DIABETES MELLITUS

Definisi
Diabetes Mellitus is a group of metabolic disease with characteristic
hyperglycemia that occurs due to abnormalities in insulin secretion,
mechanism of insulin or both of them.

- (PERKENI 2021)
Epidemiology
• Global estimates at the age of 20-79 years there are 151 million (2000)
increased to 463 million (2019)
• Asia prediction 88 million (2019), 115 million (2030), 153 million (2045)
• Type 1 DM cases: 10% , Type 2: 90%
• One in 2 adults with DM has not been diagnosed
• DM sufferers do not realize their condition for a long time, realize when
complications have occurred
• 70% of around 100 million cases of DM 2 in 2014 can be prevented/delayed
by adopting a healthy lifestyle
• 12% of global expenditure for adult DM
Classification of the Etiology of Diabetes Mellitus
Classification Description

Type 1 Pancreatic beta cell destruction, generally associated with deficiency

absolute insulin
- Autoimmune
- Idiopathic
Type 2 Varieted, starting with predominant insulin resistance accompanied by insulin deficiency relative
to predominant defects in insulin secretion with resistance insulin.

Diabetes Gestational Diabetes diagnosed in the second or third trimester of pregnancy where there was no diabetes
before pregnancy

specific type related to - Monogenic diabetes syndrome (neonatal diabetes, maturity ʹ

with other causes onset diabetes of the young [MODY])
- Diseases of the exocrine pancreas (cystic fibrosis, pancreatitis)
- Caused by drugs or chemicals (eg use
glucocorticoids in HIV/AIDS therapy or after transplantation
organ)
Diagnosis
• The diagnosis of DM is established on the basis of examination of
blood glucose levels and HbA1c.
 Diagnostic Criteria for Diabetes Mellitus
Fasting plasma glucose examination of more than 126 mg/dL. Fasting is a condition of no intake
calories for at least 8 hours

Or
Plasma glucose examination of more than 200 mg/dL 2-hours after the Oral Glucose Tolerance Test (OGTT) with a glucose
load of 75 grams

Or
Plasma glucose examination when more than 200 mg/dL with classic complaint or crisis
hyperglycemia

Or
HbA1c examination of more than 6.5% using a method standardized by
National Glycohaemoglobin Standardization Program (NGSP) and Diabetes Control and
Complications Trial assay (DCCT)
 Laboratory Blood Test Levels for Diagnosis
of Diabetes and Prediabetes
HbA1c (%) Blood glucose fasting Plasma glucose 2 hours
(mg/dL) after OGTT (mg/dL)

Diabetes >6,5 >126 >200

Pre-Diabetes 5,7 -6,4 100 -125 140 -199

Normal <5,7 70-99 70-139

Impaired Glucose Tolerance (TGT) &
Impaired Fasting Blood Glucose (GDPT)
• The condition of increasing blood glucose levels above the normal
range and below the diagnostic threshold for diabetes.
• The term "prediabetes"
• IMPORTANT!
• Indicates the risk of developing type 2 diabetes in the future
• TGT and GDPT indicate an already high CVD risk
• Early detection can be done to prevent DM 2
• About 26% and 50% after being diagnosed with TGT/GDPT can
develop DM 2 within 5 years
 Diabetes Type 1 Diabetes Tipe 2

- It is caused by an autoimmune reaction where - Impaired insulin secretion or impaired insulin

the body's immune system attacks the action (insulin resistance) on target organs,
pancreatic beta cells especially the liver and muscles

- Genetic susceptibility of chromosome 6 -> for - Hereditary diseases, can still be prevented with
immune reactions a healthy lifestyle

- Requires daily insulin injections - Still produce insulin in less levels

- Generally, sufferers have a thin body weight - Generally people with fat / obesity

- Often in children and adolescents - Often in older adults

- Frequent or easy going into ketosis (coma) - Rarely, ketosis (coma)

