diabetes treatment for bpt
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Continued……
Diabetes mellitus
1. Emergencies2. Complications3. Treatment
Diabetic EmergenciesHyperglycemic
HHNC: Hyperosmolar Hyperglycemic Nonketotic Coma
DKA: Diabetic Ketoacidosis
HypoglycemicDiabetic Coma or
Insulin Reaction
HHS: Hyperglycemic Hyperosmolar State Effects Type 2 Diabetics Prominent later in life Elevated Blood Glucose leads to increase in serum osmolarity This results in Diuresis and Fluid Shift. Increased Urination causes body wide depletion of Water and
Electrolytes.Extreme Dehydration
Physical Signs TachycardiaOrthostatic VitalsPoor Skin TurgorDrowsiness and
lethargyDeliriumComa
SymptomsNausea/vomitingAbdominal painPolydipsiaPolyuria
Treatment IV FLUIDS !!!!!
Bolus of Normal Saline/ half normal saline will help to reverse the overwhelming dehydration
Insulin? NEXT
DKA: Diabetic KetoacidosisDereased Insulin or Insulin resistance leads to Elevated
Blood Glucose levels
However, Cellular Glucose is Low without insulinEquivalent to Starvation
As a result the body attempts to CompensateUses Glucose storesBreaks Down Fat and Protein
In an attempt to save the Heart and Brain, the body produces Ketone Bodies from fatty acids
Acetoacetate, Beta-hydroxybutyrate, Acetone
Excessive Ketones lead to AcidosisBeta-hydroxybutyrate is a carboxylic Acid
Physical SignsAltered mental status TachycardiaTachypnea or
hyperventilation (Kussmaul respirations)
Normal or low blood pressure
Lethargy and weaknessFeverAcetone odor of the breath
reflecting metabolic acidosis
SymptomsOften insidiousFatigue and malaiseNausea/vomitingAbdominal painPolydipsiaPolyuriaPolyphagiaWeight lossFever
TreatmentFluids!!!!!
It is important to initiate Fluid Ressusitation Begin With Normal Saline
InsulinThis Will Start in the Emergency Dept.
HypoglycemiaTreatment
Patient’s will present with Altered Mental StatusSupplemental OxygenVitalsIV Fluids MonitorGlucometry
Glucose < 80 mg/dL, Considered Hypoglycemia
TreatmentGlucose Supplementation
Oral GlucoseJuice, Non- Diet Soda Oral Glucose Solution
D10250cc Bolus
D50 25 gram glucose in 50ml water, IV
GlucagonNaturally Occurring Hormone, From Pancreas Alpha-CellsBreaks Down Stored Glycogen to Glucose1U = 1mg Given IM/SC
Pediatric 0.025 mg/kg IM/SC to max dose 1mg
Blood GlucometryMeasurement of Blood
Glucose levelsHospital labs evaluate
Serum Glucose (10-15% higher)
Requires a small sample of bloodNo IV’s or Phlebotomy
Only seconds to obtain results
Glucometry Technique1. Wash hands with soap and warm water and dry
completely or clean the area with alcohol and dry completely.
2. Prick the fingertip with a lancet.3. Hold the hand down and hold the finger until a small
drop of blood appears; catch the blood with the test strip.
4. Follow the instructions for inserting the test strip and using the SMBG meter.
5. Record the test result.
CHRONIC COMPLICATIONS INCHRONIC COMPLICATIONS INDIABETES MELLITUSDIABETES MELLITUS
MAJOR DETERMINING FACTORS
Duration
Glycemic Control ( Hb A 1 C)
Type 1 vs. Type 2
Macrovascular Damage Affects Large (Named) Arteries:
Coronary Arteries
Coronary artery disease
MI
Carotid/Cerebral Arteries
Stroke
TIA
Lower Extremity Arteries
Peripheral vascular disease
Microvascular Damage Affects:
Retinas
proliferative and non proliferative
blindness
Glomeruli
diabetic nephropathy
Nerves
diabetic neuropathy small fibre/ large fibre
Microvascular Damage Causes:
Blindness
End-Stage Renal Disease
Neuropathy >>> Amputations
The Role of Insulin
High insulin levels as seen in insulin resistance
MAY be contributory to the development of:
Hypertension
Atherosclerosis
So HOW does diabetes damage blood vessels?
Best understood mechanism is by non-enzymatic glucosylation (glycation) of proteins and other macromolecules.
Other mechanisms postulated include changes in NADP+ and NADH levels associated with alternative glucose metabolic fates when usual pathways are saturated.
Chronic hyperglycemia causes increased glycation of proteins, resulting in Advanced Glycation Endproducts (AGEs)
These can cause damage through loss of function, turning on/off signal pathways within cells, or alteration in gene expression.
One of the proteins which is glycated is Hemoglobin. Because it is found in the blood, it is convenient to measure as HbA1c.
Because RBCs (and thus Hb) survive in the blood for 90-120 days, the HbA1c provides a means to assess glycemic control over this period.
Insulin therapy who needs what are the types How to administer
A chain
B chain
Beta cells have channels in their plasma membrane that serve as glucose detectors. Beta cells secrete insulin in response to a rising level of circulatingglucose.
Insulin is a small protein consisting of an A chain of 21 amino acids linked by two disulfide (S—S) bridges to a B chain of 30 amino acids.
