Pemicu 1

“Anakku sayang anakku malang”

Adrian pratama – 405100018
Blok endokrinologi
LO 1.1
Menjelaskan anatomi pankreas
Pancreas
 elongated, accessory digestive gland that lies
retroperitoneally and transversely across the posterior
abdominal wall
posterior to the stomach
between the duodenum on the right
the spleen on the left
The transverse mesocolon attaches to its anterior margin

 Produces
An exocrine secretion (pancreatic juice from the acinar cells)
that enters the duodenum through the main and accessory
pancreatic ducts
Endocrine secretions (glucagon and insulin from the pancreatic
islets [of Langerhans]) that enter the blood
4 parts of pancreas
head of the pancreas
 The uncinate process, a projection from the inferior part of the
pancreatic head, extends medially to the left, posterior to the SMA
 rests posteriorly on the IVC, right renal artery and vein, and the
left renal vein
neck of the pancreas
 overlies the superior mesenteric vessels
 adjacent to the pylorus of the stomach
body of the pancreas
 passing over the aorta and L2 vertebra, posterior to the omental
bursa
 in contact with the aorta, SMA, left suprarenal gland, and left
kidney and renal vessels
tail of the pancreas
 anterior to the left kidney
 closely related to the splenic hilum and the left colic flexure
Arteries & veins
Pancreatic arteries
branches of the splenic artery  body and tail of the
pancreas
anterior and posterior superior pancreaticoduodenal
arteries, branches of the gastroduodenal artery, and the
anterior and posterior inferior pancreaticoduodenal
arteries, branches of the SMA  head of the pancreas

Pancreatic veins
splenic and superior mesenteric parts of the portal vein
Lymph drainage
pancreaticosplenic
lymph nodes, that lie
along the splenic artery
& pyloric lymph nodes
 superior mesenteric
lymph nodes / celiac
lymph nodes via
hepatic lymph nodes
Innervation
derived from the vagus
& abdominopelvic
splanchnic nerves 
celiac plexus and
superior mesenteric
plexus
LO 1.2
Menjelaskan fisiologi kelenjar pankreas
Insulin & glukagon sebagai pengatur kadar gula darah
Pankreas
 organ yg terdiri dr jaringan eksokrin & endokrin
Eksokrin  larutan basa encer + enzim2 pencernaan
Endokrin (pulau2 langerhans)
 Sel beta  insulin
 Sel alfa  glukagon
 Sel dekta  somatostatin
 Sel PP  polipeptida pankreas
Insulin
Efek penting pada metabolisme karbohidrat, lemak,
protein ,dan lemak
Menurunkan kadar glukasa, asam lemak, dan asam
amino dalam darah  mendorong terjadinya
penyimpanan

Sewaktu fase penyerapan insulin meningkatkan

penyerapan mereka o/ sel & dikonversi menjadi
glikogen, trigliserida, dan protein
Efek insulin pada karbohidrat
Tergantung pada jumlah kadar glukosa dalam darah
Mempermudah masuknya glukosa ke dalam sel
 Transporter recruitment: insersi glucose transporter >>  lebih
banyak glukosa masuk ke sel
 otak, otot yg aktif & hati tdk memerlukan glucose transporter
 Di hati glukosa akan lgsg masuk tanpa bantuan transporter, peran
insulin: merangsang proses glu --> glu-6-P  kadar glukosa
intrasel tetap rendah
Merangsang glikogenesis
Menghambat glikogenolisis
Menurunkan pengeluaran glukosa oleh hati dgn
menghambat glukoneogenesis
 Menurunkan kadar asam amino darah
 Menghambat enzim2 hati yg diperlukan u/ proses
glukoneogenesis
Efek pada lemak
 menurunkan kadar asam lemak darah & mendorong
pembentukan simpanan trigliserida
Meningkatkan transportasi glukosa ke dalam sel jaringan
adiposa
 GLUT-4 recruitment >>
Mengaktifkan enzim2 yg mengkatalisasi pembentukkan
asam lemak dari turunan glukosa
Meningkatkan masuknya asam2 lemak dari darah ke
dalam sel jaringan adiposa
Menghambat lipolisis
  asam lemak darah <<
Efek pada protein
 menurunkan kadar asam amino darah
Mendorong transportasi aktif asam2 amino dr darah ke
dalam otot & jaringan lain
Meningkatkan kecepatan penggabungan asam amino ke
dalam protein
Menghambat penguraian protein
Mekanisme kontrol sekresi insulin
Diabetes melitus
Insulin berlebihan
  hipoglikemia  kelaparan otak
 2 tipe
Syok insulin
 Pada pasien diabetes jika disuntikkan insulin melebihi asupan kalori
dan tingkat olahraga
Hipoglikemia reaktif
 Pada individu non diabetes yg mengidap tumor sel beta / sel beta sangat
responsif terhadap adanya glukosa

