Diabetes Melitus (DM)

Oleh :
NUR ALIM
 Pengertian
Diabetes mellitus (DM) is a group of metabolic
disorders characterized by hyperglycemia and
abnormalities in carbohydrate, fat, and
protein metabolism.
 Metabolisme karbohidrat,lemak dan
protein
An understanding of the signs and symptoms associated with
diabetes is based on a knowledge of glucose metabolism and the
metabolic effects of insulin in nondiabetic and diabetic subjects
during the fed (postprandial) and fasting (postabsorptive) states.
Homeostatic mechanisms maintain plasma glucose concentrations
between 55 and 140 mg/dL (3.17.8 mmol/L). A minimum
concentration of 40 to 60 mg/dL (2.23.3 mmol/L) is required to
provide adequate fuel for the central nervous system, which uses
glucose as its primary energy source and is independent of insulin
for glucose utilization. When blood glucose concentrations exceed
the reabsorptive capacity of the kidneys (180 mg/dL), glucose
spills into the urine, resulting in a loss of calories and water. Muscle
and fat, which use glucose as a major source of energy, require
insulin for glucose uptake. If glucose is unavailable, these tissues are
able to use other substrates such as amino acids and fatty acids for
fuel
 Postprandial Glucose Metabolism in
the Nondiabetic Individual
After food is ingested, blood glucose concentrations rise and
stimulate insulin release. Insulin is the key to efficient glucose
utilization. It promotes the uptake of glucose, fatty acids, and amino
acids and their conversion to storage forms in most tissues. Insulin
also inhibits hepatic glucose production by suppressing glucagon
and its effects. In muscle, insulin promotes the uptake of glucose
and its storage as glycogen. It also stimulates the uptake of amino
acids and their conversion to protein In adipose tissue, glucose is
converted to free fatty acids and stored as triglycerides. Insulin also
prevents a breakdown of these triglycerides to free fatty acids, a
form that may be transported to other tissues for utilization. The
liver does not require insulin for glucose transport, but insulin
facilitates the conversion of glucose to glycogen and free fatty acids.
The latter are esterified to triglycerides, which are transported by
very-low-density lipoproteins (VLDLs) to adipose and muscle tissue.
 Fasting Glucose Metabolism in the
Nondiabetic Individual
As blood glucose concentrations drop toward normal during the
fasting state, insulin release is inhibited.
Simultaneously, a number of counter-regulatory hormones that
oppose the effect of insulin and promote an increase in blood sugar
are released (e.g., glucagon, epinephrine, growth hormone
glucocorticoids).
As a result, several processes maintain a minimum blood glucose
concentration for the central nervous system.
Glycogen in the liver is broken down into glucose (glycogenolysis).
Amino acids are transported from muscle to liver, where they are
converted to glucose through gluconeogenesis. Uptake of glucose
by insulin-dependent tissues is diminished to conserve glucose for
the brain. Finally, triglycerides are broken down into free fatty acids,
which are used as alternative fuel sources.
 Diagnosis
Criteria for diagnosis of DM include any one of the following:
1. Classic signs and symptoms of diabetes (polyuria, polydipsia,
ketonuria, and unexplained weight loss) combined with a random
plasma glucose 200 mg/dL (11.1 mmol/L).
2. HbA1C of 6.5% or more
3. Fasting (no caloric intake for at least 8 hours) plasma glucose of 126
mg/dL (7.0 mmol/L) or more
4. Two-hour plasma glucose of 200 mg/dL (11.1 mmol/L) or more
during an oral glucose tolerance test (OGTT) using a glucose load
containing the equivalent of 75 g anhydrous glucose dissolved in
water
5. Random plasma glucose concentration of 200 mg/dL (11.1 mmol/L)
or more with classic symptoms of hyperglycemia or hyperglycemic
crisis
 Patofisiologi diabetes melitus
Type 1 DM (5%10% of cases) usually develops in childhood or early
adulthood and results from autoimmune-mediated destruction of
pancreatic -cells, resulting in absolute deficiency of insulin. The
autoimmune process is mediated by macrophages and T lymphocytes with
autoantibodies to -cell antigens (eg, islet cell antibody, insulin
antibodies).
Type 2 DM (90% of cases) is characterized by a combination of some
degree of 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.
Uncommon causes of diabetes (1%2% of cases) include endocrine
disorders (eg, acromegaly, Cushing syndrome), gestational diabetes
mellitus (GDM), diseases of the exocrine pancreas (eg, pancreatitis), and
medications (eg, glucocorticoids, pentamidine, niacin, -interferon).
Microvascular complications include retinopathy, neuropathy, and
nephropathy.
