to eat to build a nation of strong and healthy citizens.
Good Diet Good Health
Bad Diet Bad Health
Bad Health Weak Nation
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Group I includes communicable, maternal, and perinatal causes and nutritional
deficiencies.
Group II includes the non-communicable causes including cancers, diabetes,
cardiovascular disorders and chronic respiratory diseases.
Group III includes unintentional and intentional injuries.
Causes of Deaths: Groups I, II and III
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Two Types of Nutrients
Macronutrients Micronutrients
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carbohydrate
fats
protein
vitamins
organic
The human body and foods are made of the same materials, arranged in different
ways.
minerals
water
Energy-yielding
nutrients
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Body Requirement for Nutrients

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“ You are what you eat”
“ Whatsoever
was the father
of a disease, an
ill diet was the
mother”
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Variables which affect nutrient needs:
1. Age
2. Gender
3. Activity Level
4. Climate
5. Health
6. State of nutrition
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Global Trends in Nutrition
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From Ancient to Modern Work
The Nutrition Transition Program
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From Traditional to Modern Leisure
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From Traditional to Modern Economic Work at Home
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From Ancient to Modern Transport
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New Remote Control Can Be Operated by Remote
Television watching became even more convenient with Sony’s introduction of a new
remote-controlled remote control.
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World Then & Now!
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From Traditional to Modern Snacking
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 61% of new cases DM is the result of uncontrolled overweight
 87 % of overweight new cases preventable if all women placed in regular dietary
control
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Why nutrition transition
Globalization: globalised food tastes such as westernised habits of meat eating, more
dairy which takes more energy to produce and drives future grain consumption.
Media encourages the food transition from traditional diets of grains and vegetables to
often high protein and fats and sugars, westernised dietary habits and lower physical
activity levels.
With rising income rising middle classes in transition economies changing their food
habits
Urbanization: More choices and less active life style in urban than rural
.
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Lower energy density
This 450-gram breakfast
delivers 500kcal, for an energy
density of 1.1 (500 kcal/450 g
= 1.1 kcal/g)
Higher energy density
This 144-gram breakfast delivers 500
kcal, for an energy density of 3.5
(500 kcal/144 g = 3.5 kcal/g)
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PART-II Nutritional assessment
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Nutrients
Nutrient is the active ingredients of the food necessary to sustain normal function of the cell
Among nutrients all cellular energy is provided by three classes of nutrients:
Energy rich nutrients are fats, carbohydrates, protein, and in some diets, ethanol
The requirement and intake of these energy-rich molecules is larger than that of the other
dietary nutrients
Therefore, these high intake nutrients are called macronutrients
 Those nutrients needed in lesser amounts, vitamins and minerals, are called the
micronutrients
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Diet
Diet
Essential nutrients obtained from diet
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Dietary reference intake
• Dietary reference intake(DRI) is set of reference values used to plan and assess
nutrient intakes of healthy people
• It is estimates of the amounts of nutrients required to prevent deficiencies and
maintain optimal health and growth
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Components of DRI
1. The EAR is the average of daily dietary intake estimated to meet the requirement of healthy
individuals in a particular life stage and gender group by half(1/2th )
2. Recommended Dietary Allowance (RDA): is daily dietary intake that is sufficient to meet the
nutrient requirements of individuals or group by (97–98%).
3. An adequate intake(AI) is the average of nutrient level consumed daily by a typical healthy
population that is assumed to be adequate for the population's needs.
 This use only when the data from EAR or RDA is not available
 The AI is judged by experts to meet the needs of all individuals in a group.
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DRI cont.…
• For example, the AI for young infants, for whom human milk is the recommended sole
source of food for the first four to six months, is based on the estimated daily mean nutrient
intake supplied by human milk for healthy, full-term infants who are exclusively breast-fed.
4. Tolerable Upper Intake Level (UL): The UL is the highest average daily nutrient intake
that is likely do not pose adverse health effects to almost all individuals in the general
population
• As intake increases above the UL, the potential risk of adverse effects may increase.
• Therefore, the UL is not intended to be a recommended level of intake
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Comparison of the components of the Dietary Reference Intakes.
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Important points in DRI
Intakes below the EAR need to be improved because the probability of adequacy is 50% or
less
Intakes between the EAR and RDA likely need to be improved because the probability of
adequacy is less than 98%
Intakes at or above the RDA and AI can be considered adequate.
Intakes between the UL and the RDA can be considered to have no risk for adverse effects
Intake above upper limit is consider as risk to pose adverse health effect.