Gejala pd kasus ringan  tremor, lelah, mengantuk,

ketidakmampuan u/ konsentrasi
Gejala berat  manifes efek hipoglikemia di otak 
penekanan fungsi otak  kesadaran <<  kematian
Terapi
Pada syok insulin  pemberian sesuatu yg manis segera
pada saat tanda hipoglikemia muncul  gula darah
kembali normal
Pada hipoglikemia reaktif  batasi asupan glukosa
Glukagon
 melawan efek insulin
Bekerja terutama di hati
Efek:
Pada karbohidrat
 Pengeluaran glukosa darah o/ hati  glukosa darah >>
 Menurunkan sintesis glikogen, meningkatkan glikogenolisis,
meningkatkan glukoneogenesis
Pada lemak
 Mendorong penguraian lemak, hambat sintesis trigliserida
 Mendorong perubahan asam lemak menjadi keton
Pada protein
 Hambat sintesis protein, meningkatkan penguraian protein di hati
 Tidak terlalu bermakna memengaruhi kadar asam amino di darah
krn tidak bekerja pada otot
Cara kerja glukagon
Mekanisme hormon lain yg jg memiliki efek metabolik
LO 1.3
Menjelaskan biokimia dari kelenjar pankreas
Insulin & glukagon sebagai pengatur kadar gula darah
Major hormones of metabolic homeostasis
Insulin
 major anabolic
hormone; promotes the
storage of nutrients
conversion of glucose to
triacylglycerols; in liver
& adipose tissue
Uptake of amino acids &
protein synthesis in
muscle
Utilization of glucose
Inhibit fuel metabolism
Glucagon
 maintain fuel
availability in the
abscence of dietary
glucose; action on liver
stimulating the release of
glucose from liver
glycogen
Stimulating
gluconeogenesis
Mobilizing fatty acid
from adipose’s TAG
Level of insulin &
glucagon Conterregulatory hormone
Physiologic actions of insulin &
other
Structure of insulin; proinsulin
Regulation of insulin release
Structure of glucagon
polypeptide hormone
synthesized in the α cells of the pancreas
Precursor form: pre-proglucagon (160 AA) +
proteolytic cleavage  mature glucagon (29 AA) &
glucagon like peptides
Has ability to stimulate insulin
Regulation of glucagon release
Signal transduction
Polypeptide hormones (insulin, glucagon,
catecholamines)  plasma membrane’s receptor
3 basic types of signal transduction
Receptor coupling to adenylate cyclase  cAMP
Receptor kinase activity
Receptor coupling to hydrolysis of phosphatidylinositol
bisphosphate (PIP2)
Signal transduction by insulin
Insulin receptor  2 type subunits (alpha & beta)
Insulin binding with the receptor  tyrosine kinase
phosphorylates tyrosine residues on the beta-subunit
(autophosphorylation)  cAMP <  effect:
insulin reverses glucagon-stimulated phosphorylation
insulin works through a phosphorylation cascade that
stimulates the phosphorylation of several enzymes
insulin induces and represses the synthesis of specific
enzymes
insulin acts as a growth factor and has a general stimulatory
effect on protein synthesis
insulin stimulates glucose and amino acid transport into cells
Signal transduction of glucagon
the glucagon receptor is coupled to adenylate cyclase
and cAMP production  changes the activity of
enzymes by phosphorylating them at specific serine
residues
The G proteins, which couple the glucagon receptor to
adenylate cyclase  releases GDP and binds GTP;
effect:
activates glycogen degradation, inhibits glycogen
synthesis, and inhibits glycolysis in the liver
LO 2
Menjelaskan diabetes melitus
Definition
 a group of common metabolic disorders that share
the phenotype of hyperglycemia (reduced insulin
secretion, decreased glucose utilization, and increased
glucose production)
Classification
Etiology
Epidemiology
Risk factor / screening
Diagnosis
Clinical features
Type 1 Diabetes Mellitus
Pathogenesis
Genetic suspectibility
HLA locus contributes as much as 50% of the genetic
susceptibility to type 1 diabetes (HLA locus on
chromosome 6p21)
 Ninety to 95% of Caucasians with this disease have either a HLA-
DR3 or HLA-DR4 haplotype
non-HLA genes also confer susceptibility to type 1
diabetes
 CTLA-4 and PTPN-22 are thought to inhibit T-cell responses 
excessive T-cell activation
 polymorphism is in CD25  encodes the α chain of the IL-2
receptor (reduced activity)  maintenance of functional
regulatory T cells <<
Environmental factors
viral infections (mumps, rubella, coxsackie B, or
cytomegalovirus)  islet cell destruction
 “bystander” damage: viral infections induce islet injury and
inflammation  release of sequestered β-cell antigens and the
activation of autoreactive T cells
 proteins that mimic β-cell antigens  cross-reacts with the self-
tissue (“molecular mimicry”)
 viral infections incurred early in life  re-infection (“viral déj
vu”  latency between infections and the onset of diabetes)
Pathophysiology
 islet cell autoantibodies
 activated lymphocytes in the islets, peripancreatic lymph
nodes, and systemic circulation
 T lymphocytes that proliferate when stimulated with islet
proteins
 release of cytokines within the insulitis. Beta cells seem to
be particularly susceptible to the toxic effect of some
cytokines [tumor necrosis factor alpha (TNF-α), interferon-
γ , and interleukin 1 (IL-1)]

