DIABETES MELLITUS

WAHYUDI, S.Farm., Apt.

 Menurut International Diabetes Federation (IDF)
terdapat 382 juta orang yang hidup dengan diabetes
didunia pada tahun 2013.
 Pada tahun 2035 jumlah tersebut diperkirakan akan
meningkat menjadi 592 juta orang
 WHAT IS DIABETES?

 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 etiology characterized by chronic hyperglycaemia
with disturbances of carbohydrate, fat and protein metabolism
resulting from defects in insulin secretion, insulin action, or
both.
PATHOPHISIOLOGY

 Type 1 DM accounts for 5% to 10% of all diabetes cases. It

generally develops in childhood or early adulthood and
results from immunemediated destruction of pancreatic β-
cells, resulting in an absolute deficiency of insulin.
 Hyperglycemia occurs when 80% to 90% of β-cells are
destroyed.
 The factors that initiate the autoimmune process are
unknown, but the process is mediated by macrophages and T
lymphocytes with circulating autoantibodies to various β-cell
antigens (e.g., islet cell antibody, insulin antibodies).
CONTINUED....
 Type 2 DM accounts for as many as 90% of DM cases
and is usually characterized by the presence of both
insulin resistance and relative insulin deficiency.
 Insulin resistance is manifested by increased lipolysis
and free fatty acid production, increased hepatic glucose
production, and decreased skeletal muscle uptake of
glucose.
 β-Cell dysfunction is progressive and contributes to
worsening blood glucose control over time.
 Type 2 DM occurs when a diabetogenic lifestyle
(excessive calories, inadequate exercise, and obesity) is
superimposed upon a susceptible genotype.
 DIAGNOSIS
 Screening for type 2 DM should be performed every 3 years in all
adults beginning at the age of 45. Testing should be considered at an
earlier age and more frequently in individuals with risk factors (e.g.,
family history of DM, obesity, signs of insulin resistance).
 The recommended screening test is a fasting plasma glucose (FPG).
Normal FPG is less than 100 mg/dL (5.6 mmol/L).
 CONTINUED...
 Impaired fasting glucose is defined as FPG of 100 to 125 mg/dL
(5.6 to 6.9 mmol/L).
 Impaired glucose tolerance is diagnosed when the 2 hour
postload sample of the oral glucose tolerance test is between
140 and 199 mg per dL (7.8 to 11.0 mmol/L).
 A1C should be considered an additional optional diagnostic
criterion, not the primary criterion for diagnosis of diabetes.

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 SYMPTOMPS
 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.
TYPE OF DIABETES
Diabetes arises when the beta cells in the pancreas fail to
produce enough of the hormone insulin
type 1 diabetes.

Or when the body cannot effectively use the insulin

produced type 2 diabetes.
GESTATIONAL DIABETES
 A form of glucose intolerance that is diagnosed in some
women during pregnancy.
 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.
INSULIN AND DIABETES
When a person has diabetes, either:
 their pancreas does not produce the insulin they need (type 1 diabetes).
 or their body cannot use this insulin effectively
(type 2 diabetes).
This leads to an increase in the amount of glucose in the blood. This high
concentration of glucose or ’high blood sugar’ is termed hyperglycaemia.
 TISSUE DAMAGE
 Chronic elevation of blood glucose eventually leads to
tissue damage.
 The kidneys, eyes, peripheral nerves and vascular tree
manifest the most significant diabetic complications.
 The mechanism for this is complex and not yet fully
understood. It involves:
 The direct toxic effects of high glucose levels
 The impact of elevated blood pressure

 Abnormal lipid levels

 Functional and structural abnormalities of small blood vessels

Type 2 diabetes,
the metabolic syndrome and cardiovascular disease in Europe
THE MAJOR DIABETIC COMPLICATIONS
Stroke Visual impairment:
(cerebrovascular disease) diabetic retinopathy,
cataract and glaucoma

Heart disease
(cardiovascular disease)
Bacterial and fungal Kidney disease
infections of the skin (diabetic nephropathy)
Severe hardening of
the arteries (atherosclerosis) Autonomic neuropathy
(including slow emptying
Sexual dysfunction
of the stomach and diarrhea)

Poor blood supply to lower limbs

(peripheral vascular disease)

Necrobiosis lipidoica
Sensory impairment
(peripheral neuropathy)
Gangrene
Ulceration
THE SHORT TERM EFFECTS OF
DIABETES
 Out-of-control diabetes, when severe, leads to the body using stored
fat for energy and a subsequent build-up of acids (ketone bodies) in
the blood. This is known as ketoacidosis and is associated with very
high glucose levels. It requires emergency treatment and can lead to
coma and even death.
 Recurrent or persistent infections (including tuberculosis).
 Both hyperglycaemia and hypoglycaemia (abnormally low blood
glucose resulting from treatment) may cause coma and, if untreated,
may be fatal.
THE LONG TERM EFFECTS OF DIABETES
The long term effects of diabetes can be divided into
 Macrovascular complications affect the larger blood vessels, such
as those supplying blood to the heart, brain and legs. The most
common macrovascular fatal complication is coronary artery
disease. Strokes are also a common cause of disability and death in
people with diabetes.
 Microvascular complications affect the small blood vessels, such
as those supplying blood to the eyes and kidneys. The microvascular
complications of diabetes are retinopathy, nephropathy and
neuropathy.
MANAGEMENT OF DM
 The major components of the treatment of diabetes are:

A ●
Diet and Exercise

Oral hypoglycaemic
B
●

therapy

C ●
Insulin Therapy
A. Diet and Exercise
THERAPEUTIC LIFESTYLE CHANGES
Parameter Treatment Goal

Weight loss
(for overweight and Reduce by 5% to 10%
obese patients)

150 min/week of moderate-intensity exercise (eg, brisk walking) plus

Physical activity
flexibility and strength training

• Eat regular meals and snacks; avoid fasting to lose weight

• Consume plant-based diet (high in fiber, low calories/glycemic
index, and high in phytochemicals/antioxidants)
Diet • Understand Nutrition Facts Label information
• Incorporate beliefs and culture into discussions
• Use mild cooking techniques instead of high-heat cooking
• Keep physician-patient discussions informal

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Carbohydrate Specify healthful carbohydrates (fresh fruits and vegetables, legumes, whole grains); target
7-10 servings per day
Preferentially consume lower-glycemic index foods (glycemic index score <55 out of 100:
multigrain bread, pumpernickel bread, whole oats, legumes, apple, lentils, chickpeas,
mango, yams, brown rice)
Fat Specify healthful fats (low mercury/contaminant-containing nuts, avocado, certain plant
oils, fish)
Limit saturated fats (butter, fatty red meats, tropical plant oils, fast foods) and trans fat;
choose fat-free or low-fat dairy products
Protein Consume protein in foods with low saturated fats (fish, egg whites, beans); there is no need
to avoid animal protein
Avoid or limit processed meats
Micronutrients Routine supplementation is not necessary; a healthful eating meal plan can generally
provide sufficient micronutrients
Chromium; vanadium; magnesium; vitamins A, C, and E; and CoQ10 are not 19
recommended for glycemic control
Vitamin supplements should be recommended to patients at risk of insufficiency or
deficiency
B. ORAL HYPOGLYCAEMIC THERAPY
SULFONILUREA

 Sulfonylureas exert a hypoglycemic action by

stimulating pancreatic secretion of insulin. All
sulfonylureas are equally effective in lowering blood
glucose when administered in equipotent doses. On
average, the A1C will fall by 1.5% to 2% with FPG
reductions of 60 to 70 mg/dL (3.3 to 3.9 mmol/L).
 The most common side effect is hypoglycemia

 Weight gain is common; less common adverse effects

include skin rash, hemolytic anemia, GI upset, and
cholestasis.
MEGLITINIDE

 Similar to sulfonylureas, meglitinides lower glucose by

stimulating pancreatic insulin secretion, but insulin release is
glucose dependent and diminishes at low blood glucose
concentrations.
 Hypoglycemic risk appears to be less with meglitinides than
with sulfonylureas.
 The average reduction in A1C is about 0.8% to 1%. These
agents can be used to provide increased insulin secretion
during meals (when it is needed) in patients who are close to
glycemic goals.
 They should be administered before each meal (up to 30
minutes prior).
 METFORMIN

 Metformin is the only biguanide available in the United States. It

enhances insulin sensitivity of both hepatic and peripheral (muscle) tissues.
This allows for increased uptake of glucose into these insulin-sensitive
tissues.
 It reduces plasma triglycerides and low-density lipoprotein (LDL) cholesterol
by 8% to 15% and modestly increases highdensity lipoprotein (HDL)
cholesterol (2%). It does not induce hypoglycemia when used alone.
 Metformin should be included in the therapy for all type 2 DM patients (if
tolerated and not contraindicated) because it is the only oral
antihyperglycemic medication proven to reduce the risk of total mortality and
cardiovascular death.
 The most common adverse effects are abdominal discomfort, stomach upset,
diarrhea, anorexia, and a metallic taste. These effects can be minimized by
titrating the dose slowly and taking it with food.
 THIAZOLIDINEDIONES
These agents activate PPAR-γ, a nuclear transcription factor
important in fat cell differentiation and fatty acid metabolism.
 PPAR-γ agonists enhance insulin sensitivity in muscle, liver,
and fat tissues indirectly. Insulin must be present in significant
quantities for these actions to occur.
ALFA GLUKOSIDASE INHIBITOR
 These agents prevent the breakdown of sucrose and
complex carbohydrates in the small intestine, thereby
prolonging the absorption of carbohydrates.
 The net effect is a reduction in the postprandial glucose
concentrations (40 to 50 mg/dL) while fasting glucose
levels are relatively unchanged (about 10% reduction).
C. INSULIN THERAPY
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.
INSULIN REGIMENS
 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.
SELF-CARE

 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
TERIMAKASIH...