Akbari kamrani A. A. MD Iranian Research Center on Ageing University of social welfare &...

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 )

Thanks