 formation of nitric oxide metabolites, apoptosis, and direct

CD8+ T cell cytotoxicity  beta cell death
Immunologic markers & prevention
Islet cell autoantibodies to GAD, insulin, and IA-2/ICA-
512, phogrin

Administration of insulin to individuals at high risk for

developing type 1 DM did not prevent type 1 DM
treatment with anti-CD3 monoclonal antibodies has
recently been shown to slow the decline in C-peptide
levels
interventions have targeted the immune system directly
(immunosuppression, selective T cell subset deletion,
induction of immunologic tolerance to islet proteins) 
success in animal
Type 2 Diabetes Mellitus
Pathogenesis
Pathophysiology
impaired insulin secretion, insulin resistance, excessive
hepatic glucose production, and abnormal fat
metabolism
Obesity is very common
Metabolic abnormalities
Abnormal muscle and fat metabolism
Skeletal muscle  impairment in nonoxidative glucose
usage (glycogen formation)
Adipocyte mass >  free fatty acids and other fat cell
products >
Impaired insulin secretion
Insulin > type 2 DM  beta cell failure
Increased hepatic glucose & lipid production
Insulin resistance  a. gluconeogenesis >  glucose >
b. glycogen storage <  glucose >
c. free fatty acid flux from adipose
 VLDL >, triglyceride >
Prevention
 a number of lifestyle modifications and pharmacologic
agents prevent or delay the onset of DM
intensive changes in lifestyle (diet and exercise for 30 min/day
five times/week)
maintain a normal BMI and engage in regular physical activity
Pharmacologic therapy for individuals with prediabetes is
currently controversial because its cost-effectiveness and safety
profile are not known
 A recent ADA Consensus panel concluded that metformin,
but not other medications, could be considered in individuals
with both IFG and IGT who are at very high risk for
progression to diabetes (age < 60 years, BMI >= 35 kg/m2,
family history of diabetes in first-degree relative, elevated
triglycerides, reduced HDL, hypertension, or A1C > 6.0%)
LO 2.2
Menjelaskan komplikasi diabetes melitus
Acute complications
DKA VS HHS
Diabetic ketoacidosis
Hallmark of type 1 DM; also occurs in individuals
who lack immunologic features of type 1 DM

