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د ﻋﻤﺮ ﻓﺎروق اﻟﻌﺰاوي
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Whole Blood Vs. Plasma Glucose Levels
¾ The difference is that plasma glucose levels read about 10 ‐ 12% higher than the whole blood
glucose.
¾ So if your fasting plasma glucose is 90 ‐ 130 mg/dl, it equals 80 ‐ 120 mg/dl whole blood.
¾ Most new meters are programmed to provide blood glucose readings as plasma glucose readings
although it use whole blood
To convert Whole Blood or Plasma Glucose from mmol/l to mg/dl. multiply by 18 and vice versa is correct
Glycated Hemoglobin (Hba1c)
The Hba1c has several advantages to the FPG and OGTT, including
¾ Convenient (fasting not needed)
¾ Greater stability, and less day‐to‐day variations during stress and illness.
Also has several disadvantages
¾ Greater cost,
¾ Limited availability in the developing world,
¾ For patients with an abnormal hemoglobin or abnormal red cell turnover, such as
• Pregnancy,
• Recent blood loss or transfusion,
• Anemias as Genetic variants (e.g. HbS trait, HbC trait), elevated fetal hemoglobin (HbF) and
chemically modified derivatives of hemoglobin (e.g. carbamylated Hb in patients with renal
failure) can affect the accuracy of HbA1c measurements.
Iron deficiency anemia, is associated with higher HbA1c and higher fructosamine also
iron replacement therapy lowers both HbA1c and fructosamine concentrations in
diabetic and non‐diabetic individuals
• Renal Failure due to carbamylated Hb and diabetic patients on dialysis due to erythropoietin
intake, and other factors in chronic renal failure
Plasma glucose tests should be used to diagnose diabetes in all above mentioned situations
Screening
Screening test for type 2 DM is recommended because
¾ large number of individuals with type 2 DM are asymptomatic and unaware of the disorder,
epidemiologic studies suggest that type 2 DM may be present for up to a decade before diagnosis,
¾ Some individuals with type 2 DM have one or more diabetes complications at the time of their
diagnosis,
¾ Early treatment of type 2 DM may favorably alter the natural history of DM.
The American Diabetes Association (ADA) recommends screening of all individuals who are
¾ >45 years every 3 years and
¾ Screening individuals at an earlier age if they are
• Overweight (BMI) >25 kg/m
2
] and have one additional risk factor for diabetes.
¾ In contrast to type 2 DM, a long asymptomatic period is rare in type 1 DM, so screening is usually
not needed.
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Prevention
The Diabetes Prevention Program (DPP) demonstrated that
¾ Intensive changes in lifestyle (diet and exercise for 30 min/day five times/week) in individuals
with IGT prevents or delay the development of type 2 DM by 58% regardless of age, sex, or ethnic
group.
¾ Also In the same study, metformin prevented or delayed diabetes by 31% compared to placebo.
Pharmacologic therapy use for individuals with prediabetes is currently controversial because it’s cost ‐
effectiveness and safety profile are not known, so:
The ADA suggested that metformin to be considered in individuals with both IFG and IGT who are at very
high risk for progression to diabetes (risks mentioned previously)
Individuals with IFG, IGT, or an A1C of 5.7–6.4% should be monitored annually for progression to
diabetes.
MODY
Maturity‐onset diabetes of the young is a subtype of DM characterized by
¾ AD inheritance,
¾ Early onset of hyperglycemia (usually <25 years),
¾ Impairment in insulin secretion
It is due to genetic defects of beta cell function and are of 6 types (MODY1 to MODY6) depending on site
of the mutation.
All respond to sulfonylureas except MODY 2 that require insulin treatment
LADA
Latent autoimmune diabetes of adults, or slow onset type 1 diabetes or diabetes type 1.5
Form of type 1 DM that occurs in adults, often with a slower course of onset
May initially be diagnosed as having type 2 diabetes based on their age.
Raised antibodies against the islets of Langerhans support the diagnosis of type 1 DM rather than type 2 .
It can only be treated with oral anti diabetics for a short period of time, after which insulin treatment is
the final and only treatment as in type 1 DM
Gestational Diabetes Mellitus (GDM)
Glucose intolerance developing during late pregnancy due to
insulin resistance
because of
¾ Metabolic changes,
¾ Increased insulin requirements
May lead to IGT or diabetes.
