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Friday, January 31, 2014

complications of Diabetes mellitus and how to over come on these complication

Pathogenesis of diabetic complications :
glycosylation
sorbitol pathway
1. Glycosylation :
_ This may lead to thickness of basement membrane of
capillaries with narrowing of their lumen affecting
retinal blood vessels, renal glomeruli & vasa nervosa
leading to vasculopathy.
2. Sorbitol pathway :
_ Glucose is reduced to sorbitol by aldole reductase of
ATPase activity & cell energy leading to neuropathy.
Complications of DM :
I. Cutaneous :
1. Infection : carbuncle & recurrent abscess.
2. Pruritis : pruritis vulvae.
3. Delayed healing of wound.
4. Xanthelasma ; due to hyperlipidemia.
5. Necrobiosis lipoidica diabeticorum :
a. painless papule with central yellowish area surrounded
by brownish border.
b. usually over i ant. surface of i legs.
c. due to cutaneous bl. vessels occlusion.
6. Vasculopathy : leads to gangrene.
II. Cardiovascular :
1. Microangiopathy :
a. diabetic retinopathy retina.
b. ~ nephropathy glomeruli.
c. ~ neuropathy vasa nervosa.
2. Macroangiopathy :
a. cerebral : thrombosis & ischemia.
b. coronary : angina & MI ( C.H.D. ).
c. peripheral : gangrene & intermittent cludication.
d. renal : reno-vascular HTN.
3. Cardiomyopathy : due to microangiopathy.
4. Blood pressure :
a. systemic hypertension.
b. postural hypotension due to autonomic neuropathy.
N.B. : Causes of HTN in diabetic patient :
1- diabetic nephropathy.
2- obesity.
3- Insulin retention of Na.
4- 2ry diabetes : Cushing & acromegaly.
III. Chest :
1. Recurrent chest infection esp. T.B.
( T.B. follows DM as its shadow ).
N.B. : Characteristically T.B. is apical lesion except in diabetes it’s basal.
2. Kussmaul respiration ( air hunger ) & acetone smell in DKA.
IV. Gastrointestinal :
Diabetes never have a normal bowel habits.
1. Diarrhea : due to :
a. Sympathetic neuropathy parasympathetic
dominance nocturnal diarrhea.
b. Vasculopathy.
c. Infection.
2. Constipation : due to vagal neuropathy.
3. Liver fatty liver hepatomegaly.
V. Genital :
1. In : impotence psychological.
neuropathy.
vasculopathy.
2. In : infections & pruritis vulvae.
3. Effects of DM on pregnancy :
a. On mother :
i. Eclampsia.
ii. post. Partum hge.
iii. puerperal sepsis.
b. On fetus :
i. High birth weight.
ii. Hypoglycemic baby.
iii. Congenital anomalies.
iv. Respiratory distress syndrome.
4. Effects of pregnancy on DM :
a. needs for insulin due to anti-insulin :
estrogen & progesterone.
b. renal threshold for glucose.
c. incidence of complications.
VI. Eye :
1. Infection : chalazion.
2. Repeated error of refraction, because i lens may be
affected by reversible osmotic changes in patients é acute
hyperglycemia.
3. New vessels formation in iris ( rubeosis iridis )
4. Optic neuritis.
5. Cranial nerve palsy ( 3,4 & 6 cranial nerves).
6. Diabetic retinopathy :
a. It’s I most characteristic form of diabetic eye diseases.
b. Especially in type 1 DM of long duration.
c. It’s of 2 types :
i. Non proliferative : micro-aneurysm, hge,
exudates ( benign form)
ii. Proliferative : neovascularization, this type must
be treated as early as possible by
photocoagulation by laser.
N.B. : without ttt 50% of proliferative patients become blind
within 5 – 10 years.
VII. Diabetic foot :
1. Def. : Trophic changes in foot of diabetic patients (
ulcers, falling of hair & gangrene ).
2. Ae. : vasculopathy, neuropathy & infection combine to
produce tissue necrosis.
3. TTT :
a. Control of diabetes.
b. Careful foot cleaning & careful nail cutting.
c. For infection : strong antibiotic & drainage of pus.
d. For ischemia : revascularization & amputation in
gangrene.
N.B. : 50% of all lower limbs amputation are performed in
people é diabetes.
VIII. Renal :
The kidney may be damaged by diabetes in 3 main ways :
_ Glomerular damage.
_ Ischemia resulting in narrowing of afferent &
efferent arterioles.
_ Ascending infection.
1. Pyelonephritis :
In usual pyelonephritis triad ( Δ ) of
_ Fever.
_ Pain.
_ Dysuria.
But, DM modify pyelonephritis through :
necrosis of tip of papillae ( acute necrotizing papillitis ).
fever, pain, dysuria + heamaturia & anuria may occur.
2. Diabetic nephropathy :
a. Ae. : long standing DM ( type1 > type2 ), onset within
15 years.
b. Pathology : Glomerular sclerosis :
i. Thickening of basement membrane of glomeruli.
ii. Deposition of glyco-protein.
iii. Hyalinization of afferent & efferent arterioles.
N.B. : DM affects efferent more than afferent.
So ; there is more narrowing in eff. than in aff., this ↑↑ intraglomerular
pressure .
So ; there is progressive leak of large molecules ( esp.
protein) into urine.
c. Types :
i. Diffuse : 80 %.
ii. Nodular : 20 % ( Kimmelestiel-Wilson’s syndrome ).
d. C/P : &!_ ٤
i. Long standing DM ( 10 – 20 years ).
ii. Proteinurea :
1. micro-albuminuria. followed by
2. macro-albuminuria. followed by
3. heavy proteinurea & nephrotic syndrome.
iii. Lately, CRF & HTN.
iv. Diabetic retinopathy & neuropathy are usually
present.
N.B.
: CRF normal sized kidney in sonar :
_ DM.
_ Amyloidosis.
CRF big sized kidney in sonar :
_ Polycystic kidney.
CRF small sized kidney in sonar :
_ Chronic glumerulo-nephritis. ( GN )
_ Chronic pyelonephritis.
IX. Neurological :
1. Diabetic macroangiopathy.
2. Diabetic neuropathy.
3. Diabetic comas.