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Nutritional requirement
Definition
• The amount of nutrient from food that allows an individual to maintain normal
physiological and structural functions, replenish storage levels and maintain
circulating levels of a nutrient.
• This definition does not included additional need for pathological and physiological
conditions which demand an additional intake (eg. Illness, exercise, pregnancy).
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Why to know nutritional requirements of an individual or group?
Diagnostic reasons: mainly to
• identify whether a group or an individual is suffering from malnutrition of any
kind; for example:
• to evaluate nutritional intervention programme
• to determine whether the food available in the stock is adequate to feed the
household or nation for a certain duration of time.
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Cont.…
Prescriptive reasons: that is,
oto provide or dispense food supplies; for example:
oto procure food for national consumption
oto secure food for institutional consumption
oto run nutritional supplementation programme.
oTo plan for therapeutic program
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Conti..
In order to estimate nutritional requirements of individuals or groups, we need to
consider the following factors:
• Physical activity: whether a person is engaged in heavy physical activity
• The age and sex: of the individual or group
• Body size and composition: what the general build is of a person or group
• Climate: whether a person or group is living in hot or cold climate
• Physiological states: such as pregnancy and lactation.
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Acceptable Macronutrient Distribution Ranges
Acceptable Macronutrient Distribution Ranges (AMDR)
 are defined as a range of intakes for a particular macronutrient that is associated with
reduced risk of chronic disease while providing adequate amounts of essential
nutrients
 The AMDR for adults is
• 45–65% of their total calories from carbohydrates,
• 20–35% from fat, and
• 10–35% from protein
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Fat in AMDR
Consumption of saturated fats is strongly associated with high levels of total
plasma cholesterol and LDL cholesterol, and an increased risk of CHD.
The main sources of saturated fatty acids are dairy and meat products and some
vegetable oils, such as coconut and palm oils a major source of fat
Unsaturated fatty acids are generally derived from vegetables and fish(olive oil).
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About bad fat
Trans fatty acids do not occur naturally in plants, but occur in small amounts in
animals.
However, trans fatty acids are formed during the hydrogenation of liquid
vegetable oils
Trans fatty acids are a major component of many commercial baked goods, such
as cookies and cakes, and most deep-fried foods.
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Quality of proteins
The quality of a dietary protein is a measure of its ability to provide the essential
amino acids required for tissue maintenance
Proteins from animal sources: Proteins from animal sources (meat, poultry, milk,
and fish) have a high quality
B/C they contain all the essential amino acids in proportions similar to those
required for synthesis of human tissue proteins
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Quality of proteins cont.…
Proteins from plant sources: Proteins from wheat, corn, rice, and beans have a
lower quality than do animal proteins.
However, proteins from different plant sources may be combined in such a way
that the result is equivalent in nutritional value to animal protein
For example, wheat (lysine-deficient but methionine-rich) may be combined with
kidney beans (methionine-poor but lysine-rich) to produce a complete protein
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Estimation of energy requirement
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Estimation of Energy Requirement
• It was agreed by the FAO/WHO/UN experts that energy requirement should be
estimated based on Energy expenditure and not Based on Energy Intake.
• Energy Requirement = Energy Expenditure
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Estimation of energy Requirement
Energy
Requirement
Energy
Expenditure
=
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Energy requirement in human
Definition: The amount of energy intake from food that replaces energy expenditure
compatible with normal health and allows an individual to be involved in economically
necessary and socially desirable activities(FAO/WHO/UN,1985).
It is difficult to accurately predict persons daily energy requirement due to various factors.
Approximately, sedentary adults require about 30 kcal/kg/day; moderately active adults
require 35 kcal/kg/day; and very active adults require 40 kcal/kg/day
The average daily requirement for energy is either 2,000 or 2,500 kcal/day
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Daily energy requirement by different person
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Major function of energy in body
The energy generated by metabolism of the macronutrients is used for three energy-requiring
processes that occur in the body:
 Resting metabolic rate,
Thermic effect of food
 Physical activity
1. Resting metabolic rate/basal metabolic rate (BMR). The energy expended by an individual in a
resting or postabsorptive state
It represents the energy required to carry out the normal body functions to maintain cellular
integrity
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Components of Total energy Expenditure (TEE)
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BMR
• Energy is continuously expended in such involuntary works throughout the life period for which
we are not conscious.
• This part of expenditure is relatively constant and expenditure in such involuntary works occurs at
a basal rate.
• About 70% of the energy we use every day is due to our organs functioning to keep us
alive and healthy
• So when there is no physical activity our daily energy intake should be 70% of the total.
• The remaining 30% is broken down into digestion of food (10%) and energy needed for
