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Diabetes mellitus, part 1:

physiology and complications


Muralitharan Nair

Abstract
In part 1 of this 2-part article the author discusses the physiology and
complications of diabetes mellitus (DM), a chronic and progressive
disorder which affects all ages of the population. The number of
people diagnosed with diabetes is approximately 1.8 million and an
estimated further 1 million are undiagnosed (Department of Health,
2005). In the UK, 12% of the population have diabetes and among
school children this is approximately 2 in 1000 (Watkins, 1996). There
are two main types of diabetes - type 1 and type 2 (Porth, 2005). The
aetiology of DM is unknown; however, genetic and environmental
factors have been linked to its development. Type 1 results from the
loss of insulin production in the beta cells of the pancreas, and type 2
from a lack of serum insulin or poor uptake of glucose into the cells.
Diabetes causes disease in many organs in the body, which may be
life-threatening if untreated. Complications such as heart disease,
vascular diseases, renal failure and blindness (Roberts, 2005) have all
been reported. The increased prevalence may be caused by factors
such as environmental aspects, diet, an ageing population and low
levels of physical exercise.
Key words: Diabetes

Physiology

Complications

iabetes mellitus (DM) is a chronic and progressive


illness that affects all ages. It can affect children,
young people and adults and is becoming more
common. There are 1.8 million people with
diagnosed diabetes and this figure is increasing every year
(Department of Health (DH), 2005), and the estimated cost
to the NHS is 5 million per day for treatment (Roberts,
2005). With an ageing population, the number of males and
females with diagnosed diabetes is projected to rise by 37%
for males and 24% for females by 2023 (Health Statistics
Quarterly, 2002).
There are two main types of DM. Type 1 accounts for 5
10% of all diagnosed cases, while type 2 accounts for 8590%
of patients with DM (Kumar and Clark, 2005). In addition
to type 1 and type 2, there are other types of diabetes,
such as gestational diabetes, diabetes due to side-effects
of steroid therapy and diabetes associated with hormonal
disorders, such as maturity-onset diabetes of the young, cystic
Muralitharan Nair is Senior Lecturer, Department of Nursing and
Midwifery, University of Hertfordshire

fibrosis-related diabetes and Cushings syndrome, caused by


prolonged exposure of the body tissues to high levels of the
hormone cortisol (Porth, 2005).

Diabetes mellitus
DM is a condition where the cells of the body cannot
utilize glucose properly. In type 1 there is reduced insulin
production as the beta cells are gradually destroyed and an
increased peripheral resistance in the uptake of insulin. In
type 2, the body produces enough insulin, however, the cells
develop a condition called insulin resistance where glucose
does not move into the cells (French, 2000). The body breaks
down fats, proteins and stored glycogen to produce glucose
resulting in high levels of glucose in the blood and excess byproducts such as ketones, which are products of incomplete
fat metabolism (Marieb, 2004).
McCance and Huether (2006) state that DM is used to
describe a condition characterized by chronic hyperglycaemia
and other disorders of carbohydrate, fat and protein metabolism.
Glucose is extracted from sweet foodstuffs, for example cakes
or from starchy foods, such as, potatoes, pasta or bread when
they are digested and absorbed. In the body glucose is utilized
by the cells to produce energy. The uptake of glucose by the
cells is regulated by the hormone insulin, which is produced
by the beta cells of the islets of Langerhans in the pancreas
(Tortora, 2005). Since a rise in blood glucose stimulates insulin
Eating foodstuff

Serum glucose elevated

Islets of Langerhans

Negative
feedback

Insulin

Cellular uptake of
glucose

Reduction in serum
glucose levels

Accepted for publication: December 2006


Figure 1. Negative feedback of insulin control.

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DIABETES MELLITUS
Figure 2. The pancreas.

Portal vein
Hepatic artery

Liver

Aorta
Gall bladder

Coeliac artery

Hepatic duct
Cystic duct
Tail of pancreas
Body of pancreas
Pancreatic duct

Common bile duct

Head of pancreas
Duodenum

Hepatic pancreatic ampulla


(ampulla of Vater)
secretion, a lowering of blood glucose caused by the action of
insulin inhibits further insulin secretion through the negative
feedback system (see Figure 1).