1. Diabetic macroangiopathy : due to atherosclerosis :
a. Stroke.
b. Hge.
c. Thrombosis.
d. Ischemia.
2. Diabetic neuropathy :
i. Pathogenesis :
unknown but there are 4 important theories :
1. Hypovitaminosis : polyuria washes water soluble B
complex.
2. Microangiopathy of vasa nervosa.
3. Metabolic ketosis : toxic effect of keton bodies.
4. Transformation of glucose to sorbitol by aldose
reductase enzyme. ط) ___ ا _   ___ (
ii. C/P :
1. Feature of polyneuropathy may precede the
discovery of DM.
2. Starts as mono-neuropathy or mono-neuropathy
multiplex, affecting
a. Peripheral nerves : sciatica , femoral,
ulnar & median.
b. Cranial nerves : III , VI or VII.
3. Frank diabetes polyneuropathy.
a. Symmetrical mainly sensory with pain & parasthesia
esp. in L.L., followed by superficial sensory of stock &
glove type.
b. Early loss of deep sensations, resulting in loss of deep
reflexes & sensory ataxia.
c. Motor weakness is late.
4. Autonomic neuropathy :
a. CVS :
i. Postural hypotension.
ii. Silent myocardial infarction
iii. At 1st tachycardia then fixed H.R.
b. Chest :
1- Respiratory arrest ( unknown ).
c. GIT :
i. Delayed gastric empting.
ii. Early nocturnal diarrhea, late constipation.
d. Genitor-urinary :
i. Impotence
ii. Sensory, motor or autonomic bladder.
e. Skin :
_ Hyperhydrosis then anhydrosis.
f. Trophic changes :
i. Ulcers.
ii. Loss of hair.
iii. Rough nail.
iii. TTT :
1. Strict control of DM : diet, oral hypoglycemic or insulin.
2. Reassurance may be all that needed.
3. Physiotherapy if motor weakness is present.
4. Drugs :
a. Analgesics of neurotic pain
b. Vit. B complex ( TRI B ) & ATP ( adenoplex ).
c. Capillary modulators : Ca diabetes ( Doxium )
d. Aldose reductase inhibitor : sorbinil.
e. Cerebrolysin.(nerve growth factor)
4- Convulsion may occur.
5- Coma.
N.B. : Hypoglycemic unawareness : means hypoglycemia
that occurs unnoticed by i patient because it’s not
associated with any adrenergic symptoms.
Ae. :
_ During night.
_ β-blocker.
_ Old age.
_ Recurrent hypoglycemia.
c. Investigation :
_ Low blood glucose < 50 mg % & absent in urine.
d. TTT :
i. If patient is conscious :
oral glucose in i form of candy.
ii. If patient is comatosed :
50 cc glucose 25 - 50 % IV followed by saline
infusion.
N.B. : Recovery is very rapid except in irreversible brain
damage.
2. Diabetic ketoacidosis “ DKA ” :
a. Def. :
DKA is an extremely serious metabolic complication
of DM due to sever insulin deficiency, it’s ch’ by i triad of :
- Acidosis.
- Ketosis.
- Hyperglycemia.
b. Ae. :
· Occurs mainly in type 1 DM, due to sever insulin
deficiency, it’s usually seen in the following
conditions :
_ Previously un diagnosed DM
_ Missed insulin ( neglected ttt ).
· PPT. factors :
_ Infection.
_ Stress : surgery,M.I .