activity (20%).
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What is considered to measure BMR?
MR determination should take into consideration the following points
1. Person should be awake but at complete rest—both physical and mental.
2. Person should be without food at least 12 to 18 hrs.,(in the “post absorptive
state)”.
 Post absorptive state: is the time at which GIT is empty and source of
energy come from reserve
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Cont..
This period is to avoid effects of digestion and absorption and to prevent any chance of
starvation.
3. Should be in recumbent/reclining position in bed.
4. Person should remain in normal condition of environment.
Under this condition energy output of the individual is to maintain
 Respiration, circulation, muscle tone (skeletal and smooth muscles),
 Functions of viscera like the kidney, liver and brain for the maintenance of the body
temperature.
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Cont.…
• The total metabolism in childhood is relatively much greater than, in adult
life.
• There is high BMR during child childhood.
• The physical activity of children is usually greater, despite the fact that
their period of sleep is longer than that of an adult.
• The food intake, therefore, must cover the caloric needs in addition to the
extra food required for growth.
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How to calculate BMR
P = (10.0*kg) + (6.25*cm) - (5.00*year) + s(-161 if female)
P-total energy production at rest
E.g. 30 years old woman, 5 feet 3 inches tall (or 63 inches) and weighs 130 pounds.
2.5 centimeters in one inch and 2.2 pounds in one kilogram, that means that our
volunteer's height is 157.5 cm and about 59 kg. P=1263 kcal.
women need to eat this much to maintain her current weight at rest.
 If she eat calorie less than 1263.4 she will lose weigh if she eat greater she will gain
weight
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Caloric value of the food
• Calories is defined as the amount of heat required to raise the temperature of 1.0 gm of
water by 1oC (specifically from 15oC to 16oC).
• Caloric value is the amount of energy obtained by burning 1.0 gm of the food stuff
completely in the presence of O2.
• Different foodstuffs on burning give different amounts of energy.
• Carbohydrates = 4.1 kcal/g, Fats = 9.3 kcal/g and Proteins = 4.1kcal/g
• The amount of energy required for any individual varies directly with the degree of activity
and environmental conditions
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How energy content of the food measured?
 In vitro the energy content of food is calculated from the heat released by the total
combustion of food in a calorimeter
 Note that the energy content of fat is more than twice that of carbohydrate or
protein
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exercise
Kasim is a moderate active who has consumed 250gm of an oxen meat, a meat contain 60g
of saturated FA and 10gm of unsaturated FA, 10gm of CHO and 30 gm of protein.
Additionally, he drank 2 bottles of coca having 20gm of CHO. Finally, he added 30gm of
vitamin C and 20gm of fibers to his eating.
1. What is the total calories Kasim obtained?
2. Is he consumed appropriate daily requirement?
3. Is Kasim food selection is inline of balanced diet/AMDR?
4. What do you think his weight if his daily consumption and current activity continue in
this way?
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Energy
Intake
Energy
Expended
=
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Positive Energy Balance
Energy
Expended
Energy
Intake
>
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Negative Energy Balance
Energy
Intake
Energy
Expended
<
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Diet Induced thermogenesis(Thermic effect of food)
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Fibers
• Fibers are complex and indigestible carbohydrate usually found in food derived from
plants
• It includes polysaccharides such as cellulose, hemicellulose, pectin, gums and
mucilage
• Also includes non-polysaccharides such as lignin, cutins and tannins
• Fibers are not a source of energy why????
• The bacteria in human GI tract can breakdown some fibers.
• Children and adults need at least 25 to 35 grams of fiber per day for good
health
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Complex Carbohydrates
Dietary Fiber
 non-digestible carbohydrates and that are intact and intrinsic in plants
(includes oligosaccharides)
Functional Fiber
 isolated, non-digestible carbohydrates that have beneficial physiological
effects in humans and available commercially
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Is too much of fiber good????
Excessive amounts of fiber may lead to:
• displacement of other foods in the diet
• intestinal discomfort
• interference with the absorption of other nutrients
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Glycemic index
The glycemic index (GI) is a value used to measure how much and how quickly
specific foods increase blood sugar levels
The GI measure of the power of foods to raise glucose levels after being eaten.
Foods are classified as low, medium, or high glycemic foods and ranked on 0-100GI.
Foods with a high GI score contain rapidly digested carbohydrate, which produces a
large rapid rise and fall in the level of blood glucose.
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Glycaemic index (GI)
High GI will lead rapidly to hyperglycaemia, which will cause a
hyperinsulinemia, which will cause a reactive hypoglycaemia
In contrast, foods with a low GI score contain slowly digested carbohydrate, which
produces a gradual, relatively low rise in the level of blood glucose.
Food high in protein, fat, or fiber typically have a low GI.
 Foods that has no Carbohydrate are not assigned a GI and include meat, fish,
poultry, nuts, seeds, herbs, spices, and oils
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Glycemic index values
• Knowing the glycemic index of the carbohydrates you eat can help you fine-tune
your meals to keep your blood sugar within a normal range.
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1. Low GI = 55 or less
2. Medium GI = 56 – 69
3. High GI = 70 or more

