Text of DIABETES MELLITUS TYPE 1 & MANAGEMENT OF DIABETIC KETOACIDOSIS
DIABETES MELLITUS DIABETES MELLITUS TYPE 1 & TYPE 1 &
MANAGEMENT OF MANAGEMENT OF DIABETIC DIABETIC
KETOACIDOSIS KETOACIDOSIS PRESENTED BY
DR ASHISH SHARMA GUIDED BY
DR MEENA PATEL
Metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects of insulin secretion, insulin action or both.
OLD CLASSIFICATION (1985)
Type 1, Insulin-dependent (IDDM) Type 2, Non Insulin-dependent (NIDDM)
– obese– non-obese– MODY
IGT Gestational Diabetes
WHO CLASSIFICATION 2000
Is based on etiology not on type of treatment or age of the patient.
Type 1 Diabetes (idiopathic or autoimmune β-cell destruction) Type 2 Diabetes
(defects in insulin secretion or action) Other specific types
Both type 1 & type 2 can be further subdivided into:Not insulin requiringInsulin requiring for controlInsulin requiring for survival
Type 1 Diabetes Mell i tus
Formerly called insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes
T1DM is characterized by low or absent levels of endogenously produced insulin
EPIDEMIOLOGY • The onset occurs predominantly in
childhood, with median age of 7-15 yr, but it may present at any age.
• Indian data suggest an incidence of 10.5/100,000/yr .
• India would have 79 million diabetes by 2030, the highest for any country in the world.
Pathogenesis & Natural history
The natural history includes distinct stages1) Initiation of autoimmunity 2)Preclinical autoimmunity with progressive loss of β-cell function3)Onset of clinical disease4)Transient remission( “Honeymoon period”)5)Established disease6)Development of complications
Both genetic ,environmental and autoimmune factors contribute to the pathogenesis.
Genetic factors- Genetic susceptibility to T1DM is determined by several genes .HLA complex accounts for almost 50 % of genetic risk for type 1 diabetes.Some of the known associations include the HLA DR3/4-DQ2/8 genotype
Association with DR3 has been reported in Indians.
Risk of diabetes is also increased when a parent has diabetes and this risk differs between the 2 parents; the risk is 2% if the mother has diabetes, but 7% when the father has diabetes.
In monozygotic twins, the concordance rate ranges from 30-65%, whereas dizygotic twins have a concordance rate of 6-10%.
Envoirmental factors Many envoirmental agents are thought to
trigger the development of type 1 diabetes including,
Viral infections- Enterovirus , mumps , rubella
Diet- Breast-feeding may lower the risk of T1DM.
Early introduction of cow's milk protein and early exposure to gluten have both been implicated in the development of autoimmunity
Autoimmune factorsWhatever the triggering factor, it seems that in most cases of T1DM that are diagnosed in childhood.
The 1st signs of autoimmunity appear before age 2 yr.
Insulin associated antibodies (IAA)
Glutamic acid decarboxylase 65 kd (GAD65)
tyrosine phosphatase insulinoma-associated
. The earliest antibodies are predominantly of the IgG1 subclass
The appearance of autoimmunity is followed by progressive destruction of β cells.
Antibodies are a marker for the presence of autoimmunity, but the actual damage to the β cells is primarily T-cell mediated
PathophysiologyInsulin performs a critical role in the storage and retrieval of cellular fuel.
In normal metabolism, there are regular swings between the postprandial, high-insulin anabolic state and the fasted, low-insulin catabolic state that affect liver, muscle, and adipose tissue
Pathophysiology….T1DM is a progressive low-insulin catabolic state in which feeding does not reverse but rather exaggerates these catabolic processes.
At even lower insulin levels, the liver produces excessive glucose via glycogenolysis and gluconeogenesis, and fasting hyperglycemia begins.
Pathophysiology….Hyperglycemia produces an osmotic diuresis (glycosuria) when the renal threshold is exceeded (180 mg/dL; 10 mmol/L). The resulting loss of calories and electrolytes, as well as the persistent dehydration, produce a physiologic stress with hypersecretion of stress hormones (epinephrine, cortisol, growth hormone, and glucagon)
Pathophysiology….These hormones, in turn, contribute to the metabolic decompensation by promoting glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis (glucagon, epinephrine, growth hormone, and cortisol) while decreasing glucose utilization and glucose clearance.
Classical symptom triad: polyuria, polydipsia and weight loss
DKAAccidental diagnosisAnorexia nervosa like illness
TREATMENT GOALS Prevent death & alleviate symptoms
Achieve biochemical control
Maintain growth & development
Prevent acute complications
Prevent or delay late-onset complications
Education Insulin therapy Diet and meal planning Monitoring
HbA1c every 2-monthsHome regular BG monitoring Home urine ketones tests when indicated
Educate child & care givers about: Diabetes Insulin Life-saving skills Recognition of Hypo & DKA Meal plan Sick-day management
INSULIN A polypeptide made of 2 β-chains. Discovered by Bants & Best in 1921. Animal types (porcine & bovine) were used
before the introduction of human-like insulin (DNA-recombinant types).
