Carbohydrate Metabolism And Disorders

Question 1

What is the normal range for fasting blood glucose

Answer 1

3.4-6.4 mmol/l

Question 2

What is the normal range for RBS

Answer 2

3.3-7mmol/l

Question 3

Physiological glucose does not fall below …….. mmol/l or rise above …… mmol/l (Renal threshold value)

Answer 3

4.0, 10

Question 4

Three ways through which glucose enters the body

Answer 4

Dietary carbohydrates
Hepatic glycogenolysis
Gluconeogenesis

Question 5

Glucose leaves the blood through

Answer 5

It is oxidized to carbon dioxide and water
Glucose conversion to fatty acids in adipose tissues.
Glycogenesis
Excretion when the renal threshold is exceeded

Question 6

What are the physiological response to increase in blood glucose

Answer 6

Increase uptake of glucose by the liver and brain
Release of insulin by the cells of the islets of langerhans
Increased uptake of glucose by the peripheral tissues
Inhibition of the release by glucagons

Question 7

What are the effects of insulin on increased blood glucose

Answer 7

It increases the permeability of cell membrane to glucose
It increases the oxidation of glucose
Increase glycogenesis
Depression/inhibition of gluconeogenesis
Increased lipogenesis
Increased transfer of potassium, phosphates and amino acids into the cell
Increased protein synthesis

Question 8

What are the effects of glucagon, growth hormone, adrenaline, thyroid hormones and glucocorticoids on blood glucose

Answer 8

•Glucagon (secreted by -cells) stimulates an increase in glycogenolysis and promotes gluconeogenesis
•Growth hormone:-inhibits glucose uptake by the tissues and also inhibits the synthesis of fat from carbohydrates and the release of free fatty acids
•Adrenaline:-stimulates glycogenolysis and also inhibits the uptake of glucose by the tissues
Thyroid hormones (T3 and T4) increase the absorption of glucose from the GIT and stimulates glycogenolysis. They may also accelerate the degradation of insulin
•Glucocorticoids e.g. Cortisol stimulates hepatic gluconeogenesis and inhibits glucose metabolism at the peripheral tissues

Question 9

What is the effect of hypercortisolism on glucose

Answer 9

Hypercortisolism increases the rate of intestinal glucose absorption to produce an early and elevated postprandial peak serum glucose concentration. The additional effects of increased gluconeogenesis and inhibition of glucose uptake in peripheral tissue generally causes an elevated 2 hour postprandial value and an elevated fasting serum glucose

Question 10

What is the effect of acromegaly on glucose

Answer 10

Acromegaly - Increased growth hormone stimulates glycogenolysis and inhibits the uptake of glucose in peripheral tissue causing elevated fasting and postprandial serum glucose concentrations

Question 11

What is the effect of hyperthyroidism on glucose

Answer 11

Hyperthyroidism increases the rate of intestinal glucose absorption to produce an early and elevated peak postprandial serum glucose concentration. The effect of thyroid hormone on peripheral tissue causing increased glucose utilization is generally greater than the effect of increased glycogenolysis on the liver so that the 2 hour postprandial value is usually normal as is the fasting serum glucose concentration

Question 12

What is the effect of pheochromacytoma on glucose

Answer 12

Pheochromacytoma (or “emotional hyperglycemia”) - Increased epinephrine increases glycogenolysis resulting in increased fasting and postprandial serum glucose concentrations.

Question 13

What are the two classes of diabetes mellitus

Answer 13

IDDM and NIDDM

Question 14

What FBS could confirm DM

Answer 14

A fasting blood [glucose] > 7.0mmol/l and a postprandial [glucose] > 11.1 mmol/l confirms the diagnosis of Diabetes Mellitus

Question 15

Talk about IDDM

Answer 15

•Essentially an autoimmune disease condition, occurring in young adults and sometimes children
•There is no genetic predisposition for this disease however, subjects carrying haplotypes (Human leukocyte antigen) HLA B8, BW 15, DR 3 and DR 4. (the HLA class II antigens on cell surface present as foreign antigens and stimulate T-lymphocyte autoimmune response) are more susceptible.
•Subjects carrying HLA Dq B57 ala/val are at risk
•And those carrying HLA Dq B57 are protected
• LADA-Latent autoimmune disease of the aged.