How to measure GI
Took Reference food: Usually white bread or Glucose =100
• To determine the glycemic index of a food, volunteers are typically given a test
food that provides 50 grams of carbohydrate and a control food (white bread or
pure glucose) that provides the same amount of carbohydrate on different days.
• Blood samples for the determination of glucose are taken prior to eating and at
regular intervals after eating over the next several hours.
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Measuring the Glycaemic Index of Foods
• The changes in blood glucose over time are plotted as a curve.
• The glycemic index is calculated as the area under the glucose curve after the test
food is eaten, divided by the corresponding area after the control food is eaten.
• The value is multiplied by 100 to represent a percentage of the control food.
• Higher index  faster and greater rise of postprandial glucose and/or insulin
• low glycemic index supposedly helpful in reducing glucose load via reduced insulin
response required
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How to measure Glycemic Index (GI)
The GI reflects the rate of digestion and absorption of CHO
GI =
Blood glucose area after test food
Blood glucose area after reference food
X 100
104
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• Glycemic index is defined as the area
under the blood glucose curves seen
after ingestion of a meal with
carbohydrate-rich food, compared
with the area under the blood
glucose curve observed after a meal
consisting of the same amount of
reference food
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Glycemic index curve
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Food with low GI
A healthy, low glycemic diet should comprise mostly low GI foods, such as:
Fruits: apples, berries, oranges, lemons, limes, grapefruit
Non-starchy vegetables: broccoli, cauliflower, carrots, spinach, tomatoes
Whole grains: quinoa, couscous, barley, buckwheat, farro, oats
Legumes: lentils, black beans, chickpeas, kidney beans
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Foods with a high GI include:
white and whole wheat bread
white rice
breakfast cereals and cereal bars
cakes, cookies, chips, ice-cream, watermelon, biscuits and sweet
treats
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Food with no GI or very low GI
Meat: beef, bison, lamb, pork
Seafood: tuna, salmon, shrimp, mackerel, anchovies, sardines
Poultry: chicken, turkey, duck, goose
Oils: olive oil, coconut oil, avocado oil, vegetable oil
Nuts: almonds, macadamia nuts, walnuts, pistachios
Seeds: chia seeds, sesame seeds, hemp seeds, flax seeds
Herbs and spices: turmeric, black pepper, cumin, dill, basil, rosemary, cinnamon
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GI of food
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Fastest Glucose
Dextrose
Starch (branched-chain)
Sucrose/Corn Syrup
Fructose
Starch (straight-chain)
Lactose
Galactose
Slowest Sugar Alcohols
• Use of Glycemic Index
Lower GI foods digest & convert
to glucose more slowly
High-fiber slower than low
High-fat slower than low
Solids slower than liquids
Cold foods slower than hot
Type of sugar/starch affects GI
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Role of low glycemic index food
• Low GI diets help people lose and control weight
• Low GI diets increase the body's sensitivity to insulin
• Low GI carbs improve diabetes control
• Low GI carbs reduce the risk of heart disease
• Low GI carbs reduce blood cholesterol levels
• Low GI carbs reduce hunger and keep you fuller for longer
• Low GI carbs prolong physical endurance
• High GI carbs help re-fuel carbohydrate stores after exercise – muscle glycogen.
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Factors affect glycemic index of food
Nutrient composition, protein and fat reduce GI of carb diet
Fibers content
Ripeness,
Cooking method increase digestibility of food
Amount of processing it has undergone
Physiological state of food: liquid has higher GI than solid
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Factors Influencing GI Ranking
Type of Starch
• Absorbs less water
• Molecules form tight clumps
• Slower rate of digestion
• Absorbs more water
• Molecules are more open
• Faster rate of digestion
Amylose Amylopectin
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Viscosity of Fiber
Viscous, soluble fibers transform intestinal contents into gel-like matter that slows down
enzymatic activity on starch.
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Cooking swells starch molecules and softens
foods, which speeds up the rate of digestion.
Cooking

