DIABETES MELLITUS

Prepared by:
Dr. Zacharia (MD)
CONTENTS
• Definition
• Types of DM
• Clinical Features
• Investigations
• Complications DM
• Treatment
• Follow up
 Definition:
Diabetes mellitus is a clinical syndrome
characterized by chronic hyperglycemia due to
absolute or relative deficiency of insulin (defects in
insulin secretion, action or both).Lack of insulin
affects the metabolism of carbohydrate, protein and
fat and causes a significant disturbance of water
and electrolyte homeostasis.
 Diabetes mellitus (DM) comprises a group of
common metabolic disorders that present with
hyperglycemia (elevated blood glucose).
 Defect in body energy regulation and utilization
leading to multi-organ complications and early
mortality.
 Hyperglycemia is a cardinal manifestation due to
insulin deficiency or insulin resistance.
 Several distinct types of DM exist and are caused
by a complex interaction of genetics,
environmental factors and life-style choices.
 Depending on the etiology of DM, factors
contributing to hyperglycemia may include
o Reduced insulin secretion
o Decreased glucose usage, and
o Increased glucose production
 The metabolic dysregulation associated with
DM causes secondary pathophysiologic
changes in multiple organ systems that
impose a tremendous burden on the individual
with diabetes and on the health care system.
TYPES OF DM:
TYPE 1 DM(IDDM)

 Type 1 DM is an autoimmune disease. The pancreas shows

lymphocytic infiltration and destruction of insulin-secreting cells
of the islets of Langerhans, causing insulin deficiency.
Approximately 85% of patients have circulating islet cell
antibodies, and the majority also have detectable anti-insulin
antibodies before receiving insulin therapy
 Type 1 DM is a catabolic disorder in which circulating insulin is
very low or absent (absolute insulin deficiency), plasma glucagon
is elevated, and the pancreatic beta cells fail to respond to all
insulin- secretory stimuli
 Patient are dependent on exogenous insulin for life.
PATHOPHYSIOLOGY
 Currently One theory regarding the etiology of type
1 DM is that it results from damage to pancreatic
beta cells from an infectious or environmental agent.
It triggers the immune system in a genetically
susceptible individual to develop an autoimmune
response against altered pancreatic beta cell
antigens or molecules in beta cells that resemble a
viral protein, autoimmunity is considered the major
factor in the pathophysiology of type 1 DM.
Prevalence is increased in patients with other
autoimmune diseases, such as Graves disease,
Hashimoto thyroiditis, and Addison disease.
 Genetic factors account for about one third of the susceptibility of
type 1 DM
 Environmental agents that have been hypothesized to induce an
attack on beta cell function include viruses (eg, mumps, rubella,
Coxsackie B4), toxic chemicals, exposure to cow's milk in
infancy contains bovine serum albumin), and cytotoxins
 Nitrosamines found in smoked meat and fish and coffee, are
proposed diabetogenic

 Roughly 5-15% of all cases of diabetes are type 1 DM. It is the

most common metabolic disease of childhood, with a yearly
incidence of 15 cases per 100,000 people younger than 18 years
EPIDEMIOLOGY
 Race
 Type 1 DM is more common among non-Hispanic whites,
followed by African Americans and Hispanic Americans. It is
comparatively uncommon among Asians.
 Sex
 Type 1 DM is more common in men than in women.
 Age
 Type 1 DM usually starts in children aged 4 years or older, with
the peak incidence of onset at age 11-13 years, coinciding with
early adolescence and puberty. Also, a relatively high incidence
exists in people in their late 30s and early 40s, when it tends to
present in a less aggressive manner,
TYPE 2 DM(NIDDM)
 Commonly occurs in subjects who are obese, insulin resistant and
relative insulin deficiency.
PATHOPHYSIOLOGY:
 Hyperglycemia is produced by lack of endogenous insulin, which is
either absolute, as in type 1 diabetes mellitus, or relative, as in type
2 diabetes mellitus. Relative insulin deficiency usually occurs
because of resistance to the actions of insulin in muscle,
adipocytes, and the liver and an inadequate response by the
pancreatic beta cell. This pathophysiologic abnormality results in
decreased glucose transport in muscle, elevated hepatic glucose
production, and increased breakdown of fat.
 Insulin resistance may be due to any of the following: abnormal
insulin molecule, excess amount of circulating antagonists, or target
tissue deffects.
 Insulin resistance→ ↑blood glucose →↑insulin secretion
AETIOLOGY
 Genetics: Genetic factors are more important
in the aetiology of type 2 than type 1 dm,as
shown by studies in monozygotic twins where
concordance rates for type 2 dm
approaches100%.

