The Endocrine System|
Synonyms : Diabetes; Hyperglycaemia; Hyperglycemia
mellitus is a clinical syndrome characterised by hyperglycaemia
due to absolute or relative deficiency
of insulin, which affects the metabolism of carbohydrate, proteins and
fat. Diabetes has been crudely and conveniently classified in two main types:
diabetes mellitus (IDDM; also known as juvenile onset or Type I diabetes),
which accounts for 10% of all diabetic cases
diabetes mellitus (NIDDM; also known as maturity onset or Type II diabetes)
which is responsible for the remaining 90% of cases
Although the precise aetiology
is still uncertain in both main types of diabetes environmental factors
interact with a genetic susceptibility to determine which of those with the
genetic predisposition will actually develop the clinical syndrome.
IDDM is a slow autoimmune disease
against pancreatic islet insulin secreting cells, which could be triggered by
certain environmental factors (an early infection with Echo or Coxsackie
viruses is suggested, as well as early exposure to cow protein in milk).
inheritance is polygenic (more than one gene appear to be involved) with
strong association with a tissue antigenic marker HLA DR4. Many presumed
autoimmune disorders are associated with specific HLA markers (e.g.,
ankylosing spondylitis with B27, multiple sclerosis DR2 etc.) although the
exact pathophysiologic basis of this association in unknown.
accompanied by the classical symptoms of diabetes occurs only when
90% of insulin-secreting cells are already destroyed.
b-cell and insulin autoantibodies can be identified, and also lymphocyte infiltration
of pancreatic islets resulting in selective destruction of insulin-secreting
cells can be demonstrated.
onset is at age 11 to 13, it is rare in adults over 30 years of age.
is not HLA linked and there is no
evidence that autoimmunity or viruses have anything to do with its
seems that genetic factors are more
important in the development of this type of diabetes than in IDDM (it
is now thought that susceptibility is inherited through an autosomal
studies provide evidence that over-eating, especially when combined with
obesity and underactivity, is associated with the development of NIDDM.
Obesity probably acts as a diabetogenic factor through increasing resistance
to the action of insulin in those genetically predisposed (80% of Type II
diabetics are obese). This resistance is reversible and weight loss can
restore sensitivity to insulin in most cases.
is probably due to a decreased number of cellular insulin receptors in
peripheral tissues, maybe even associated with a post-receptor defect in the
action of insulin.
ageing is an important risk factor for NIDDM; the condition starts to increase
after age of 40; but younger people may be affected (so called MODY ?
maturity onset in young)
Insulin has several essential metabolic actions as a
fuel-storage hormone, and also affects cell growth and differentiation. It
decreases blood glucose by: increasing glucose uptake, increasing glycogen
synthesis, decreasing gluconeogenesis and decreasing glycogen breakdown
increases fatty acid synthesis and triglyceride formation in the liver and
adipose tissue (lipogenesis) and decreases lipolysis. Insulin stimulates the
uptake of amino acids into muscle and increases
protein synthesis. It also decreases
protein catabolism and the oxidation of amino acids, particularly in the
the aetiology, in all cases the hyperglycaemia of diabetes develops because of
an absolute (IDDM) or relative (NIDDM) deficiency of insulin which leads to:
reduced rate of removal of glucose from the blood by peripheral tissues
increased rate of release of glucose from the liver into the circulation due
to action of counter-regulatory hormones (adrenaline and glucocorticosteroids),
which is a compensatory mechanism; however this mechanism manages only to
further increase the blood glucose levels.
the renal threshold for glucose reabsorption is exceeded, glucose spills over
into the urine (glycosuria) and
causes an osmotic diuresis (polyuria)
which in turn results in thirst and increased fluid intake (polydipsia). Patients also consume more food to compensate for lost
glucose (polyphagia). Muscle
wasting occurs in severe diabetes due to the fact that protein metabolism
is deranged and an excessive amount of protein is converted to glucose
the absence of insulin and consequently impaired carbohydrate metabolism,
energy can only be sourced from lipid breakdown (lipolysis)
of fatty acids. Unfortunately not all tissues are capable of b-oxidation
but they (including the brain) can use partially metabolised fatty acids
bodies (aceto-acetic acid, b-hydroxybutyric acid and acetone) formed from
fatty acids in the liver (ketogenesis).
When the rate of production exceeds that of removal by peripheral tissues
(which is relatively slow in the absence of glucose metabolism), then
hyperketonaemia results. Aceto-acetic and b-hydroxybutyric acids are relatively strong
acids that cause a fall in pH (ketoacidosis)
and stimulate pulmonary ventilation so that clinically hyperpnoea or ‘air
hunger?is observed (respiratory compensation of metabolic acidosis).
When insulin deficiency is partial, as in NIDDM, the anticatabolic effect of insulin (anti-lipolytic and anti-proteolytic) may be relatively well preserved while other metabolic actions are more seriously defective. In these circumstances lipolysis is not markedly accelerated and the concentration of ketone bodies in the blood remains relatively normal despite severe hyperglycaemia. In its most serious form this condition is known as hyperosmolar diabetic coma.
