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Monday, November 1, 2010

Diabetes mellitus

Types
Type1 -insulin sensitive
Type2 -ins. Resistant
MODY- maturity onset diabetis of young

criteria for diagnosis
@ symptoms plus random alone sugar >200 mg% or fasting >125%
@ after 2hr GTT >200mg %

Pathogenesis
# Type1-
1 autoimmune factor -
insulitis
2 immunological marker- islet cell Ab
3 Enviromental- coxsackie n rubella

# Type 2
1 impaired Secretion, peripheral insulin resistance
excessive hepatic glucose production

# MODY
homozygous mutation of glucokinase

Complication
#acute
diabetic ketoacidosis n hyperglycemic hyperosmol. Coma
# chronic
@ microvascular
retinopathy , macular edema, sensory n motor mono or polyneuropathy, nephropathy
@ macrovascular
coronary art dis. , PVD, cerebral vascular dis,
@ other
GI: diarhea , gastroparesis
genitourinary: uropathy n sexual dysfunctn
dermatological , infection, cataract glaucoma

C/F
Type 1
age < 40, duration- days 2 wks, normal 2 wasted body habitus, polyuria, polydysia, polyphagia, plasma insulin low Type 2 age>40, mths 2 yrs duration, obese, diabetic ketoacidosis doesnt develop, norm or increased pl insulin.

Benedicts test
If reducing sugar in glucose it gives quantitive rslts
light green- 0.1 - 0.5 g%
green - 0.5-1 g%
yellow -1-2g%
red - >2g%

Treatment
Drugs
1 sulphonylurea
@ insulin secretogogues
@ chlorpropamide 100- 500 mg, tolbutamide 500-3000mg, glibenclamide n glipizide 2.5-20mg
@ side eff. Hypoglycemia , wt gain

2 meglitinide
@ repaglinide, nateglinide, meglitinide-o.5-16 mg/day

3 Biguanide
@ metformin - reduce hepatic glucose prod. N improve periphera glu. utilisation.
@ doesnt produce wt gain so useful in obese pts wth type DM
@ started at dose of 500mg twicd day n gradually increased 2 max of 1g tds
@ side eff. acidosis, anorexia, diarhea, metallic taste.

4 alpha glucosidase inhibitors
@ acarbose n miglitol- 25mg
@ inhibits alpha glucosidase enzyme leads to poor absorption of carbohydrates thereby causing reduced rise in post prandial glucose

5 thiazolidinediones
@ rosiglitazone 2-8 mg OD or pioglitazone 15-25 mg/day
@ the bind 2 peroxisome proliferator activated receptor that regulates transcription of genes involved in lipid metabolism n insulin action. This promotes adipocyte diff. N reduce ins resistnce
@ side eff. Wt gain

6. other
@glucagon like peptide 1 analogues
@ dipeptidyl peptidase IV inhibitor - vildagliptin n sitagliptin

#Insulin was discovered in 1921 .
#until 1980 it was obtained by extraction & purification from pancreas of cow & pig.
#the use of recombinant DNA technology has enabled large scale production of human insulin.
#it has transformed the management of type 1 DM.

CLASSIFICATION.

It is classified as per duration of action.(all figures in hours)

1. Rapid acting (insulin analogues- lispro, aspart, glulisine)
onset= <0.5
peak= 0.5 to 2.5
duration =3 to 4.5

2. Short acting(soluble regular)
o=0.5 to 1
p=1 to 4
d=4 to 8

3. Intermediate acting (isophane, lente)
o=1 to 3
p=3 to 8
d=7 to 14

4. Long acting(bovine ultralente)
o=2 to 4
p=6 to 12
d=12 to 30

5. Long acting(insulin analogue- glargine, detemir)
o=1 to 2
p=none
d=18 to 24

INSULIN DELIVERY.

1.It is injected s.c. into d anterior abdominal wall, upper arms, outer thigh & buttocks.
2.The rate of absorption of insulin is influenced by many factors other than the insulin formulation including the site, depth and volume of injection, skin temp, local massage & exercise.
3. Absorption is delayed from areas of lipohypertrophy at injection sites, which results from the local trophic action of insulin. So repeated injections at d same sites should be avoided.
4. Short acting has to be injected atleast 30min b4 a meal..
5. Fast acting ones can be administered immediately b4 food or even after meals.
6. Once in blood it has a half life of few minutes.
7. It is removed mainly by liver & also the kidneys.

INSULIN REGIMEN.

1. The choice of regimen depends on d desired degree of glycemic control, patient's lifestyle & ability to adjust the insulin dose.
2. Most ppl require 2 or more injections of insulin daily.
3. Once daily regimen is rarely sufficient.
4. Twice daily administration of a short acting and intermediate acting insulin given in combination b4 breakfast & evening meal is d simplest regimen & is still commonly used.
5. Individual requirement vary considerably act usually 2/3rd of total daily dose is given in morning in ratio of 1:2, short:intermediate acting insulin.
6. The remaining third is given in d evening.

SIDE EFFECTS.

1. Hypoglycemia
2. Weight gain
3. Peripheral edema
4. Insulin antibodies
5. Local allergy
6. Lipodystrophy @ injection site

DAWN PHENOMENON.
It is fasting hypoglycemia caused by release of counter regulatory hormones during d night as part of d normal circadian rhythm which increase insulin requirement b4 wakening.

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