Liza Yudistira Yusan,S.Farm.,M.Farm-Klin.,Apt.

Universitas Hang Tuah

2016
 Diabetes mellitus (DM) is a chronic condition that is
characterised by raised blood glucose levels
(Hyperglycemia).
 KRONIK

Penyakit Potensial
metabolik Diabetes mengganggu
utama pada Mellitus tumbuh
anak kembang

Pengobatan
Mandiri
 INSULIN

Assessment
& Monitoring NUTRITION
EXERCISES
Glycemic OR DIET

Control

EDUCATION
 Glucose homeostasis
Body
cells
Insulin take up more
glucose

Beta cells
of pancreas stimulated
to release insulin into
the blood Liver takes Blood glucose level
up glucose declines to a set point;
High blood and stores it as stimulus for insulin
glucose level glycogen release diminishes

STIMULUS:
Rising blood glucose
level (e.g., after eating
a carbohydrate-rich
meal) Homeostasis: Normal blood glucose level
(about 90 mg/100 mL) STIMULUS:
Declining blood
glucose level
(e.g., after
skipping a meal)

Blood glucose level

rises to set point; Alpha
stimulus for glucagon cells of
release diminishes pancreas stimulated
to release glucagon
into the blood
Liver
breaks down
glycogen and Glucagon
releases glucose
to the blood
 Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose
Metabolism and Regulation: Beyond Insulin and Glucagon.
Diabetes Spectrum 2004;17(3):183-90.
 Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose Metabolism and
Regulation: Beyond Insulin and Glucagon. Diabetes Spectrum
2004;17(3):183-90.
Diabetes is huge and
growing problem,
and the costs of
society are high and
escalating
 INDONESIA
??

Jumlah Penderita DM Indonesia

A
Terbanyak ke-5 di Dunia
B
IDF Diabetes Atlas, 2013 penderita DM di
Indonesia mencapai 8.554.155 orang

C
Tahun 2014 diperkirakan naik hingga mencapai
9,1 juta orang, berdasarkan data 2015 (Perkeni)

D
Tahun 2035 penderita DM diprediksi 14,1 juta orang dg
tingkat prevalensi 6,67%  populasi orang dewasa
 Oversecretion of insulin
to compensate for insulin
resistance1,2
Glucotoxicity
2
Lipotoxicity
3

Chronic Pancreas High circulating

hyperglycemia free fatty acids

-cell dysfunction
1Boden G & Shulman GI. Eur J Clin Invest 2002; 32:14–23.
2Kaiser N, et al. J Pediatr Endocrinol Metab 2003; 16:5–22.
3Finegood DT & Topp B. Diabetes Obes Metab 2001; 3 (Suppl. 1):S20–S27.
 Poliuria, Polifagia, Polidipsia, BB turun,  GEJALA KHAS
 Luka sulit sembuh, kebal rasa di kaki atau kesemutan
 Pandangan kabur
• Any one test should be confirmed with a second
test, most often fasting plasma glucose (FPG).

• This criteria for diagnosis should be confirmed by

repeating the test on a different day.
 A1c > 6,5 % Without fasting

Fasting gluc > 126 mg/dl Fasting : 8 -12 hours

Blood glucose 2 j PP 2 hours after consuming glucose 75

> 200 mg/dl gram

Blood glucose at random

Without fasting
> 200

MKSAP13 Endocrinology and Metabolism. American College of Physicians 2004

Overweight and obesity are diagnosed by
measuring weight and height (Body Mass Index
(BMI):
Weight in Kg
BMI =
Height in metres2

Normal = 20-25
Overweight = 25-30
Obese = more than 30

Everyone should know their BMI!!

 Usually diagnosed in children and young adults, although
disease onset can occur at any age.
 Previously known as “juvenile diabetes” or insulin-
dependent diabetes mellitus (IDDM).
 In this type of diabetes, the body does not produce
insulin.
 Insulin is required in order for the body to properly use
sugar, in the form of glucose.
 Sugar is the basic fuel for the cells in the body.
 Insulin’s role is to take the sugar from the blood and
carry it into cells where it can be used to provide energy
for the body to work.
 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.
 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.
 Type 1 DM
 There are four stages in the development of
Type 1 DM:

1. Preclinical period with positive -cell antibodies

2. Hyperglycemia when 80-90% of the

β- cells are destroyed.