Clinical manifestations
Pathophysiology
Diagnosis & laboratory
abnormalities
 hyperglycemia, ketosis, and metabolic acidosis (increased
anion gap) along with a number of secondary metabolic
derangements
 serum glucose is only minimally elevated
 Serum bicarbonate is frequently <10 mmol/L
 arterial pH ranges between 6.8 and 7.3
 Dehydration & hyperglycemia  sodium, chloride,
phosphorous, and magnesium are also reduced
 Leukocytosis, hypertriglyceridemia, and
hyperlipoproteinemia
 the ketone body, β-hydroxybutyrate, is synthesized at a
threefold greater rate than acetoacetate
DD
starvation ketosis
alcoholic ketoacidosis (bicarbonate usually > 15
meq/L)
other increased anion gap acidosis
Treatment
Hyperglycemic hyperosmolar state
elderly individual with type 2 DM

Clinical features
several week history of polyuria, weight loss
diminished oral intake  mental confusion, lethargy, or
coma
Physical examination
dehydration and hyperosmolality
hypotension, tachycardia, and altered mental status
Absent: nausea, vomiting, and abdominal pain and the
Kussmaul respirations
Precipitating factors
myocardial infarction or stroke
Sepsis, pneumonia, and other serious infections
debilitating condition (prior stroke or dementia)
social situation that compromises water intake
Pathophysiology
Underlying cause  relative insulin deficiency and
inadequate fluid intake
 insulin deficiency  increases hepatic glucose
production & impairs glucose utilization in skeletal
muscle  hyperglycemia  osmotic diuresis 
intravascular volume depletion
Lower levels of counterregulatory hormones and free
fatty acids have been found in HHS than in DKA
Diagnosis & laboratory
abnormalities
marked hyperglycemia [plasma glucose may be >55.5
mmol/L (1000 mg/dL)]
hyperosmolality (>350 mosmol/L), and prerenal
azotemia
serum sodium may be normal or slightly low despite the
marked hyperglycemia
acidosis and ketonemia are absent or mild
A small anion gap metabolic acidosis may be present
secondary to increased lactic acid
Moderate ketonuria, if present, is secondary to
starvation
Treatment
 careful monitoring of the patient's fluid status, laboratory
values, and insulin infusion rate is crucial
Fluid replacement should initially stabilize the hemodynamic
status of the patient (1–3 L of 0.9% normal saline over the first 2–
3 h)
If the serum sodium > 150 mmol/L (150 meq/L), 0.45% saline
should be used
After hemodynamic stability is achieved  hypotonic fluids
(0.45% saline initially then 5% dextrose in water, D5W)
 IV insulin bolus of 0.1 units/kg followed by IV insulin at a
constant infusion rate of 0.1 units/kg per hour
 glucose should be added to IV fluid when the plasma glucose
falls to 13.9 mmol/L (250 mg/dL), and the insulin infusion rate
should be decreased to 0.05–0.1 units/kg per hour
Chronic complications
Mechanism
increased intracellular glucose  formation of
advanced glycosylation end products (AGEs): cross-link
proteins (e.g., collagen, extracellular matrix proteins) 
accelerate atherosclerosis, promote glomerular
dysfunction, reduce nitric oxide synthesis, induce
endothelial dysfunction, and alter extracellular matrix
composition and structure
Hyperglycemia  glucose metabolism via the sorbitol
pathway  sorbitol > 
alters redox potential, increases cellular osmolality,
generates reactive oxygen species, and likely leads to other
types of cellular dysfunction
Hyperglycemia  diacylglycerol >  activation of
protein kinase C (PKC) 
alters the transcription of genes for fibronectin, type IV
collagen, contractile proteins, and extracellular matrix
proteins in endothelial cells and neurons
Hyperglycemia  flux through the hexosamine
pathway > 
alter function by glycosylation of proteins such as
endothelial nitric oxide synthase or by changes in gene
expression of transforming growth factor beta (TGF-β)
or plasminogen activator inhibitor-1 (PAI-1)
Diabetic retinopathy
DM  progressive diabetic retinopathy and clinically
significant macular edema  blindness

