Diabetes Mellitus MZ. Zamanpour - PowerPoint Presentation

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Diabetes Mellitus

MZ.

Zamanpour

Md

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Definition & Diagnosis

(

1)

Fasting serum glucose concentration ≥126 mg/dL, (2) a random venous plasma glucose ≥200 mg/dL with symptoms of hyperglycemia,(3) an abnormal oral glucose tolerance test (OGTT) with a 2-hour postprandial serum glucose concentration ≥200 mg/dL, and (4) a HgbA1c ≥6.5%.impaired fasting glucose (IFG) (FBS: 100-125 mg/dl)impaired glucose tolerance (IGTT) 2-hour plasma glucose following an OGTT is 140 to 199 mg/dLSporadic hyperglycemia (Stress Hyperglycemia)

 

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Insulin-dependent (type 1) Diabetes Mellitus

Autoimmune destruction

of

insulin-producing beta cells (islets) (T cell–mediated)(Destruction of 80-90%)Environmental factors: Cow’s milk feeding at an early ageViral infectious agents (Coxsackie virus, cytomegalovirus, mumps, rubella)Vitamin D deficiencyPerinatal factorsIslet cell antibodies, Insulin autoantibodies, antibodies to tyrosine phosphatase IA-2, antibodies to glutamic acid decarboxylase, and others1 antibody: 10-15% risk, 2 antibodies: 55-90%4

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Epidemiology &Genetics

Siblings or

offspring

of patients with diabetes have a risk of 2% to 8%Identical twin has a 30% to 50% riskClass II DR and DQ HLA alleles (HLA DR3 and HLA DR4) increase the risk.More than 90% of children with DM1 possess HLA DR3 alleles, HLA DR4 alleles, or both5

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Clinical Manifestations

Insulin

deficiency usually

first causes postprandial hyperglycemia and then fasting hyperglycemiaKetogenesis is a sign of more complete insulin deficiencyGlycosuria occurs when the serum glucose concentration exceeds the renal threshold for glucose reabsorption (from 160 to 190 mg/dL).Polydipsia occurs as the patient attempts to compensate for the excess fluid lossesWeight loss results from the persistent catabolic state and the loss of calories through glycosuria and ketonuriaThe classic presentation of DM1 includes polyuria, polydipsia, polyphagia, and weight loss6

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Schematic representation of the autoimmune

evolution of diabetes in genetically predisposed individuals

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Diabetic Ketoacidosis

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 urinePathophysiologyAbsence of adequate insulin secretion → Persistent partial hepatic oxidation of fatty acids to ketone bodies → High anion gap metabolic acidosis8

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Pathophysiology

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Clinical Presentation

Polyuria, polydipsia, nausea

, and

vomiting, Abdominal painAbdomen may be tender from vomiting or distended secondary to a paralytic ileus.Küssmaul respirationsfruity odor of acetoneAltered mental status can: ranging from disorientation to coma10

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Laboratory Studies

hyperglycemia

(

glucose concentrations ranging from 200-1000 mg/dL).Arterial pH <7.30, and the serum bicarbonate concentration <15 mEq/L.Serum Na concentrations may be elevated, normal, or lowBUN can be elevated with prerenal azotemia secondary to dehydrationWBC is usually elevated and can be left-shifted without implying the presence of infectionFever is unusual and should prompt a search for infectious sources11

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Careful replacement of

fluid

deficits

Correction of acidosis and hyperglycemia via insulin administrationCorrection of electrolyte imbalancesMonitoring for complications of treatment12

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Complications

cerebral

edema

1-5%the most serious complicationmortality rate of 20% to 80%.Subclinical cerebral edema is common in patients with DKA,occurs 6 to12 hours after therapyRisk factors:higher initial BUN concentrationlower initial Pco2failure of the serum sodium concentration to increase as glucose concentration decreasestreatment with bicarbonate13

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Complications

cerebral

edema

14Clinical manifestation:Obtundation, Papilledema, Pupillary dilation or inequality, Hypertension, Bradycardia, and ApneaTreatment:Rapid use of IV mannitol, endotracheal intubation, and ventilation and may require the use of a subdural bolt

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Other complications

Intracranial thrombosis

or

infarctionATN with ARF caused by severe dehydrationpancreatitisarrhythmias caused by electrolyte abnormalitiespulmonary edemabowel ischemiaPeripheral edema occurs commonly 24 to 48 hours after therapy is initiated and may be related to residual elevations in antidiuretic hormone and aldosterone15

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Transition to Outpatient Management

