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Diabetes mellitus
DEFINITION
Diabetes mellitus (DM) comprises a group of
common metabolic disorders that share the
phenotype of hyperglycemia. Factors
contributing to hyperglycemia may include:
• Reduced insulin secretion,
• Decreased glucose utilization
• Increased glucose production
PHYSIOLOGY - digestion of carbohydrates
• This metabolism of carbohydrates is achieved through the
secretion of a number of digestive enzymes into the
gastrointestinal tract where they attack carbohydrates and
gradually convert them into simple sugars like glucose so
they can be absorbed into the blood.
• The process of digesting carbohydrates begins in the
mouth. Our saliva contains an enzyme called amylase that
starts breaking down the more complex carbs into simpler
types.
PHYSIOLOGY - digestion of carbohydrates
• Another version of amylase is secreted by the pancreas
into the duodenum. This cuts down carbohydrates into
simple sugars - maltose, lactose and sucrose.
• As the carbohydrate passes further into the intestine, the
enzymes maltase, lactase and sucrase chop maltose,
lactose and sucrose into smaller bits, which are eventually
converted to glucose and absorbed through the intestinal
walls into the bloodstream.
PHYSIOLOGY - glucose metabolism
The Liver
• The glucose is taken to the liver through portal vein.
There it is stored or distributed to cells throughout the
body for energy. In this way, the liver regulates blood
glucose levels to provide sufficient energy for the body.
• Excess glucose is converted in the liver to glycogen
(glycogenogenesis).
• If blood sugar levels fall, the glycogen is re-converted
to glucose (glycogenolysis) by the hormone glucagon,
to prevent hypoglycemia.
• If glycogen levels are exhausted, glucagon can trigger
the formation of glucose from some amino acids or
glycerol (gluconeogenesis).
PHYSIOLOGY - glucose metabolism
• Glucose from blood to cells is carried across the cell
membrane by a family of specialised transporter
proteins called glucose transporters (GLUTs)
• GLUT 1 – is involved in basal and non-insulin-mediated
glucose uptake in many cells
• GLUT 2 – in the islet B cell
• GLUT 3 – non-insulin-mediated glucose uptake in the
brain
• GLUT 4 – responsible for insulin-stimulated glucose
uptake in muscle and adipose tissue
PHYSIOLOGY - glucose metabolism
• Glucose is the main stimulator of insulin release from
the B cell, through GLUT 2
• Insulin works by binding to a receptor on the target cell
surface.
• Insulin has many functions such as glucose transport,
protein synthesis, lipid synthesis, glycogen synthesis,
growth and gene expression
• Insulin recruits the cytoplasmatic vesicles with GLUT 4
and causes them to be translocated to the cell surface
where GLUT 4 functions as s pore for glucose entry.
PHYSIOLOGY
• In normal subjects, blood glucose levels are
maintained within relatively narrow limits at
around 5 mmol/l (90 mg/dl) by the balance
between glucose entry into the bloodstream
from the liver and from intestinal absorption
after meals, and glucose uptake into the
peripheral tissues such as muscle.
EPIDEMIOLOGY
DM have 23.6 million children and adults in the
United States (7.8% of the population).
While an estimated 17.9 million have been
diagnosed with diabetes, unfortunately, 5.7
million people (or nearly one quarter) are
unaware that they have the disease.
In USA, DM is the leading cause of:
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end-stage renal disease,
nontraumatic lower extremity amputations,
adult blindness.
CLASSIFICATION
Diabetes mellitus is classified on the basis of the
pathogenic process that leads to hyperglycemia.
We can distinguish:
• Type 1 DM
• Type 2 DM
• Other specific types of diabetes
• Gestational diabetes mellitus (GDM)
TYPE 1 DIABETES MELLITUS
TYPE 1 DIABETES MELLITUS
Type 1A DM results from autoimmune beta cell
destruction, which leads to insulin deficiency
Type 1B DM lack immunologic markers indicative of an
autoimmune destructive process of the beta cells.