Diabetic retinopathy
Non-proliferative
 appears late in the first decade or early in the second decade of
the disease and is marked by retinal vascular microaneurysms,
blot hemorrhages, and cotton wool spots
Proliferative
 macular edema
Pathophysiology
Loss of retinal pericytes, increased retinal vascular
permeability, alterations in retinal blood flow, and
abnormal retinal microvasculature  retinal ischemia
 neovascularization (newly formed vessels appear
near the optic nerve and/or macula)
 rupture easily, leading to vitreous hemorrhage,
fibrosis, and ultimately retinal detachment
Treatment
Prevention  Intensive glycemic and blood pressure
control
Diabetic retinopathy  prophylactic photocoagulation
Aspirin therapy (650 mg/d) does not appear to
influence the natural history of diabetic retinopathy

limit physical activities associated with repeated

Valsalva maneuvers
Diabetic nephropathy
microalbuminuria and macroalbuminuria in
individuals with DM are associated with increased risk
of cardiovascular disease
commonly have diabetic retinopathy
Pathogenesis
chronic hyperglycemia + (growth factors, angiotensin
II, endothelin, AGEs) 
hemodynamic alterations in the renal microcirculation
(glomerular hyperfiltration or hyperperfusion, increased
glomerular capillary pressure)
structural changes in the glomerulus (increased
extracellular matrix, basement membrane thickening,
mesangial expansion, fibrosis)
Screening
Treatment
Treatment’s purpose
normalization of glycemia
strict blood pressure control
administration of ACE inhibitors or ARBs
Dyslipidemia should also be treated

many glucose-lowering medications (sulfonylureas

and metformin) are contraindicated in advanced renal
insufficiency
calcium channel blockers (non-dihydropyridine class),
beta blockers, or diuretics should be used (if ACE /
ARB not possible)
restriction of protein intake in diabetic individuals with
microalbuminuria (0.8 g/kg per day) or
macroalbuminuria (<0.8 g/kg per day, which is the
adult Recommended Daily Allowance, or ~10% of the
daily caloric intake)
Diabetic neuropathy
 occurs in ~50% of individuals with long-standing type 1 and
type 2 DM
 Risk factor >  BMI & smoking
 Peripheral neuropathy  cardiovascular disease, elevated
triglycerides, and hypertension

 ADA recommends screening  distal symmetric neuropathy

beginning with the initial diagnosis of diabetes and screening
for autonomic neuropathy 5 years after diagnosis of type 1 DM
and at the time of diagnosis of type 2 DM

 Type  poly/mononeuropathy & autonomic neuropathy

Polyneuropathy/Mononeuropathy
 Most common  distal symmetric polyneuropathy

 presents with distal sensory loss (Hyperesthesia, paresthesia,

and dysesthesia), 50% do not have symptoms of neuropathy
 sensation of numbness, tingling, sharpness, or burning that
begins in the feet and spreads proximally
 Pain typically involves the lower extremities, is usually present
at rest, and worsens at night.
 Late  sensory deficit in the lower extremities persists