Sugar Content
sugar sucrose glucose + fructose
starch maltose glucose + glucose
(GI 60) (GI 100) (GI 19)
(GI 105) (GI 100) (GI 100)
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Fat and protein slow down gastric emptying, and thus,
slows down digestion of starch
Fat & Protein Content

Acid Content
Acid slows down gastric emptying, and thus,
slows down the digestion of starch.
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Highly processed foods require less digestive
processing.
Food Processing

How does all this affect our glycemic levels?
How does all this make us feel after eating
carbohydrate-containing foods?
Type of starch
Physical entrapment
Viscosity of fiber
Sugar content
Fat content
Protein content
Acid content
Food processing
Cooking
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Glycemic load
• Glycemic index measure how fast carbohydrate raise blood glucose
• Glycemic load measure the amount/how much of carbohydrate per serving of food
• Glycemic load accounts for how much carbohydrate is in the food and how much
each gram of carbohydrate in the food raises blood glucose levels
• GL = (GI x CHO/serving)/100
• Ratings of glycemic loads
• Low GL = 0-10
• Medium GL = 11-19
• High GL = >20
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Glycemic load
 Glycemic Index alone does not provide enough information about the glycemic affect of
a food.
 Example, 100g serve of carrot with a GI of 92 has 4.2 g per serve.
92 x 4.2 / 100 = 3.9
Similarly, 100g serve of water melon with a GI of 72 has 5.6 g per serve.
72 x 5.6/100 = GL = 4
Foods with a low GI usually have a low GL.
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Glycemic Load (GL): What does it mean?
Glycemic load measures the degree of
glycemic response and insulin demand produced
by a specific amount of a specific food.
Glycemic load reflects both the quality and
the quantity of dietary carbohydrates.
GL = GI/100 x CHO (grams) per serving
Example: GL of an apple = 40/100 x 15g = 6g
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GI vs. GL
Glycemic Index: ranks carbohydrates based on
their immediate blood glucose
response.
GI = glycemic quality
Glycemic Load: helps predict blood glucose
response to specific amount of
specific carbohydrate food.
GL = glycemic
quality
quantity
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Benefits of Low GI Diet
Are there any documented benefits to
lowering the GI of one’s diet?
YES!
BG levels
cholesterol levels
weight
heart disease risk
type 2 DM risk
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Caution!
Do not focus exclusively on achieving a low
glycemic load diet with all low glycemic index
food choices.
Result could be: high fat
low carbohydrate
high fiber
calorically dense
Instead…
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A Better Idea
Aim for a well-balanced diet that includes low
glycemic index carbohydrates. Use glycemic
load as a guide for controlling portions.
Hint:
Low GI CHOs allow for larger portions, while
regulating the GL.
High GI CHOs require smaller portions to
regulate the GL.
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Brain storm
• How many gram of glucose our body require per a day?
• Which organ consume large daily recommended glucose and why?
• Why we need glucose maintained normal level? b/c
• What is the problem when blood glucose is above normal and below normal?