The pancreas and insulin formation


The pancreas is an elongated organ situated next to the first
part of the small intestine. It is both an endocrine gland that
produces hormones, such as insulin and glucagon, and an
exocrine gland producing digestive enzymes, such as trypsin
and chymotrypsin (Martini, 2004). It is located behind the
stomach, between the spleen and the duodenum (see Figure 2).
It contains a group of cells called the islets of Langerhans, in
which the beta cells secrete insulin and the alpha cells secrete
glucagon. The islets have a rich blood supply supplying both
the exocrine and the endocrine portions of the pancreas
(Tortora, 2005). Although the islets comprise 1-2% of the mass
of the pancreas, they receive about 1015% of the pancreatic
blood flow (Marieb, 2004). Additionally, they are innervated
by sympathetic and parasympathetic nerves, which play an
important role in the secretion of insulin.
The islets of Langerhans have four types of hormone
secreting cells. These are the:
n Alpha cells - secrete glucagon
n Beta cells - secrete insulin
n Delta cells - secrete gastrin
n F cells - produce pancreatic polypeptide.
These cells within an islet are not randomly distributed;
beta cells occupy the central portion of the islet and are
surrounded by alpha, delta and F cells (Figure 3).
Insulin is a polypeptide hormone (Porth, 2005). The
synthesis of insulin takes place in the beta cells and is stored
in granule form in the pancreas (Bonk, 1999).

British Journal of Nursing, 2007, Vol 16, No 3

Pulsatile secretion of insulin is regulated by chemical,


hormonal and neuronal control (McCance and Huether,
2006). An increase in blood glucose levels, amino acids
(arginine and leucine) and the vagus nerve (parasympathetic
nervous system) all aid the release of insulin. Other hormones
such as gastric inhibitory peptide, human growth hormone
and adrenocorticotropic hormone, all stimulate the release of
insulin (Marieb, 2004).
The insulin receptor is an enzyme which transfers phosphate
groups from adenosine triphosphate (ATP) to tyrosine residues
on the intracellular proteins. Binding of insulin to the alpha
sub-units causes the beta sub-units to autophosphorylate
(phosphorylation is the addition of a phosphate group to a
protein which then makes the protein active) thus activating
the catalytic activity of the receptor in the cytoplasm. The
activated receptor then phosphorlates a number of intracellular
proteins to make them active (Matta et al, 1996).
This then signals the vesicle containing GLUT 4 (see
Figure 4) to move from inside the cell to the membrane to
form an integral protein (see Figure 4). GLUT 4, now as
an integral protein, allows glucose molecules to enter the
cells by facilitated diffusion. GLUT 4 belongs to a group
of hexose transporters (Table 1). These are large integral
membrane proteins (Silverman, 1991) transporting glucose
down a concentration gradient. Once the glucose molecules
have entered the cell, the vesicle containing GLUT 4 integral
proteins then relocates itself in the cytoplasm.

Effects of insulin
Insulin increases glucose transport into liver, skeletal
muscles, and adipose tissue cells. The only mechanism by
which cells can take up glucose is by facilitated diffusion

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through transporter proteins called GLUT 4 (see Figure 4).


In the absence of insulin, GLUT 4 glucose transporters are
present in cytoplasmic vesicles (Shepherd and Kahn, 1999)
and are inactive.
n Insulin stimulates the liver to store glucose in the form of
glycogen. A large amount of absorbed glucose from the
small intestine is immediately taken up by hepatocytes,
which convert it into glycogen for storage (Holz and
Habner, 1992)
n Insulin promotes synthesis of fatty acids in the liver
n Insulin increase protein synthesis
n Insulin inhibits breakdown of fat in adipose tissue by
inhibiting the intracellular lipase that hydrolyses triglycerides
to release fatty acids
n Insulin stimulates the uptake of amino acids by the cells
n Insulin increases the permeability of many cells to potassium
(K+), magnesium (Mg2+) and phosphate (PO43-) ions.