Question 16

Talk about NIDDM

Answer 16

Hyperglycaemia may be due to either peripheral insulin resistance or delayed insulin action
•It is late onset,
•Obese individuals are high risk candidates
•Subjects may not require insulin (dietary) therapy unless hyperglycaemia get out of control.
•MODY-Mature onset diabetes of the young

Question 17

Talk about LADA

Answer 17

1.Type 1 DM in adults may present similar to that of type 2 diabetes
2.Patients actually have the islet cell lesion of type 1 diabetes which progresses at a slower rate than in children
3.Postprandial serum C-peptide levels are lower than those of the non-insulin treated groups
4.Glutamic acid decarboxylase (GAD) is neuronal enzyme involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA) …GAD65 antibody is also the major pancreatic islet antibody and an important serological marker of predisposition to type 1 diabetes

5. Moreover, the insulin-treated subjects have a higher mean concentration of antibodies to GAD.
6. Therefore testing for anti-GAD in adults-onset non-obese diabetic patients should be a routine procedure in other to detect the latent insulin-dependency at the earliest possible stage

Question 18

Explain insulin resistance

Answer 18

A condition in which cells are no longer responding appropriately to circulating insulin .Insulin resistance is a multi-faceted disruption of the communication between insulin and the interior of a targetcell.
The underlying cause of insulin resistance appears to be inflammation that can either be increased or decreased by the fatty acid composition of the diet. However, the molecular basis for insulin resistance can be quite different in various organs.
If insulin receptor substrate-1 (IRS-1) is phosphorylated at a critical serine/threonine positions, this will lead to an accelerated degradation of the phosphorylated IRS-1 protein thereby reducing
the strength of the insulin signaling
insulin resistance
Insulin resistance has long been associated with obesity. More than 40 years ago, Randle and
colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through
inhibition of glycolysis at key points. However, work over the past two decades has shown that
lipid-induced insulin resistance in skeletal muscle stems from defects in insulin-stimulated glucose
transport activity.
The steatotic liver is also resistant to insulin in terms of inhibition of hepatic
glucose production and stimulation of glycogen synthesis. In muscle and liver, the intracellular
accumulation of lipids—namely, diacylglycerol—triggers activation of novel protein kinases C
with subsequent impairments in insulin signalling. This unifying hypothesis accounts for the
mechanism of insulin resistance in obesity, type 2 diabetes, lipodystrophy, and ageing; and the
insulin-sensitising effects of thiazolidinediones

Fasting insulin level ≥ 15 µU/ml is considered elevated

Question 19

What are the characteristics of type 1 diabetes

Answer 19

Usually under 30
Rapid onset
Normal or underweight
Little or no insulin
Ketosis common
Make up 15% of cases
Autoimmune plus environmental factors
Low familial factor
Treated with insulin, diet and exercise

Question 20

What are the characteristics of type 2 diabetes

Answer 20

Usually over 40
Gradual onset
80% are overweight
Most have insulin resistance
Ketosis rare
85% of diagnosed cases
Part of metabolic insulin resistance syndrome
Strongly hereditary, diet & exercise, progressing to tablets, then insulin

Question 21

What may secondary diabetes be due to

Answer 21

•May be due to either a pancreatic (pancreatitis) or endocrine disorder
•Endocrine disorders which may be associated with diabetes includes acromegaly, Cushing’s’ syndrome, phaeochromocytoma and occasionally thyrotoxicosis
•Gestational Diabetes: detected after 20 weeks of gestation

Question 22

What are the predisposing factors of type I diabetes

Answer 22

1.Stress: stimulates counter regulating hormones and increasing hepatic gluconeogenesis resulting in hyperglycaemia
2.Diet: children fed on cow milk which contains BSA, which may cross neonatal gut and raise antibodies that may damage beta cell fxn
3.Viruses: mumps, cytomegavirus, Esptein-Bar virus, rubella, coxsack B4 and retroviruses are known to cause beta cell destruction

Question 23

What are the predisposing factors of a type 2 diabetes

Answer 23

1.Obesity/Overweight
2.Hyperlipidaemia
3.Oxidative stress
4.Insulin resistance
5.Thrifty genotype
6.Thrifty phenotype
7.Age

