Transcript Diabetes Mellitus

Diabetes Mellitus
MZ.Zamanpour MD
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Definition & Diagnosis
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(1) Fasting serum glucose concentration ≥126 mg/dL,
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(2) a random venous plasma glucose ≥200 mg/dL with symptoms of
hyperglycemia,
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(3) an abnormal oral glucose tolerance test (OGTT) with a 2-hour
postprandial serum glucose concentration ≥200 mg/dL, and
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(4) a HgbA1c ≥6.5%.
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impaired fasting glucose (IFG) → (FBS: 100-125 mg/dl)
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impaired glucose tolerance (IGTT) → 2-hour plasma glucose following an
OGTT is 140 to 199 mg/dL
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Sporadic hyperglycemia (Stress Hyperglycemia)
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Insulin-dependent (type 1) Diabetes
Mellitus
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Autoimmune destruction of insulin-producing beta cells (islets) (T cell–
mediated)(Destruction of 80-90%)
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Environmental factors:
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Cow’s milk feeding at an early age
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Viral infectious agents (Coxsackie virus, cytomegalovirus, mumps, rubella)
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Vitamin D deficiency
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Perinatal factors
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Islet cell antibodies, Insulin autoantibodies, antibodies to tyrosine
phosphatase IA-2, antibodies to glutamic acid decarboxylase, and others
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1 antibody: 10-15% risk, 2 antibodies: 55-90%
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Epidemiology &Genetics
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Siblings or offspring of patients with diabetes have a risk of 2% to 8%
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Identical twin has a 30% to 50% risk
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Class II DR and DQ HLA alleles (HLA DR3 and HLA DR4) increase the risk.
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More than 90% of children with DM1 possess HLA DR3 alleles, HLA DR4
alleles, or both
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Clinical Manifestations
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Insulin deficiency usually first causes postprandial hyperglycemia and then
fasting hyperglycemia
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Ketogenesis is a sign of more complete insulin deficiency
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Glycosuria occurs when the serum glucose concentration exceeds the renal
threshold for glucose reabsorption (from 160 to 190 mg/dL).
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Polydipsia occurs as the patient attempts to compensate for the excess fluid
losses
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Weight loss results from the persistent catabolic state and the loss of calories
through glycosuria and ketonuria
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The classic presentation of DM1 includes polyuria, polydipsia, polyphagia, and
weight loss
Schematic representation of the autoimmune
evolution of diabetes in genetically predisposed
individuals
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Diabetic Ketoacidosis
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Diagnosis:
(1) The arterial pH is below 7.3
(2) The serum bicarbonate level is below 15 mEq/L
(3) Ketones are elevated in serum or urine
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Pathophysiology
Absence of adequate insulin secretion → Persistent partial hepatic oxidation of
fatty acids to ketone bodies → High anion gap metabolic acidosis
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Pathophysiology
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Clinical Presentation
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Polyuria, polydipsia, nausea, and vomiting, Abdominal pain
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Abdomen may be tender from vomiting or distended secondary to a
paralytic ileus.
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Küssmaul respirations
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fruity odor of acetone
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Altered mental status can: ranging from disorientation to coma
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Laboratory Studies
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hyperglycemia (glucose concentrations ranging from 200-1000 mg/dL).
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Arterial pH <7.30, and the serum bicarbonate concentration <15 mEq/L.
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Serum Na concentrations may be elevated, normal, or low
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BUN can be elevated with prerenal azotemia secondary to dehydration
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WBC is usually elevated and can be left-shifted without implying the
presence of infection
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Fever is unusual and should prompt a search for infectious sources
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Careful replacement of fluid deficits
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Correction of acidosis and hyperglycemia via insulin administration
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Correction of electrolyte imbalances
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Monitoring for complications of treatment
Complications
cerebral edema
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1-5%
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the most serious complication
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mortality rate of 20% to 80%.
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Subclinical cerebral edema is common in patients with DKA,
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occurs 6 to12 hours after therapy
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Risk factors:
higher initial BUN concentration
lower initial Pco2
failure of the serum sodium concentration to increase as glucose concentration decreases
treatment with bicarbonate
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Complications
cerebral edema
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Clinical manifestation:
Obtundation, Papilledema, Pupillary dilation or inequality, Hypertension,
Bradycardia, and Apnea
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Treatment:
Rapid use of IV mannitol, endotracheal intubation, and ventilation and may
require the use of a subdural bolt
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Other complications
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Intracranial thrombosis or infarction
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ATN with ARF caused by severe dehydration
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pancreatitis
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arrhythmias caused by electrolyte abnormalities
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pulmonary edema
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bowel ischemia
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Peripheral edema occurs commonly 24 to 48 hours after therapy is initiated
and may be related to residual elevations in antidiuretic hormone and
aldosterone
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Transition to Outpatient Management
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Correction of acidosis: Ph≥7.3 & HCO3 ≥15
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Patient tolerates oral feedings
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First SC insulin dose should be given 30 to 45 minutes before discontinuation of
the IV insulin infusion (0.1 U/Kg)
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Insulin Dose: 0.5-0.7 U/kg/24h for prepubertals, 0.7-1 U/kg/24h for adolescents
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Available Insulin: fast-acting (bolus) insulin (lispro, aspart, or glulisine insulin)
and long-acting (basal) insulin (glargine or detemir) at bedtime.