Macrovascular complications include coronary heart disease, stroke, and
peripheral vascular disease.
Tipe-tipe diabetes melitus
Karakteristik diabetes tipe 1 dan 2
 Diabetes Melitus Tipe 1
Diabetes tipe ini merupakan diabetes yang jarang atau
sedikit populasinya, diperkirakan kurang dari 5-10%
dari keseluruhan populasi penderita diabetes.
Gangguan produksi insulin pada DM Tipe 1 umumnya
terjadi karena kerusakan sel-sel pulau Langerhans
yang disebabkan oleh reaksi otoimun. Namun ada pula
yang disebabkan oleh bermacam-macam virus,
diantaranya virus Cocksakie, Rubella, CMVirus, Herpes,
dan lain sebagainya. Ada beberapa tipe otoantibodi
yang dihubungkan dengan DM Tipe 1, antara lain ICCA
(Islet Cell Cytoplasmic Antibodies), ICSA (Islet cell
surface antibodies), dan antibodi terhadap GAD
(glutamic acid decarboxylase)
 Diabetes Melitus Tipe 1
1. ICCA
ICCA merupakan otoantibodi (autoimun) utama yang
ditemukan pada penderita DM Tipe 1. Hampir 90%
penderita DM Tipe 1 memiliki ICCA di dalam darahnya. Di
dalam tubuh non-diabetik, frekuensi ICCA hanya 0,5-4%.
Oleh sebab itu, keberadaan ICCA merupakan prediktor yang
cukup akurat untuk DM Tipe 1.
ICCA merupakan otoantibodi utama yang ditemukan pada
penderita DM Tipe 1. Hampir 90% penderita DM Tipe 1
memiliki ICCA di dalam darahnya. Di dalam tubuh non-
diabetik, frekuensi ICCA hanya 0,5-4%. Oleh sebab itu,
keberadaan ICCA merupakan prediktor yang cukup akurat
untuk DM Tipe 1.
ICCA tidak spesifik untuk sel-sel pulau Langerhans saja,
tetapi juga dapat dikenali oleh sel-sel lain yang terdapat di
pulau Langerhans.
 Diabetes melitus tipe 1
Sebagaimana diketahui, pada pulau Langerhans kelenjar
pankreas terdapat beberapa tipe sel, yaitu sel , sel dan
sel . Sel-sel memproduksi insulin, sel-sel memproduksi
glukagon, sedangkan sel-sel memproduksi hormon
somatostatin. Namun demikian, nampaknya serangan
otoimun secara selektif menghancurkan sel-sel . Ada
beberapa anggapan yang menyatakan bahwa tingginya titer
ICCA di dalam tubuh penderita DM Tipe 1 justru
merupakan respons terhadap kerusakan sel-sel yang
terjadi, jadi lebih merupakan akibat, bukan penyebab
terjadinya kerusakan sel-sel pulau Langerhans. Apakah
merupakan penyebab atau akibat, namun titer ICCA makin
lama makin menurun sejalan dengan perjalanan penyakit.
 Diabetes melitus tipe 1
2. ICSA
Otoantibodi terhadap antigen permukaan sel atau Islet Cell
Surface Antibodies (ICSA) ditemukan pada sekitar 80%
penderita DM Tipe 1.
Sama seperti ICCA, titer ICSA juga makin menurun sejalan
dengan lamanya waktu.
Beberapa penderita DM Tipe 2 ditemukan positif ICSA.
Otoantibodi terhadap enzim glutamat dekarboksilase (GAD)
ditemukan pada hampir 80% pasien yang baru didiagnosis
sebagai positif menderita DM Tipe 1. Sebagaimana halnya
ICCA dan ICSA, titer antibodi anti-GAD juga makin lama
makin menurun sejalan dengan perjalanan penyakit.
Keberadaan antibodi anti-GAD merupakan prediktor kuat
untuk DM Tipe 1, terutama pada populasi risiko tinggi
 Terapi Nonfarmakologi
Medical nutrition therapy is recommended for all patients.
For type 1 DM, the focus is on physiologically
regulating insulin administration with a balanced diet to
achieve and maintain healthy body weight. The meal plan
should be moderate in carbohydrates and low in saturated
fat, with a focus on balanced meals.
Patients with type 2 DM often require caloric
restriction to promote weight loss.
Aerobic exercise can improve insulin sensitivity and
glycemic control and may reduce cardiovascular risk
factors, contribute to weight loss or maintenance, and
improve well-being.
Terapi Farmakologi
 Sumber-sumber insulin
Insulin manusia (human insulin) diproduksi
dengan teknologi DNA rekombinan
menggunakan untai-untai (strain) khusus
bakteri Eschericia coli atau ragi