Who need insulin medicineType I (insulin dependent) diabetes patients whose body
produces no insulin.Type 2 diabetes patients that do not always produce enough
insulin.
Stage 1 Insulin was extracted from the glands of cows and pigs. (1920s)
Stage 2 Convert pig insulin into human insulin by removing the one amino acid that distinguishes them and replacing it with the human version.
Insulin drug evolution
Stage 3 Insert the human insulin gene into E. coli and culture the recombinant E.coli to produce insulin (trade name = Humulin®). Yeast is also used to produce insulin (trade name =
Novolin®) (1987).
Recombinant DNA technology has also made it possible to manufacture slightly-modified forms of human insulin that work faster (Humalog® and
NovoLog®) or slower (Lantus®) than regular human insulin.
Types of insulin
Regular insulins
Insulin analogs
Pre-mixed insulin
Short peptide mimics
Regular insulins:
Human insulin: Humulin® (from E.coli),
Novalin® (from yeast) NPH - neutral protamine Hagedorn (NPH), protamine mixed.
Lente® insulin / Ultralente® insullin- zinc added
Atrapid yellow short actingPeak 2- 4 hrsTotal duration of action 6 hrs
Insulatard green intermediate actingPeak 4- 6 hrsTotal duration of action 8 – 10 hrs
Split and mixed doseTotal insulin needFBS – 50 10 = total requirement2/3 rd as insulatard1/3 rd as atrapid
2/3 rd in morning 1/3 rd at night
How to monitorMorning atrapid – prelunchMorning insulatard 6 pm RBS
Evening atrapid – bed time Night insulatard FBS
How to administer insulin1.Subcutaneous2.Never mix NPH/ glargine
with other insulin3.Rotate sites4.Deltoid, abdomen, thigh
Every area has different amount of blood supply and absorption varies
Change sites once in ten to fourteen days
Chronic insulin therapy may lead to lipodystrophy
Insulin Analogs:
Fatty Acid Acylated insulins
Insulin Lispro (Humalog®) (1996)
Insulin Aspart (NovoLog®) (2000)
Insulin Glargine (Lantus®) (2002)
Insulin Detemir (Levemir®) (Jun.,2005)
Insulin Glulisine (Apidra®) (Jan., 2006)
Diabetes – Oral Medications
Sulfonylureas
Biguanides
Thiazolidinediones
Alpha-glycosidase inhibitors
Meglitinides
Sulfonylureas : stimulate β cells to produce more insulin
1st generationtolbutamidetolazamideChlorpropamide
2nd generationglipizideGlyburidemicronized glyburide
3rd generation glimepiride
Sulfonylureas interact with receptors on pancreatic b-cells to block ATP-sensitive potassium channels
This, in turn, leads to opening of calcium channelsWhich leads to the production of insulin
Biguanides : improves insulin’s ability to move glucose into cells (esp. muscle)
Metformin
- Metformin was first described in the scientific literature in 1957 (Unger et al). - It was first marketed in France in 1979 but did not receive FDA approval for Type 2 diabetes until 1994.
Metformin is a widely used monotherapy, and also used in combination with the sulfonylureas in treatment of type 2 diabetes
Thiazolidinediones (TZD’s) : make cells more sensitive to insulin (esp. fatty cells)
PioglitazoneRosiglitazone
TZD s binds to and activates the gamma isoform of the
- peroxisome proliferator-activated receptor (PPAR ).γ
-PPAR is a member of the steroid hormone nuclear receptor γsuperfamily,
- and is found in adipose tissue, cardiac and skeletal muscle, liver and placenta
PPAR - γ
Thiazolidinediones
GlucoseInsulin
resistanceInsulin andproinsulin
HDL2
PAI-1
Other vasculareffects
Anti-inflammatory effects CRP, IL-6
ROS, MCP-1P47phox
TNFα
? Cardiovascular implications
PPAR
ACR
MMP-9
sdLDL
HDL2
Vasc react.
Αlpha – glycosidase inhibitors :
Block enzymes that help digest starches
slowing the rise in blood glucose.
Polysacchride to monosachhride conversion is blocked
Better for post prandial glucose control
One with each mealS/E flatulenceAGI’s
- Precose ® (acarbose),
- Glyset ® (miglitol)
Meglitinides : Stimulate more insulin production ; dependant upon level of glucose present
Repaglinide
Nateglinide
Sulfonylureas stimulate cells βBiguanides improves insulin’s ability to move glucose Thiazolidinediones cells more sensitive to insulin Alpha-glycosidase inhibitors Block enzymes that help
digest starches Meglitinides stimulate cells (dependant upon glucose β
conc.)
Diabetes – Oral MedicationsSummary
To conclude….
2 major types of diabetes (3 with Gestational)
Type 1 => insulin dependant (5-10%)Type 2 => may treat with oral medication which may
alter insulin production &/or sensitivity ; disease often succumbs to insulin dependence (>90%)
Diabetes is a leading cause of blindness, kidney failure, amputation, heart attack, stroke, and premature death.
Target FBS 90 – 130 mg/dL HbA1C < 7
These complications can be minimized!Early Diagnosis of DM Monitoring for complicationAggressive treatment of co-risk factorsTeam approach - access to multiple specialists