Type 1
Type 1 accounts for 510% of the people diagnosed with DM.
The aetiology of DM is still unknown, although it is thought
to be the result of genetic, chemicals and environmental
factors (Port, 2005). Type 1 is not directly inherited; however,
individuals may inherit a predisposition, in that people with
certain Human Leukocyte Antigen (HLA) (Kumar and Clark,
2005), which is found in the short arm of chromosome 6, show

increased susceptibility to type 1. Studies on monozygotic


twins (Atkinson and Eisenbarth, 2001) have identified that 40%
of monozygotic twins of a person with type 1 will develop
diabetes. The increased percentage among monozygotic twins
is because of the strong genetic component of the disease
(Atkinson and Eisenbarth, 2001).
Cohn and Roth (1996), however, state that genetics alone may
not be the only contributory factor to type 1. Environmental
factors such as viruses (Davendra et al, 2004) should also
be considered in patients with type 1. Epidemic parotiditis
(mumps), rubella and enteroviruses have all been considered in
relation to the possible cause of type 1. Other possible theories
include exposure to food-borne chemical toxins and exposure
as a very young infant to cows milk where certain proteins may
trigger an autoimmune reaction (Hirschhorn, 2003).
Type 1 is characterized by the failure of the pancreatic beta
cells to secret insulin (Bonk, 1999), and this appears to be due
to the destruction of the beta cells by the immune system.
As a result there is a rise in blood glucose, since there is no
insulin to stimulate glycogen synthesis in the liver (Cohn and
Roth, 1996).

Type 2
Type 2 is a condition where the synthesis and secretion of
insulin by the islets of Langerhans is diminishing, or there is
increased insulin whereby glucose does not move into the cells

Tail of pancreas
Body of pancreas

Acinar cells

Head of
pancreas

Islet of Langerhans
Alpha cells

Beta cells

Delta cells

F cells

Figure 3. Islets of Langerhans.

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DIABETES MELLITUS
(Walsh, 2002).The onset tends to be slow and therefore may not
be detected in the early stages of the disease. Obesity and lack of
exercise are the most commons cause of insulin resistance in the
cells (Springhouse Corporation, 2000) and thus develop type
2 diabetes. The age of onset for the disease is becoming more
common in those over 50 years (Kumar and Clark, 2005), and
in children and young people (Diabetes UK, 2006).
A combination of genetic and environmental factors
contribute to the development of type 2. Feingold and Funk
(1997) state that there is a stronger genetic link in type 2 than
in type 1. The incidence with monozygotic twins in type 2 is
between 34% and 72% compared with 40% in type 1. Erens
et al (2001) state that certain families and ethnic groups are
much more likely to develop type 2. In the UK, for example,
Pakistani and Bangladeshi people are five times more likely
to develop type 2 than the general population while the
British Indian population are three times more likely to
develop type 2 (Roberts, 2005).
Whatever the cause, the result is a deficiency of insulin
or inadequate insulin function (Walsh, 2002). This leads
to inadequate transportation of glucose into the cells for
energy production and the conversion of excess glucose into
glycogen or fat for storage. Thus, glucose accumulates in the
blood plasma causing hyperglycaemia. See Table 2 for the
summary of characteristics of type 1 and type 2.

Figure 4. GLUT 4 protein transporter (a) and fused GLUT 4 to cell membrane (b).

British Journal of Nursing, 2007, Vol 16, No 3

Insulin

Extracellular

Insulin
receptor

Alpha subunit

Cell membrane
Beta subunit

Fuses with plasma


membrane

Insulin
signalling

Cytoplasm

Glut-4 vesicle

Extracellular

Glucose
molecules

Insulin

Alpha subunit

Potential complications
Wallace (1999) states that the morbidity and mortality
associated with macrovascular degeneration far outweigh
the risks of microvasular complications in older people with
diabetes. In microvascular degeneration, the base membrane
of the capillaries are thick and become hard thus affecting
osmosis and diffusion of nutrients and gases. Microvascular
changes normally affect the retina, kidneys and the skin
(York Centre for Reviews and Dissemination, 2000). In
the UK Prospective Diabetes study (Turner et al, 1996) 9%
of patients with type 2 diabetes developed microvascular
disease after 9 years of follow-up, compared with rates of
20% for macrovascular complications. Nevertheless, patients
with DM will present with microvascular or macrovascular
degeneration (Winters and Jernigan, 2000).
Macrovascular disease denotes arterial diseases, in particular
the coronary arteries and the arteries supplying the brain and
the feet (National Institute of Health and Clinical Excellence,
2002). Degeneration of these vessels involves the build-up of
fatty substances (cholesterol), which leads to atherosclerosis.
The effect of this is the narrowing of the arteries, which
could lead to complications such as hypertension and also
reduced circulation in the affected tissues (Walsh, 2002).
Retinopathy is the major cause of blindness (Bullock and
Henze, 2000) in patients with diabetes. It is the result of
microvascular changes associated with hyperglycaemia (Feingold
and Funk, 1997). The changes include microaneurysms,
exudate from the leaking capillaries and retinal oedema.
Diabetic nephropathy first affects the glomerular vessels and
later the base membrane of the glomerulus become thick and
hard, losing their filtration functions. This can lead to kidney
damage and the patient with diabetes will need a peritoneal
dialysis, a renal transplant or haemodialysis (Bauer, 1994).