Patients with this type of diabetes develope insulin
deficiency by unknown mechanisms
Few patients with type 1 DM are in the type 1B
idiopathic category; many of these individuals are
either African-American or Asian in heritage
Type 1 DM most commonly develops before the age of
30, an autoimmune cell destructive process can
develop at any age (Latent Autoimmune Diabetes in
Adults – LADA).
SIGNS AND SYMPTOMS
The early detection of diabetes symptoms and treatment can
decrease the chance of developing the complications of
diabetes.
Some typical symptoms for diabetes type 1 include:
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Frequent urination (polyuria)
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Excessive thirst (polydypsia)
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Extreme hunger (polyphagia)
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Unusual weight loss
Others symptoms
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Increased fatigue
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Irritability
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Blurry vision
LAB STUDIES
• Blood sugar level (hyperglycemia)
• Urine analysis
– Acetonuria
– Glucosuria
• Gasometry (acidosis)
• Specific autoantibodies (present)
• C-peptide (low) – part of pro-insulin which is
co-secreted with insulin
TYPE 2 DIABETES MELLITUS
TYPE 2 DIABETES MELLITUS
Is a heterogeneous group of disorders characterized
by variable degrees of insulin resistance, impaired
insulin secretion and increased glucose production
Distinct genetic and metabolic defects in insulin action
and/or secretion give rise to the common
phenotype of hyperglycemia in type 2 DM
Type 2 DM more typically with increasing age, but it
also occurs in children, particularly in obese
adolescents
Type 2 DM is more often than type 1 DM
TYPE 2 DIABETES MELLITUS
RISK FACTORS
Family history of diabetes
Obesity (BMI ≥25 kg/m2)
Habitual phisical inactivity
Race/ethnicity (African American, Native American, Asian
American, Pacyfic Islander)
Previously identified impaired fasting glucose (IFG) or impaired
glucose tolerance (IGT)
History of gestational diabetes mellitus or delivery of baby >4kg
Hypertension
HDL cholesterol level ≤ 35 mg/dl (0.90 mmol/l) and/or
triglyceride level ≥250 mg/dl (2.82 mmol/l)
Polycystic ovary syndrome
Acantosis nigricans
History of vascular disease
SIGNS AND SYMPTOMS
Diabetes often goes undiagnosed because many of its symptoms seem so
harmless. It can be diagnosed accidently. Recent studies indicate that
the early detection of diabetes symptoms and treatment can
decrease the chance of developing the complications of diabetes.
Some diabetes symptoms include:
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Frequent urination (polyuria)
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Excessive thirst (polydypsia)
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Extreme hunger (polyphagia)
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Unusual weight loss
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Increased fatigue
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Irritability
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Blurry vision
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Skin infections
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Genital and urine infections
LAB STUDIES
• Blood sugar level (hyperglycemia)
• Urine analysis
– Glucosuria
– Leucocyturia
– Bacteriuria
• Gasometry (normal)
• C-peptide (normal or high)
ACCESSORY INVESTIGATIONS
• When you diagnose DM type 2 you have to
look for chronic complications.
– Eye examination – fundoscopy for retinopathy
– Creatinin level, microalbuminuria for
nephropathy
– Testing of vibration, temperature and touch
sense for neuropathy
• When you diagnose DM type 1 you have to
look for chronic complications after around 5
years.
OTHER SPECIFIC TYPES OF DIABETES
Other ethiologies for DM include specific genetic defects in insulin
secretion or action, metabolic abnormalities that impair
insulin secretion, mitochondrial abnormalities, and a host of
conditions that impair glucose tolerance.