3. Transient remission (honeymoon phase).

3. Establishment of the disease

Time (years)
Cryer PE. J Clin Invest. 2006;116(6):1470-1473.
Pharmacological effect:
Anabolic Anticatabolic
- Glucose uptake
- Inhibits gluconeogenesis
- Glycogen synthesis
- Lipogenesis
- Inhibits glycogenolysis
- Inhibits lipolysis
- Protein synthesis
- Inhibits proteolysis
- Triglyceride uptake - Inhibits fatty acid oxidation
 The synthesis and release
of insulin is modulated by:

1. Glucose (most
important), AAs, FAs
and ketone bodies
stimulate release.
2. Glucagon and
somatostation inhibit
relases
3. α-Adrenergic
stimulation inhibits
release (most
important).
4. β-Adrenergic
stimulation promotes
release.
5. Elevated intracellular
Ca2+promotes release.
 Insulin binds to specific
high affinity membrane
receptors with tyrosine
kinase activity
 Phosphorylation cascade
results in translocation of
Glut-4 (and some Glut-1)
transport proteins into the
plasma membrane.
 It induces the transcription
of several genes resulting in
increased glucose
catabolism and inhibits the
transcription of genes
involved in
gluconeogenesis.
 Insulin promotes the uptake
of K+into cells.
Liver Muscle Adipose
↓ glucose production ↑ Glucose transport ↑ glucose transport

↑ glycolysis ↑ glycolysis ↑ lipogenesis&

lipoprotein lipase
activity
↑ TG synthesis ↑ glycogen deposition ↓ intracellular lipolysis

↑ Protein synthesis ↑ protein synthesis

 Short term:
◦ Symptoms of diabetes
◦ Dehydration
◦ Diabetic Coma
◦ Infections
◦ Ketoacidosis
◦ HHS (Hyperglycemic Hyperosmolar State)

 Long term:
◦ Kidney
◦ Eye
◦ Heart
◦ Circulation
◦ Amputation
 Ketoacidosis

 Results from a failure to treat

hyperglycemia
 Rarely occurs in individuals with type
2 diabetes
 It is a serious condition that can lead
to diabetic coma or even death.
 Treatment for this condition usually
takes place in the hospital.
 You can prevent this by learning the
warning signs and by checking blood
and urine regularly.
 Thirst or a very dry  Nausea, vomiting,
mouth or abdominal pain
 Frequent urination  A hard time breathing
 High blood glucose (short, deep breaths)
(sugar) levels  Fruity odor on breath
 High levels of ketones  A hard time paying
in the urine attention or confusion
 Constantly feeling
tired
 Dry or flushed skin
Microvasuclar:
damage to eyes,
kidneys, nerves
(retinopathy,
nephropathy,
neuropathy)

Macrovascular: 2X risk
for heart attack and
stroke, peripheral
vascular disease
 20 Retinopathy
15 Nephropathy
Neuropathy
Relative Risk (%)

13 Microalbuminuria
Aim for AIc of < 7%
11
9
7
5
3
1
6 7 8 9 10 11 12
A1c (%)
DCCT, Diabetes Control and Complications Trial.
1. Adapted from Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243-254.
2. DCCT. N Eng J Med. 1993;329:977-986.
3. DCCT. Diabetes. 1995;44:968-983.
 Blood test that measures the amount of glucose
that has been incorporated into the hemoglobin
protein of the red blood cell (RBC).
 Reflects the lifespan of a RBC, so test will reveal
the effectiveness of diabetes therapy for the
preceding 8-12 weeks.
 HbA1c levels remain more stable than sugar
levels.
 Not affected by short-term fluctuations in sugar
 Normal is 4-6%
 Evaluated periodically (1-2 per year if well
controlled, more frequently if not)
 Definition: plasma glucose <70 mg/dL
 A complication of treatment!
 40 mg/dL is the minimum for brain function
 < 40 mg/dL = Risk for diabetic coma,
seizures
 Heat  Visual
palpitations disturbances
 Confusion  Seizure
 Tremor  Loss of
 Sweating Consciousness
 Anxiety
 Hunger
 Glucose
◦ 15 grams of simple carbohydrates
 8oz. fruit juice
 3 glucose tabs
 1 tablespoon honey

◦ IV dextrose in patients with lost consciousness

 Glucagon injection
◦ Stimulates glycogen breakdown
 Insulin must be administered into the
subcutaneous (sc) between fat & muscle &
avoid injection into fat or muscle.