Clinical features: < BACK TO TOP >
usually show no physical signs attributable to diabetes, but instead present
with salt and water depletion (loose
dry skin which lifts in folds, a dry furred tongue and cracked lips,
tachycardia, hypotension and reduced intraocular pressure noticed as soft
eyeballs on palpation). Breathing may be deep and sighing due to acidosis, the
breath is usually fetid and the fruity-sweet
smell of acetone may be apparent (acetone is the only volatile ketone
body). Mental apathy, confusion or coma may also be present due to brain
dehydration and reduced energy production.
physical signs present in patients with NIDDM at diagnosis are variable. In many instances NIDDM is
discovered in asymptomatic patients during routine testing of urine/blood.
Other may complain of polyuria, polydipsia and polyphagia, as well as vaginal
thrush and balanitis (inflammation of the penis glans) since the external
genitalia are especially prone to infection by fungi (Candida) which flourish on skin and mucous membranes soaked
in glucose. Bacterial skin infections such as boils are also common.
Impairment of vision may be reported when ophthalmoscopy may show the typical
appearances of diabetic retinopathy,
which are virtually diagnostic of the condition. Depression or loss of the
tendon reflexes at the ankles and impaired sensory perception distally in the
legs indicate neuropathy. The
presence of diabetic nephropathy may
be indicated initially by proteinuria in addition to glycosuria.
Diagnosis: < BACK TO TOP >
The earlier diabetes is
diagnosed the easier it is to treat effectively and greater the chance of
avoiding the development of serious vascular disease. When the symptoms
suggest diabetes the diagnosis may be confirmed by finding glycosuria
(glucose in urine), with or without ketonuria
(ketone bodies in urine), and a plasma (serum) glucose concentration
greater than 7.7 mmol/L (normally
up to 6 mmol/L) after an overnight fast.
Testing the urine
for glucose by using reagent strips is the most usual screening
procedure for detecting diabetes, but not completely reliable due to
individual variations in renal threshold (false positive and false negative
results in terms of diabetes diagnosis are possible). Ketonuria si common in
IDDM but usually not in NIDDM. However, ketonuria may be found in healthy
people, e.g., who have been fasting or on very strict diet poor in
carbohydrates, and therefore it is not pathognomonic of diabetes. However if
both ketonuria and glycosuria are found, the diagnosis of diabetes is
practically certain. All
patients with glycosuria should be considered diabetic until proved otherwise
on the basis of blood measurements.
Glucose tolerance test is done when plasma glucose concentration is between 6 and 7.7 mmol/L. A sample of blood is taken to measure the fasting plasma glucose level and 75 g glucose is dissolved in 300 mL of water and given by mouth. Thereafter samples of blood are collected at half-hourly intervals for at least two hours and their glucose content is measured. The patient is diabetic if plasma glucose 2 hours after glucose drink is >11 mmol/L (normally is less than 7.8 mmol/L). Intermediate readings are classified as Impaired Glucose Tolerance and it may be necessary to keep the patient under observation and to repeat the test at a later date. However in many patients with impaired glucose tolerance test the condition does not progress or it resolves spontaneously.
Management < BACK TO TOP >
methods of treatment are available:
?diet and oral hypoglycaemic drug
?diet and insulin
50% of new cases of diabetes can be controlled adequately by diet alone,
20-30% will need an oral hypoglycaemic drug, and 20-30% will require insulin.
1. Dietary management. Dietary measures are required in the treatment of all diabetic patients
to achieve the overall therapeutic goal: normal metabolism. Two basic types
of diet are used:
energy, weight reducing diet for obese diabetics
maintenance diet, which purpose is to keep the intake of food constant in
content and pattern of distribution from day to day
is important to realise, and to explain to the individual patient, that the ‘diabetic diet?/i> is simply that which is now recommended for the
population in general, which includes intake of complex carbohydrates and
avoidance of too much refined sugar, small meals more frequently instead of
infrequent large meals.
2. Oral hypoglycaemic drugs rely in their action upon a supply of endogenous insulin and they
therefore have no hypoglycaemic effect in patients with IDDM.
(e.g., chlorpropamide [Diabinese], tolbutamide [Rastinon], glibenclamide [Daonil,
Semi-Daonil, Euglucon, Glimel], glipizide [Minidiab, Melizide], gliclazide [Diamicron],
troglitazone [Rezulin] and glimepiride [Amaryl]) act by stimulating the
release of insulin from the pancreatic beta cells, and are valuable in the
treatment of non-obese patients with NIDDM, who fail to respond to dietary
measures alone (sulphonylureas increase appetite that may result in weight
gain and increased resistance to insulin).
