Diabetes Flashcards
Where is insulin secreted from?
- b-cells of islets of langerhans
- secreted as pro insulin & splits into insulin & C-peptide
What is the function of insulin?
- increases uptake & utilization of glucose
- stimulates glycogenesis
- inhibits gluconeogenesis
- stimulates lipogenesis
- inhibits lipolysis
- inhibits ketogenesis
- anabolic
- intracellular shift -> K
What stimulates the secretion of insulin?
- glucose
- aminoacids
- sulphonylurea
What will inhibit the secretion of insulin?
- hypoglycemia
- hypokalemia
- somatostatin
What are the effects of insulin deficiency on the body?
hyperglycemia
- decreased uptake & utilization of glucose
- decreased glycogenesis & lipogenesis
- increased glycogenolysis & gluconeogenesis
- increased lipolysis
- increased ketogenesis
- catabolism
- loss of K
What is the definition of diabetes mellitus?
disturbance of carbohydrate metabolism due to insulin deficiency or resistance or both
leading to hyperglycemia & glucosuria with secondary disturbance of protein & fat metabolism
What is the classification of diabetes mellitus?
PRIMARY
- type I: insulin-dependent DM
- type II: insulin-independent NIDDM
SECONDARY
- pancreatic diseases (cystic fibrosis, hemochromatosis, pancreatitis)
- endocrinal diseases (acromegaly, cushing’s, pheochromocytoma, thyrotoxicosis)
- chronic liver failure
- drugs (corticosteroids, contraceptive pills, thiazide)
- genetic diseases (DIDMOAD, down, myotonia atrophica)
What is the cause of type I DM?
damage of b-cell in islets of langerhans
- genetic: HLA dr3-dr4
- infection: coxsackie B, rubella, mumps
- immunological mechanisms: islet cell antibodies ICA, antiGAD (glutamic acid decarboxylase), insulin autoantibodies IAA
What are the causes of type II DM?
- insulin resistance at receptor or post-receptor level
- dysinsulinogenesis
What are the phases of type II DM?
- early: high insulin levels & loss pulsatile insulin secretion
- late: decrease in insulin levels & loss of 1st phase insulin secretion
How does a patient with diabetes mellitus present?
- polyuria
- polydipsia (thirsty)
- polyphagia (hungry)
- pruritis
- parathesia & premature loosening of the teeth
- repeated infection
- complications
- diabetic coma
What investigations are done for diagnosis of diabetes?
1- plasma glucose 2- urine analysis 3- investigate for cause (only if secondary diabetes is suspected) 4- investigate for complications 5- monitor treatment
How is the plasma glucose measured & what are the normal results?
- fasting glucose: normal from 70-99mg
- 2 hours post-prandial: <140mg
- oral glucose tolerance OGTT: <200mg
When is a diabetes diagnosis confirmed after measuring the plasma glucose?
- fasting glucose: 126 or more
- 2 hours post-prandial: 200 or more
- OGTT: >200 in 2 readings
- symptoms of diabetes + random plasma glucose of 200 or more
What is the most important marker for diagnosis of DM?
Hemoglobin A1-C (HAIC): normal is < 5.7
How should the treatment of DM be monitored?
- home blood glucose monitoring (HBGM)
- HA1c (glycosylated hemoglobin): formed by linkage of glucose to B-chain of HbA (used to estimate control for preceding 8-12 weeks)
- fructosamine: glycosylated plasma protein (control over past 2 weeks)
What is the classification of findings of HA1C?
- normal: 5 - 5.6 (<5.7)
- prediabetes: 5.7 - 6.4
- diabetes: 6.5 & above
What are the causes of mellituria (sugar in urine)?
- DM
- renal glycosuria: due to low renal threshold for glucose (Dentoni-fanconi syndrome & pregnancy)
How should diabetes be treated?
1- dietetic control 2- general measures 3- oral hypoglycemia drugs 4- insulin 5- new lines of treatment 6- ttt of complications - ttt of the cause is secondary
What are the proportions of food elements in dietetic control?
- CARBS -> 50% of total caloric intake
- FATS -> 30%
- PROTEINS -> 20%
What are the values of weight reduction?
- decrease hepatic glucose production
- decrease insulin resistance
- improve b-cell function
What is the exercise guide for diabetic FITness?
