DIABETES MELLITUS

FILDZAH BADZLINA, S.Gz., M.K.M

 OVERVIEW

Diabetes affects people of all ages, typically 1 in 5 people older than 65 years old have 87% of diabetes-related deaths occur in low-
showing higher prevalence with increasing diabetes and middle-income countries. But only 35% of
age up to 60-69 years diabetes-related health expenditure is spent
there
 OVERVIEW

4 out of every 5 adults with undiagnosed 1 in 3 adults at risk of developing type 2 67% of adults with diabetes live in top 10
diabetes live in low- and middle-income diabetes, live in the Western Pacific Region countries and 70% of diabetes-related health
countries expenditure is spent in these countries
(including Indonesia)
 OVERVIEW
A third (35%) of the total number of
people with diabetes come from
Western Pacific with the highest number
of deaths (1.3 millions)

1 in 8 live births are affected by

1 in 10 adults have diabetes
hyperglycemia in pregnancy

The total diabetes related health More than half (56%) of people with
expenditure estimated in 2019 is USD diabetes remain undiagnosed and are
162 billion and expected to reach to at a higher risk of developing harmful
USD 185 billion (14% increase) by 2045 and costly complications

IDF Diabetes Atlas 9th edition 2019 for Western Pacific Region
Diagnosed Diabetes Mellitus Prevalence in Indonesia
 Definition
Sekelompok penyakit metabolik yang
ditandai dengan hiperglikemia akibat
kerusakan sekresi insulin, kerja insulin,
atau keduanya.
 Type of Diabetes Mellitus

Type 1 diabetes Type 2 diabetes

Penyebab utama diabetes pada masa kanak- Mayoritas (sekitar 90%) penderita diabetes
01 kanak dan tidak dapat dicegah. Orang
dengan diabetes tipe ini dapat hidup sehat
02 di seluruh dunia. Diabetes tipe ini bisa
dicegah dengan pola hidup sehat
dan memenuhi hidup hanya dengan
penyediaan insulin yang tidak terputus

Other specific types Gestational diabetes mellitus

Disebabkan oleh penyakit pankreas eksokrin, Wanita hamil dapat memiliki bayi yang besar
03 gangguan endokrin, obat-obatan dan bahan
kimia, dan infeksi
04 untuk usia kehamilan (biasa disebut dengan
“Giant Baby"), sehingga meningkatkan risiko
komplikasi kehamilan dan kelahiran baik bagi
ibu maupun bayinya.
Type 1 Diabetes
 TYPE 1 DIABETES
Characteristics

Penghancuran sel beta menyebabkan

defisiensi insulin absolut; immune-mediated
Idiopatik (10%)
diabetes adalah bentuk yang paling umum
(90%)
• Penghancuran cellular-mediated autoimmune • No defined etiologies; Tidak ada etiologi yang
dari sel beta pankreas ditentukan; kebutuhan absolut untuk terapi
• Individu rentan terhadap ketoasidosis penggantian insulin pada individu yang
• Sedikit atau tidak ada sekresi insulin terkena sporadis
• Insulin-dependent
• 75% individu berkembang sebelum usia 30
tahun; dapat terjadi hingga dekade kesepuluh
• Biasanya tidak obes
 TYPE 1 DIABETES
Primary Beta Cell Defect or Failure

CHARACTERISTICS
Age at onset • Peak onset at age 11–13 yr (slightly earlier for girls than for
boys)
• Rare in children younger than 1 yr and adults older than 30 yr
Sex Similar in males and females
Racial • Rates for whites 1.5–2 times higher than those for nonwhites
distribution • Higher rates for those of Scandinavian descent than for those
of central or southern European descent
Obesity Generally normal or underweight
 TYPE 1 DIABETES
Primary Beta Cell Defect or Failure

ETIOLOGY
Common theory • Autoimmune: Genetic and environmental factors, resulting in gradual process of
autoimmune destruction in genetically susceptible individuals
• Nonautoimmune: Unknown
• Strong association with HLA-DQA and HLA-DQB genes