 Risk Factors
• Less physical activity
• Family history of DM in the first generation
• Enter ethnic groups (African America, Latino, Native American, Asian American, Pacific
Islander)
• Women with a history of giving birth to babies weighing > 4000g or a history of DMG
• Hypertension (blood pressure > 140/90 mmHg or currently on antihypertensive drug
therapy)
• HDL cholesterol <35 mg/dL and/TAG >250 mg/dL
• Women with polycystic ovary syndrome
• History of impaired glucose tolerance (IGT) or impaired fasting blood glucose (GDPT)
• Other conditions associated with insulin resistance (obesity, acanthosis migraines
• History of cardiovascular disease
• Age
Pathogenesis of Diabetes Mellitus
Clinical Manifestations (PERKENI)
DM Typical Symptoms Symptoms not typical of DM
- Polyuria (lots of urine) - Weak
- Polydipsia (drinking a lot) - pins and needles
- Polyphagia (lots of eating) - Itchy
- BB ↓ for no apparent reason - Blurred eyes
- Erectile dysfunction (men)
- Vulvar pruritus (women)
 Diagnosis
done by
Screening: identify through
people who are at
risk/asymptomatic
Diagnostic test: identify
through symptoms/signs of
DM
The diagnosis of DM is based on
examining blood glucose
concentrations
For diagnosis, an enzymatic
examination is recommended with
venous plasma blood material but
adjust it to local conditions.
Monitoring of treatment results can
be done by using a capillary blood
glucose check with a glucometer
 Diagnostic criteria for DM (PERKENI 2021 consensus):
Fasting plasma glucose examination ≥126 mg/dl. Fasting is
a condition where there is no calorie intake for at least 8
hours, or
Plasma glucose examination ≥200 mg/dl 2 hours after the
Oral Glucose Tolerance Test (OGTT) with a glucose load of
Examination can be 75 grams, or
done through Current plasma glucose test ≥200 mg/dl with classic
examination of complaints (polyuria, polydipsia, polyphagia and
concentration unexplained weight loss), or
Glucose during / Examination of HbA1c ≥6.5% using a method standardized
fasting blood glucose by the National Glycohaemoglobin Standardization
This is followed by an Program (NGSP).
Oral Glucose
Tolerance Test
1. Three days before the examination, the patient
continues to eat (with sufficient carbohydrates) and
perform physical activities as a daily habit
2. Fast for at least 8 hours (starting at night) before the
examination, drink plain water without
glucose is still allowed
3. Examination of fasting blood glucose levels
4.Given glucose 75 grams (adults) or 1.75 g/kgBB
(children), dissolved in water 250 ml and drink within 5
minutes
5.Fasting again until blood sampling for examination 2
hours after drinking complete glucose solution
6. Check blood glucose levels 2 hours after the glucose
load
7. During the examination process, the subject being
examined remains resting and does not smoke
Diagnostic approach
DM and TGT
Management of Diabetes Mellitus
1. General management measures
Medical evaluation is carried out at the first meeting:
2. Disease history
3. Physical examination
4. Laboratory Evaluation
5. Complication Screening
2. Specific Management Measures
NON PHARMACOLOGY
Performed continuously side by side with pharmacological therapy
1. Education
2. Medical Nutrition Therapy (TNM)
Nutrition therapy goals:
To achieve and maintain: GD level, lipid profile (CVD risk), BP
To prevent or slow down the rate of development of chronic
complications of diabetes by modifying nutritional intake and lifestyle
growth
Nutrition is given individually taking into account nutritional needs
and paying attention to the eating habits of people with diabetes
Oral antihyperglycemic drugs
Insulin Sensitizing Group
1. Biguanids - Side effects:
Metformin is the most widely used - Gastrointestinal disorders not
High concentrations in the intestine and in the liver uncommon (-50%)
- Lactic acidosis aggravated by alcohol
In excretion: urine
(rare)
Half-life 2-5 hours - Interferes with absorption of vit B12 and
MOAs: ↓ serum B12 concentration
↓ GD on insulin action at the cellular level and distal to the- Anemia (17%)  monitor hematology
insulin receptor
Suppresses alpha cell function shg ↓ serum glucagon and - - Contraindicated