Diabetes mellitus
• Dm is not a single disease/a group of metabolic derangement characterized by chronic
hyperglycemia
• Dm is heterogenous group of metabolic disorder characterized by elevation fasting blood glucose
caused by relative or absolute insulin deficiency.
• Diabetes mellitus is the leading cause of adult blindness and amputation
• It is also the major cause of renal failure, heart attacks, and strokes.
• The incidence and prevalence of T2DM is relatively higher than T1DM due to sedentary life style

Comparison of type-1 and type-2 DM

Pathophysiology of type-1 DM
• Type -1 DM is characterized by absolute deficiency of insulin secretion
• Beta cell of pancreases is damaged by autoimmune attack and islet of Langerhans infiltrated with
activated T-lymphocytes leads to insulitis
• The autoimmune attack on the β cells gradually leads to depletion of the β-cell population
• However, symptoms appear abruptly when 80–90% of the β cells have been destroyed
• Because at this point, the pancreas fails to respond adequately to ingestion of glucose

• β Cell destruction requires both a stimulus from the environment (such as a viral infection) and a
genetic determinant that allows the β cells to be recognized as “no self
• Among identical twins, if one sibling develops Type 1 diabetes mellitus, the other twin has only a
30–50% chance of developing the disease
• In type-2 in which genetic influence is stronger both identical twins virtually become diseased.

Diagnosis of Type-1 DM
• It occur typically during childhood or puberty, and symptoms develop rapidly
• Patients with Type 1 diabetes can usually be recognized by the abrupt appearance of polyuria,
polydipsia, and polyphagia.
• These symptoms are usually accompanied by fatigue, weight loss, and weakness
• The diagnosis is confirmed by a fasting blood glucose (FBG) greater than or equal to 126 mg/dl
• Fasting is defined as no caloric intake for at least 8 hours and FBG 100–125 mg/dl is categorized
as an impaired FBG

Metabolic changes in Type 1 diabetes
1. Hyperglycemia and ketoacidosis:
 Elevated levels of blood glucose and ketones are the hallmarks of untreated Type 1 diabetes mellitus
 The main cause of hyperglycemia is hepatic production of glucose and diminished plasma glucose
uptake by peripheral cells
 Ketosis results from increased mobilization of fatty acids from adipose tissue and accelerated hepatic
fatty acid β-oxidation and synthesis of 3-hydroxybutyrate and acetoacetate
 Acetyl coA from β-oxidation is the substrate for ketogenesis and the allosteric effector of pyruvate
carboxylase, a gluconeogenic enzyme

2. Hypertriacylglycerolemia:
Not all the fatty acids flooding the liver can be disposed of through oxidation or ketone body
synthesis.
These excess fatty acids are converted to triacylglycerol, which is packaged and secreted in very-
low-density lipoproteins (VLDL).
 Chylomicrons are synthesized from dietary lipids by the intestinal mucosal cells increased b/c
lipoprotein lipase activated by insulin decrease its function

Treatment of T1DM
• Type 1 diabetics must rely on exogenous insulin injected subcutaneously to control the
hyperglycemia and ketoacidosis
• Hypoglycemia caused by excess insulin is the most common complication of insulin therapy,
occurring in more 90% of patients

Type-2DM
• Type 2 diabetes is the most common form of the disease, afflicting approximately 90% of the
diabetic population
• Patients with Type 2 diabetes have a combination of insulin resistance and dysfunctional β cells
• Typically, Type 2 diabetes develops gradually without obvious symptoms and obtained by routine
screening
• However, Type 2 diabetes have symptoms of polyuria and polydipsia of several weeks duration
• the inadequate insulin secreted in T2DM restrain ketogenesis and blunts the development of DKA