Heredity • Risk to sibling: 5%–10%

• Risk to offspring: 2%–5%
Presence of antibody Islet cell autoantibodies (ICAs) and/or autoantibodies to insulin, and
autoantibodies to glutamic acid decarboxylase (GAD65) and tyrosine phosphatases
IA-2 and IA-2β are present in 85%–90% of individuals when fasting; hyperglycemia
is initially detected
Insulin resistance Insulin resistance at diagnosis is unusual, but insulin resistance may occur as the
individual ages and gains weight
Insulin secretion Severe insulin deficiency or no insulin secretion at all
TYPE 1 DIABETES
Pathophysiology
 TYPE 1 DIABETES
Pathophysiology
Explanation:
Autoimmune type 1 DM is a slowly progressive autoimmune T-cell–mediated disease that destroys
beta cells of the pancreas and occurs in genetically susceptible individuals. There is a deficient
immune tolerance linked to abnormalities in immune cells and changes in beta-cell antigens. Gene-
environment interactions result in the loss of tolerance to self-antigens with formation of autoantigens
that are expressed on the surface of pancreatic beta cells and circulate in the bloodstream and
lymphatics. Cellular immunity (T-cytotoxic cells and macrophages) and humoral immunity
(autoantibodies) are stimulated, resulting in beta-cell destruction and apoptosis.
Stage of destruction:
1) Lymphocyte and macrophage infiltration of the islets resulting in inflammation (insulinitis) and
islet beta-cell death. Autoantigens are expressed on the surface of pancreatic islet cells and
circulate in the bloodstream and lymphatics.
2) Production of autoantibodies against islet cells, insulin, glutamic acid decarboxylase (GAD), and
other cytoplasmic proteins. Activated T helper 2 (Th2) lymphocytes produce IL-4, which
stimulates B lymphocytes to proliferate and produce antibodies.
3) Relative inactivity of T regulatory cells that contribute to a decrease in beta-cell mass and insulin
production. Normally these T lymphocytes serve to inhibit the immune response and maintain
self-tolerance.
 TYPE 1 DIABETES
Clinical Manifestations

MANIFESTATION
Polydipsia Because of elevated blood glucose levels, water is osmotically attracted from body
cells, resulting in intracellular dehydration and hypothalamic stimulation of thirst
Polyuria Hyperglycemia acts as an osmotic diuretic; the amount of glucose filtered by the
glomeruli of the kidneys exceeds the amount that can be reabsorbed by the renal
tubules; glycosuria results, accompanied by large amounts of water lost in the urine
Polyphagia Depletion of cellular stores of carbohydrates, fats, and protein results in cellular
starvation and a corresponding increase in hunger
Weight loss Weight loss occurs because of fluid loss in osmotic diuresis and the loss of body
tissue as fat and proteins are used for energy as a result of the effects of insulin
deficiency
Fatigue Metabolic changes result in poor use of food products, contributing to lethargy and
fatigue; sleep loss from severe nocturia also contributes to fatigue
Type 2 Diabetes
 TYPE 2 DIABETES

Characteristics

• Usually not insulin dependent but may be insulin requiring

• Individual not ketosis prone (but may form ketones under stress)
• Obesity common in the abdominal region
• Generally occurs in those older than 40 years, but the frequency is
rapidly increasing in children
• Strong genetic predisposition
• Often associated with hypertension and dyslipidemia
 TYPE 2 DIABETES
Insulin Resistance with Inadequate Insulin Secretion

CHARACTERISTICS
Age at onset Risk of developing diabetes increases after age 40 yr; in general, incidence increases
with age into the 70s; among Pima Indians, incidence peaks between ages 40 and 50
yr, then falls

Sex Similar in males and females overall, although black females have the highest
incidence and prevalence of all groups
Racial distribution For all diabetes (e.g., type 1 and type 2): American Indians/Alaska Natives 15.1%;
black, non-Hispanic 12.7%; Hispanic 12.1%; Asian, non-Hispanic 8.0%; white, non-
Hispanic 7.4%
Obesity • Frequent contributing factor to precipitate type 2 diabetes among those
susceptible; a major factor in populations recently exposed to westernized
environment
• Increased risk related to duration, degree, and distribution of obesity
 TYPE 2 DIABETES
Insulin Resistance with Inadequate Insulin Secretion

