Obesity and metabolic syndrome

1. Obesity and
metabolic
syndrome
By Shama
Physiology department

2. Obesity
Obesity is caused by an excess of energy input over energy output. Muscular activity is by far
the most important means by which energy is expended in the body, accounting for more than
a third of the daily energy expenditure. Obesity results from a high ratio of food intake to daily
exercise.
Obesity is increasing in incidence and relates to the regulation of food intake and energy
balance and overall nutrition.
A reliable indicator for body fat is body mass index (BMI)

3. As body weight increases, insulin resistance
increases.
Weight reduction decreases insulin resistance.
Associated with obesity there is hyperinsulinemia,
dyslipidemia (characterized by high circulating
triglycerides and low high-density lipoprotein
[HDL]), and accelerated development of
atherosclerosis. This combination of findings is
commonly called the metabolic syndrome, or
syndrome X

4. Predisposing factors
Genetic inheritance
Unhealthy diet
Inactivity or decrease activity
Unhealthy cooking practices
Aging
Pregnancy
Quitting smoking
Stress or lack of sleep

5. Metabolic
syndrome
Obese individuals tend to have a higher-
thannormal insulin level due to a decrease in
insulin receptors. They develop type 2 diabetes
when the compensatory rise in insulin is
inadequate for overcoming the insulin
resistance.
The metabolic consequences of diabetes
mellitus result not just from the inadequacy or
ineff ectiveness of insulin but equally
importantly, from the unopposed action of
glucagon.
Signs of metabolic syndrome: High blood
pressure, huh blood sugar, excessive body fat
around waist, abnormal cholesterol or
triglyceride levels and low HDL levels.

6. Consequences
Adipose tissue in obese persons are more
resistant to insulin actions than normal adipose
tissue I.e, a decrease ability to insulin to move
glucose into cells and to block the glucose
release from the liver
Circulating FFA act on muscle and liver to
increase insulin resistance. Therefore, plasma
insulin increases in non diabetic obese persons.
The increase strain an beta islets cells activity
in producing more insulin may lead to
exhaustion of beta cells with onset of diabetes
mellitus.

7. Complications of
metabolic
syndrome
Heart disease and strokes secondary to high
cholesterol levels.
Type 2 diabetes mellitus secondary to insulin
resistance.
Increase risk of cancer especially of the
uterus, cervix, ovary, breast, colon, rectum,
esophagus, liver, gall bladder, pancreas,
kidney and prostate.
Fatty liver
Sleep apnea
Osteoarthritis due to stress placed over
weight bearing joints.
Psychiatric problems

8. Metabolic
consequences
The combination of insulin inadequacy
and glucagon excess has four major
metabolic consequences:
(1) hyperglycemia and its
consequences,
(2) polyphagia despite the
hyperglycemia,
(3) hyperlipidemia and its consequences,
and
(4) ketoacidosis and its consequences

9. Hyperglycemia and its consequences
The hyperglycemia is due to (1) reduced hepatic glucose uptake and (2) stimulation of
gluconeogenesis. Since lack of insulin reduces protein synthesis, large quantities of amino
acids are available for gluconeogenesis.
When the hyperglycemia exceeds the renal threshold of glucose, it results in glycosuria. The
glucose in urine acts as an osmotic diuretic and results in polyuria, that is, passage of large
volumes of urine.
The polyuria results in dehydration and polydipsia. Severe dehydration leads to coma.
The dehydration is usually not severe enough to cause peripheral circulatory failure or renal
failure

10. Hyperglycemia increases the cellular uptake
of glucose. This extra glucose that enters the
cell is metabolized through the sorbitol
pathway.
The sorbitol produced accumulates in the
cells of retina, lens, kidney, and nerves,
leading to osmotic swelling and contributing
to the retinopathy, cataract, nephropathy, and
neuropathy of diabetes mellitus.
If the hyperglycemia is very high, it increases
the plasma osmolarity to very high levels,
causing hyperosmolar coma.

11. Polyphagia despite
hyperglycemia
a high level of blood glucose should
produce satiety. In diabetes, there is
polyphagia despite the hyperglycemia. The
catch in this paradox is that hunger is
related to the glucose utilization by the
cells of the satiety center and not to the
blood glucose level. In diabetes mellitus,
the glucose utilization is reduced in the
cells of the satiety center, which therefore
signals a glucose defi ciency to the feeding
center. As a result, hunger is perceived
and food intake increases.

12. Hyperlipidemia and its consequences
The increase in plasma triglyceride occurs mainly due to the reduced breakdown of VLDL and
chylomicrons. The increase in plasma free fatty acid (FFA) is due to lipolysis in adipose
tissues.
The rise occurs despite a decrease in the hepatic synthesis of fatty acids. In the long run, the
hyperlipidemia and related hypercholesterolemia result in hypertension and coronary heart
disease.

13. Hyperlipidemia

14. Ketosis and its consequences
Due to the excess FFA present in blood, there is increased uptake and oxidation of FFA by the cells.
In the liver, increased oxidation of FFA results in accumulation of excess acetyl CoA. As glycolysis is inhibited
in diabetes mellitus, the excess acetyl CoA forms ketoacids.
The H+ of the ketoacids is buffered by the blood buffers. However, when the production of ketoacids exceeds
the buffering capacity of the blood, it results in metabolic acidosis with all its complications.
A characteristic clinical feature of the acidosis is Kussmaul breathing, a form of hyperventilation associated with
increased tidal volume and a lesser increase in frequency.
Vomiting is another complication of ketoacidosis. The vomiting causes dehydration and if it is followed by
ingestion of plain water instead of an electrolyte solution, hyponatremia results

15. The ketoacids are buffered by blood buffers,
releasing organic anions. For example, buff
ering of acetoacetic acid produces
acetoacetate. These organic anions increase
the plasma anion gap.
When excreted in urine, these organic anions
carry with them an equal number of cations,
mainly Na+ and K+ . However significant
hyponatremia occurs only due to vomiting.
Hyperkalemia with intracellular depletion of
potassium stores is an important feature of
diabetes mellitus. Insulin causes K+ to move
into the cells and therefore insulin defi ciency
results in movement of K+ from ICF to ECF.
The hyperkalemia is associated with kaliuresis,
resulting in the depletion of body K+ stores.

16. Degree of ketoacidosis is directly proportional
to the amount of fat stores, therefore, it is more
severe in obese compared to thin individuals.
Moreover, disturbances in fat metabolism is so
prominent in diabetes mellitus, that it has been
called more a disease of lipids than of
carbohydrate metabolism.
FFA levels parallel the blood glucose level in
diabetes mellitus, therefore FFA estimation is a
better index to assess the severity of diabetes
mellitus than the blood glucose.
Acidosis is the most common cause of death in
DM due to markedly decrease in total Na+.

17. Hemoglobin A1c
Glycosylation of hemoglobin Hemoglobin is
nonenzymatically glycosylated by the glucose that
enters the erythrocytes. The amount of
glycosylated hemoglobin (HbA1c) is proportionate
to the blood glucose concentration and is normally
about 5%. The rate of glycosylation is slow and
therefore the HbA1c level reflects the average
blood glucose concentration over the preceding 6
to 8 weeks and serves as an index of long-term
control of diabetes mellitus. Thus a patient who is
mostly careless about controlling his hyperglycemia
and takes an insulin injection only before visiting
the physician would have a normal blood glucose
but his HbAIc would remain elevated.

18. Thank you