Transcript Diabetes mellitus

Akbari kamrani A. A. MD
Iranian Research Center on Ageing
University of social welfare & rehabilitation sciences
Payambaran Hospital

Repeated FBS > 125 mg/dl ( 6.9 mmol/l )
at least 8 hours


Any postprandial Bs > 200 mg/dl (>11.1 mmol)
Oral glucose tolerance test (OGTT=75 gr ) //

Type I = early onset + dependency on Insulin

Type II = much more common in the Elderly

Glycosylated hemoglobin ( HB A1c ) :
is not specific for diagnosis
indicates existing diabetes
estimate blood glucose control
determined every 1-3 months
goal : level < 8%

Prevalence DM type II increases with age

3-5%
40 - 50 yrs.

10-20%
70 – 80 yrs.

Impaired insulin secretory
response to glucose
Decreased

Insulin resistance :
( increasing insulin secretion)
insulin effectiveness in glucose uptake by skeletal muscle decreased
Heterogeneous group with hyperglycemia ( type III )
Genetic factors / chronic pancreatitis / other endocrine diseases
( Cushing, acromegaly, pheochromocytoma, glucagonoma,
somatostatinom, hyperaldosteronism, )

Is not genetic alteration in the insulin receptor
or glucose transporter

Is genetically postreceptor intracellular defects

The resulting :
Hyperinsulinemia / hyperlipidemia /
hypertension / visceral & abdominal obesity /
waist to hip ratio> 1 / coronary artery disease
Asymptomatic hyperglycemia BS < 200
Symptomatic BS > 200
polyuria,
(in elderly because the kidneys` ability to reabsorbed
filtrated glucose increases, polyuria is less common )
polydipsia, weight loss,
dehydration, blurred vision,
fatigue, nausea, infections,
perineal itching due to Candidiasis
 Nonketotic hyperglycemic hyperosmolar coma ( NKHHC )
 Clinical manifestation of late complication of diabetes



Macrovascular complications :
stroke, CAD, claudication,
skin breakdown, infection,
amputation of a lower limb
The risk :
hyperglycemia ↑ 5 fold
hypertension ↑ 10 – 20 fold
smoking
↑ 10 – 20 fold
dyslipidemia ( TG ↑ & HDL ↓ )
Prevention :
treatment of concomitant risk factors
ASA (higher doses than those non diabetics )
ACE inhibitor , Statins

Microvascular complications :
retinopathy :
macular edema, prolifferative retinopathy
retinal detachment, hemorrhage,
blindness
85% all DM have some degree of retinopathy
7 yrs. Before DM diag.
oral pentoxifyline ( some data support )

Microvascular complications :
nephropathy :
usually asymptomatic until ESRD
1/3 in type I DM
smaller in type II DM
albuminuria> 300 mg/L after 5 yrs.
DM & diastolic BP> 90 2.5 fold
DM & diastolic BP< 70 albuminuria
ACEI ( captopril ) recommended

Microvascular complications :
neuropathy :
polyneuropathy:
predominantly sensory
distal, symmetric, (stocking-glove)
numbness, tingling, paresthesia,
less often: sever deep seated pain &
hyperesthesia, Ankle jerks ↓
mononeuropathy :
acute, painful,
affecting 3th , 4th, 6th , 7th cranial nerve
other nerves such as femoral
spontaneously improve over weeks to months

neuropathy :
Autonomic neuropathy :
postural hypotension
sweating
impotence
retrograde ejaculation
impaired bladder function
delayed gastric emptying
esophageal dysfunction
constipation / diarrhea / nocturnal diarrhea
blunted decreased in HR in response to
Valsalva maneuver & standing & deep breathing

Foot ulcers & joint problems
important causes of morbidity
predisposing cause is polyneuropathy
sensory denervation ( trauma )
proprioception alteration(weight bearing)
Charcot`s joints

Infection :
cellular immunity decreased by :
acute hyperglycemia
circulatory deficits by :
chronic hyperglycemia
Fungi, bacteria,
foot ulcers often feel no pain (neuropathy)