inhibits hyperglycemia during fasting - Gg F(x) kidney
Does not have a stimulus effect on beta cells x - Impaired liver F(x), severe infections,
hypoglycemia and weight gain excessive alcohol use, heart failure
↓ Mild-moderate weight due to appetite suppression patients who require therapy
- Close monitoring of elderly > 80 years
Combination therapy : Solfonylureas (SU) , repaglinide,
- Radiocontrast  stop treatment before
nabeglinid, alpha glycosidase inhibitors, glitazone
24 hours and 48 after the procedure
2. Glitazone (thiazolidindione)
Side effects :
Rapid absorption reaches highest concentration
1-2 hours Weight gain from SU, edema, ARI
MOA: glizatone (Thiazolidinediones) is a selective (16%), headache (7.1%), dilutional
and potent angonist peroxisome proliferator- anemia, extremity fractures in
activated receptor gamma (PPARÝ), present in
target tissues of insulin action such as skeletal postmenopausal women
muscle, adipose tissue, liver
Contraindications:
Does not stimulate insulin production by beta
cells, even ↓ insulin secretion > than metformin Use is discontinued if ↑ liver
↑ BW and edema enzymes (ALT&AST) > 3x normal
Rosiglitazone & pioglitazone have an effect on the limits, previous history of liver
patient's lipid profile disease, class 3 heart failure
Rosiglitazone (4 & 8 mg), pioglitazone (15 & 30 (NYHA), edema, cardiovascular
mg) can be used as monotherapy and in
combination (metformin, insulin secretagogue) and myocardial infarction
It is not recommended to use with insulin
because it will ↑ BB and fluid retention
• Insulin secretagogue group • 1. First generation (acetohexamide, tolbutamide,
• Stimulates insulin secretion by pancreatic chlorpropamide)
beta cells, Has a hypoglycemic effect, SU • 2. Second generation (glibenclamide, glipizide and
gliclazide)
and non-SU (glinid) group
• 3. Third generation (glimepiride)
• 1. Sulfonylurea (SU) • Fasting GD concentration < 200 mg/dL SU starting
• Often in combination with krn to ↑ and with small doses titrated in 1-2 week increments
maintain insulin secretion • GD > 200 mg/dL given a larger initial dose. The drug is
given ½ hour before meals  so that it is better
• Glibenclamide  half-life: 4 hours (acute absorbed
use). >12 hours (long time use), Once a • Side effects:
day use is recommended • Hypoglycemia, Older people  choose the drug with
• MOA: stimulates pancreatic beta cells  the shortest duration of action , Elderly  long acting
period , BB ↑ around 4-6 kg , Impaired digestion,
release stored insulin (good for patients photosensitivity, Impaired liver enzymes, Flushing
who are still able to secrete insulin) x • Contraindications:
type 1 DM • Kidney failure, Gg F(x) severe liver, eat less, do not
• Hypoglycemia: because it stimulates the take with sulfate drugs, DM 1, pregnant, lactating
ATP-dependent K channels of beta cells
2. Glinids - MOAs:
In contrast to SU, the working period is shorter - Inhibiting the action of the alpha glucosidase
Repaglinid and Nateglinid enzyme in the gastrointestinal tract so that it can
reduce glucose absorption and reduce postprandial
It is rapidly absorbed after oral administration and hyperglycemia
rapidly excreted via liver metabolism
- The drug acts in the intestinal lumen
Given 2-3x a day
- Does not cause hypoglycemia, has no effect on
Lowers postprandial glucose with minimal hypoglycemic insulin levels
effect
- Acarbose can be monotherapy or combination
(insulin, metformin, glitazone/SU)
Inhibitors of glucose absorption in the digestive tract - The drug is given during the main meal drink
Alpha Glucosidase Inhibitors before 15 minutes and after eating
Acarbose is not absorbed and acts locally in the digestive - Side effects:
tract. - meteorismus, flatulence (50%) often, diarrhea
Undergoes metabolization, digestion by normal flora, - Contraindications:
intestinal hydrolysis and digestive enzyme act
- - Irritable bowel syndrome, gastrointestinal
Half-life: Elimination from plasma is approx. 2 hr in obstruction, cirrhosis of the liver, impaired kidney
healthy individuals function
Excretion: faeces
• DPP-IV inhibitors (Dipeptidyl Peptidase IV)