Question 24

What is a thrifty genotype

Answer 24

The ‘thrifty gene’ theory suggests that populations of people who experience alternating period of famine and abundance of good rich food gradually develop a way to store fat more efficiently during periods of plenty to better survive famine

Question 25

What is a thrifty phenotype

Answer 25

Thrifty’ Phenotype theory : Obesity in the developing world has been reported to be associated with poverty, particularly in those countries in which inadequate pre-natal nutrition and low birth weight is followed by relative affluence

Question 26

What is oGGT

Answer 26

The term tolerance (originally) indicates the quantity of glucose that can be administered without glycosuria

Question 27

How do you prepare patients for an GTT

Answer 27

•Patient should have been on a diet containing at least 150g carbohydrates per day for at least three days (?)
•The patients should not have indulged in unusual exercise.
•Patient should be sitting upright during the test or if lying on the right side to ensure gastric emptying
•Patient should have overnight fast or at least 4-5h fast.
•No food or smoking during the test

Question 28

What is given to prevent nausea in during a GGT in adults first, then children

Answer 28

75g of glucose dissolved in 250-300ml water flavoured with lime to avoid nausea for adults
For children 1.75g/Kg body weight

Question 29

Explain the glucose tolerance curve

Answer 29

Fasting blood glucose is usually higher 6.6mmol/l or more
•Blood glucose is above 10mmol/l after 60min
•Glycosuria is normally present throughout the test

Lag phase
•Glucose rise steeply to max. in the first 30min
•2h could be low or hypoglycaemia in 120min (due to overshot or reactive hypoglycaemia)
•Transient glycosuria due to rapid absorption
• Condition associated with gastrectomy, gastroenterostomy, vagotomy, and liver disease
Flat curve
Blood glucose level fails to rise in the normal fashion.
•due to mal-absorptive disease of the small intestine,
•incorrect positioning of the patient during the test resulting in delayed gastric emptying
•Also occurs in hypopituitarism and in Addision’s disease (Addison’s disease occurring in Type I polyglandular autoimmune disease (PGA) is associated with chronic mucocutaneous candidiasis and/or acquired hypoparathyroidism. The age of onset is predominately in childhood or in the early adult years. Type I PGA syndrome is also frequently associated with chronic active hepatitis, malabsorption, juvenile onset pernicious anemia, alopecia and primary hypogonadism
Glycosuria
•Occurs when blood glucose exceeds threshold values (10mmol/l) and up to 16.6mmol/l for diabetics
•Renal glycosuria: congenital, or acquired
•Acquired maybe idiopathic or secondary to Fanconi syndrome (hereditary disorder of the kidney tubules unable to reabsorb into the blood stream and rather release into the urine)
•Pregnancy
•Some new borns: particularly those of diabetic mothers
•Stress or anxiety

Interpreting test results
Normal fasting individual, blood glucose is 5.6mmo/l
•Blood glucose does not rise above 10mmol/l
•After two hours blood glucose should be less than 6.6mmol/l
•Urine is free from glucose

Question 30

What are some conditions presenting in a diabetic curve

Answer 30

•Acutely ill or early stages of convalescence or recovery from surgical operation
•Elderly patients
•Stress

Question 31

What are some other types of OGTT

Answer 31

•Extended GTT : Glucose measured for 4-5 hrs after giving glucose to see how the curve behaves below the normal fasting glucose limits. Done in
some conditions causing hypoglycaemia.
•Cortisone Stressed GTT:
Can be used for detecting latent DM.
• Intravenous GTT:
~ Is done if oral glucose is not tolerated or oral GTT curve is
flat
~ In these cases 20% glucose as 0.5g glucose/Kg body weight
~ Usually peak occurs within 30 min after infusion and returns

Question 32

What number curve fits hypercortisolism in a glucose tolerance curve (GTC)

Answer 32

Curve 5

Question 33

What number curve fits acromegaly in a glucose tolerance curve (GTC)

Answer 33

Between curves 4 and 5

Question 34

What is insulin resistance

Answer 34

A condition in which cells are no longer responding appropriately to circulating insulin .Insulin resistance is a multi-faceted disruption of the communication between insulin and the interior of a target cell.

Question 35

What is the cause of insulin resistance

Answer 35

The underlying cause of insulin resistance appears to be inflammation that can either be increased or decreased by the fatty acid composition of the diet. However, the molecular basis for insulin resistance can be quite different in various organs.