 Physical exam  sensory loss, loss of ankle reflexes, and

abnormal position sense
Autonomic Neuropathy
 can involve multiple systems
Cardiovascular
 tachycardia and orthostatic hypotension
gastrointestinal
genitourinary
metabolic systems

 Hyperhidrosis of the upper extremities

 anhidrosis of the lower extremities (dry skin with cracking, which
increases the risk of foot ulcers)

 Autonomic neuropathy  reduce counterregulatory hormone

release  inability to sense hypoglycemia appropriately
(hypoglycemia unawareness)
Treatment
 improve glycemic control
 hypertension and hypertriglyceridemia should be treated
 Avoidance of neurotoxins (alcohol) and smoking
 supplementation with vitamins for possible deficiencies (B 12,
folate)
 check their feet daily and take precautions (footwear) aimed at
preventing calluses or ulcerations
 Chronic, painful diabetic neuropathy 
antidepressants (tricyclic antidepressants such as amitriptyline,
desipramine, nortriptyline, imipramine or selective serotonin
norepinephrine reuptake inhibitors such as duloxetine)
anticonvulsants (gabapentin, pregabalin, carbamazepine,
lamotrigine)
Diabetic neuropathy that result in pain  duloxetine
and pregabalin (U.S. Food and Drug Administration
(FDA))
Therapy of orthostatic hypotension (fludrocortisone,
midodrine, clonidine, octreotide, and yohimbine)
Nonpharmacologic maneuvers (adequate salt intake,
avoidance of dehydration and diuretics, and lower
extremity support hose)
Gastrointestinal dysfunction
Hyperglycemia + parasympathetic dysfunction 
delayed gastric emptying (gastroparesis)
anorexia, nausea, vomiting, early satiety, and abdominal
bloating
DM-related GI autonomic neuropathy  altered
small- and large-bowel motility (constipation or
diarrhea)
Nocturnal diarrhea, alternating with constipation
Treatment
Improved glycemic control should be a primary goal
Smaller, more frequent meals that are easier to digest
(liquid) and low in fat and fiber
dopamine agonists metoclopramide, 5–10 mg, and
domperidone, 10–20 mg, before each meal
Erythromycin interacts with the motilin receptor 
promote gastric emptying
Diabetic diarrhea  loperamide and may respond to
octreotide (50–75 micro-g three times daily, SC)
Genitourinary dysfunction
 Diabetic autonomic neuropathy  genitourinary dysfunction
cystopathy, erectile dysfunction, and female sexual dysfunction
(reduced sexual desire, dyspareunia, reduced vaginal lubrication)

 Clinical manifestations
inability to sense a full bladder and a failure to void completely
bladder capacity and the post-void residual increase, leading to
symptoms of urinary hesitancy, decreased voiding frequency,
incontinence, and recurrent urinary tract infections

 Diagnsosis  cystometry and urodynamic studies

Treatment
timed voiding or self-catheterization, possibly with the
addition of bethanechol
Erectile dysfunction  Drugs that inhibit type 5
phosphodiesterase
Sexual dysfunction in women  vaginal lubricants,
treatment of vaginal infections, and systemic or local
estrogen replacement
Cardiovascular disease
  atherosclerotic vascular disease
 cardiac ischemia, peripheral or carotid arterial disease, a
resting electrocardiogram indicative of prior infarction
 proteinuria, or two other cardiac risk factors  plans to
initiate an exercise program
 The absence of chest pain ("silent ischemia") is common
in individuals with diabetes