[Diaformin, Glucophage, Glucohexal, Diabex] increases insulin sensitivity and
peripheral glucose uptake, without increasing insulin secretion, and may be a
better option for obese patients with NIDDM.
main types of insulin preparations are used clinically:
unmodified, soluble with rapid onset and short duration of action (6-8
hours) such as Actrapid, Humulin R and Hypurin Neutral.
such isophane insulin where insulin is adsorbed on to a foreign protein,
normally fish protamine [Protaphane, Humulin NPH, Hypurin Isophane, Isotard
MC] have duration of action of 12-24 hours. They can be mixed with soluble
insulin and they are given subcutaneously.
e.g., insulin zinc suspension [Monotard, Humulin L, Lente MC, Ultratard,
Humulin UL] has duration of action of 24-36 hours. This suspension contains
excess free zinc and when mixed with unmodified insulin the zinc will blunt
the onset of its actions. This is why they should not be mixed together.
Insulin zinc can be administered only subcutaneously.
can be extracted from porcine or bovine pancreas. ‘Human?
insulin is made by micro-organisms, usually E coli, modified through
recombinant DNA technology and today is most commonly used. It is usually
given subcutaneously, sometimes in an emergency room by intravenous infusion.
regimes of insulin administration may be used. A common regime for IDDM
patients is to inject a combination of
short and intermediate-acting insulins twice daily, before breakfast and
before the evening meal. These pre-mixed preparations are marketed as Mixtard
50/50, Mixtard 30/70, Mixtard 15/85, Humulin 50/50, Humulin 30/70, Humulin
20/80. Intravenous infusion of soluble insulin is used routinely in emergency
treatment of diabetic ketoacidosis, in conjunction with large volumes of
isotonic saline and potassium chloride to rectify Na+, K+ and Cl- depletion.
4. New developments
are insulin that is
administered into the nose through a spray (no need for injection) and drugs
that mimic the action of insulin by activating insulin receptors but are
given orally. They are still in research phase.
Acute Complications Of Treatment
may occur due to over-dosage with insulin, missed meal or unaccustomed too
strenuous exercise. Symptoms:
weakness, emptiness, hunger, diplopia (seeing in duplicate), blurring of
vision, mental confusion, abnormal behaviour (e.g., aggression, poor
co-ordination), lassitude, somnolence, muscular twitching, nausea, vomiting,
in established diabetics develops if patients for some reason reduce their
dose of insulin, or sustain a stress particularly that produced by
intercurrent infection. Hyperglycaemia is combined with acidosis due to
accumulation of ketone bodies, as well as severe dehydration and
intracellular potassium depletion because of redistribution of potassium from
intracellular to extracellular compartments in exchange for hydrogen ions. If
potassium is not replenished, serious cardiac arrhythmias can occur.
ketoacidosis is a medical emergency which should be treated in hospital by:
administration of unmodified insulin by intramuscular or intravenous
and potassium replacement
administration of antibiotics if infection is present
Long Term Complications Of Diabetes
Large blood-vessel disease
accounts for about 70% of all deaths. Atherosclerosis
occurs commonly and extensively in diabetic patients with pathological
changes similar to those seen in non-diabetics but occurring earlier and
being more widespread, causing ischaemic
heart disease, cardiac failure,
intermittent claudication (crampy pain in calves on walking due to
ischaemia), gangrene and stroke.
Myocardial infarction is the most common cause of death in diabetics.
Disease of small blood vessels
in form of widespread thickening of their walls is specific to diabetes and
is termed diabetic microangiopathy.
It contributes to the mortality, particularly in younger people, by causing
chronic renal failure (second most
common cause of death) due to diabetic
nephropathy (it takes at least 15 years).
retinopathy can cause
severely impaired vision and blindness (it is now the commonest cause of
blindness in the 35-65 age group in most developed countries). Diabetic neuropathy (affecting motor, sensory and autonomic nerves) can cause
difficulty in walking, chronic ulceration of the feet, bowel and bladder
dysfunction (constipation and urine retention), erectile dysfunction in men,
diminished sensory perception, paraesthesiae (tingling), pain in the lower
limbs, burning sensations in the soles of the feet.
incidence of the diabetic complications is mainly related to duration
of diabetes and the degree of
metabolic control achieved indicated by the mean blood glucose
concentration. In most centres periodical determination of glycosylated haemoglobin (Hb A1c)
is done to estimate plasma glucose in the last 1-3 months. Hb A1c is a stable product of non-enzymatic
glycosylation of the b–chain
of Hb by plasma glucose and hyperglycaemia as in diabetes generally increases
the rate of formation of this type of Hb. Normal Hb A1c
level is about 6%, and in poorly controlled diabetics it is 9-12%. Similar
test is fructosamine level which measures the level of fructosamine which is
formed by a chemical reaction of glucose with plasma protein. Fructosamine
reflects glucose control in the previous 1-3 weeks.
seems that all complications are irreversible and an effort must be put to
prevent their occurrence by better control of diabetes, with full
participation of patients.
Prognosis < BACK TO TOP >
Nutrition < BACK TO TOP >
Nutrition that alleviate or prevent Diabetes mellitus :-
Herbs < BACK TO TOP >
Herbs that alleviate or prevent Diabetes mellitus :-
(source : -)
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