N.B. : In type 1 DM : DKA occurs with or without ppt factors.
In type 2 DM : DKA occurs with ppt factors only.
c. Pathogenesis & C/P :
sever insulin deficiency leads to
i. Glucose can’t enter cells hyperglycemia
> 250 mg %.
ii. ↑↑ lipolysis → ↑ production of keton bodies
( β-hydroxy-buteric acid, acetoacetic acid & acetone )
ketoacidosis ( PH < 7.3 ).
iii. Effects of ketosis : gradual onset
1- Muscles :
a. generalized weakness.
b. muscle pain.
2- Kidney :
ketonuria together with glucosuria lead to sever
a. polyuria.
b. polydepsia.
c. dehydration.
3- GIT :
a. anorexia.
b. nausea.
c. vomiting.
d. abdominal pain.
4- Respiration :
a. Kussmaul respiration ( deep rapid )
b. acetone odour of breath.
5- CVS :
a. depressed contractility.
b. rapid weak pulse.
c. low BL.P.
iv. Shift of K outside cells in absence of insulin.
v. End stage : coma due to combined effect of
1. ketone bodies.
2. acidosis.
3. dehydration.
4. electrolyte disturbance.
d. Investigations :
i. Blood :
1. glucose.
2. ketone bodies.
3. FFA.
4. HCO3.
5. ↓↓ Na ( pesdohyponatremia due to polyuria).
6. ↑↑ K due to extra-cellular shift of K
seen with insulin deficiency.
ii. Urine :
1. glucosuria.
2. ketonuria.
e. TTT :
i. Insulin :
_ short acting insulin.
_ low dose of insulin therapy 5 – 10 u/ h
infusion.
_ when blood glucose < 250 mg /dl
reduce insulin to 2 – 4 u/ h.
ii. Fluid therapy :
_ 6 – 8 L is usually required.
_ at first saline is given, then change to
glucose 5% when bl. glucose < 250 mg/dl.
iii. K therapy :
_ hypokalemia occurs é insulin ttt due to
intracellular shift, so ad ( 20 – 40 m. eq )
to each 1 L of fluid.
iv. Na bicarbonate :
_ in sever acidosis [ PH < 7.1 ]
v. Broad spectrum antibiotics.
Hypoglycemic coma DKA
_ Patient : - follow ttt. - neglect ttt.
_ Onset : - acute. - gradual.
_ Pulse : - tachycardia.
- good volume.
- weak.
- rapid.
_ Bl.P. : - -
_ Skin : - Sweaty. - dry.
_ Pupils : - dilated. - not dilated.
_ Breath : - normal. - acetone odour.
_ Urine : - no sugar. - +ve sugar & acetone.
_ Coma : - Irritable. - not irritable.
_ IV glucose : - rapid recovery. - no effect.
3. Hyperglycemic-hyperosmolar non ketotic coma : ( HHNK )
· There is minimal insulin level which is not enough to inhibit
hyperglycemia but enough to ↓↓ ketogenesis , so there is
hyperglycemia without ketosis.
· It occurs in old type 2 DM.
· Patients typically having sever hyperglycemia ( > 600
mg/dl ), sever dehydration & plasma osmolarity ( > 340
mg/dl ) is the landmark of this condition.
N.B. :
- sever dehydration may lead to renal failure.
- sever hyperosmolarity may lead to neurological
symptoms ( convulsions & coma ).
· TTT :
o Aggressive fluid replacement.
o Insulin.
o Low molecular weight heparin to prevent
thrombotic complications.