ETIOLOGY
Common theory • Disease results from genetic susceptibility (polygenic) combined with
environmental determinants and other risk factors; inherited defects in betacell
mass and function combined with peripheral tissue insulin resistance
• Associated with long-duration obesity

Heredity Risk to first-degree relative (child or sibling): 10%–15%

Presence of antibody Islet cell antibodies not prevalent
Insulin resistance Insulin resistance is generally caused by altered cellular metabolism and an
intracellular post-receptor defect
Insulin secretion Typically increased at time of diagnosis, but progressively declines over the course
of the illness
TYPE 2 DIABETES
Pathophysiology
 TYPE 2 DIABETES
A suboptimal response of
insulinsensitive tissues
(especially liver, muscle,
Insulin Resistance and adipose tissue) to
insulin and is associated
with obesity.

Mechanisms

An abnormality of the insulin molecule, high amounts of

insulin antagonists, downregulation of the insulin receptor,
decreased or abnormal activation of postreceptor kinases,
and alteration of glucose transporter (GLUT) proteins.
TYPE 2 DIABETES

Multi-organ Causes and Common

Consequences of Chronic
Hyperglycemia in Type 2 Diabetes
Mellitus. GIP, Gastric inhibitory
peptide; GLP-1, glucagon-like
peptide-1; IL, interleukin; PVD,
peripheral vascular disease; TNF,
tumor necrosis factor.
 TYPE 2 DIABETES
Clinical Manifestation

MANIFESTATION
Recurrent infections (e.g., boils and Growth of microorganisms is stimulated by increased glucose levels;
carbuncles; skin infections) and impaired blood supply hinders healing; decline in immune protection
prolonged wound healing
Genital pruritus Hyperglycemia and glycosuria favor fungal growth; candida infections,
resulting in pruritus, are a common presenting symptom in women
Visual changes Blurred vision occurs as water balance in the eye fluctuates because of
elevated blood glucose levels; diabetic retinopathy is another cause of visual
loss
Paresthesias Paresthesias are common manifestations of diabetic neuropathies
Fatigue Metabolic changes result in poor use of food products, contributing to
lethargy and fatigue
Acanthosis nigricans Brown to black pigmentation in body folds associated with insulin resistance

* Type 2 diabetes mellitus also can have symptoms of polyuria, polydipsia, polyphagia, and weight loss as
in type 1 diabetes mellitus. The affected individual often is overweight, dyslipidemic, hyperinsulinemic, and
hypertensive.
OTHER SPECIFIC TYPES
 OTHER SPECIFIC TYPES
Name
Genetic defects of beta-cell function
Genetic defects in insulin action
Diseases of the exocrine pancreas
Endocrinopathies
Drug- or chemical-induced beta-cell dysfunction
Infections
Uncommon forms of immune-mediated diabetes
mellitus
Other genetic syndromes sometimes associated
with diabetes mellitus
Characteristics
Genetic abnormalities that decrease the ability of the beta cell to secrete insulin:
1. Maturity-onset diabetes of youth (MODY) includes six specific autosomal dominant
mutations including genes for hepatocyte nuclear factor-1α (HNF-1α; MODY 3),
glucokinase (MODY 2), HNF-4α (MODY 1), insulin-promoter factor-1(IPF-1; MODY 4),
HNF-1β (MODY 5), and NeuroD1 (MODY 6)
2. Defects in mitochondrial deoxyribonucleic acid (DNA)
3. Other (including an inability to convert proinsulin to insulin)
Mutations in the insulin receptor with hyperinsulinism or hyperglycemia or severe diabetes
Any process that diffusely injures the pancreas, including pancreatitis, neoplasia, and cystic
fibrosis
Endocrine disorders including acromegaly, Cushing syndrome, glucagonoma,
pheochromocytoma, hyperthyroidism, somatostatinoma, and aldosteronoma
Commonly associated drugs include glucocorticoids, treatment of HIV/AIDS, and after
organ transplantation although many others may be implicated
Beta-cell destruction by viruses including cytomegalovirus, congenital rubella
• Anti–insulin receptor antibodies
• Reported with “stiff man syndrome” and individuals receiving interferon-α
Down, Klinefelter, Turner, and Wolfram syndromes
Gestational Diabetes
 GESTATIONAL DIABETES

