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