4. Lactic acid coma :
· There is sever metabolic acidosis without significant
hyperglycemia or ketosis.
· It’s due to tissue hypoxia ( e.g. : high dose of biguanids )
anaerobic glycolysis lactic acid.
· TTT : NaHCO3
X. Diabetic infections :
1. skin : staph & candiasis.
2. GB : cholecystitis.
3. urinary tract : pyelonephritis & perinephric abscess.
4. lung : T.B. & pneumonia.
N.B. :
1- Acute diabetic complications :
= diabetic coma + infections.
2- Micro-vascular complications :
= diabetic triopathy.
3- Hyperglycemic coma :
= DKA + HHNK.
TTT of D.M. :
I. General measures.
II. Diet.
III. Oral hypoglycemic.
IV. Insulin.
V. TTT of complication.
I. General measures 
a. Reassurance.
b. Education about nutrition & lifestyle modifications.
c. Exercise.
II. Diet :
a. It’s an important item in ttt of D.M.
b. Diet alone can control mild cases of type II D.M.
c. Total calories/day :
depending on weight & physical activity :
i. mild activity 1500 cal /d.
ii. moderate ~ 2500 cal /d.
iii. sever ~ & pregnancy 3500 cal /d.
d. Food components :
i. CHO : 50%.
- avoid simple sugars.
- artificial sweeteners may be used.
ii. fat : 30%.
- avoid saturated fat.
iii. protein : 20%.
iv. vitamins : B-complex & vit.A.
v. ↑↑ fibers : satiety.
e. Number of meals :
3 main meals + 2 snacks in between,
to avoid hyperglycemia or hypoglycemia with ttt.
III. Oral hypoglycemic :
a. Sulphonylureas :
i. mech. of action :
1. ↑↑ release of insulin from pancreas.
2. ↑↑ peripheral action of insulin.
3. ↓↓ hepatic production of glucose.

