CHO METABOLISM
BY Dr. Naglaa Ibrahim AzabAssistant professor of medical
biochemistry
BLOOD GLUCOSE HOMEOSTASIS
(REGULATION OF BLOOD GLUCOSE LEVEL)
It is the maintenance of blood glucose level within the normal
range
What is glucose homeostasis???
Normal blood glucose level (mg/dl)
70-110(126)Fasting
( 6-12 h after meals)
1 h after CHO meals 130-150
70-110(126)
60-70
2 h after CHO meals
Starvation(prolonged fasting)
Importance of glucose homeostasis
Coma and even death
Maintain a continuous supply of sufficient blood glucose to the
brain and CNS
Sudden hypoglycemia (< 40 mg/dl) lead to????
mostly
Uptake by Tissues as muscles,
adipose tissue & brain
lipogenesis
Dietby digestion
and absorption
Glycogenolysis(Liver glycogen)
Gluconeogenesis (mainly from amino
acids)
Blood glucose
Main source during
prolonged starvation
>( 18 hrs)
Source during
early fasting(12 -18 hrs)
Oxidation glycogenesis
tissues
How to maintain the balance between addition and removal of glucose???
(What are the factors important for maintaining glucose homeostasis
What are the factors that regulate blood glucose level????
hormones
GIT
Tissues regulating blood glucose level
Liver Muscles and adipose tissues
Kidney
GIT
Glucose
Maximum rate of glucose absorption is 1 gm glucose/Kg body weight / hour → prevents sudden
hyperglycemia after meal.
- - -gastric evacuation
↑intestinal factors ↑enterogastrone hormone from duodenum
stimulate insulin secretion from pancreas
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Uptake
Liver(Blood glucostat)
Glucose
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Blood glucose
Oxidation
LIPOGENESIS
Glycogenesis
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Gluconeogenesis
Glycogenolysis
After CHO dietFasting
Blood glucose
Uptake
Muscle &Adipose tissue
Glucose
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Blood glucose
Oxidation
LipogenesisIn adipose
tissue
Glycogenesis in muscle\
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GluconeogenesisMuscle: Release alanine to liver
Adipose tissue:by lipolysis release glycerol and f.as
After CHO dietFasting
Blood glucose
Kidneys
Renal threshold for glucose is 180 mg/dl
Hormones
Uptake (except brain,
liver,RBCs- non dependant)
Insulin
Glucose
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\ Oxidation
LIPOGENESIS
Glycogenesis
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Gluconeogenesis
Glycogenolysis
Lipolysis
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Blood glucose
Uptake
Glucagon and adrenaline
Glucose
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\ \Oxidation
LIPOGENESIS
Glycogenesis
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Gluconeogenesis
Glycogenolysis
Lipolysis
\
Blood glucose
Uptake
Clucocorticoids and G.H.
Glucose
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Oxidation\
\Gluconeogenesis
Lipolysis ( G.H)
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Blood glucose
a.as
(glucocorticoids)
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Uptake
Thyroid hormones
Glucose
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\ \Oxidation
LIPOGENESIS
Glycogenesis
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Gluconeogenesis
Glycogenolysis
Absorption
Blood glucose
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GLUCOSURIA
Presence of detectable amounts of glucose in urine (> 0.5 g/day,
normally < 150 mg/day).
Causes:I. Hyperglycemic glucosuria:
1) Diabetes mellitus glucosuria2) Adrenaline glucosuria - Pheochromocytoma.- Emotions.- Stress (oral examination).- Hypotension- Injection
3) Alimentary glucosuria: It is due to intake of large amounts of glucose after prolonged
carbohydrate deprivation.
Causes:II. Renal glucosuria (plasma glucose < 180 mg/dl):1) Congenital glucosuria : = renal diabetes = Diabetes innocence = benign glucosuria.2) Pregnancy glucosuria : Occurs in about 20% of normal pregnancies.3) Nephritis & Nephrosis : Only some cases show glucosuria.4) Phlorrhizin Glucosuria : Phlorrhizin inhibits renal tubular reabsorption of glucose.
DIABETES MELLITUS
hyperglycemia
DM
syndrome\ \
glucosuria
polydepsia
polyuria\
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Loss of weight
polyphagia\
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Type I: Insulin dependent DM =IDDM = Juvenile diabetes.
