Transcript Sugar Disorders

Sugar Disorders
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SUGAR DISORDERS
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DM (2008: 8 percent of the U.S.
population has diabetes.)
 15.8 million (2005)
 T1- 1 million
 T2-14.8 million
 ‘Other’ DM-<20,000
 2008: 24 million, an increase of more than 3 million in two
years (2007)
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T1 and T2 Features
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T1: (10% of cases)
immune mediated 90%
DKA+++
Children and under 20
(15/100,000)
Absent insulin
Increased Glucagon
Insulin antibodies
FH+
?virus: rubella/ coxsackie/
cow’s milk
 T2: (90% of cases)
 DKA absent
 Genetics- insulin resistance and
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Beta cell loss (chr.2- in Hispanics)
High insulin levels
Gut Obesity#1 cause
? leptin and
adiponectin
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Metabolic Syndrome
Syndrome X (Insulin resistance
Syndrome)
Increased TGL (triglycerides)
Decreased HDL (high density lipoproteins – the good kind)
HTN (hypertension)
Increased LDL (low density lipoproteins – bad kind)
Increased Uric Acid
Truncal obesity (aka central obesity)
Increased clotting tendency and pro-inflammatory state
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Clinical Features of DM
T1
T2
Polyuria and thirst
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Weakness or Fatigue
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Polyphagia and Weight loss
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Recurrent blurred vision
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Vulvovaginitis or pruritus
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Peripheral neuropathy
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Nocturnal enuresis
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Often asymptomatic
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T2 diabetics
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Waist to Hip ratioMen greater than 0.9
Women greater than 0.8
Indicates increased risk of diabetes in obese people
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Current Blood Sugar Numbers
Normal
Impaired
Diabetes
Mellitus
Fasting plasma
glucose
Less than
100 mg/dL
100-125
mg/dL
≥126 mg/dL*
Two hours after
glucose load
≤ 140 mg/dL ≥140-199 mg/dL
*126 or more on 2 occasions is diagnostic
≥ 200 mg/dL
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Glycated Hemoglobin A1c
 Normal HgbA1c is 4-6%
 Abnormally elevated in diabetics
 Reflects blood sugar levels over past 8-12 weeks
 If the value is greater than 2% then drug dose
adjustments can be done
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Lipid abnormalities in DM
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In T1 patients initial LDL is high but returns to normal
In T2 patients- TGL is high/ low HDL/ altered LDL more
atherosclerosis
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Non Diabetic causes for
high blood sugar
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Endocrinal- high steroids/ high GH/ glucagon tumors
Drugs- niacin/ steroids/ diuretics
Liver disease
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Diabetes Management
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Clinical Trials Data:
T1 patients:
 Tight glycemic controls reduce complications by 60% but
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increase the risk of therapy induced hypoglycemia three fold!
T2 patients: ‘impaired glucose/ “prediabetes” groupPREVENTION!: Low fat diet and 150 minutes of brisk walk/week
reduced progression to Dm by 71%. Preventive drug therapy not
useful
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Kumamoto study
UKPDSstudy
Steno-2 study
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Data: Intensive treatment of T2 DM with drugs/ achieving
HgbA1c levels less than 7% with glypizide/ glyburide (not
metformin or chlorpropamide) reduced diabetes related
microvascular complications by 50%
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DM management
 Diet
 Drugs
 Insulin
 Steps- Diagnosis/ Patient education
 Acceptable levels of glycemic control
 Chronic Complications of DM
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DIET
 Determine calorie requirements
 45-65% from carbohydrate sources*
 25-35% from fat (7% saturated)
 10-35% from proteins
•*In
T2 patients limit carbohydrates by
substituting calories with mono-unsaturated
fatty acids: olive oil/ rapeseed (canola)/ oils
in nuts or avocados. This will help to lower
TGL/ increase HDL
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Additional dietary caveats:
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Limit cholesterol consumption to 200-300 mg/day
Restrict protein intake to 10% of calorie requirements if there
is renal failure
High soluble fiber diet
Artificial sweeteners only in limited usage
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T2: Drugs for sugar control
1. Stimulate beta cells sulfonyl urea receptors
2. Alter insulin action
3. Affect dietary glucose absorption
4. Incretin mimetics or prolong incretin action
5. Glucagon suppressors
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# 1 -Stimulate beta cells
 Second generation sulfonylureas-
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Glyburide (Diaβeta)/ Glipizide (Glucotrol)
Glimeperide (Amaryl) : Act for 12-24 hrs
Can cause prolonged hypoglycemia
Caution in hepatic impaired patients
Repaglinide (Prandin)/ Nateglinide (Starlix):
stimulates insulin secretion, but less hypoglycemic
Induce weight gain
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# 2 Drugs that alter insulin action
 Biguanides- Metformin (Glucophage)
 Reduces hepatic gluconeogenesis
 Appetite suppressant
 GI upset- (20%) anorexia/nausea/vomiting/bloating/
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diarrhea
Lactic acidosis
Does not cause hypoglycemia
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# 2 Drugs that alter insulin action
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‘Glitazones’: Rosi (Avandia)/ Pio (Actos)
Alters the genetic expression of resistin (blocked) and adiponectin (stimulated)
from fat cells.