Glucose
molecules

Insulin
receptor

Cell membrane
Beta subunit

Fused
Glut-4 vesicle

Cytoplasm

b
Disease of the peripheral nerves is common in DM and
the symptoms depend on which nerve(s) is/are affected.
Not only are the peripheral nerves affected, but also the
cranial and the autonomic nerves (Clark and Lee, 1995).
In patients with DMs, this may lead to loss of sensation in
the legs and render the patient prone to arterial ulcers. If
the leg is untreated, gangrene may occur, which could lead
to limb amputation. Autonomic dysfunction can affect the

Table 1. Hexose transporters


Transporters

Major sites of action

Functions

GLUT 1

Brain, erythrocytes, endothelial


cells, fetal tissues
Liver, pancreas, kidney,
small intestine
Brain, placenta, testes

Transports glucose and


galactose. Found in many cells.
Transports glucose, galactose
and fructose
Transports glucose and
galactose. It is the primary
glucose transporter for neurons.
Glucose transporter

GLUT 2
GLUT 3

GLUT 4
GLUT 5

Skeletal and cardiac muscles,


fat cells
Small intestine, sperm
kidney, fat cells, muscles

Transports fructose but not


glucose or galactose.

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Table 2. Summary of characteristics of type 1 and type 2


Characteristics

Type 1

Type 2

Age of onset

Generally in pre- or
adolescence

Nature of onset
Genetic predisposition

Sudden onset
Related to specific HLA
factors
Viruses, toxins
Present at initial stage
Generally absent or
delayed

Occurs in people <50


years, children and young
people
Slow, insidious onset
Strongly familial.
Unrelated to HLA
Obesity
Not present
Normal to reduced
amount and/or increased
peripheral resistance
Usually normal or obese

Environmental factors
Beta-cell autoimmunity
Insulin secretion

Body structure
Symptoms at onset

Long-term effects
Treatment

Lean. Can appear


cachectic
Polyuria, polydipsia,
fatigue, weight loss,
hunger, ketoacidosis
Retinopathy, nephropathy,
neuropathy
Insulin

Often none or mild


symptoms of IDDM.
No ketoacidosis
Similar to IDDM but later
in life
Diet, insulin and oral
hypoglycaemics

HLA=Human leukocyte antigen; IDDM=Insulin-dependent diabetes mellitus

Source: Adapted Cohn and Roth (1996)

bladder, heart, gastrointestinal tract and vascular tone (Cohn


and Roth, 1996).

Conclusion
DM is a major endocrine disorder involving the beta cells of
the islets of Langerhans. Although the disease is recognized
to have a genetic trait, its precise aetiology is unknown. It is
a condition where the cells of the body cannot metabolize
sugar effectively due to a total or relative lack of insulin. The
body then breaks down its own fats, proteins and glycogen
to produce sugar, resulting in high levels of blood glucose
(hyperglycaemia) because without insulin, cellular uptake
and utilization of glucose is limited. There are two main
types of DM - type 1 and type 2. The disease causes many
complications in other organs such as diabetic neuropathy,
retinopathy and micro/macrovascular complications.
DM is a disease that affects all age groups and is an
increasing health problem. The estimated cost to the NHS
is approximately 5 million per day for treatment (Roberts,
2005). Diabetes can be controlled using insulin, diet,
exercise and oral hypoglycaemics, and in Part two of this
article the nursing management of the person with DM is
BJN
discussed.

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KEY POINTS
I
Diabetes mellitus is a chronic
and a progressive disease which affects all ages of the
population.
I
It is estimated that about 1.8
million people are diagnosed with diabetes and a further
1 million are undiagnosed.
I
There are two main types of
diabetes type 1 and type 2. Type 1 result from the loss
of insulin production in the beta cells and in type 2 there
is a poor uptake of glucose into the cells.
I
If untreated it can cause severe
complications such as retinopathy, diabetic nephropathy
and vascular complications

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