What is insulin resistance
• Insulin resistance is the decreased ability of target tissues, such as liver, adipose, and muscle, to
respond properly to normal circulating concentrations of insulin
• Insulin resistance is characterized by uncontrolled hepatic glucose production, and decreased
glucose uptake by muscle and adipose tissue
• Insulin resistance alone will not lead to Type 2 diabetes unless impaired β-cell function occurred
• In insulin resistance high insulin is required to required to control blood glucose

Cxn of DM
• Macro(e.g. CAD, cerebrovascular and peripheral extremity vessel) nonspecific to D.
• Macrovascular cxn is due to abnormal lipid accumulation in blood vessels
• Micro vascular complication are specific to diabetes . The major cause of diabetic microangiopathy
is nonenzymatic glycation of vascular protein and lipid components
• This glycation cause thickening/crack and leaky of the small vessels
• Microangiopathy expressed as peripheral neuropathy is comments

DKA
The main cause of DKA Is severe deficiency of insulin
It can be the initial presentation in DM or after diagnosed of diabetes mellitus
In diabetic patients DKA occur due to
 Absence of insulin secretion
 Increase insulin demand
 Underdose or forgottenness of insulin treatment

• When insulin absent/low counterregulatory hormones like glucagon, epinephrine ,norepinephrine
,cortisol and growth hormone increase
• adrenal medulla and sympathetic nervous system fibers produce E and NE
• Adrenal cortex produce cortisol hormone
These counter regulatory hormone cause glycogenolysis and Gluconeogenesis in liver
Glycogen break down and proteolysis for gluconeogenesis
Lipolysis and beta oxidation take place increase FFA acid and precursor for gluconeogenesis

• High proton in DKA is buffered by extracellular(HCO3) and intracellular by exchange with K
• When proton inters cell K leave cells leads to hyperkalemia, then K will be secreted and lost
• Additionally, once fluid treatment start leads to hypokalemia
• FFA acid released from adipose tissue to liver has three fates
Inter into liver mitochondria to give ATP and water
To give excess acetyl CoA for ketone body
To synthesize live TAG that loaded to circulation as VLDL

Insulin and blood glucose level in obese and normal

Obesity
Obesity is a disorder of body weight regulatory systems characterized by an accumulation of
excess body fat
Normally the energy expenditure is balanced with energy gain otherwise misbalance is pathologic
In primitive societies 'daily life required a high level of physical activity and food was only
available intermittently
 Therefore, genetic tendency favoring storage of excess calories as fat for a survival value only.

How to assess obesity
It is very difficult to measure directly the excess fat accumulated in body of individual
It is usually determined by indirect measurement of body mass index(BMI)
Measuring the waist size with a tape measure is also used to screen for obesity
B/C this measurement reflects the amount of fat in the central abdominal area of the body.
The presence of excess central fat is associated with an increased risk for morbidity and mortality
A waist size ≥ 40 inches in men and ≥ 35 inches in women is considered a risk factor

Regulation of body weight
The body weight of most individuals tends to range within ten percent of a set value
Each individual has a biologically predetermined “set point” for body weight.
The body attempts to add adipose tissue when the body weight falls below the set point
Our body also tend to lose weight when the body weight is higher than the set point
When weight loss, appetite increases and energy expenditure falls,
Whereas with overfeeding, appetite falls and energy expenditure increases
However, genetic, behavioral and environmental factors that influence energy balance are constant

Factors contribute for obesity
1. Environmental factors
 Factors like availability of palatable, energy-dense foods, play a role in the increased prevalence of obesity.
 Furthermore, sedentary lifestyles, encouraged by TV watching, automobiles, computer usage, and energy-sparing
devices in the workplace and at home, decrease physical activity and enhance the tendency to gain weight
2. Eating behaviors
Eating behavior such as snacking, portion size, variety of foods consumed, an individual's unique
food preferences, and the number of people with whom one eats also influence food consumption and
the tendency toward obesity

3. Genetic factors
 If both parents are obese, there is a 70–80% chance of the children being obese.
 In contrast, only 9% of children were fat when both parents were lean
 mutations in the gene for the adipocyte hormone leptin or its receptor produce hyperphagia
(increased appetite for and consumption of food) and massive obesity
Identical twins with combined weight of 1,300 pounds