Genetic defects of beta cell function
Genetic defects in insulin action
Disease of the exocrine pancreas – pancreatitis, pancreatectomy,
neoplasia, cystic fibrosis, hemochromatosis
Endocrinopathies – acromegaly, Cushing’s syndrome,
pheochromocytoma, glucagonoma
Drugs or chemical-induced – glucocorticoids, thyroid hormone
Infections – congenital rubella, cytomegalovirus, coxackie
Uncommon forms of immune-mediated diabetes
Other genetic syndroms sometimes associated with diabetes –
Down’s syndrom, Klineferter’s syndrom, Turner’s syndrom
GESTATIONAL DIABETES MELLITUS (GDM)
Diabetes mellitus developed during pregnency.
Insulin resistance related to the metabolic changes of late
pregnency increases insulin requirements.
Most women revert to normal glucose tolerance post-partum but
have a substantial risk (30 to 60%) of developing DM later
in life.
DIAGNOSIS
Glucose tolerance is classified into three categories based on the
fasting plasma glucose (FPG)
FPG <5.6 mmol/l (100 mg/dl) is considered normal
FPG ≥5.6 mmol/l (100 mg/dl) but <7,0 mmol/l (126 mg/dl) is
defined as impaired fasting glucose (IFG)
FPG ≥7,0 mmol/l (126 mg/dl) warrants the diagnosis of DM
When patient have impaired fasting glucose (IFG) we make 75g
oral glucose load and assey glucose level after 2 hours
Glucose level 2 h after a 75g oral glucose load:
<7.8 mmol/l (140 mg/dl) is normal
≥7.8 mmol/l (140 mg/dl) but <11,1 mmol/l (200 mg/dl) is
defined as impaired glucose tolerance (IGT)
≥ 11,1 mmol/l (200 mg/dl) is DM
DIAGNOSIS
Criteria for the diagnosis of DM:
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fasting plasma glucose (FPG) ≥7,0 mmol/l (126 mg/dl)
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2 h plasma glucose ≥ 11,1 mmol/l (200 mg/dl) during an
oral glucose tolerance test
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Symptoms of diabetes plus random blood glucose
concentration ≥ 11,1 mmol/l (200 mg/dl)
In absence of unequivocal hyperglycemia and acute metabolic
decompensation, these criteria should be confirmed by
repeat testing on a different day.
Patient with impaired fasting glucose (IFG) or impaired glucose
tolerance (IGT) are at substantial risk for developing type 2
DM (40% risk over the next 5 years) and cardiovascular
disease.
SCREENING
The American Diabetes Association (ADA) recomends screening
all individuals >45 years every 3 years and screening
individuals with additional risk factors for type 2 DM at an
earlier age.
LONG-TERM TREATMENT OF DM
The goals of therapy for type 1 or type 2 DM are to:
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Eliminate symptoms related to hyperglicemia
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Reduce or eliminate the long-therm microvascular and
macrovascular complications of DM
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Allow the patient to achive as normal a life style as possible
The
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patient with type 1 or type 2 DM should receive education about:
nutrition,
exercise,
self-monitoring of blood glucose,
Urine ketone monitoring (type 1 DM),
Insuline administration,
Management of hypoglycemia,
Foot and skin care,
care of diabetes during illness,
medications to lower the plasma glucose.