Recently more potent insulin analogs are produced by changing aminoacid sequence.
FUNCTION OF INSULIN
Insulin being an anabolic hormone stimulates protein & fatty acids synthesis.
Insulin decreases blood sugar 1. By inhibiting hepatic glycogenolysis and
gluconeogenesis.2. By stimulating glucose uptake, utilization
& storage by the liver, muscles & adipose tissue.
Characteristics of Insulin
There are three characteristics of insulin:
Onset- Is the length of time before insulin reaches the bloodstream and begins lowering blood glucose.Peaktime- Is the time during which insulin is at maximum strength in terms of lowering blood glucose.Duration- Is how insulin continues to lower blood glucose.
The Basics of Insulin: 4 Types
Regular or short-acting insulin
Rapid-acting InsulinExamples: insulin lispro or insulin aspart
Onset: Begins to work at about 5 minutes
Peaktime: Peak is about 1 hour
Duration: Continues to work for about 2-4 hours
Regular or Short-acting Insulin
Examples: insulin lispro, Aspart
Onset: Reaches the bloodstream within 30 minutes after injection.
Peaktime: Peaks anywhere from 2-3 hours after injection.
Duration: Effective for approximately 3-6 hours.
Onset: Reaches the blood stream about 2 to 4 hours after injection.
Peaktime: Peaks 4-12 hours later.
Duration: Effective for about 12 to 18 hours
Examples: insulin glargine
Onset: Reaches the bloodstream 6-10 hours after injection
Non-availability of insulin in poor countries injection sites & technique Insulin storage & transfer Mixing insulin preparations Insulin & school hours Adjusting insulin dose at home Sick-day management Recognition & Rx of hypo at home
DIET REGULATION Regular meal plans with calorie exchange
options are encouraged. 50-60% of required energy to be obtained
from complex carbohydrates. Distribute carbohydrate load evenly during
the day preferably 3 meals & 2 snacks with avoidance of simple sugars.
Encouraged low salt, low saturated fats and high fiber diet.
EXERCISE Decreases insulin requirement in
diabetic subjects by increasing both sensitivity of muscle cells to insulin & glucose utilization.
It can precipitate hypoglycemia in the unprepared diabetic patient.
It may worsen pre-existing diabetic retinopathy.
Compliance (check records) HBG tests HbA1 every 2 months Insulin & meal plan Growth & development Well being & life style School & hobbies
ADVANCES IN MONITORING
Smaller & accurate meters for intermittent BG monitoring
Glucowatch continuous monitoring using reverse iontophoresis to measure interstitial fluid glucose every 20 minutes
Glucosensor that measures s/c capillary BG every 5 minutes
Implantable sensor with high & low BG alarm
ADVANCES IN MANAGEMENT
Better understanding of diabetes allows more rational approach to therapy.
Primary prevention could be possible if the triggering factors are identified.
The DCCT studies proves beyond doubt that chronic diabetic complication can be controlled or prevented by strict glycemic control.
TREATMENT MADE EASY
Insulin pens & new delivery products Handy insulin pumps Fine micro needles Simple accurate glucometers Free educational material Computer programs for comprehensive
management & monitoring
IT has improved diabetes care Internet sites for education & support Web-based systems for telecare are
now available. The patient feeds his HBGM data and get the physician, nurse & dietician advice on the required modification to diet & insulin treatment.
PITFALLS OF MANAGEMENT
Delayed diagnosis of IDDM The honey-moon period Detection & treatment of NIDDY Problems with diagnosis & treatment of
DKA & hypoglycemia Somogyi’s effect & dawn phenomenon
may go unrecognized.
FUTURE PROMISES The cure for IDDM is successful islet cell
transplantation, which will be available in the near future.
Primary prevention by a vaccine or drug will be offered to at risk subjects identified by genetic studies.
Gene modulation therapy for susceptible subjects is a promising preventive measure.
Pancreas & Islet Cell Transplantation
Pancreas transplants are usually given to diabetics with end stage renal disease.
Islet cell transplants, the ultimate treatment of type 1 diabetes is under trial in many centers in the US & Europe with encouraging results but graft rejection & recurrence of autoimmunity are serious limitations.
IMMUNE MODULATION Immunosuppressive therapy for
Newly diagnosedProlonged the honey moonFor high risk children
Immune modulating drugsNicotinamidemycophenolate
Blocks the immunologic attack against islet-cells by DNA-plasmids encoding self antigen.
Primary prevention• Identification of diabetes gene• Tampering with the immune system• Elimination of environmental factor
Secondary prevention• Immunosuppressive therapy
Tertiary prevention• Tight metabolic control & good monitoring
. INTRODUCTION DKA,a life threatning complication of
diabetes mellitus,occurs more commonly in children with type 1 DM than type 2 DM.