Frequency -> 3x to 4x a week
Intensity -> 60-80% of maximal heart rate
Time -> 20-30mins
What is the classification of oral hypoglycemic drugs?
SULPHONYLUREA old generation (long half-life -> high risk of hypoglycemia) - tolbutamide - acetohexamide - chloropropamide new generation (short half-life -> less hypoglycemia) - glibenclamide - glipizide - gliclazide - glimepiride
BIGUANIDES
- metformin
what are the adverse effects sulphonylureas?
- hypoglycemia: most severe with chloropropamide
- hyponatraemia with chloropropamide
- skin reactions: alcoholic flush, dermatitis
- hepatitis & cholestatic jaundice
What drugs affect the function of sulphonyureas?
- INCREASED BY: NSAIDS, sulfonamides, chloramphenicol
- DECREASED BY: corticosteroids, estrogen, rifampicin
What is the mechanism of action of (biguaninde) metformin?
- decrease plasma glucose & gluconeogenesis
- decrease intestinal absorption of glucose
- increase sensitivity of insulin receptor
- decrease body weight through its anorexogenic
What is the recommended dose for metformin (glucophage)?
start with 500mg & increase up tp 2500mg
What are the side effects of metformin?
- nausea
- vomiting
- diarrhea
- B12 malabsorption
- anorexia
What are the indications for insulin therapy?
- all IDDM patients (type I)
- NIDDM (type II) if not responding to diet & oral drugs
- diabetic ketoacidosis
- diabetes during pregnancy
- complicated diabetes
What are the types of insulin?
rapid-acting
- onset: 10-15mins
- peak: 60-90mins
- duration: 4-5 hours
short-acting
- onset: 0.5-1 hour
- peak: 2-4 hours
- duration: 5-8 hours
intermediate-acting
- onset: 1-3 hours
- peak: 5-8 hours
- duration: up to 18 hours
extended long-acting
- onset: 90 minutes
- no peak
- duration: 24 hours
premixed
- taken twice a day: once with breakfast & once before supper
What are the methods of insulin administration?
CONVENTIONAL INSULIN THERAPY
- 2 SC injections -> 2/3rd before breakfast & 1/3 before dinner
- each dose 30% short acting & 70% intermediate acting
MULTIPLE SUBCUTANEOUS INSULIN INJECTION (MSII)
- 40% intermediate insulin AT BEDTIME
- 60% regular insulin before the 3 main meals (20% for each meal)
CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII)
- 40% of total dose is given basally & remainder (60%) is given as preprandial boluses
- risk of hypoglycemia & hyperglycemia
What are the side effects of insulin administration?
- hypoglycemia
- hypersensitivity
- insulin resistance
- insulin lipodystrophy (atrophy or displacement) at site of injection
- Somogi phenomenon
- Dawn phenomenon
How can we differentiate between Somogi & Dawn phenomenas?
measure glucose at midnight
- Somogi -> hypoglycemia THEN hyperglycemia
- Dawn -> hyperglycemia
What is the difference between Somogi & Dawn phenomenas?
- Somogi -> overdose of insulin given at night (treat by decreasing evening insulin)
- Dawn -> night dose of insulin was not enough
What is the honeymoon phase & what should be done during this phase?
decrease in insulin requirement in IDDM due to TEMPORARY islet cell function
What are the acute complications of diabetes?
- diabetic ketoacidosis DKA
- hypoglycemia
- hyperglycemic-hyperosmolar non ketonic coma HHNC
- lactic acidosis
What are the predisposing factors for DKA?
1- inadequate insulin administration in type I 2- increase in insulin requirement - infections - MI - emotional stress - excess fat intake - starvation - endocrinal disorders - pregnancy & labour - trauma, operation, burn, & shock - non cause (25%)
What is the pathogenesis of DKA?
1- severe insulin deficiency
2- utilization of fats for energy
3- increase glycerol & FFA
4- formation of ketone bodies (acetone, aceto-acetic acid, B-hydroxy-buteric acid)
The increase of ketone bodies will lead to?
- metabolism acidosis -> air hunger & acetone odor
- hyperglycemia -> glucosuria -> polyuria & dehydration
- electrolyte imbalance -> decreased level of consciousness
What is the clinical picture of DKA?