• DPP-IV inhibitor class drugs inhibit the action of the DPP-IV

enzyme so that GLP-1 (Glucose Like Peptide-1) remains in high
concentrations in its active form.
• GLP-1 activity to increase insulin secretion and suppress
glucagon secretion depends on blood glucose levels (glucose
dependent). Examples of this class of drugs are Sitagliptin and
Linagliptin.
• SGLT-2 inhibitors (Sodium Glucose Cotransporter 2)

• SGLT-2 inhibitors are a new type of oral antidiabetic drug that

inhibits the re-absorption of glucose in the distal tubules of the
kidney by inhibiting the performance of the SGLT-2 glucose
transporter. Drugs that belong to this group include:
Canagliflozin, Empagliflozin, Dapagliflozin, Ipragliflozin.
 Injectable anti-hyperglycemic drug
Including injectable anti-hyperglycemia, namely insulin, GLP-1 agonists and combinations of
insulin and GLP-1 agonists.
1. Insulin
Required under the circumstances:
- HbA1c > 9% with metabolic decompensation conditions
- Rapid weight loss Severe hyperglycemia with ketosis
- Hyperglycemic Crisis
- Failed with optimal dose of OHO combination
- Severe stress (systemic infection, major surgery, acute myocardial infarction, stroke)
- Pregnancy with uncontrolled gestational diabetes mellitus/diabetes with meal planning
- Severe impairment of kidney or liver function
- Contraindications and or allergy to OHO
- Perioperative conditions as indicated
Types and duration of action of insulin
• Based on the duration of action, insulin is divided into 5 types, namely:
- Fast-acting insulin (rapid-acting insulin)
- Short-acting insulin (Short-acting insulin)
- Intermediate acting insulin
- Long-acting insulin (Long-acting insulin)
- Ultra long acting insulin (Ultra long acting insulin)
- Fixed mixed insulin, short-acting medium and fast-acting medium (Premixed insulin)
• Insulin therapy side effects
- The main side effect of insulin therapy is hypoglycemia
- Management of hypoglycemia can be seen in the section on acute complications of
DM
- Another side effect is an allergic reaction to insulin
 Injectable anti-hyperglycemic drug
2. GLP-1/Incretin Mimetic Agonists
GLP-1 agonists can act on beta-cells so that there is an increase in
insulin release, has the effect of losing weight, inhibiting glucagon
release, and inhibiting appetite. The weight loss effect of GLP-1 agonists
is also used as an indication of weight loss in DM patients with obesity.
• Side effects: nausea and vomiting.
• Drugs in this class: Liraglutide, Exenatide, Albiglutide,
and Lixisenatide.
• Indonesia  (Liraglutide) each pen contains 18 mg in
3 ml. Initial dose of 0.6 mg daily which may be
increased to 1.2 mg after one week to achieve the
desired glycemic effect. Dosage can be increased up to
1.8 mg. Daily doses of more than 1.8 mg are not
recommended. The working life of Liraglutide is 24
hours and is administered subcutaneously once a day.
Complications
1. Acute
- Hyperglycemic crisis: diabetic ketoacidosis, hyperosmolar hyperglycemia
- Hypoglycemia

2. Chronicle
1. Macroangiopathy :
- Cardiac vessels: coronary heart disease
- Peripheral vessels: ischemic ulcers on the legs
- Cerebral vessels: ischemic stroke or hemorrhagic stroke
2. Microangiopathy
- Diabetic retinopathy
- Diabetic nephropathy
- Neuropathy loss of distal sensation risk for ulcer and ↑ risk of amputation
Prognosis
Diabetes mellitus is a metabolic disease that can cause various
complications. This situation greatly affects the quality of life of
people with DM so that it needs serious attention from all parties.

Until now, there has not been found a way or treatment that can
completely cure diabetes. However, DM can be controlled
properly, by: diet, exercise and by using antidiabetic drugs.