ii. preparations :
Drug Trade name Dose ( mg/d ) Duration of
action
_ 1st generation :
- Cholropropamide Pamidine 100 - 500 long acting
- Acetoheamide Dimelor 250 - 750 intermediate
- Tolbutamide Diamol 500 - 2000 short
_ 2nd generation :
- Glibenclamide Doanil. 2.5 - 15 long acting
- Glimepiride Amaryl. 1 - 6 long acting
- Gliclazide Diamicron. 40 - 240 intermediate
- Glipizide Minidiab 2.5 - 30 short

iii. indication :
type II DM not controlled by diet alone esp.
in non obese patients.
iv. side effect :
1. allergy.
2. hypoglycemia.
3. GIT upset & cholestatic jaundice.
b. Biguonides :
i. mech. of action :
1. anaerobic glycolysis.
2. ↓↓ glucose absorption.
3. ↓↓ appetite.
ii. preparations :
Metformin ( Glucophage – Cidophage )
- 500 mg t.d.s. - 850 mg t.d.s.
iii. indications :
1. type II DM not controlled by diet alone esp. if in
obese patients.
2. combined with suphonylurea or insulin to
achieve control.
iv. side effects :
1. GIT irritation.
2. lactic acidosis.
c. Recent drugs :
i. Glucosidase inhibitors : ( Glucobay ) 50 mg t.d.s.
breakdown of CHO in intestine glucose absorption.
ii. Repaglinide ( Novonorm ) insulin production at meal.
IV. Insulin :
a. Action :
i. Rapid action : ↑↑ entery of glucose, K & a.a. into i
cells.
ii. Gradual action :
1. CHO : hypoglycemia:
a. glycogensis.
b. gluconeogenesis.
c. peripheral utilization of glucose.
2. fat :
a. ↑↑ lipogenesis.
b. ↓↓ lipolysis.

3. protein : anabolic.
b. Preparations : was discovered in 1921.
Type Trade names Duration of action
1- Short-acting :
( soluble,
crystalline )
- Insulin Actarapid.
- Humulin R
· Each 1ml = 20 units
Onset : < ½ h.
Peak : 2 – 4 h.
Duration : 6 – 8 h.
2- Intermediate : - Insulin NPH
- Humulin N
- Monotard
- Lente
· Each 1 ml = 40 units
Onset : 2 h.
Peak : 6 – 8 h.
Duration : 12 – 24 h.
3- Long-acting : - Ultralente
- Ultratard
- Humulin L
· Each 1 ml= 40 units.
Onset : 6 – 8 h.
Peak : 12 – 24 h.
Duration : up to 36 h.
4- Insulin mixture : 30% short + 70% NPH ( mixtard )
c. Indications
i. Type 1 DM.
ii. Type 2 DM not controlled é diet & oral hypoglycemic.
iii. During pregnancy, infection & surgery.
iv. DKA & HHNK ( critical episodes of type 2 DM ).
v. ↑↑ K ( Hyperkalemia ).
vi. Insulin stimulation test for GH assessment.
vii. Insulin stimulation test in pan-hpypopituitarism.
d. Dose : trial & error. ( s. c. )
i. Start é 20 u ( ½ cm )/d mixtard non obese patient&
start é 30 u ( ¾ cm )/d mixtard obese patient.
ii. The dose is gradually ( 5 u ) until control is achieved.
iii. 2/3 of dose in i morning & 1/3 of dose in i evening.
N.B. : 1 cm mixtard = 40 u.
: If mixtard is not available 1/3 crystalline insulin + 2/3
NPH can be mixed in i syringe & injected as rapid as you can.
e. Administration :
i. S.C.
ii. Insulin pump.
iii. Insulin pens.
N.B. : Oral insulin under trial.
f. Complications :
i. Hypoglycemia & hypoglycemic coma.
ii. Allergy : use human insulin.
iii. Insulin resistance :
1. obesity mild resistance.
2. antibodies against insulin.
iv. Insulin lipodystrophy : atrophy or hypertrophy of s.c.
fatty tissue at i site of insulin injection.
v. Insulin edema : Na & H2O retention.
vi. Weight gain.
vii. Pseudo insulin resistance ( Somogi effect ) : nocturnal
hypoglycemia due to over insulin dose → ↑↑ anti-insulin
hormones rebound hyperglycemia in I morning.
N.B. : the ideal goals for glycemic control in patient with DM
(Q : criteria for good diabetic control ?)
_ Lab. :
- Fasting plasma glucose ( 90 - 130 ) mg/dl
- Post prandial plasma glucose : < 180 mg/dl.
- HbA1c < 7%.
_ Clinical :
- No symptoms of DM.
- No symptoms of hypoglycemia.
V. TTT of complication :
see the pictures 

complications of Diabetes mellitus

complications of Diabetes mellitus


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