POLYURIA
- polydipsia
- dehydration -> weakness, tachycardia, hypothermia
KUSSMAUL RESPIRATION shallow rapid breathing
GIT
- acetone odor
- anorexia nausea, vomiting, & hematemesis
- iléus -> abdominal distention, constipation & gastric dilatation due to hypokalemia
- severe abdominal pain due to ketonemia
CNS
- hypotonia & hyporeflexia due to hypokalemia
- coma due to -> ketone bodies, dehydration, acidosis, & electrolyte disturbance
What will be found on investigation of DKA?
- plasma glucose -> higher than 300 (hyperglycemia)
- urinalysis -> glucosuria, ketonuria, ketonemia
- ABG -> decrease in HCO3 <10 with pH <7.3
- electrolytes -> hyperkalemia (extracellular shift)
if hypokalemic from the start -> patient is severely dehydrated & need aggressive K treatment - increase in PCV due to marked dehydration
How should DKA be treated?
1- preventive 2- curative - fluid replacement - insulin treatment - electrolyte correction - sodium bicarb - treat cause
What is the adequate fluid replacement therapy in case of DKA?
- up to 8 liters per day
- 1L in first 1/2h -> after 1 hr 1L -> after 2h 1L -> after 3h 1L -> after 4h 1L = 5L in half the day
- normal saline is used until blood glucose is <200mg THEN changed to dextrose - saline
How should insulin be given in treatment of DKA?
IV infusion insulin
- start with 0.1 u/kg/h -> MAX decrease blood glucose 50-100mg/h (could cause brain edema if more)
- continue until glucose conc. <200mg
What is the normal potassium level?
3.5 - 5.5
How do we correct electrolyte disturbances in DKA?
- if K is more than normal (5.5) -> do nothing because insulin will bring it down
- if K is normal (3.5 - 5.5) -> give K with insulin
- if K is <3.5 -> DO NOT START INSULIN & give potassium 40mmol/L of saline
When should bicarb be given in DKA?
when
- HCO3 is <10
- pH is <7.1
What are the complications of DKA?
- Rhinocerebral mucormycosis -> fatal within 1 week -> treat with amphotericin + necrotic tissue removal
- shock -> due to severe dehydration
- vascular thrombosis -> due to severe dehydration
- pulmonary edema -> due to aggressive fluid therapy -> give furesumide
- cerebral edema -> rapid decrease of glucose levels -> movement of water into intracellular space
What are the manifestations of brain edema & how are they treated?
- increased intracranial tension -> papilloedema, opthalmoplegia
- confusion & recurrence of coma
treat by mannitol or dexamethasone
how is hypoglycemic coma treated?
IV glucose
hyperglycemic-hyperosmolar non-ketotic coma is common in which patients?
old diabetic patients
What is the pathogenesis of HHNC?
1- low level of insulin that prevents lipolysis & ketosis BUT NOT enough to prevent hyperglycemia (>800mg)
2- osmotic diuresis
3- severe dehydration
What are the predisposing factors of HHNC?
- conditions increasing insulin requirement
- drugs inhibiting insulin secretion -> steroids, K-wasting diuretics, diazoxide, & phenytoin
How should HHNC be treated?
1- half tonic saline
2- lower rate of insulin infusion 3u/h -> because there is a higher risk of cerebral edema
3- low dose s.c heparin -> prevent thrombosis damage from dehydration
What will cause lactic acidosis is diabetic patients?
patients receiving BIGUANIDES -> anaerobic glycolysis -> accumulation of lactic acid in excess -> coma
GIVE A LARGE AMOUNT OF HCO3
What are the chronic complications of diabetes?
1- neurological complications -> cerebral, spinal cord, neuropathy
2- cardiovascular complications -> atherosclerosis, microangiopathy, cardiomyopathy, increase HTN
3- respiratory complication -> infections (TB), kussmaul breathing, acetone odor
4- gastro-intestinal complications
5- urinary complications -> UTI, diabetic nephropathy
6- genital complications -> impotence, loss of testicular sensations, pruritis vulvae, vaginalis moniliasis, menorrhagia, sterility
7- ocular complications -> infections, error of refraction, diabetic cataract, rubeosis iridis, diabetic retinopathy
8- skin complications
What are the neurological complications?