Question 36

What did Randle and his colleagues postulate

Answer 36

Randle and colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through
inhibition of glycolysis at key points. However, work over the past two decades has shown that
lipid-induced insulin resistance in skeletal muscle stems from defects in insulin-stimulated glucose
transport activity.

The steatotic liver is also resistant to insulin in terms of inhibition of hepatic
glucose production and stimulation of glycogen synthesis. In muscle and liver, the intracellular
accumulation of lipids—namely, diacylglycerol—triggers activation of novel protein kinases C
with subsequent impairments in insulin signalling. This unifying hypothesis accounts for the
mechanism of insulin resistance in obesity, type 2 diabetes, lipodystrophy, and ageing; and the
insulin-sensitising effects of thiazolidinediones

Question 37

What is glycosuria

Answer 37

Occurs when blood glucose exceeds threshold values (10mmol/l) and up to 16.6mmol/l for diabetics
•Renal glycosuria: congenital, or acquired
•Acquired maybe idiopathic or secondary to Fanconi syndrome(hereditary disorder of the kidney tubules unable to reabsorb into the blood stream and rather release into the urine)
•Pregnancy
•Some new borns: particularly those of diabetic mothers
•Stress or anxiety

Question 38

How do you interpret test results for glycosuria

Answer 38

Normal fasting individual, blood glucose is 5.6mmo/l
•Blood glucose does not rise above 10mmol/l
•After two hours blood glucose should be less than 6.6mmol/l
•Urine is free from glucose

Question 39

What are some pathologic conditions which cause flat or depressed glucose tolerance results

Answer 39

Insulinoma - Curve 2 or even more depressed
•Intestinal malabsorption - curve 2 - or even less of an increase
•Low renal Tm for glucose reabsorption - may be normal curve 1 or may be depressed as in curve 3
•Hypothyroidism curve 2.

Question 40

What are some acute metabolic complications of diabetes mellitus

Answer 40

The main complications are:
•Diabetes ketoacidosis
•Hyper-osmolal nonketotic coma
•Hypoglycaemia

Question 41

What is diabetic ketoacidosis

Answer 41

Result from infection,
•Withholding insulin due to lack of food
•Blood glucose conc. 20-40mmol/l
•It is aggravated by vomiting leading to the following conditions

1.fluid loss ultimately from both compartments
2.decreased circulatory blood volume
3.decreased renal plasma flow
4.decreased GFR
•The ketone bodies (acetoacetate, 3-hydroxy butyrate and acetone) may give rise to metabolic acidosis

These could cause cellular dehydration leading to
• plasma [urea]
• haematocrit
• total protein
• pCO2

Question 42

What is hypososmolal non-ketotic coma

Answer 42

Marked hyperglycaemia but no detectable ketonaemia or acidosis.
•Plasma [glucose] is usually about 50mmol/l
•associated glycosuria produces osmotic diuresis with severe water and electrolyte depletion
•Coma results due to cerebral cellular dehydration

Question 43

What is hypoglycemia

Answer 43

Plasma [glucose] less than 2.5mmol/l.
•symptoms vary depending on onset and glucose concentration
Mild symptoms include: hunger, gastric hyperactivity, irritability
Severe- e.g overdose of insulin (low C-peptide)
Symptoms include; mental confusion, thickness of speech, drunkenness, convulsion or coma
•Untreated chronic hypoglycaemia in children may lead to mental retardation.

Question 44

What are some causes of hypoglycemia

Answer 44

1.Reactive hypoglycaemia
b.After alimentary hyperglycaemia
c.Latent diabetes
d.Postabsorptive hypoglycaemia in neurotic individuals
2. Insulinoma
3. Glucagon deficiency

Infantile hypoglycaemia
a.Hypoglycaemia of the newborn
b.Idiopathic hypoglycaemia of infancy
c.Infantile sensitivity to leucine
d.Hereditary fructose intolerance
e.Post excessive exercise hypoglycaemia
5. Hepatic hypoglycaemia
f.Severe liver disease
b. Glycogen storage disease
c. Failure of epinephrine response to incipient hypoglycaemia
6. Hypopituitarism
7. Hypocorticoadrenalism
8. ethanol-induced hypoglycaemia
9. Hypoglycaemia associat