GDM occurs in 7% (range 2–10%) of pregnancies in the United States;
Most women revert to normal glucose tolerance postpartum but have a substantial risk (35–60%) of
developing DM in the next 10–20 years.
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Diagnosis of GDM
¾ International Diabetes and Pregnancy Study Groups recommends that diabetes diagnosed at the
initial prenatal visit should be classified as "overt" diabetes and not gestational diabetes
¾ At 24–28 weeks of gestation women not previously diagnosed with overt diabetes should perform
either
¾
One‐step
test 75‐g OGTT, after an overnight fast of at least 8 h with plasma glucose
measurement, at fasting, 1 and 2 h,
Diagnosis of GDM is made when any of the following plasma glucose values are exceeded:
¾ Fasting: ≥92 mg/dL (5.1 mmol/L)
¾ 1 h: ≥ 180 mg/dL (10.0 mmol/L)
¾ 2 h: ≥ 153 mg/dL (8.5 mmol/L)
Or
the
¾ Two‐step test
• (Step 1)
nonfasting
50‐g OGTT
If the plasma glucose level measured 1 h after the load is less than 140 mg/dL so she has no GDM but if
the plasma glucose is ≥ 140 mg/dL (7.8 mmol/L)., proceed to
(Step 2). The 100‐g OGTT which should be performed when the patient is
fasting
.
The diagnosis of GDM is made when the plasma glucose level measured 3 h after the test is ≥ 140 mg/dL
(7.8 mmol/L).
Treatment of GDM
¾ Diet and life style changes
¾ Insulin remains the mainstay of therapy for gestational diabetes due to the close glucose control it
affords
¾ Oral glucose‐lowering agents studies using metformin or glibenclamide (called glyburide in USA)
have shown efficacy and have not found toxicity, they should only be used during pregnancy
when the benefit outweighs the risk.
Acute Complications of DM
I‐ DIABETIC KETOACIDOSIS (DKA)
Pathophysiology
DKA results from the combined effects of insulin deficiency and increased counter regulatory
hormones ESPECIALLY Glucagon which is necessary for DKA to develop.
Other hormones as catecholamines, cortisol, and growth hormone).also play important role.
The decreased ratio of insulin to glucagon leads to
¾ Glycolysis stops so energy is formed by
¾ Glycogenolysis, then
¾ Gluconeogenesis,
¾ Lipolysis
¾ Increase in substrate delivery from fat to the liver by increasing the release of FFA )
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Normally, these free fatty acids are converted to triglycerides or VLDL with little amount of ketone
bodies in the liver.
In DKA, hepatic metabolism is altered to favor ketone body formation, rather than triglycerides or
VLDL because:
• Prolonged insulin deficiency stimulate production of mitochondrial HMG‐CoA
synthase and of HMG‐CoA lyase
[HMG‐CoA is (3‐hydroxy‐3‐methylglutaryl‐coenzyme A) ]
• These and the exhaustion of substrates notably oxaloacetate for gluconeogenesis and for the
Citric acid cycle results in shunting of excess acetyl‐CoA into the ketone synthesis pathway
and leading to
¾ Ketone body formation in the liver, and the development of diabetic ketoacidosis.
¾ Ketone bodies are neutralized by bicarbonate. As bicarbonate stores are depleted, metabolic
acidosis ensues.
¾ Also there is increased lactic acid production which contributes to the acidosis.
Clinical Features of DKA
¾ Due to the absolute or relative insulin deficiency and increased glucagon will lead to sever
volume depletion, ketone formation, hyperglycemia, electrolyte and acid‐base abnormalities.
¾ DKA most commonly occur in type 1 DM, however, patients with type 2 diabetes are also at risk
during the catabolic stress of acute illness.
¾ Contrary to popular belief, DKA is more common in adults than in children.
¾ It may be the initial symptom that leads to a diagnosis of type 1 DM
Symptoms
¾ Excessive Thirst/polyuria
¾ Nausea/vomiting
¾ Abdominal pain
¾ Shortness of breath
Physical Findings
¾ Tachycardia (rapid thready)
¾ Dehydration/Postural hypotension
¾ Tachypnea/Kussmaul breathing (rapid, deep and labored breathing/ respiratory distress
¾ Abdominal tenderness (may resemble acute pancreatitis or acute abdomen)
¾ Lethargy
¾ Altered level of consciousness
¾ Cerebral edema and possibly coma
Features suggesting severe dehydration in general and in DKA includes:
¾ Postural hypotension
¾ Cold extremities.