Diabetic patient should be assessed :
on each visit :
check of the feet
pulses
sensation
urine test for albumin
every year :
lipid profile
BUN
creatinine
ECG
ophthalmologic examination
Linear relationship between complications & HB A1c
HB A1c < 8 is threshold for prevention of complication
Weight management is important
insulin sensitivity increased with weight-loss
 Diet management is also important
total daily caloric / proportions of carbohydrate,
fat , protein /distributing calories among meals
 Regular exercise , especially in obese
mod-sever exercise can lead to hypoglycemia




Oral antidiabetic drugs :
Antihyperglycemic :
biguanides ( metformin -10h )
ᾳ- glucosidase inhibitors (acarbose -6h )
thiazolidinedions ( pioglitazone -24h )
hypoglycemic drugs :
sulfonylureas :
( first generation ) : don’t use in elderly
tolbutamide (12h) / chlorpropamide (60h)
(second generation ): 100 times more potency than 1th
glibenclamide/ glyburide/ glipizide/ ( 24h )
meglitinide analog :
repaglinide ( 3h ) ( novonorme )

Insulin therapy






Drug of choice in : newly , obese , type II DM
Decreases hepatic glucose production
Decreases lipid levels
Improve insulin sensitivity
Promotes weight loss
Decreases MI, & diabetes related deaths ( 30-40 % )
Contraindication :
kidney disease crea.> 1.4
liver disease/ alcoholism
lactic acidosis
elderly > 80 yrs. ( renal func.)
acute hospitalization
 Adverse effect :
gastrointestinal

Inhibits hydrolysis of oligo & monosacharides
 Delay carbohydrate digestion & absorption
 Less PP hyperglycemia
 Ideal for elderly , & mild hypoglycemia
FBS < 150 mg/dl or Postprandial hyperglycemia
 Drug with each main meal ( 25-100 mg/TDS )
 Adverse effect : GI ( often transient )





Improve insulin sensitivity in skeletal muscle
Suppress hepatic glucose output
Useful in elderly with renal function failure
No longer marketed in the USA because :
idiosyncratic liver disease & hepatic failure
which led to liver transplantation or death




Differ in potency & duration
Stimulating insulin secretion
Improve peripheral & hepatic insulin
sensitivity
Adverse effects : allergic reactions
cholestatic jaundice
hypoglycemia
( 3 days monitored in the hospital )
Most type II DM don’t need insulin
Insulin antibody develop however in
human insulin preparations
 Nearly all of type II DM have significant
insulin resistance
( require more insulin than type I DM )
 started with bedtime NPH insulin
 Later divided ( ½ breakfast , ¼ dinner , ¼ bedtime)
 Increments in insulin 10% at a time over 3 days
 Goal : pre-prandial BS 80-150 & stabilize the fluctuations


preparation
Onset of action
Peak
Duration
Rapid acting Lispro
0-15 min
½ - 1½ h
4h
Rapid acting
Regular
15-30 min
2-4 h
6-8 h
Rapid acting
Semilente (zinc)
1-2 h
4-9 h
10-16 h
Intermediate
(NPH) & Lente
1-3 h
6-12 h
18- 24 h
Long acting (PZI )
& Ultralente
4-8 h
14-24 h
28-36 h
Hypoglycemia :
error in dosage/ missed meal/ unplanned
exercise/
concurrent illness in hospitalized :(sliding scale)
 Dawn phenomenon ( Somogyi phenomenon)
 Local fat atrophy or hypertrophy (no treat.)
 Local allergic reactions (antihistamines )
 Generalized insulin allergy (after restarted)
( Skin testing , desensitization )
 Insulin resistance : > 200 U/day
( insulin antibody )
prednisolone 30 mg bid 2 weeks & tapered


BS>500 mg/dl & dehydration & ↓consciousness / seizures

More common in the elderly
High mortality rate
Inadequate fluid intake & dehydration
Precipitated by : acute infection /
glucocorticoids / diuretics
dementia (insensitive to thirst )