Characteristics
Any degree of glucose • Insulin resistance combined with inadequate insulin secretion
intolerance with onset or in relation to hyperglycemia
first recognition during • Women who are obese, older than 25 years of age, have a
pregnancy family history of diabetes, have a history of previous GDM, or
are of certain ethnic groups (Hispanic, Native American, Asian,
or black) are at increased risk of developing GDM
• The metabolic stress of pregnancy may uncover a genetic
tendency for type 2 diabetes mellitus
 GESTATIONAL DIABETES

• Women who had a pregnancy affected by GDM and normal results on

postpartum screening should be screened at 6 to 12 weeks after delivery
with repeat testing every 1 to 3 years depending on risk factors
• GDM results in increased risk for type 2 DM and long-term metabolic and
cardiovascular complications later in life for both mother and baby.
DIAGNOSIS OF DIABETES
 DIAGNOSIS
Criteria for Diabetes Mellitus
1. HbA1c (as measured in a DCCT-referenced assay)
≥6.5% OR
2. FPG ≥126 mg/dL (7.0 mmol/L); fasting is defined as
no caloric intake for at least 8 hr OR
3. 2-hr plasma glucose ≥200 mg/dL (11.1 mmol/L)
during an OGTT OR
4. In a patient with classic symptoms of hyperglycemia
or hyperglycemic crisis, a random plasma glucose
≥200 mg/dL (11.1 mmol/L)
DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose;
HbA1c, hemoglobin A1c; hr, hour(s); OGTT, oral glucose tolerance test.
 DIABETES TIMELINE

NORMAL PREDIABETES DIABETES

Fasting : <100 mg/dl IFG : 100-125 mg/dl >126 mg/dl

2-hr PG: <140 mg/dl IGT : 140-199 mg/dl >200 mg/dl

IFG, impaired fasting glucose, caused by enhanced hepatic glucose output secondary to hepatic insulin resistance
IGT, impaired glucose tolerance, results from diminished insulin secretion
PG, plasma glucose.
4 SIMPLE STEPS FROM SCREENING TO DIAGNOSIS

3. Conduct
1. Screen patients second blood test 4. Inform patient
2. Conduct first
with diabetes risk (if required) and and initiate
blood test
factors establish treatment
diagnosis
Step 1: Risk Factors – PERKENI screening risk factor guideline

Unmodifiable Risk Modifiable Risk Diabetes Associated Risk

• Race and Ethnic • Overweight (BMI >23) • Polycystic Ovary Syndrome
• Family History of Diabetes • Hypertension > 140/90 mmHg (PCOS) or another clinical
• History of Gestational Diabetes • Dyslipidemia (HDL < 35 mg/dl condition related to insulin
• History of delivery a baby more and/or triglycerides >250 resistance
than 4.000g mg/dl • Metabolic Syndrome (IGT, IFG,
• History of low birth weight • Unhealthy Diet History of Coronary Artery
<2.500g • Limited Physical Activity Disease , stroke and/or PAD)

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Step 2: Conduct First Blood Test
Clinical Test

(+) Classic Symptoms (-) Classical Symptoms

FBG >126 <126 FBG >126 100-125 <100

RBG >200 <200 RBG >200 140-199 <140

Repeat FBG or RBG

2 Hour Post loading Plasma Glucose

Diabetes Mellitus IGT IFG Normal

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Step 3: Conduct Second Blood Test (if Required) and Establish Diagnosis

Clinical Test

(+) Classic Symptoms (-) Classical Symptoms

FBG >126 <126 FBG >126 100-125 <100

RBG >200 <200 RBG >200 140-199 <140

Repeat FBG or RBG

>126 <126 2 Hour Post loading Plasma Glucose

>200 <200

PPG >200 140-199 <140

Diabetes Mellitus IGT IFG Normal

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

 Step 4: Inform Patient and Initiate Treatment

Diabetes Mellitus IGT IFG

• Evaluation of Nutritional Status • Education

• Evaluation of Diabetes Complications • Food Regulation
• Evaluation of Required Food Regulation • Physical Exercise
• Decision on medicines • Ideal Body Weight
• OADs are unnecessary at this stage