Causes
Type II: Non Insulin dependent DM =NIDDM = Maturity onset DM
↑anti-insulin hormones
(glucagon, adrenalin)
↓insulin level or insulin resistance
Types
Metabolic changes in DM
2-Disturbed lipid metabolism: hyperlipidemia and hypercholesterolemia due to- Increased lipolysis and plasma FFA- Increased ketogenesis: which may cause ketoacidosis
1-Disturbed Carbohydrates metabolism:hyperglycemia due to- Decreased glucose uptake and utilization by tissues.- Decreased glycogenesis &lipogenesis.- Increased glycogenolysis &gluconeogenesis.
Metabolic changes in DM
4-Disturbed water and electrolyte balance: - Glucosuria → osmotic dieresis → polyuria → dehydration
→ polydepsia - Increased loss of Na+ & K + in urine.
3-Disturbed protein metabolism:Negative nitrogen balance ,wasting ,weakness of muscle and delayed healing of wounds due to- Decreased protein anabolism.- Increased protein catabolism.
• Points of differences
• Insulin-dependent diabetes mellitus (IDDM)
• Non-insulin-dependent diabetes mellitus (NIDDM)
• Other name • Type I; juvenile-onset • diabetes • Type II; adult-onset diabetes
• Age of onset • Usually during childhood or puberty
• Frequently after age 35
• Nutritional status at time of onset of the disease
• Frequently undernourished •Obesity usually present
• Prevalence • 10-20% of diagnosed diabetics
• 80-90% of diagnosed diabetics
• Genetic predisposition
• Moderate • Very strong
• Defect or deficiency • b-cells destroyed, eliminating production of
insulin
• Inability of b–cells to produce appropriate quantities of insulin,
insulin resistance
• Ketosis • Common • Rare• Plasma insulin • Low or absent • Normal or high• Acute
complications• Ketoacidosis • Hyperglycemia
• Oral hypoglycemic drugs
• Unresponsive • Responsive
• Treatment with insulin
• Always necessary • Usually not required
Complications of DM
2- Microvascular complications:They affect the small blood capillaries and lead to :
Diabetic retinopathy and neuropathy . These are due to vascular damage caused by protein glycation and sorbitol (the alcohol of glucose ) accumulation.
1-Macrovascular complications of DM:(atherosclerosis, hypertension, myocardial infarction and renal failure). • Most of these complications are due to damage of the
large blood vessels by glycosylation of protein molecules in the wall of blood vessels secondary to hyperglycemia.
• The presence of hypercholesterolemia and hyperlipoproteinemia increase the risk for the development of atherosclerosis and its complications.
Complications of DM
4-Diabetic coma:Coma is loss of consciousness. There are many types of coma.
3- Diabetic cataract :It usually occurs in young age .
It is due to accumulation of sorbitol in the eye lens, which leads to osmotic accumulation of fluid in the lens lead to its opacity.
Points of differences
Diabetic ComaHyperglycemic coma
Hypoglycemic Coma
Cause Severe uncontrolled DM. Insulin overdose
Mouth Odor of acetone Absent
Respiration Hyperventilation (acidosis) Normal
Pulse Rapid & weak (dehydrated) Rapid & strong (increased sympathetic activity)
Skin Dry (dehydrated) Sweating
Blood Glucose Hyperglycemia Hypoglycemia
Urine Glucose Present Absent
Urine Acetone Present Absent
Differences between hyperglycemic and hypoglycemic coma
Treatment of coma hyperglycemic coma treated by • insulin and glucose intravenous to avoid
sever drop of blood glucose• correction of electrolyte imbalance
resulting from acidosis and polyuria .hypoglycemic coma treated by• glucose infusion.
Diagnosis of DM 1- By measuring the blood glucose level in fasting( 8-12 h) state and two-hour postprandial blood glucose level.a) Normally: Fasting blood sugar = 70 – 110 mg/dl. 2-hours postprandial = up to 140 mg/dl.
b) In Diabetics: Fasting blood glucose = > 140 mg/dl. 2-hours postprandial = > 200 mg/dl.
Diagnosis of DM
2- Oral glucose tolerance test (OGTT):- After fasting 8-12 hours, the patient is given 70 gm D-
glucose (1 g/Kg body weight) in a cup of water - Blood and urine samples are taken fasting, ½,
1, 1½, 2, 2½ hours. - Samples are analyzed for glucose.- A blood sugar curve is plotted.