 Can be administered by needle and syringe

or by pen device
Administration of insulins are arranged to mimic the normal basal,
prandial and post-prandial secretion of insulin. Short acting forms
are usually combined with longer acting preparations to achieve
this effect.
1. Regular insulin: short acting, soluble, crystalline zinc insulin is usually
given subcutaneously; it rapidly lowers glucose levels. All regular
insulin is now made using genetically engineered bacteria; cow and
pig no longer used.
2. Lispro, Aspart&Glulisine preparations are classified as ultrashort
acting forms with onset more rapid than regular insulin and a shorter
duration. These are less often associated with hypoglycemia. Lispro
insulin is given 15 minutes prior to a meal and has its peak effect 30-
90 minutes after injection (vs. 50-120 minutes for regular insulin).
3. Glulisine can be given anywhere from 15 minutes prior to 20 minutes
after beginning a meal.
1. Lente insulin: This is a
amorphous precipitate of
insulin with zinc ion
combined with 70%
ultralente insulin. Onset is
slower but more sustained
than regular insulin. It
cannot be given IV ( this
has not been produced
since 2005).

2. Isophane NPH insulin:

Neutral protamine
Hagedorn insulin is a
suspension of crystalline
zinc insulin combined with
protamine (a polypeptide).
The conjugation with
protamine delays its onset
of action and prolongs it
effectiveness. It is usually
given in combination with
regular insulin.
1.Ultralente: a
suspension of zinc Pump vs. Standard Insulin Therapy
insulin forming large
particles which
dissolve slowly,
delaying onset and
prolonging duration
of action.
2.Insulin glargine:
Precipitation at the
injection site extends
the duration of
action of this
preparation.
3. Detemir insulin: has
a FA complexed with
insulin resulting in
slow dissolution.
 Insulin Preparations and Treatment
 Various types of insulin are characterized
by their onset and duration of action
 Rapid Rapid Rapid
(lispro, (lispro, (lispro,
aspart, aspart, aspart,
Plasma insulin

glulisine) glulisine) glulisine)

Glargine or
detemir

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Breakfast Lunch Dinner Bed

1. Hypoglycemia may occur due to insulin overdose,
insufficient caloric intake (missed meal, improper
meal content, delayed meal, etc.). Ethanol
consumption promotes hypoglycemic response.
Symptoms: ↑ HR, diaphoresis, MS changes,
anything (diabetics are usually really good at
recognizing hypoglycemic symptoms).
2. Hypokalemia: insulin draws K+into the cell with
glucose (hyperglycemia with normal K+).
3. Anaphylaxis: when sensitized to non-human
insulin gets non-human insulin (now rare).
4. Lipodystrophy at injection site
5. Weight gain
6. Injection complications
 Diabetes
Management
Algorithm
 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.
 An effective insulin regimen
 Monitoring of glucose
 As flexible with food and activity as possible
 Must remember
◦ Young children need routine and rules
◦ Young children need to develop autonomy
◦ Young children need to explore and experience
◦ Young children need to begin to make decisions
 Self-monitoring of blood glucose
◦ Extremely useful for outpatient monitoring specially for
patients who need tight control for their glycemic state.
◦ A portable battery operated device that measures the
color intensity produced from adding a drop of blood to
a glucose oxidase paper strip.
◦ e.g. One Touch, Accu-Chek, DEX, Prestige and
Precision.
Monitoring
 Desired outcome
- Relieve symptoms
- Reduce mortality
- Improve quality of life
- Reduce the risk of microvascular and
macrovascular disease complications
- Macrovascular complications:
Coronary heart disease, stroke and peripheral vascular
disease
- Microvascular Complications:
Retinopathy, nephropathy and neuropathy
Treatment

- Near normal glycemic control reduce the

risk of developing microvascular disease
complications

- Control of the traditional CV risk factors

such as smoking, management of
dyslipidemia, intensive BP control and
antiplatelet therapy.
- Medications
- Dietary and exercise modification
- Regular complication monitoring
- Self monitoring of blood glucose
- Control of BP and lipid level
Drugs interfering with glucose tolerance
 The most significant interactions are with drugs that alter
the blood glucose level:
- Diazoxide
- Thiazide diuretics
- Corticosteroids
- Oral contraceptives
- Streptazocine
- Phenytoin

 All these drugs increase the blood glucoseconcentration.

 Monitoring of BG is required