 The genetics of type 2 diabetes are complex

and not completely understood, but
presumably this disease is related to multiple
genes
 Environmental factors: Overeating,
combined with obesity and underactivity is
associated with type 2 DM.
 Although the majority of middle aged diabetic
people are obese, only a few obese people
develop DM.
 Obesity probably acts as a diabetogenic
factor, through increasing resistance to the
action of insulin in those genetically
predisposed to develop type2 DM.
 Age is an important risk factor for type 2 DM.Over 70% of all
cases of dm occur after the age of 50yrs. Type 2 DM was
principally a disease of the middle aged and elderly, affecting
10% of the population over the age of 65.
 While type 2 diabetes mellitus traditionally has been thought to
affect individuals older than 40 years, it is being recognized
increasingly in younger persons, particularly in highly susceptible
racial and ethnic groups. In some areas, more type 2 than type 1
diabetes mellitus is being diagnosed in prepubertal children,
teenagers, and young adults. Type 2 diabetes mellitus is
observed even in some obese children. Virtually all cases of the
disease in older individuals are type 2 diabetes mellitus.
 Pregnancy:
 During normal pregnancy, insulin sensitivity is reduced through
the action of placental hormones, and this affects glucose
tolerance. Gestational diabetes refers to hyperglycemia occurring
for the first time during pregnancy.
 Race
 The prevalence of type 2 diabetes mellitus varies widely among
various racial and ethnic groups. Type 2 diabetes mellitus is
becoming virtually pandemic in some groups of Native
Americans and Hispanic people. Recent work suggests more
retinopathy and nephropathy in blacks, Native Americans, and
Hispanic groups.
 Sex
 Type 2 diabetes mellitus is slightly more common in older women
than men.
CLINICAL FEATURES OF DM
 The most common symptoms of diabetes mellitus (DM) are
polyuria, polydipsia, and polyphagia, along with lassitude,
nausea, and blurred vision, all of which are due to the
hyperglycemia itself.
 Polyuria and thirst: Polyuria is due to osmotic diuresis secondary
to hyperglycemia. Thirst is due to the hyperosmolar state and
dehydration.
 Polyphagia with weight loss: The weight loss with a normal or
increased appetite is due to depletion of water and a catabolic
state with reduced glycogen, proteins, and triglycerides.
 Fatigue and weakness: This may be due to muscle wasting from
the catabolic state of insulin deficiency, hypovolemia, and
hypokalemia.
 Muscle cramps: This is due to electrolyte imbalance.
 Nocturnal enuresis: Severe enuresis secondary to polyuria can be an
indication of onset of diabetes in young children.
 Blurred vision: This also is due to the effect of the hyperosmolar state on the
lens and vitreous humor. Glucose and its metabolites cause dilation of the
lens, altering its normal focal length.

 Gastrointestinal symptoms: Nausea, abdominal discomfort or pain, and

change in bowel movements may accompany acute DKA. Chronic
gastrointestinal symptoms in the later stage of diabetes are due to visceral
autonomic neuropathy.

 Patients may maintain their normal weight or exhibit wasting, depending on

the interval between the onset of the disease and initiation of treatment.
 Peripheral neuropathy: This presents as numbness and tingling in
both hands and feet, in a glove and stocking pattern. It is bilateral,
symmetric, and ascending neuropathy, which results from many
factors, including the accumulation of sorbitol in peripheral sensory
nerves due to sustained hyperglycemia.

