Diabetes mellitus (DM) is a group of diseases
characterized by high levels of blood glucose
resulting from defects in insulin production, insulin
action, or both.
The term diabetes mellitus describes a metabolic
disorder of multiple aetiology characterized by
chronic hyperglycaemia with disturbances of
carbohydrate, fat and protein metabolism resulting
from defects in insulin secretion, insulin action, or
both.
The effects of diabetes mellitus include long–term
damage, dysfunction and failure of various organs.
Diabetes mellitus may present with characteristic
symptoms such as thirst, polyuria, blurring of vision,
and weight loss.
In its most severe forms, ketoacidosis or a non–
ketotic hyperosmolar state may develop and lead to
stupor, coma and, in absence of effective treatment,
death.
Often symptoms are not severe, or may be absent,
and consequently hyperglycaemia sufficient to cause
pathological and functional changes may be present
for a long time before the diagnosis is made.
The long–term effects of diabetes mellitus
include progressive development of the specific
complications of retinopathy with potential
blindness, nephropathy that may lead to renal
failure, and/or neuropathy with risk of foot
ulcers, amputation, Charcot joints, and features
of autonomic dysfunction, including sexual
dysfunction.
People with diabetes are at increased risk of
cardiovascular, peripheral vascular and
cerebrovascular disease.
The development of diabetes is projected to reach
pandemic proportions over the next10-20 years.
International Diabetes Federation (IDF) data
indicate that by the year 2025, the number of
people affected will reach 333 million –90% of these
people will have Type 2 diabetes.
In most Western societies, the overall prevalence
has reached 4-6%, and is as high as 10-12% among
60-70-year-old people.
The annual health costs caused by diabetes and its
complications account for around 6-12% of all
health-care expenditure.
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Gestational Diabetes
Other types:
LADA (latent autoimmune diabetes in
adults)
MODY (maturity-onset diabetes of
youth)
Secondary Diabetes Mellitus
Was previously called insulin-dependent diabetes
mellitus (IDDM) or juvenile-onset diabetes.
Type 1 diabetes develops when the body’s
immune system destroys pancreatic beta cells,
the only cells in the body that make the hormone
insulin that regulates blood glucose.
This form of diabetes usually strikes children and
young adults, although disease onset can occur at
any age.
Type 1 diabetes may account for 5% to 10% of all
diagnosed cases of diabetes.
Risk factors for type 1 diabetes may include
autoimmune, genetic, and environmental factors.
Was previously called non-insulin-dependent diabetes mellitus
(NIDDM) or adult-onset diabetes.
Type 2 diabetes may account for about 90% to 95% of all
diagnosed cases of diabetes.
It usually begins as insulin resistance, a disorder in which the
cells do not use insulin properly. As the need for insulin rises,
the pancreas gradually loses its ability to produce insulin.
Type 2 diabetes is associated with older age, obesity, family
history of diabetes, history of gestational diabetes, impaired
glucose metabolism, physical inactivity, and race/ethnicity.
African Americans, Hispanic/Latino Americans, American
Indians, and some Asian Americans and Native Hawaiians or
Other Pacific Islanders are at particularly high risk for type 2
diabetes.
Type 2 diabetes is increasingly being diagnosed in children and
adolescents.
A form of glucose intolerance that is diagnosed in
some women during pregnancy.
Gestational diabetes occurs more frequently
among African Americans, Hispanic/Latino
Americans, and American Indians. It is also more
common among obese women and women with a
family history of diabetes.
During pregnancy, gestational diabetes requires
treatment to normalize maternal blood glucose
levels to avoid complications in the infant.
After pregnancy, 5% to 10% of women with
gestational diabetes are found to have type 2
diabetes.
Women who have had gestational diabetes have a
20% to 50% chance of developing diabetes in the
next 5-10 years.
Other specific types of diabetes result
from specific genetic conditions (such
as maturity-onset diabetes of youth),
surgery, drugs, malnutrition,
infections, and other illnesses.
Such types of diabetes may account for
1% to 5% of all diagnosed cases of
diabetes.
Latent Autoimmune Diabetes in Adults (LADA)
is a form of autoimmune (type 1 diabetes)
which is diagnosed in individuals who are older
than the usual age of onset of type 1 diabetes.
Alternate terms that have been used for "LADA"
include Late-onset Autoimmune Diabetes of
Adulthood, "Slow Onset Type 1" diabetes, and
sometimes also "Type 1.5
Often, patients with LADA are mistakenly
thought to have type 2 diabetes, based on their
age at the time of diagnosis.
MODY – Maturity Onset Diabetes of the Young
MODY is a monogenic form of diabetes with an
autosomal dominant mode of inheritance:
◦ Mutations in any one of several transcription factors or in the
enzyme glucokinase lead to insufficient insulin release from
pancreatic ß-cells, causing MODY.
◦ Different subtypes of MODY are identified based on the mutated
gene.
Originally, diagnosis of MODY was based on presence of
non-ketotic hyperglycemia in adolescents or young
adults in conjunction with a family history of diabetes.