LONG-TERM TREATMENT OF DM
Optimal monitoring of glycemic control involves plasma glucose
measurements by the patient and an assessment of longterm control by the physician (measurement of hemoglobin
A1c and review of the patient’s self-measurements of
plasma glucose). These measurements provide a picture of
short-term glycemic control, whereas the A1c reflects
average glycemic control over the previous 2 to 3 months
Ideal goals for glicemic control
Preprandial plasma glucose – 5.0-7.2 mmol/l (90-130 mg/dl)
Peak postprandial plasma glucose – <10 mmol/l (180 mg/dl)
Hemoglobin A1c – <7.0%
TREATMENT OF TYPE 1 DM
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Insulin therapy
TREATMENT OF TYPE 2 DM
Menagement of type 2 diabetes:
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Glycemic control
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Diet/lifestyle
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Exercise
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Medication
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Treat associated conditions
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Dyslipidemia
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Hypertension
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Obesity
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Coronary heart disease
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Screen for/manage complications of diabetes
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Retinopathy
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Cardiovascular disease
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Nephropathy
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Neuropathy
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Other complications
TREATMENT OF TYPE 2 DM
Advances in therapy of type 2 DM have generated considerable
enthusiasm for oral glucose-lowering agents that target
different pathophysiologic processes in type 2 DM. Based on
their mechanisms of action, oral glucose-lowering agents
are subdivided into agents that:
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increase insulin secretion,
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reduce glucose production, or increase insulin secretion,
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reduce glucose production or increase insulin sensitivity
Insulin therapy in type 2 DM
Insulin therapy is ultimately required by a substantial
number of the disorder and the relative insulin deficiency
that develops in patients with long standing diabetes.
COMPLICATIONS OF DM
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ACUTE
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Diabetic ketoacidosis
CHRONIC
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Microangiopathy
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Macroangiopaty
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Retinopathy
Nuropathy
Nephropathy
Coronary artery disease
Peripheral vascular disease
Cerebrovascular disease
Other
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Infectious
Cataracts
Glaucoma
Diabetic ketoacidosis
• Is a state of severe, uncontrolled diabetes due
to insulin deficiency, and characterised by high
blood glucose, volume depletion, ketone body
concentrations and acidosis.
• Is a serious condition with a mortality of 510%
Diabetic ketoacidosis – causes
The common precipitating causes of ketoacidosis
are:
1. Infection (pneumonia, urine tract infection,
gastroenteritis, sepsis)
2. Management errors (giving the wrong dose of
insulin or failing to increase dosage during
intercurrent illness)
3. Newly presenting type 1 diabetes
4. Myocardial infarction
5. Drugs (cocaine)
6. Pregnancy
7. In about 40% there is no obvious cause
Diabetic ketoacidosis – mechanism
• Relative or absolute insulin deficiency in the
presence of catabolic counter-regulatory ‘stress’
hormones (catecholamines, cortisol, glucagon and
growth hormone) leads to hepatic overproduction
of glucose and ketones.
• Lipolysis is promoted with the relase of nonestrified fatty acids from adipose tissue, which in
the liver are oxidised to the ketone bodies:
acetoacetic acid, 3-hydroxybutyric acid and
acetone.
• Ketone bodies contribute to the acidosis and fluid
depletion
Diabetic ketoacidosis – clinical features
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Polyuria and nocturia
Thirst
Weight loss
Weakness
Blurred vision
Abdominal pain (can resemble acute pancreatitis
or surgical abdomen)
• Leg cramps
• Nausea and vomiting
• Confusion and drowsiness
Diabetic ketoacidosis – physical findings
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Tachycardia
Dry mucous membranes/reduced skin turgor
Dehydration/hypotension
Tachypnea
Acidotic (Kussmaul) respiration (hyperventilation)
Abdominal tenderness
Coma (10% of cases)
Acetone which is volatile can often be smelled on
the breath of ketoacidotic patients (fruity odor)
Diabetic ketoacidosis – laboratory
abnormalities
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Hyperglycaemia
Ketosis
Metabolic acidosis (increased anion gap)
Creatinine – elevated due to volume depletion
Leukocytosis
Hypertriglyceridemia, hyperlipoproteinemia
Serum osmolality is mildly to moderately elevated
Diabetic ketoacidosis – treatment
1. Fluids (isotonic saline 1l/h; usually 4-6 l in first
24h)
2. Potassium; if serum potassium is:
<3.5 mmol/l add 40 mmol K+
3.5-5.5 mmol/l add 20 mmol K+
>5.5 mmol/l add no K+
3. Insulin
Bolus IV 0.1 units/kg
and than 0.1 units/kg per hour by continous IV
infusion
Thank you for your attention!!!