Correction of acidosis: Ph≥7.3 & HCO3 ≥15

Patient tolerates oral feedings

First SC insulin dose should be given 30 to 45 minutes before discontinuation of the IV insulin infusion (0.1 U/Kg)Insulin Dose: 0.5-0.7 U/kg/24h for prepubertals, 0.7-1 U/kg/24h for adolescentsAvailable Insulin: fast-acting (bolus) insulin (lispro, aspart, or glulisine insulin) and long-acting (basal) insulin (glargine or detemir) at bedtime.BS monitoring: before each meal, at bedtime, and periodically at 2 to 3 amHoneymoon16

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Goals

Intensive insulin therapy

Maintaining blood glucose concentrations as close to normal as possible

Delay the onset and slow the progression of complications of diabetesAttaining this goal can increase the risk of hypoglycemiaTarget glucose:Children younger than 5 years old: 80-180 mg/dlSchool-age children (5-12 y): 80-150 mg/dlAdolescents (12-18): 70-130 mg/dl17

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Available Insulin

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Insulin Regimens

Calculate total daily dose of insulin

30% to 50% are given as long-acting insulin

Remainder is given as fast-acting insulinCorrect for hyperglycemiaDetermine the insulin sensitivity using the 1800 ruleInsulin:carbohydrate ratio: to calculate insulin for the carbohydrate content of food using 450 ruleNewly diagnosed patients in the honeymoon period may require 0.4 to 0.6 U/kg/24 hours19

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Nutrition

Calculate calorie according to patient’s age, activity

Carbohydrates: 50% to 65% of the total calories

Three meals & three snacksProtein 12% to 20% of the total caloriesFat <30% of the total caloriesSaturated fat should contribute <10% of the total caloric intakeCholesterol intake should be less than 300 mg/24 hours20

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Blood Glucose Testing

NPH & Regular: 6a.m, 10

a.m

, 4 p.m, 10 p.m, 4-5 a.mAsp & Glr: Before each meal and 2-3 a.mDuring periods of illness or when blood glucose concentrations are higher than 300 mg/dL, urine ketones also should be testedContinuous glucose monitors (CBG)hemoglobin A1c (HgbA1c) reflect the average blood glucose concentration over the preceding 3 monthsHgbA1c should be measured four times a yearchildren 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%21

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Complications & Other Disorders

Retinopathy: Annual ophthalmologic examination After 3-5 y

Nephropathy: Annual 24h urine for

microalbuminuria After 3-5 yACE-inhibitors for proteinuriaAnnual cholesterol measurements and periodic assessment of blood pressure are recommendedChronic autoimmune lymphocytic thyroiditis (Hashimoto Thyroiditis)TFT: AnnuallyCeliac disease, IgA deficiency, Addison disease, and peptic ulcer disease22

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Hypoglycemia

Patients in

adequate or better

control,: once or twice a weekSevere episodes of hypoglycemia: 10% to 25% of these patients per yearDefective counterregulatory responses also contribute to hypoglycemiaAbnormal glucagon responses: within the first few years of the diseaseAbnormalities in epinephrine release: after a longer durationHypoglycemia unawareness: 25% of patientsSymptoms resulting from neuroglycopenia (headache, visual changes, confusion, irritability, or seizures)symptoms resulting from the catecholamine response (tremors, tachycardia, diaphoresis, or anxiety)23

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Non-insulin−dependent (Type 2) Diabetes

Mellitus

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Peripheral insulin resistance

Compensatory

hyperinsulinemia

Failure of the pancreas to Maintain adequate insulin secretionPrevalence of DM2 in children is increasing in parallel with childhood obesityRisk factors: Obesity, X syndrome, ethnicity, and a family history of DM2Auto-antibodies to the pancreas are present among some NIDDMs25Pathophysiology & Epidemiology

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Clinical Manifestations &

Differential

Diagnosis

The same as those for DM1Differentiating DM2 from DM1 in children on only clinical grounds can be challengingAcanthosis nigricans:Hyperkeratotic pigmentation in the nape of the neck and in flexural areasKetoacidosis occurs far more commonly in DM1Insulin or C-peptide responses to stimulation with oral carbohydrateAbsence of islet cell autoreactivity26

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Therapy

Asymptomatic patients with mildly elevated glucose

values (126-200)

Initially with lifestyle modifications→ dietary adjustments & ↑exerciseNew-onset, uncomplicated DM2 → oral agents (first line)MetforminInsulin secretagogueLactic acidosis (rarely in renal insufficiency)Gastrointestinal upset (the most common)InsulinIf adequate glycemic control is not achieved with lifestyle modifications and metforminIf ketonuria or ketoacidosis occursMay be discontinued within weeks with continuation of oral medications27

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Maturity-onset Diabetes Of Youth

(MODY)

Dominantly inherited

Relatively mild diabetesInsulin resistance does not occurInsufficient insulin secretory response to glycemic stimulation28