 Risk factor
dyslipidemia, hypertension, obesity, reduced physical
activity, and cigarette smoking
Pathophysiology
insulin resistance and type 2 DM  levels of
plasminogen activator inhibitors (especially PAI-1)
and fibrinogen >  enhances the coagulation process
and impairs fibrinolysis  thrombosis
Diabetes is also associated with endothelial, vascular
smooth-muscle, and platelet dysfunction
Treatment
Revascularization procedures for CAD, including
percutaneous coronary interventions (PCI) and
coronary artery bypass grafting (CABG)
drug-eluting stents and a GPIIb/IIIa platelet inhibitor
ACE inhibitors (or ARBs)
beta blockers  safe
Antiplatelet therapy reduces cardiovascular events in
individuals with DM who have CAD
aspirin dose (75–162 mg)
 Dislipidemia management

*Second-line treatment: fibric acid derivative, ezetimibe, niacin, or bile acid–binding resin.
See text for pharmacologic treatment based on age and risk profile. LDL, low-density
lipoprotein; HDL, high-density lipoprotein
Lower Extremity Complications
Pathogenesis
neuropathy, abnormal foot biomechanics, PAD, and poor
wound healing
Disordered proprioception  abnormal weight bearing 
formation of callus or ulceration
Motor and sensory neuropathy  abnormal foot muscle
mechanics  structural changes in the foot (hammer toe,
claw toe deformity, prominent metatarsal heads, Charcot
joint)
Autonomic neuropathy  anhidrosis and altered
superficial blood flow in the foot  of the skin and fissure
formation  minor breaks in the skin, allowing them to
enlarge and to become infected
Risk factor for foot ulcer
male sex,
diabetes >10 years' duration,
peripheral neuropathy,
abnormal structure of foot (bony abnormalities, callus,
thickened nails),
peripheral arterial disease,
smoking,
history of previous ulcer or amputation,
poor glycemic control
Treatment
Education
careful selection of footwear
daily inspection of the feet to detect early signs of poor-
fitting footwear or minor trauma
daily foot hygiene to keep the skin clean and moist
avoidance of self-treatment of foot abnormalities and
high-risk behavior (e.g., walking barefoot)
prompt consultation with a health care provider if an
abnormality arises
Management
off-loading
Debridement
wound dressings
appropriate use of antibiotics
Revascularization
limited amputation
Hyperbaric oxygen has been used, but rigorous proof
of efficacy is lacking
Negative wound pressure has been shown to accelerate
wound healing of plantar wounds
Initial antimicrobial regimens include ertapenem,
piperacillin/tazobactam, cefotetan,
ampicillin/sulbactam, linezolid, or the combination of
clindamycin and a fluoroquinolone
Approach to the patient
History
 Symptoms of hyperglycemia
polyuria, polydipsia, weight loss, fatigue, weakness, blurry
vision, frequent superficial infections (vaginitis, fungal skin
infections), and slow healing of skin lesions after minor trauma
 Metabolic derangements
hyperglycemia
 osmotic diuresis, reduced glucose entry into muscle and to
the catabolic state of the patient
 urinary loss of glucose and calories, muscle breakdown due to protein
degradation and decreased protein synthesis
 Blurred vision results from changes in the water content of
the lens
Physical examination
Blood pressure > 130/80 mmHg is considered
hypertension in individuals with diabetes
examination of the lower extremities should seek
evidence of peripheral neuropathy, calluses, superficial
fungal infections, nail disease, ankle reflexes, and foot
deformities (such as hammer or claw toes and Charcot
foot)
periodontal disease is more frequent in DM, the teeth
and gums should also be examined
Laboratory findings
Look at the goal of treatment

the patient should be screened for DM-associated

conditions (e.g., microalbuminuria, dyslipidemia,
thyroid dysfunction)
Serum insulin or C-peptide measurements do not
always distinguish type 1 from type 2 DM, but a low
C-peptide level confirms a patient's need for insulin
Treatment
Goal
Education
self-monitoring of blood glucose;
urine ketone monitoring (type 1 DM);
insulin administration;
guidelines for diabetes management during illnesses;
management of hypoglycemia;
foot and skin care;
diabetes management before, during, and after
exercise;
risk factor–modifying activities
Nutrition
Exercise
 useful for lowering plasma glucose (during and following
exercise) and increasing insulin sensitivity
 ADA recommends 150 min/week (distributed over at least
3 days) of aerobic physical activity