 Symptoms at the time of the first clinical presentation can usually be

traced back several days to several weeks; however, beta cell
destruction may have started months, or even years, before the
onset of clinical symptoms.
INVESTIGATIONS
A. URINE FOR :
 Sugar; Is a usual procedure for detecting diabetes
using sensitive glucose specific dipstick methods.
 Disadvantage of this procedure is the individual
variation in renal threshold for glucose
 Low renal threshold for glucose is common during
pregnancy and in young people and is more
frequent cause of glycosuria than diabetes.
 Protein; in diabetic nephropathy
 Dipstick testing for albumin- microalbimininuria
indicates Diabetic nephropathy
 Ketones; in diabetic ketoacidosis.
Test done using dipsticks

Other causes of ketonuria

 Fasting and streneous exercise for long
 Vomiting repeatedly
 Eating a high fat and low Carbohydrate diet

Ketonuria alone then not diagnostic of DM, but if associated

with glycosuria.
B. RANDOM/FASTING BLOOD GLUCOSE:
 Diagnosis of DM may be confirmed by
RBG/FBG.
 DM is defined by a FBG of 7.0mmol/l and above
or RBG of 11.1mmol/l and above.
C. ORAL GLUCOSE TOLERANCE TEST:
 When RBG /FBG values are elevated but are not
diagnostic of diabetes, oral glucose tolerance test is
performed.
 The indications for OGTT:
 FBG 6.1-6.9mmol/l
 RBG 7.0-11.0mmol/l
 The pancreas is challenged with 75mg of oral
glucose. if insulin is adequate, at 2hrs, blood
glucose will be within normal range. If insulin is not
adequate, blood glucose will be above normal rage.
D. GLYCATED Hb:
 Provides an accurate and objective measure
of glycaemic control over a period of weeks
to months. It is utilized as an assessment of
glycaemic control in a patient with known DM,
but is not sufficiently sensitive to make
diagnosis of DM as it can be normal in
patients with impaired glucose tolerance
 Blood lipids: Total cholesterol, HDL and LDL.
Should be measured in the fasting state.
COMPLICATIONS OF DIABETES
 SHORT TERM
 LONG TERM
SHORT TERM

 Hypoglycaemia
Blood glucose < 3.5mmol/L
Occurs as manifestation of treatment than disease
itself in those on insulin and infrequently
sulphonylureas.
Signs and symptoms;
 Autonomic – sweating, hunger, trembling, anxiety,
pounding heart
 Neuroglycopenic – confusion, drowsiness, speech
difficulty, incoordination, inability to concentrate.
 Non specific – nausea, tiredness, headache
 Diabetic ketoacidosis
Occurs mainly in type I DM. Caused by
insulin deficiency and increased catabolic
hormones leading to hepatic overproduction
of glucose and ketone bodies.
Cardinal features
 Hyperglycaemia
 Hyperketonaemia
 Metabolic acidosis
 Non ketotic hyperosmolar diabetic coma
Characterised by severe hyperglycaemia >
50 mmol /L without signs of hyperketonaemia
or acidosis. Affects elderly type 2 DM
especially previously undiagnosed.
Signs/symptoms
 Severe dehydration
 Pre renal uraemia
 Lactic acidosis.
Occurs in patients who are taking metformin.
S/S
 Increased breathing (but not dehyadrated)
 Other features; ketonuria -mild/absent, low
plasma bicarbonate, pH < 7.2, increased
blood lactate > 5 mmol/L
 Acute circulatory failure
LONG TERM
These are associated with vascular changes.
Thickening of the capillary or arteriolar
basement membrane, and increased capillary
permeability.
They include diabetic retinopathy,
Nephropathy, neuropathy, diabetic foot and
Diabetic heart disease.
 Diabetic retinopathy
Is the most common cause of blindness in diabetic
adults btn 30 – 65 yrs
Pathogenesis
Hyperglycaemia leads to increased retinal blood flow
and metabolism, this has effect on retinal endothelial
cell . Uncontrolled blood flow leads to increased
production of vasoactive substances and endothelia
cells proliferation leading to capillary closure. Hypoxia
ensues stimulating growth factors production including
vascular endothelia growth factors.
 Diabetic nephropathy
About 30% of patients with type I DM have
developed DN after 20 yrs.
Commonest cause of end stage renal failure.
 Diabetic neuropathy
 Early and common complication affecting about
30% of diabetics, and symptomless in majority
 Diabetic foot
Aetiology
 Foot ulceration due to a minor trauma in the presence of somatic
neuropathy, autonomic neuropathy and peripheral vascular disease
lead to increased foot pressure, callus formation, infection.
Basement membrane thickening limits migration of WBC to site of
injury.
Clinical features
 Neuropathy - paraesthesia, numbness, warm,intact pulse, pain
 Ischaemia – claudication, rest pain ,cold,pulseless.
 Structural damage - ulcer, sepsis, abscess, osteomylitis, gangrene
and charcot joint.
MANAGEMENT
 DIETARY MANAGEMENT
General principles
Types of Diabetic Diet
 PHARMACOLOGICAL MANAGEMENT