¾ Peripheral cyanosis.
¾ Rapid thready pulse.
¾ Oliguria.
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Features indicating sever DKA
¾ Postural hypotension
¾ Cold extremities.
¾ Peripheral cyanosis.
¾ Rapid thready pulse.
¾ Kussmaul respiration.
¾ Altered level of consciousness.
Tachycardia. Hypotension can occur because of volume depletion ( hypovolemic shock)
Kussmaul respiration and a fruity odor on the patient's breath are classic signs of the disorder.
(secondary to metabolic acidosis and increased acetone).
Altered level of consciousness and possibly coma due to combination of severe hyperglycemia, severe
dehydration, acidosis, shock, and exhaustion.
Precipitating Factors
¾ Inadequate or Omission of insulin administration or wrong treatment.
¾ Infection (pneumonia/UTI /sepsis …etc) Signs of infection, should be sought even in the absence
of fever. It is the most common precipitating factor for DKA,
¾ Tissue ischemia (cerebral, coronary, pulmonary embolism, mesenteric, peripheral)
¾ Newly diagnosed type 1 DM
¾ Trauma , surgery, psychological stress
¾ Pregnancy
¾ Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic
agents, and pentamidine may precipitate the development of DKA.
¾ Alcohol/ cocaine abuse,
Diagnosis and Laboratory Abnormalities
Early diagnosis and treatment of DKA is crucial
The diagnosis is usually straightforward, as there is usually a short period of 12‐24 hours when the
symptoms and signs develop.
¾ Plasma Glucose: To support the diagnosis of DKA and provide a baseline to assess response to
treatment. Occasionally, the serum glucose is only minimally elevated.
¾ Urinary & plasma ketones: There are three ketone bodies, all of which are organic acids:
1. Acetoacetone.
2. Beta ‐ hydroxybutyrate.
3. Acetone.
Acetoacetone is easily detected by commonly used available ketone detection kit (nitroprusside).certain
medications such as captopril or penicillamine may cause false‐positive reactions, so it is not very
accurate
Serum or plasma assays for hydroxybutyrate are preferred since they are more accurate and reflect the
true ketone body level.
Ketonemia is a consistent finding in DKA and distinguishes it from simple hyperglycemia.
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¾ Arterial and now Venous blood gases is the best and easiest way if available to measure
electrolyte and acid base balance
• Serum bicarbonate is frequently <10 mmol/L, and arterial pH ranges between 6.8 and 7.3,
leading to metabolic acidosis (increased anion gap)
• Serum osmolality is mildly to moderately elevated, calculated In "conventional" units
[2 x (serum sodium + serum potassium) + plasma glucose (mg/dL)/18 + BUN/2.8]
Electrolytes:
• Sodium plasma concentrations are usually normal or slightly low despite large urinary
losses, due to dehydration and hyperglycemia.
• Plasma potassium is usualy at the upper end of normal or slightly increased secondary to
the acidosis. This does not reflect the total body potassium deficit, which is always
present.
¾ Elevated blood urea nitrogen (BUN) and serum creatinine levels reflect intravascular volume
depletion.
Interference from acetoacetate may falsely elevate the serum creatinine measurement.
¾ Hyperamylasemia may suggest a diagnosis of pancreatitis, especially when accompanied by
abdominal pain. However, in DKA the amylase is usually of salivary origin
Serum lipase should be obtained if pancreatitis is suspected.
¾ White cell count: often raised to 15000 ‐ 20 000. and does not signify infection in the absence of
obvious clinical signs.
¾ Blood culture: For sepsis which may have precipitated DKA.
¾ Chest X‐ ray: for signs of infection.
¾ ECG: for underlying myocardial ischemia, especially in those > 40 years of age or with long
duration of diabetes.
The differential diagnosis of DKA
includes
¾ Starvation ketosis,
¾ Alcoholic ketoacidosis (bicarbonate usually >15 meq/L)
¾ And other forms of increased anion‐gap acidosis
Treatment
The therapeutic goals consist of:
1. Correcting circulatory volume and tissue perfusion
2. Correcting blood glucose, serum osmolality and metabolic acidosis
3. Clearing of ketones.
4. Correcting electrolyte imbalances
5. Identifying and treating precipitating factors.