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

\

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)

\

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