However, genetic testing has shown that MODY can
occur at any age and that a family history of diabetes is
not always obvious.
Secondary causes of Diabetes mellitus include:
Acromegaly,
Cushing syndrome,
Thyrotoxicosis,
Pheochromocytoma
Chronic pancreatitis,
Cancer
Drug induced hyperglycemia:
◦ Atypical Antipsychotics - Alter receptor binding characteristics, leading to
increased insulin resistance.
◦ Beta-blockers - Inhibit insulin secretion.
◦ Calcium Channel Blockers - Inhibits secretion of insulin by interfering with
cytosolic calcium release.
◦ Corticosteroids - Cause peripheral insulin resistance and gluconeogensis.
◦ Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive potassium
channels.
◦ Naicin - They cause increased insulin resistance due to increased free fatty acid
mobilization.
◦ Phenothiazines - Inhibit insulin secretion.
◦ Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.
◦ Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also cause
increased insulin resistance due to increased free fatty acid mobilization.
Prediabetes is a term used to distinguish people
who are at increased risk of developing diabetes.
People with prediabetes have impaired fasting
glucose (IFG) or impaired glucose tolerance (IGT).
Some people may have both IFG and IGT.
IFG is a condition in which the fasting blood sugar
level is elevated (100 to 125 mg/dL) after an
overnight fast but is not high enough to be
classified as diabetes.
IGT is a condition in which the blood sugar level is
elevated (140 to 199 mg/dL after a 2-hour oral
glucose tolerance test), but is not high enough to
be classified as diabetes.
Progression to diabetes among those with
prediabetes is not inevitable. Studies suggest
that weight loss and increased physical activity
among people with prediabetes prevent or delay
diabetes and may return blood glucose levels to
normal.
People with prediabetes are already at increased
risk for other adverse health outcomes such as
heart disease and stroke.
Research studies have found that lifestyle changes
can prevent or delay the onset of type 2 diabetes
among high-risk adults.
These studies included people with IGT and other
high-risk characteristics for developing diabetes.
Lifestyle interventions included diet and moderate-
intensity physical activity (such as walking for 2 1/2
hours each week).
In the Diabetes Prevention Program, a large
prevention study of people at high risk for diabetes,
the development of diabetes was reduced 58% over
3 years.
Studies have shown that medications have been successful in
preventing diabetes in some population groups.
In the Diabetes Prevention Program, people treated with the
drug metformin reduced their risk of developing diabetes by
31% over 3 years.
Treatment with metformin was most effective among younger,
heavier people (those 25-40 years of age who were 50 to 80
pounds overweight) and less effective among older people and
people who were not as overweight.
Similarly, in the STOP-NIDDM Trial, treatment of people with
IGT with the drug acarbose reduced the risk of developing
diabetes by 25% over 3 years.
Other medication studies are ongoing. In addition to
preventing progression from IGT to diabetes, both lifestyle
changes and medication have also been shown to increase the
probability of reverting from IGT to normal glucose tolerance.
Management of
Diabetes
Mellitus
The major components of the treatment of
diabetes are:
Diet is a basic part of management in every
case. Treatment cannot be effective unless
adequate attention is given to ensuring
appropriate nutrition.
Dietary treatment should aim at:
◦ ensuring weight control
◦ providing nutritional requirements
◦ allowing good glycaemic control with blood
glucose levels as close to normal as possible
◦ correcting any associated blood lipid
abnormalities
The following principles are recommended as dietary
guidelines for people with diabetes:
Dietary fat should provide 25-35% of total intake of calories
but saturated fat intake should not exceed 10% of total
energy. Cholesterol consumption should be restricted and
limited to 300 mg or less daily.
Protein intake can range between 10-15% total energy (0.8-1
g/kg of desirable body weight). Requirements increase for
children and during pregnancy. Protein should be derived from
both animal and vegetable sources.
Carbohydrates provide 50-60% of total caloric content of the
diet. Carbohydrates should be complex and high in fibre.
Excessive salt intake is to be avoided. It should be particularly
restricted in people with hypertension and those with
nephropathy.
Physical activity promotes weight reduction and
improves insulin sensitivity, thus lowering blood
glucose levels.
Together with dietary treatment, a programme
of regular physical activity and exercise should
be considered for each person. Such a
programme must be tailored to the individual’s
health status and fitness.
People should, however, be educated about the
potential risk of hypoglycaemia and how to
avoid it.
There are currently four classes of oral anti-
diabetic agents:
i. Biguanides
ii. Insulin Secretagogues – Sulphonylureas
iii. Insulin Secretagogues – Non-
sulphonylureas
iv. α-glucosidase inhibitors
v. Thiazolidinediones (TZDs)
If glycaemic control is not achieved (HbA1c >
6.5% and/or; FPG > 7.0 mmol/L or; RPG
>11.0mmol/L) with lifestyle modification within
1 –3 months, ORAL ANTI-DIABETIC AGENT
should be initiated.
In the presence of marked hyperglycaemia in
newly diagnosed symptomatic type 2 diabetes
(HbA1c > 8%, FPG > 11.1 mmol/L, or RPG > 14
mmol/L), oral anti-diabetic agents can be
considered at the outset together with lifestyle
modification.