Cerebral
- coma
- cerebral atherosclerosis & thrombosis
- rhino-cerebral mucor mycosis
Spinal
- posterior column affection -> diabetic pseudotabes
- pyramidal tract affection -> diabetic lateral sclerosis
Neuropathy
- sensory
- motor
- autonomic
What are the symptoms of sensory neuropathy?
peripheral symmetrical paraesthesia or hyperesthesia with nocturnal intensification
- starts in the feet -> glove & stocking hypoesthesia
- deep sensations are lost early
what are the complications of sensory neuropathy?
- neuropathic skin ulcers
- neuropathic (Charcat’s) joint
What are the types of motor neuropathy?
- mononeuropathy -> isolated motor nerve paralysis
- mononeuropathy multiplex -> isolated unrelated multiple motor nerve paralysis
- polyneuropathy -> bilateral symmetrical distal motor weakness with sensory loss
What is the pathogenesis of diabetic neuropathy?
- ischemia secondary to narrowing to vasa nervosum -> mononeuropathy & mono multiplex
- accumulation of sorbitol -> polyneuropathy
What are the symptoms of autonomic neuropathy in the genito-urinary system?
parasympathetic is affected first -> sympathetic takes the upper hand in the beginning
EARLY (parasympathetic affection)
- straining, dribbling, reduction in the force of stream
- failure of erection
LATE (both affected)
- bladder distention with overflow incontinence
- failure of ejaculation
What are the symptoms of autonomic neuropathy in the cardiovascular system?
- persistent sinus tachycardia
- postural hypotension -> due to pooling of blood
- painless MI
What are the symptoms of autonomic neuropathy in the gastro-intestinal tract?
- gastroparesis diabeticorum -> slow emptying, distention, vomiting
- intermittent bouts of diarrhea alternating with constipation
- fecal incontinence
What are the effects of autonomic neuropathy on sweating?
- initially excessive nocturnal sweating
- gustatory sweating -> during eating
- later -> diminished sweating in the lower limb (anhydrous)
What are the vasomotor disturbances that occur due to autonomic neuropathy?
- edema of the feet & legs
- increase temperature in lower extremities -> burning hot feet at night
- unawareness of hypoglycemia
How should painful neuropathies be treated?
1- NSAIDS or tramadol
2- phenytoin or carbamazepine, gabapentin, pregabalin
3- TCA
4- topical Capsaicin (VIX)
What are the special features of atherosclerosis in diabetes?
- more extensive
- occurs earlier
- equal sex incidence
- > peripheral vascular disease
- > CAD & stroke (CVA)
What are the effects of microangiopathy?
- vasa nervosa -> neuropathy
- glomeruli -> nephropathy
- retinal vessels -> retinopathy
How should hypertension be controlled incase of diabetic patients?
ACEs & ARBs
contraindications
- non selective BB -> masks hypoglycemia manifestations
- thiazides -> worsens blood sugar control
- methyl dopa & guanethidine -> worsens postural hypotension
What are the chronic GI complications of diabetes?
- tongue -> dry, beefy, oral moniliasis (red & inflamed)
- teeth -> loose, dental caries
- gastroparesis diabeticorum
- gallbladder stones & chronic cholecystitis
- nausea, vomiting, & hematemesis
- nocturnal diarrhea & constipation
- NAFLD
What are the stages of diabetic nephropathy?
- stage I -> hypertrophy & hyper filtration (normally GFR is 125)
- stage II -> hyper filtration & microalbuminuria (on exercise) -> 30-300mg/24hrs
- stage III -> hyperfiltration & constant microalbuminuria
- stage IV -> proteinuria > 300mg/24hrs & decrease GFR
- stage V -> end stage RF
How is diabetic nephropathy delayed?
- diabetic control -> reverses microalbuminuria
- hypertension control -> MAX 130/80 but the lower the better -> ACE inhibitors
- low protein diet
What are the effects of pregnancy on diabetes?
- insulin resistance
- decreased renal threshold for glucose
- increased incidence of ketosis & acceleration of diabetic complications
What are the effects of diabetes on pregnancy?
ON FETUS
- neonatal hypoglycemia
- large birth weight
- congenital anomalies
- increased incidence of abortion, premature delivery & neonatal death
ON MOTHER
- increase incidence of toxemia, hydramnios, & placental dysfunction
- post partum hemorrhage
- puerperal sepsis
What are the types of errors of refractions due to diabetes?
- hyperglycemia -> myopia
- hypoglycemia -> hypermetropia
What are the stages of diabetic retinopathy?
