akbari kamrani a. a. md iranian research center on ageing university of social welfare &...
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Diabetes mellitus
Akbari kamrani A. A. MD Iranian Research Center on AgeingUniversity of social welfare & rehabilitation sciencesPayambaran Hospital
Diagnosis of Diabetes mellitus 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
Diagnosis of Diabetes mellitus
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
Prevalence DM type II increases with age
3-5% 40 - 50 yrs.
10-20% 70 – 80 yrs.
Pathogenesis type II DM
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, )
Insulin resistance
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
Symptoms & signs
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
Complications
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
Complications
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 )
Complications
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
Complications
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
Complications
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
Complications
Foot ulcers & joint problems important causes of morbidity predisposing cause is polyneuropathy sensory denervation ( trauma ) proprioception alteration(weight bearing) Charcot`s joints
Complications
Infection : cellular immunity decreased by : acute hyperglycemia circulatory deficits by : chronic hyperglycemia Fungi, bacteria, foot ulcers often feel no pain (neuropathy)
Prognosis & treatment
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
Prognosis & treatment
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
Pharmacotherapy
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
Metformin
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
Acarbose
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 )
Pioglitazone & rosiglitazone
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
Sulfonylureas
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 )
Insulin therapy
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
Insulin preparations
preparation Onset of action
Peak Duration
Rapid acting Lispro
0-15 min ½ - 1 ½ h 4 h
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
Complications of insulin treatment
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
Nonketotic hyperglycemia-hyperosmolar coma
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 )
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