 Caution !!
If the insulin level is too low, the rise in catecholamines may
increase the plasma glucose excessively, promote ketone body
formation, and possibly lead to ketoacidosis
if the circulating insulin level is excessive, this relative
hyperinsulinemia may reduce hepatic glucose production
(decreased glycogenolysis, decreased gluconeogenesis) and
increase glucose entry into muscle, leading to hypoglycemia
 To avoid exercise-related hyper- or hypoglycemia, individuals
with type 1 DM should
monitor blood glucose before, during, and after exercise
delay exercise if blood glucose is >14 mmol/L (250 mg/dL) and
ketones are present
if the blood glucose is <5.6 mmol/L (100 mg/dL), ingest
carbohydrate before exercising
monitor glucose during exercise and ingest carbohydrate to prevent
hypoglycemia
decrease insulin doses (based on previous experience) before
exercise and inject insulin into a nonexercising area
arn individual glucose responses to different types of exercise and
increase food intake for up to 24 h after exercise, depending on
intensity and duration of exercise
Type 1 DM treatment (insulin)
Type 2 DM
General aspects
Glucose lowering agents
Insulin Secretagogues
Glycemic management
Pediatric aspect
Type 1 DM
Epidemiology
Pathogenesis 
Natural history
Pathophysiology
 look how insulin works
Clinical manifestations
 < β cell mass   Glycosuria > 
insulinopenia  hyperphagia
progressive hyperglycemia  Glycosuria > hyperphagia
& ketoacidosis  loss of body fat; weight
 Serum glucose > renal loss
threshold  polyuria /  Insulin <<<  keto acids
nocturia accumulate  deteriorates
 Persistent diuresis   Ketosis (abdominal

polydipsia discomfort, nausea, and

emesis, preventing oral
 Glycosuria  monilial
replacement of urinary
vaginitis (women) water losses)  dehydration
Dehydration  Cautions !!
weakness or orthostasis  About 20-40% of
Ketoacidosis  children with newonset
kussmaul respirations diabetes progress to
(deep, heavy, rapid DKA before diagnosis
breathing);
aceton breath;
prolonged corrected Q-T
interval
diminished
neurocognitive function,
and possible coma
Diagnosis
inappropriate polyuria in any child with dehydration,
poor weight gain, or “the flu”
Hyperglycemia, glycosuria, and ketonuria can be
determined quickly
Nonfasting blood glucose > 200 mg/dL (11.1 mmol/L)
autoimmunities associated with T1DM
Treatment
Nutrition
Monitoring
Complication  DKA
Treatment
Type 2 DM
heterogeneous disorder, characterized by peripheral
insulin resistance and failure of the β cell to keep up
with increasing insulin demand

Natural history
aggravated by environmental factors (< physical activity,
excessive caloric intake  obesity  insulin resistance
 hyperglicemia & hyperlipidemia)
Clinical features
 Obese + mild symptoms of polyuria & polydipsia;
asymptomatic

 Physical exam
Acanthosis nigricans
striae and an increased waisthip ratio

Laboratory findings
Hyperlipidemia (LDL >)
HbA1c >
Diagnosis
Treatment
Monitoring
References
Dalley, Arthur F. Keith L Moore. Clinically Oriented
Anatomy. 5th edition. Lippincott Williams & Wilcins;
2006
Nelson Textbook of Pediatric, 19th edition
Sherwood,Lauralee. Fisiologi Manusia dari Sel ke
Sistem. Cetakan pertama edisi 2. Jakarta: EGC; 2001
Fauci. Braunwald. Dkk. Harrison’s Principles of
Internal Medicine. 17th edition. United State: The
McGraw-Hills; 2008
Marks Basic Medical Biochemistry