 LONG TERM SUPERVISION

 Three methods of treatment are available for
diabetic patients, Diet only, Diet and OHDs,
and Diet and insulin.
 Determinants for the required treatment are
Age and Weight of the patient at time of
diagnosis.
 Also depent on type of DM,modifiable risk
factors,and level of blood glucose
 GOALS
 Abolish symptoms of hyperglycaemia
 Avoid hypoglycaemia due to drugs
 Avoid atherogenic compliction
 Achieve weight reduction in obese patients
DIET
 High fibre CHO,such as;brown bread,brown
wheat,matoke,irish
potato,soghum,unpolished maize flour.
 No simple sugar juices
 Adequate protein,unsaturated oil
 Moderate salt intake
 Quit smoking(vascular ds risk factor)
ORAL HYPOGLCAEMIC DRUGS
 Sulphonylureas
 Biguanides
SULPHONYLUREAS
 Indicated in non obese pt with type 2 DM who fail to
respond to dietary measures alone
 Stimulate release of insulin from pancreatic beta
cells
 Reduce hepatic release of glucose
 Diminish insulin resistances
 Indicated in non obese diabetic patients who fail to
respond to dietary measures alone
 Different compounds differ in their potency,duration
of action and its cost.
 include,chlorpropamide(diabenes) 250mg od
1/12and Tolbutamide 500mg od 1/12
Side effects of sulphonylureas
 May cause severe and prolonged
hypoglycaemia due to biological half life of
about 36 hrs
BIGUANIDES
 Mechanism of action is not precisely defined
 BUT,Known to increase insulin sensitivity
 Less widely used than sulphonylureas
 increase peripheral glucose uptake
 impair glucose absorption from the gut
 inhibit hepatic gluconeogenesis
 May be used in obese diabetic patient
 Contraindicated in patients with renal or hepatic problem and
those with excessive alcohol consumption in whom the risk of
lactis acidosis is signifcant increased
 Metformin is the only biganide available
 Metformin 500mg od 1/12
INSULIN
 Indications
 In DKA
 Severe infections;coz metabolic rate ↑ thus insulin
requirement ↑
 Diabetic pt undergoing major surgery
 During pregnancy,coz OHD are teratogenic
 When using high dose of drugs like corticosteroids
 Failure of OHD
 Hyperosmolar non ketotic coma
 In type 1DM
INSULIN DELIVERY
 Insulin is administerd subcutenously on
anterior abdominal wall,upper arms,outer
thighs and buttocks
 Is administered using a disposible plastic
syringe with a fine needlle.
REGIME.
 Twice daily administration of short acting and
intermediate acting insulin is most common and
simplest.
 Two thirds of the required daily dose is given in the
morning,in which two thirds is lente(long acting) and
one third is soluble(short acting).
 The remaining one third is given in the evening,in
the ratio of 2;1,lente;soluble.
 The formulation is designed to mimic the nomal
variation of insulin in normal individual
Complications of insulin
 Hypoglycaemia
 Allergic manifestations
 Somogyi effect;this follow high dosage of insulin in the evining,the pt will
go to hypoglycaemia at night .as the result the body pour counter
regulatory hormones resulting to morning hyperglycaemia.
 Glucagon acts on the liver to stimulate glycogenolysis and
gluconeogenesis and is probably the earliest and most important
hormone in the Somogyi phenomenon.
 Epinephrine increases the delivery of substrates from the periphery;
decreases insulin release; stimulates glucagon release; inhibits glucose
utilization by several tissues; and stimulates a warning system with
sweating, anxiety, and tachycardia.
 Cortisol may aid in prolonged and severe cases of Somogyi
phenomenon by blocking glucose use and stimulating hepatic glucose
output.
 Growth hormone is similar to cortisol
FOLLOW UP VISIT
 Diabetic patients should be seen at a regular
intervals for the remainder of their lives.
 The following should be checked.
 Body weight
 urinalysis
 glycaemic contro,
 hpoglycaemic episodes
 vision
 lower limbs.
THANX