Source: KONSENSUS: Pengelolaan Dan Pencegahan DM Type 2

COMPLICATION
 Diabetic Complication

Acute Chronic

Microangiopathy Macroangiopathy
Hiperglikemia Hipoglikemia

Retinopathy CAD
DKA PVD
HHS Nephropathy
Neuropathy Stroke
ACUTE COMPLICATION: HIPERGLIKEMI

Two of the most serious acute hiperglycemiac

complications of diabetes
 Diabetic Ketoacidosis (DKA) : Hyperglycemia, ketosis,
acidemia
Mortality rates :
< 1% (adult subjects)
> 5 % (elderly and patient with concomitant life
threatening illnesses)
 Hyperosmolar Hyperglycemic State (HHS):
Hyperosmolarity, Hyperglycemia, dehydration
Mortality rate 5-20 %
ACUTE COMPLICATION: HIPERGLIKEMI
Precipitating Factors
o Infection
o Management errors
o Medical, surgical or emotional stress
o Drugs
o Other factors
ACUTE COMPLICATION: HIPERGLIKEMI

PATHOPHYSIOLOGY
ACUTE COMPLICATION: HIPERGLIKEMI
Diagnosis
• History and physical examination
• Laboratory findings
• Differential diagnosis
ACUTE COMPLICATION: HIPERGLIKEMI

THERAPHY
ACUTE COMPLICATION: HIPOGLIKEMI
Defined

Whipple’s triad:
• A state of neuroglycopenic and/or neurogenic
symptoms due to low plasma glucose levels
≤ 70 mg/dl (ADA)
< 60 mg/dl (PERKENI)
< 72 mg/dl (CDA)
• relief of those symptoms when the plasma glucose
concentration is raised
ACUTE COMPLICATION: HIPOGLIKEMI
Symptoms

Autonomic Neuroglycopenic Malaise

Sweating Confusion Nausea
Pounding heart Drawsiness Headache
Tremor Speech difficulty
Hunger Incoordination
Atypical behaviour
Visual disturbance
Circumoral
paraesthesia
ACUTE COMPLICATION: HIPOGLIKEMI
Treating Early Signs

First: 10–20 g fast-acting carbohydrate, e.g.:

 3–6 glucose tablets
 90–180 ml fizzy drink or squash (not diet)
 Two teaspoons of sugar added to a cup of cold drink
 50–100 ml energy drink (e.g. Lucozade®)

Then:
• If next meal is due, add extra carbohydrate
• If next meal is not due, eat longer-acting carbohydrate, such as biscuits or a
sandwich
ACUTE COMPLICATION: HIPOGLIKEMI
Treating Late Signs

Patient requires assistance with treatment

If conscious:
• Carer should help the patient to consume
10–20 g fast-acting carbohydrate
• Dextrose gel may be useful
If unconscious:
• Don’t put anything in patient’s mouth
• IM or SC glucagon or IV glucose should be administered
• Emergency services should be called
CHRONIC COMPLICATION

Stroke
2-4 x risk for stroke
The most frequent cause of and coronary heart
new cases of blindness disease
among adults aged 20 to
74. Diabetic
Retinopathy

Cardiovascular
disease

Diabetic
Nephropathy Myocardiac infarct
Most common cause of
death in diabetics
Accounts for ~40% of all new
cases of end-stage renal Diabetic
disease (ESRD).
Neuropathy

A Malignant Vascular Disorder Most common cause of

lower limb amputation
CHRONIC COMPLICATION
Hyperglycemia
AGE Formation Glucose autoxidation Sorbitol pathway

 Antioxidants
 Oxidative Sress

Lipid peroxidation Endothelial dysfunction Hypercoagulability

 Leukocyte adhesion  NO  Endothelin Fibrinolysis
 Foam cell formation  Prostacyclin  Coagulability
 TNF a  TXA2  Platelet reactivity

Vascular complications

Retinopathy Nephropathy Neuropathy

CHRONIC COMPLICATION
Classification of Micro- and Macrovascular Complications

• Microvascular complications
• Eyes – retinopathy » blindness
• Kidney – nephropathy » kidney failure
• Nerves – neuropathy » disability
• Amputations » disability
• Erectile Dysfunction

• Macrovascular complications
• Heart – myocardial infarction
• Brain – stroke
• Atherosclerosis – myocardial infarction

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