Hyperglycemia,metabolic acidosis, ketonemia,dehydration and vaious electolyte abnormalities result from a relative and absolute deficiency of insulin with or without excess of counter regulatory hormones
. Definition DKA in children is defined as
hypgerglycemia(serum glucose conc. >200-300mg/dl) in the presence of metabolic acidosis (blood pH<7.3 with serum bicarbonate level<15 mEq/L) and ketonemia(presence of ketones in blood).
When measured sr ketones (b hydroxy butyrate plus acetoacetate)exceed 31 mg/dl with or without ketonuria >80mg/dl
. CLINICAL HISTORY Polyuria Polydipsia Weight loss Nausea,vomiting,abdominal pain Headache Restlessness,irritability Lethargy,altered sensorium,loss of
.EXAMINATIONFruity odour in breathTachycardiaLow volume pulsesHypotensionImpaired skin turgorDelayed capillary refill timeDehydrationRapid,Deep sighing respiration Kussumaul respiration(met. Acidosis)Bradycardia,hypertension,pappiloedemaAbnormal pupillary reflex,cranial n. palsyposturing
.Biochemical signs• Ketones in urine• Elevated blood glucose(>200 mg%)• Acidemia(pH<7.3)• Collect blood for RFT , CBC, SGOT, SGPT,
InsulinStart subcutaneius insulin and then stop iv insulin infusion 1 hr later
DIABETIC KETOACIDOSIS TREATMENT PROTOCOL.
1ST hr 10-20 ml/kg IV bolus 0.9% NaCl or LRInsulin drip at 0.05 to 0.10 u/kg/hr
Quick volume expansion;may be repeated.NPO.Monitor I/O,neurological status.Usefloe sheet. Have Mannitol at bedside;1 g/kg IV push for cerebral edema
2nd hr until DKA resolution
0.45%NaCl:plus continue Insulin drip20 mEq/l Kphos and 20 mEq/l Kac.5% glucose if blood sugar <250 mg/dl
IV rate= 85 ml/kg+maintainence-bolus/23hr
If K<3mEq/L,give 0.5 to 1 mEq/kg as oral K solution OR increase IV K to 80 mEq/L
Variable Oral intake with subcutaneous insulin
No emesis;CO2> 16 mEq/L;normal electrolytes
TIME THERAPY COMMENTS
.• Note that initial IV bolus is considered as
part of the total fluid allowed in the 1st 24 hr and is sutracted before calculating the IV rate.
• Sample calculation for a 30 kg child:• 1st hr=300ml IV bolus 0.9%NaCl or LR• 2nd and subsequent hrs=(85x30)+1750-
300/23=175 ml/hr• (0.45%NaCl with 20 mEq/L Kphos and 20
• The Milwaukee protocol can be used for children of all ages and with all degree of DKA.
• Children with milder DKA recover in 10-20 hr(and need less total IV fluid before switching to oral intake.)
• Those with more severe DKA require 30-36 hrs with this protocol.
• Blood testing should occur every 1-2 hr for children with severe DKA and 3-4 hr for those with mild to moderate DKA.
INSULIN THERAPYTiming-1-2 hr after starting fluid replacement.
Type-Only IV Regular insulin used for m/m of DKA.
Dose-low dose iv insulin 0.1 u/kg/hr is standard.high dose has risk of hypoglycemia,hypokalemia and rapid decline in osmolality.
Prepration-50 units diluted in 50 ml NS to arrive conc. Of 1 u/ml
Duration-administered at same rate(0.1u/kg/hr) until resolution of DKA
Dose adjustment-If hypoglycemia occurs despite increase in strength of dextrose sol. the dose of insulin reduced in decrement of 0.02u/kg/hr upto 0.05 u/kg /hr
Transition to subcutaneous insulin therapy
• As oral feeds advanced iv fluids reduced and change to subcutaneous insulin planned.
• Timing-ideal time to begin is just before a meal.• Rapid acting insulin(lispro,aspart) are
administered sc 15-30 mins prior and regular insulin 1-2 hr prior to stopping infusion to avois rebound hyperglycemia.
• Dose-For pt with DKA at ds onset,recommended TDD is 0.75-1 u/kg(pre pubertal) and 1-1.2 u/kg(pubertal).
• Before Breakfast-2/3 tdd(1/3 r.a. and 2/3 i.a. insulin)
• Before dinner-1/3 tdd(1/3 r.a. and 2/3 i.a. insulin)
Cerebral Edema.Management•Head end elevation•Give Mannitol 0.5-1 gm/kg and repeat if there is no response in 30 mins-2hrs•3% Hypertonic saline (5 ml/kg over 30 mins) can be given•Restrict iv fluids to 2/3•Replace deficit in 72 hr rather than 48 hr•Intubation and ventilation if required