1- sclerosis of retinal arteries
2- microaneurysms
3- deep round hemorrhages & yellowish-white waxy exudates
4- vitreous hemorrhages & fibrous tissue formation (retinitis proliferans) -> obscure vision & subsequent shrinkage of fibrous tissue -> retinal traction & detachment
What are the primary skin complications due to diabetes?
- diabetic dermopathy (shin spots)
- bullosis diabeticorum
- necrobiosis lipoidica diabeticorum
- acanthuses nigerians
- eruptive xanthomas
- insulin lipodystrophy
- scleroderma
- lipohypertrophy
How should we screen for gestational diabetes?
- any pregnant female with diabetes risk factors -> screen at first prenatal visit
- if pregnant female has no risk factors -> screen on the 24-28 week using 2h OGTT (75g load)
What is the diagnostic criteria for gestational diabetes?
- fasting blood glucose ≥92 mg/dL
- 1hr post-glucose challenge ≥180mg/dL
- 2hr ≥153mg/dL
How should gestational diabetes be treated?
PREPREGNANCY PLANNING
- HBA1c must be normalized
DURING PREGNANCY
- keep FBG 60 - 110
- check glycosylated Hb every month
DURING LABOUR
- maternal blood glucose should be kept within 80 - 100mg
What are the causes of hypoglycemia?
FASTING HYPOGLYCEMIA
- decrease glucose production
- increase glucose utilization
POSTPRANDIAL HYPOGLYCEMIA
- hyperalimentation: after gastrectomy -> brisk glucose absorption -> excessive insulin release -> hypoglycemia after 2 - 3 hrs
- idiopathic reactive hypoglycemia: hypoglycemia after 3-5 hrs
What are the causes of decreased glucose production?
- hormone deficiency -> hypopituitarism, adrenal insufficiency, hypothyroidism
- enzyme deficiency -> decrease in enzymes responsible to breakdown of glycogen
- substrate deficiency
- acute liver disease -> severe hepatitis
What are the causes of increased glucose utilization?
- increased insulin: insulinoma, exogenous insulin, sulphonylurea
- increase insulin life growth factor: fibroma, sarcoma, hepatoma
- decreased enzymes of fat oxidation: decreased carnitine enzyme -> all tissue becomes obligate consumers like the brain
What is the clinical picture of hypoglycemia?
ADRENERGIC MANIFESTATIONS
- anxiety
- sweating
- tremors
- palpitations
- weakness
- tingling of mouth
- hunger
BRAIN
- headache
- mental dullness, confusion, & visual disturbance
- convulsions
- coma
How can we diagnose fasting hypoglycemia?
Confirming of fasting hypoglycemia
- fasting for 16 - 72 hrs -> estimate plasma glucose & insulin every 6 hours
- ratio of insulin/plasma glucose should always be less than 0.4 in normal people
Determining the cause of FH
- abdominal US or CT
- endocrine or enzyme assay
How should fasting hypoglycemia be treated?
- adrenergic reaction without CNS abnormalities -> oral carbohydrates
- if coma or confusion -> IV glucose 25 - 50 as a bolus -> constant infusion until patient is able to eat
treat the cause
How should post prandial hypoglycemia be treated?
1- diet -> small frequent meals with limited amounts of carbs
2- drugs -> propanthelin & phenytoin
3- surgery -> for refractory cases
What is the criteria for diagnosis of metabolic syndrome?
1- central obesity -> in saudi ≥102 in males & ≥84 in females
2- any two of the following
-> raised triglycerides >150 mg/dL
-> reduced HDL cholesterol < 40 mg/dL in males & < 50 mg/dL in females
-> systolic BP > 130 or diastolic BP > 85
-> raised FPG > 100mg/dL
OR TREATMENT OF ANY
What is the mechanism of action of metformin & its contraindications?
suppresses hepatic glucose output
contraindicated in:
- renal compromise (CR > 1.4 in women & 1.5 in men)
- CHF requiring treatment
- increased lactic acidosis
What is the mechanism of action of sulfonylureas & its precautions?
increases pancreatic secretion of insulin (gli-)
leads to
- weight gain
- hypoglycemia
What is the mechanism of action of acarbose & its precautions?
delays glucose absorptions by inhibition of pancreatic a-amylase & intestinal a-glucoside
causes GI
- flatulence
- cramps
- diarrhea