• The BMI (weight in kg)/(height in meters)2 provides a measure of relative weight, adjusted for
height.
• BMI = [weight in pounds/ (height in inches)2] x 703.
BMI less than 18.5 is underweight
BMI is between 18.5 and 24.9 is considered as healthy
BMI between 25 and 29.9 are considered overweight
BMI >=30 are defined as obese,
BMI over 40 is considered as extremely obese

Anatomic differences in fat deposition
• Obesity associated health risks depend on anatomic distribution of body fat
• Based on the location of fat accumulatio obesity can be classified as upper and low body obesity
• Excess fat in the central abdominal area is called android, “apple-shaped,” or upper body obesity
• Central obesity is defined as a waist to hip ratio of more than 0.8 for women and more than 1.0
for men
• In contrast, fat distributed in the lower extremities around the hips or gluteal region is call gynoid,
“pear-shaped,” or lower body obesity. It is common for female and low risk for disease
• It is defined as a waist to hip ratio of less than 0.8 for women and less than 1.0 for men

Anatomic location of fat distribution

Biochemical difference of central and lower obesity
• Abdominal fat cells are much larger and have a higher rate of fat turnover than lower body fat
cells
• Therefore, abdominal fat tend to mobilize fatty acids more quickly than those from the lower body
depots
• Visceral adipocytes are the most metabolically active and hormonally more responsive
• Due to quick mobilization of abdominal fat, male generally lose weight more readily than women
• Furthermore, fat released from abdomen are absorbed via the portal vein and, direct access to the
liver

• Fatty acids taken up by the liver may lead to insulin resistance b/c increased synthesis of
triacylglycerols, which are released as very-low-density lipoprotein (VLDL)
• By contrast, free fatty acids from gluteal fat enter the general circulation, and have no preferential
action on hepatic metabolism.

Effect of adipocytes for obesity
• When triacylglycerols are deposited in adipocytes, the cells initially show a modest increase in size
• However, the ability of a fat cell to expand is limited, and when its maximal size is reached, it
divides
• Obesity is, therefore, thought to involve an increase in both the number and size of adipocytes
• Fat cells, once gained, are never lost.
• Thus, when an obese individual loses weight, the size of the fat cells is reduced, but the number of
fat cells is not affected

Function of adipocytes
Endocrine role
White adipose tissue is a passive reservoir of TAGs and play an active role in body weight
regulation
Leptin is produced proportionally to the adipose mass and informs the brain the fat store level
Leptin's secretion is suppressed by depletion of fat stores (starvation) and enhanced by expansion
of fat stores (well-fed state).
leptin increases the metabolic rate and decreases appetite through suppression hunger

When we consume fewer calories than we need, body fat declines, and leptin production from
the fat cell decreases
At this The body adapts by minimizing energy utilization (decreasing activity) and increasing
appetite
Since the level of leptin correlate to body mass it is high in obese individual, but resistant
Adiponectin reduces levels of FFAs in the blood and has been associated with improved lipid
profiles,

Action of leptin in maintaining fat store(long term
effect)

Short term-signals control feeding
Short-term signals from the gastrointestinal tract control hunger and satiety
This regulation affect the size and number of meals over a time course of minutes to hours.
In the absence of food intake (between meals), the stomach produces ghrelin an orexigenic
(appetite-stimulating) hormone that drives hunger
As food is consumed, gut hormones (cholecystokinin (CCK) and peptide YY), among others,
induce satiety (an anorexigenic effect) thereby terminating eating

Obesity and health
• Obesity is correlated with an increased risk of death and is a risk factor for a number of chronic
conditions, including
• T2D, dyslipidemias, hypertension, heart disease, nonalcoholic fatty liver disease, and sleep apnea

Obesity management
• The goals of weight management in the obese patient are, first, to induce a negative energy balance
to reduce body weight, that is, decrease caloric intake and/or increase energy expenditure
• Typically, a prescription for weight reduction combines dietary change; increased physical activity;
and behavioral modification
• Persons who combine caloric restriction and exercise with behavioral treatment may expect to lose
about 5%–10% of initial body weight over a period of 4–6 months.

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