Pleno Skrenario a Blok 7 2014

8/12/2019 Pleno Skrenario a Blok 7 2014

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Pleno Skenario A

blok 7

dr.Swanny, MSc

Dept. Physiology


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Kasus Nona, 19 thn

Nona, 19 thn, penderita DM sejak

kecil, rutin injeksi Insulin.

Mendapat injeksi Insulin pagi

tidak makan siangpingsan

kadar gula darah 58 mg%.

Gangguan homeostasis Glukosa


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OVERVIEW OF METABOLIC PATHWAYS

AminoAcids

Glucose-6-P

Pyruvate

ATP

Acetyl-CoA

Urea

AND SYSTEMS OF ENERGY METABOLISM

b a

o

eh

p

NucleicAcidsGLYCOGEN PROTEIN TRIACYLGLYCEROLS

dc

Ribose-5-Pf g i j

k l

a

b

Glucose

Lactate

n

m

Ketone

Bodies

Figure 1. Energy systems

Free Fatty Acids


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Figure 2. Summary of metabolic events in the well-fed (absorptive) state

Intestine

glucose

viablood

Brain

CO2

Muscle

glycogen

AdiposeTissue

fat

Liver

triacylglycerol

glycogen

RBC

Pancreas

insulin

fattyacids

CO2


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Figure 3.Metabolic transport of glucose; = stimulation by insulin

A) Insulin-insensitive glucose transport (GLUT-1 or GLUT-2)

GLUCOSE

Red

bloodcell

brain

liverkidney

B) Insulin-stimulatable glucose transport (GLUT-4)

GLUCOSE

INSULIN+ +

muscle

heart

adipocyte


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BLOOD GLUCOSE HOMEOSTASIS

maintenance of blood glucose concentration

brain depends on glucose; >50% of total

prolonged starvation has


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Hypoglycemia in Diabetes


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Hypoglycemia:

Definitions

Mild: Adrenergic (BG


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Hypoglycemia:

Cause

Imbalancebetween factors raising andlowering blood glucose levels

Blood Glucose Blood Glucose

Food Insulin/Oral Meds

Counterregulatory

Hormones

Physical Activity


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Hypoglycemia

The Greatest Limiting Factor

In Diabetes Management


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The Great Limiting Factor

Performance

Impairment


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Accident Risk


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Anxiety /Embarrassment


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LastingDamage?

Spatial memory /performance (if

before age 5)


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DiminishedSymptoms

(HypoglycemicUnawareness)


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Rebound


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Weight Gain


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Frequency of Iatrogenic Hypoglycemia (2)

Type 2 diabetes

event rates for severe hypoglycemia during aggressive insulin therapy intype 1 diabetes range from 62 through 110 to 170 episodes per 100patient-years.

Those during aggressive insulin therapy in type 2 diabetes range from 3through 10 to 73 episodes per 100 patient-years.

the rates of severe hypoglycemia in type 2 diabetes are roughly 10% ofthose in type 1 diabeteseven during aggressive therapy with insulin.

Over 6 years of follow-up of patients with type 2 diabetes in UKPDS, 2.4%of those using metformin, 3.3% of those using a sulfonylurea, and 11.2%of those using insulinreported major hypoglycemia (that requiringmedical attention or admission to hospital)

For comparison, 65%of the intensively treated patients with type 1diabetes in the DCCTsuffered severe hypoglycemia (that requiring theassistance of another individual) over 6.5 years of follow-up


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Physiology of Glucose Counterregulation (1)

Glycemic thresholds

Decreased insulin secretionas glucose concentrations decline within thephysiological range. The physiological postabsorptive plasma glucoseconcentration range is 72108 mg/dl(4.06.0 mmol/l). The meanarterialized venous glycemic threshold for a decrease in insulin is 81

mg/dl (4.5 mmol/l).

Increased glucagon and epinephrine secretion, among otherneuroendocrine responses, as glucose concentrations fall just below thephysiological range. The glycemic threshold is 6570 mg/dl(3.63.9mmol/l).

Neurogenic and neuroglycopenic symptoms, and cognitive impairments,at lower plasma glucose concentrations. The glycemic threshold forsymptoms is 5055 mg/dl(2.83.0 mmol/l).


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N Engl J Med350:22722279, 2004


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Physiology of Glucose Counterregulation (2)

they shift to higherplasma glucose concentrations in peoplewith poorly controlledtype 1 and type 2 diabetes and tolowerplasma glucose concentrations in people with tightlycontrolled type 1 diabetes

The magnitude of the neuroendocrine responsestohypoglycemia is a function of the nadir plasma glucoseconcentration, not the rate of fall of plasma glucose.

womenexhibit a less vigorous responseto a given level ofhypoglycemia than men.


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Pathophysiology of Glucose Counterregulation

In Diabetes Type 1 diabetes

Furthermore, as glucose levels fall, glucagon secretion doesnot increasein established type 1 diabetes

the epinephrine secretory responseto falling glucose levels istypically attenuatedin type 1 diabetes

is shifted to a lowerplasma glucose concentration largely theresult of recent antecedent hypoglycemia

a functional disorderrather than the result of a structuralabnormality of the adrenal medullae


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Clinical Syndromes of Compromised Glucose

Counterregulation In Diabetes(1)

Defective glucose counterregulation

Patients with type 1 diabetes and combined deficiencies oftheir glucagon and epinephrine responsesto hypoglycemiahave been shown, in prospective studies, to be at 25-fold or

even higher increased riskfor severe iatrogenic hypoglycemiaduring aggressive glycemic therapy compared with those withabsent glucagon but normal epinephrine responses.

rates of endogenous glucose productionwere found to be20% lowerin patients with type 1 diabetes than in

nondiabetic control subjects.


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Figure 1Diagrammatic representation of the concept of hypoglycemia-associated autonomic failure in diabetes.


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Figure 1.Hypoglycemia-Associated Autonomic Failure in Diabetes. N Engl J Med350:22722279, 2004


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Pleno Skrenario a Blok 7 2014

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