Diagnosis of DM
Diagnosis of DM Time Blood Glucose
0 time Fasting
½ an hour
1 hour
1 ½ hour
2 hours
2½ hours
Normal Minimum curve
80 mg/dl
90 mg/dl
105 mg/dl
105 mg/dl
90 mg/dl
80 mg/dl
Normal Maximum curve
120 mg/dl
135 mg/dl
160 mg/dl
140 mg/dl
120 mg/dl
120 mg/dl
Curve with mild diabetes
115 mg/dl
145 mg/dl
180 mg/dl
160 mg/dl
160 mg/dl
130 mg/dl
Curve with severe diabetes
200 mg /dl
235 mg/dl
265 mg/dl
280 mg/dl
290 mg/dl
300 mg/dl
Comments on normal & abnormal oral glucose tolerance curves
Diagnosis of DM
- In normal persons: • fasting 70 – 120 it increases after 1 hour and returns
back to fasting after 2 hours:• The blood glucose never exceeds 170 mg/dl.• No glucosuria.
- In Diabetes mellitus: • the fasting is more than normal ( > 110 mg/dl or more
) and the curve takes 3 hours or more to return back to fasting level.
• One or more samples exceed 180 mg/dl.• There is glucosuria.
Diagnosis of DM 3-Measurement of glycosylated –Hb (HbA1C)• Glycosylated Hb (HbA1c) results from non enzymatic
binding of glucose with Hemoglobin .The process is irreversible and continues during the half life of RBCs.
• Normal subjects and controlled cases of DM have 4-8% glycosylated –Hb .
• The increase in the percent of HbA1c is related to the blood glucose level.
• The test is used for follow up of diabetic patients.• Not affected by fasting or feeding or any factor that
affect blood glucose immediately so it gives an idea about the glycemic control of the patient throughout the life span of RBCs ( 120 days ).Also it gives an idea about the efficiency of the drugs used in treatment and adjustment of proper dose.
Other types of DM 1- Diabetes insipidus: Deficiency of antiduretic hormone (ADH). Urine volume > 10 L/day, watery specific gravity 1003.2- Steroid diabetes: Long term treatment with glucocorticoids which cause hyperglycemia. Prolonged hyperglycemia causes exhaustion of β-cell of pancreas.
3- Stress diabetes : Due to increased adrenaline in emotional states.
4- Experimental diabetes; could be caused by :• Alloxan• Streptozotocin• Dehydroascorbic acid• Surgically by removal of pancreas
Other types of DM
Points of differences Diabetes Mellitus Diabetes
Insipidus
Cause Decreased ratio of Insulin / Anti-insulin
Decreased ADH
Urine volume< 10 L/ day 15 – 25 L/ day
Urine specific gravity
>1030 <1030
Glucose in urinePresent
Absent
Differences between diabetes mellitus and diabetes insipidus
HYPOGLYCEMIA
It is the decrease of blood glucose level to less than 50 mg /dl.
Importance
The CNS is very dependent on a continuous supply of blood glucose as a fuel for energy.
• Anxiety• Palpitation • Tremors• sweating
Symptoms
impairment of brain functions causing headache,
confusion ,slurred speech, seizures, coma and even
death
Neuroglycopenic symptoms (neuroglycopenia)
Mediated by impaired delivery of glucose to the brain
Adrenergic symptomsmediated by epinephrine
release
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Liver cell failure (no glycogenolysis or gluconeogenesis)
Causes
Alimentary hypoglycemia due to exaggerated insulin release
following a carbohydrates meal or after gastrectomy
Postprandial hypoglycemia:
Overdose of insulin
(most common
cause)\\
Fasting hypoglycemia
Chronic Alcoholism due to excessive alcohol intake with decreased food intake (no gluconeogenesis)
Adrenocortical insufficiency (Addison's disease). (glucocorticoids)
Glycogen storage diseases (Von Gierke's disease) G-6-p can not leave liver (no G-6-phosphatase
Hereditary fructose intolerance : Ingestion of
sucrose causes hypoglycemia due to accumulation of fructose -1-P which inhibits glycogenolysis by
allosteric inhibition of liver phosphorylase enzyme .
Fructose-6-P
Fructose-1,6-BP
Fructose-2,6-BP
Phosphofructo-kinase-1 (PFK-1)
PFK-2
Fructose-1,6-Bisphosphatase
Gluconeogenesis
Glycolysis
CH3-CH2OH → CH3-CHO CH3-COOH →ACTIVE ACETATE - - Phosphofructokinase enzyme