As first line therapy:
Obese type 2 patients, consider use of metformin,
acarbose or TZD.
Non-obese type 2 patients, consider the use of
metformin or insulin secretagogues
Metformin is the drug of choice in overweight/obese
patients. TZDs and acarbose are acceptable alternatives
in those who are intolerant to metformin.
If monotherapy fails, a combination of TZDs, acarbose
and metformin is recommended. If targets are still not
achieved, insulin secretagogues may be added
Combination oral agents is indicated in:
Newly diagnosed symptomatic patients with
HbA1c >10
Patients who are not reaching targets after
3 months on monotherapy
If targets have not been reached after optimal dose of
combination therapy for 3 months, consider adding
intermediate-acting/long-acting insulin (BIDS).
Combination of insulin+ oral anti-diabetic agents (BIDS) has
been shown to improve glycaemic control in those not
achieving target despite maximal combination oral anti-
diabetic agents.
Combining insulin and the following oral anti-diabetic agents
has been shown to be effective in people with type 2 diabetes:
◦ Biguanide (metformin)
◦ Insulin secretagogues (sulphonylureas)
◦ Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an
approved indication)
◦ α-glucosidase inhibitor (acarbose)
Insulin dose can be increased until target FPG is achieved.
Diabetes
Management
Algorithm
In elderly non-obese patients, short acting insulin
secretagogues can be started but long acting Sulphonylureas
are to be avoided. Renal function should be monitored.
Oral anti-diabetic agents are not recommended for diabetes in
pregnancy
Oral anti-diabetic agents are usually not the first line therapy
in diabetes diagnosed during stress, such as infections. Insulin
therapy is recommended for both the above
Targets for control are applicable for all age groups. However,
in patients with co-morbidities, targets are individualized
When indicated, start with a minimal dose of oral anti-diabetic
agent, while reemphasizing diet and physical activity. An
appropriate duration of time (2-16 weeks depending on agents
used) between increments should be given to allow
achievement of steady state blood glucose control
Short-term use:
Acute illness, surgery, stress and emergencies
Pregnancy
Breast-feeding
Insulin may be used as initial therapy in type 2 diabetes
in marked hyperglycaemia
Severe metabolic decompensation (diabetic ketoacidosis,
hyperosmolar nonketotic coma, lactic acidosis, severe
hypertriglyceridaemia)
Long-term use:
If targets have not been reached after optimal dose of
combination therapy or BIDS, consider change to multi-dose
insulin therapy. When initiating this,insulin secretagogues
should be stopped and insulin sensitisers e.g. Metformin or
TZDs, can be continued.
The majority of patients will require more than one daily
injection if good glycaemic control is to be achieved.
However, a once-daily injection of an intermediate acting
preparation may be effectively used in some patients.
Twice-daily mixtures of short- and intermediate-acting insulin
is a commonly used regimen.
In some cases, a mixture of short- and intermediate-
acting insulin may be given in the morning. Further doses
of short-acting insulin are given before lunch and the evening
meal and an evening dose of intermediate-acting insulin is
given at bedtime.
Other regimens based on the same principles may be used.
A regimen of multiple injections of short-acting insulin before
the main meals, with an appropriate dose of an intermediate-
acting insulin given at bedtime, may be used, particularly
when strict glycaemic control is mandatory.
Almost a third of all diabetics do not know
they have the disease until they are at a
critical stage.
Type I symptoms can be instant and
obvious, while the problem with Type II is
that the symptoms can take a long while to
appear.
People who are at risk, such as those who
are severely overweight or have a family
history of diabetes, should be aware of the
signs that coincide with diabetes.
Once people know what the warning symptoms
are they can prevent or delay the onset of
diabetes. Simple adjustments to a persons way of
life,like diet and exercise,can make a huge
difference.
Diabetic awareness,either preventative or after
diagnoses care,can be achieved through
educational booklets such as those by Eli Lilly and
company or the American Diabetes Association.
Patients should be educated to practice self-
care. This allows the patient to assume
responsibility and control of his / her own
diabetes management. Self-care should
include:
◦ Blood glucose monitoring
◦ Body weight monitoring
◦ Foot-care
◦ Personal hygiene
◦ Healthy lifestyle/diet or physical activity
◦ Identify targets for control
◦ Stopping smoking
National Diabetes Fact Sheet 2003, DEPARTMENT OF
HEALTH AND HUMAN SERVICES Centres for Disease Control
and Prevention
World Health Organization. Definition, Diagnosis and
Classification of Diabetes Mellitus and its Complications. Report of
WHO. Department of Non-communicable Disease
Surveillance. Geneva 1999
Academy of Medicine. Clinical Practice Guidelines. Management of
type 2 diabetes mellitus. MOH/P/PAK/87.04(GU), 2004
NHS. Diabetes - insulin initiation - University Hospitals of
Leicester NHS Trust Working in partnership with PCTs across
Leicestershire and Rutland, May 2008.