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BS monitoring: before each meal, at bedtime, and periodically at 2 to 3 am
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Honeymoon
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Goals
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Intensive insulin therapy
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Maintaining blood glucose concentrations as close to normal as possible
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Delay the onset and slow the progression of complications of diabetes
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Attaining this goal can increase the risk of hypoglycemia
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Target glucose:
Children younger than 5 years old: 80-180 mg/dl
School-age children (5-12 y): 80-150 mg/dl
Adolescents (12-18): 70-130 mg/dl
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Available Insulin
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Insulin Regimens
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Calculate total daily dose of insulin
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30% to 50% are given as long-acting insulin
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Remainder is given as fast-acting insulin
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Correct for hyperglycemia
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Determine the insulin sensitivity using the 1800 rule
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Insulin:carbohydrate ratio: to calculate insulin for the carbohydrate
content of food using 450 rule
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Newly diagnosed patients in the honeymoon period may require 0.4 to 0.6
U/kg/24 hours
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Nutrition
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Calculate calorie according to patient’s age, activity
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Carbohydrates: 50% to 65% of the total calories
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Three meals & three snacks
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Protein 12% to 20% of the total calories
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Fat <30% of the total calories
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Saturated fat should contribute <10% of the total caloric intake
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Cholesterol intake should be less than 300 mg/24 hours
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Blood Glucose Testing
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NPH & Regular: 6a.m, 10 a.m, 4 p.m, 10 p.m, 4-5 a.m
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Asp & Glr: Before each meal and 2-3 a.m
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During periods of illness or when blood glucose concentrations are higher than
300 mg/dL, urine ketones also should be tested
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Continuous glucose monitors (CBG)
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hemoglobin A1c (HgbA1c) reflect the average blood glucose concentration
over the preceding 3 months
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HgbA1c should be measured four times a year
children less than 6 years: 7.5%-8.5%
ages 6 to 13 years HgbA1c target of less than 8%
ages 13 to 18 years HgbA1c target of less than 7.5%
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Complications & Other Disorders
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Retinopathy: Annual ophthalmologic examination After 3-5 y
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Nephropathy: Annual 24h urine for microalbuminuria After 3-5 y
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ACE-inhibitors for proteinuria
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Annual cholesterol measurements and periodic assessment of blood
pressure are recommended
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Chronic autoimmune lymphocytic thyroiditis (Hashimoto Thyroiditis)
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TFT: Annually
Celiac disease, IgA deficiency, Addison disease, and peptic ulcer disease
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Hypoglycemia
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Patients in adequate or better control,: once or twice a week
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Severe episodes of hypoglycemia: 10% to 25% of these patients per year
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Defective counterregulatory responses also contribute to hypoglycemia
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Abnormal glucagon responses: within the first few years of the disease
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Abnormalities in epinephrine release: after a longer duration
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Hypoglycemia unawareness: 25% of patients
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Symptoms resulting from neuroglycopenia
(headache, visual changes, confusion, irritability, or seizures)
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symptoms resulting from the catecholamine response
(tremors, tachycardia, diaphoresis, or anxiety)
Non-insulin−dependent
(Type 2) Diabetes Mellitus
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Pathophysiology & Epidemiology
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Peripheral insulin resistance
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Compensatory hyperinsulinemia
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Failure of the pancreas to Maintain adequate insulin secretion
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Prevalence of DM2 in children is increasing in parallel with childhood obesity
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Risk factors: Obesity, X syndrome, ethnicity, and a family history of DM2
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Auto-antibodies to the pancreas are present among some NIDDMs
Clinical Manifestations & Differential
Diagnosis
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The same as those for DM1
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Differentiating DM2 from DM1 in children on only clinical grounds can be challenging
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Acanthosis nigricans:
Hyperkeratotic pigmentation in the nape of the neck and in flexural areas
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Ketoacidosis occurs far more commonly in DM1
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Insulin or C-peptide responses to stimulation with oral carbohydrate
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Absence of islet cell autoreactivity
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Therapy
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Asymptomatic patients with mildly elevated glucose values (126-200)
Initially with lifestyle modifications→ dietary adjustments & ↑exercise
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New-onset, uncomplicated DM2 → oral agents (first line)
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Metformin
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Insulin secretagogue
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Lactic acidosis (rarely in renal insufficiency)
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Gastrointestinal upset (the most common)
Insulin
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If adequate glycemic control is not achieved with lifestyle modifications and metformin
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If ketonuria or ketoacidosis occurs
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May be discontinued within weeks with continuation of oral medications
Maturity-onset Diabetes Of Youth
(MODY)
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Dominantly inherited
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Relatively mild diabetes
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Insulin resistance does not occur
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Insufficient insulin secretory response to glycemic stimulation
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