Adiponectin normally increases insulin sensitivity of the tissues
Resistin normally causes insulin resistance. Blocking it reduces insulin resistance
Decreases free fatty acids/ decreases hepatic glucose output. Does not cause
hypoglycemia
BUT increase- total cholesterol/LDL/HDL
AVANDIA increases risk of angina/MI not prescribed but ACTOS is ok.
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# 3 Affect dietary glucose absorption
 Alpha glucosidase inhibitors Acarbose (Precose) / Miglitol (Glyset)
 Reduces postprandial hyperglycemia
 Side effects – flatulence (30%)
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Gila Monster Heloderma suspectum
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# 4 Incretins
 Exenatide (Byetta)- GLP-1 receptor
agonist from the saliva of venomous
lizard- Gila Monster
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Suppresses glucagon release and delays gastric emptying
Helps to reduce HbA1c and lose weight – risks hypoglycemia and
pancreatitis, affects other drugs gastric emptying
 Sitagliptin (Januvia)
(DPP-4= Di-Peptidyl-Peptidase-4 enzyme) inhibitor
Improves HbA1c. No weight loss. Nasopharyngitis/URTI
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# 5 Other drugs
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Pramlintide (Symlin) analog of islet cell polypeptide amylin
Delays gatric emptying, suppresses glucagon secretion and
decreases appetite.
Used in T1 and T2
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# Insulin and T1/T2
 Produced by rDNA technology ‘human’ insulins
 Action: Onset/Peak/Duration
 Rapidly acting-5’-15’/1-1.5hrs/3-4hrs
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Insulin lispro (Humalog), aspart (Novolog), glulisine (Apidra)
 Short acting regular- 30-60’/2hrs/6-8hrs
 Intermediate acting- 2-4hrs/6-7hrs/10-20hrs
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NPH insulin
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‘Premixed’ NPH/Regular marketed as 70/30 or 50/50 or
75/25
Long-Acting glargine (Lantus)- 1.5hrs/falt/~24 hrs
detemir (Levemir)- 1 hr/ flat/17hrs
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DM Issues
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Watch out and recognize hypoglycemic features in patients
being treated with insulin
Complications of DM that increase the risk of hypoglycemiaautonomic neuropathy/ gastroparesis/ renal failure
Lipodystrophy at injection site
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Chronic complications of DM
1. Ocular- Cataracts/ Retinopathy/ Glaucoma
2. Renal- ESRD (T1>T2)/(good glycemic control and use of ACEi can reduce
the development) Always check for proteinuri
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Neuropathy-Distal symmetrical ‘neuritis’- pain, touch, temp, vibration/
claw toes-calluses and ulcers Charcot’s arhtropathy; burning pain
(hypersensitivty)
Autonomic neuropathy/ ED
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Chronic complications of DM
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Cardiovascular- heart failure-cardiomyopathy-IHD-metabolic
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Skin and mucous membrane- necrobiosis-candidiasis
Pregnancy and DM- tight control with normal HbA1c critical to
syndrome-HTN-microvasculitis - peripheral vascular disease and
gangrene
reduce spontaneous miscarriages-congenital malformationspolyhydramnios-preterm labor-still birth-fetal macrosomia; risk of
retinopathy/ preeclmapsia
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HYPOGLCEMIA!
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Fasting- insulinomas/ Addison’s/ myxedema/liver
malfunction/
PostprandialAlcohol mediated- blocks conversion of glycogen to glucose in
the liver
Drug induced- Quinine/ Quinidine/ Quinolones (?)
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Managing hypoglycemia
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If blood glucose is 70 mg/dL or below:
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Eat or drink 15 g of carbohydrates#
Recheck your blood glucose in 15
minutes. If the reading is not above 60
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mg/dL.
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Test again in 15 minutes
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If blood glucose is not > 70 mg/dL, repeat 
treatment with another 15 g of
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carbohydrate, then call your health care
provider
#The following contain 15 g of carbohydrate and
are appropriate for the treatment
of hypoglycemia:
Glucose tablets (3, 5 g tablets)
4 oz of juice or soda (not diet)
1 tablespoon of table sugar or honey
1 small box of raisins
Another useful formula that can help
patients emerge safely from hypoglycemia
without spiking into a glycemic state:
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(100 - blood glucose) X 0:2 = grams of carbohydrates
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necessary for blood glucose correction
Thus, if the blood glucose is 50 mg/dL, the
patient would consume
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100–50 = 50; 50X 0.2 = 10 g of carbohydrates
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Useful Lab Tests in Diabetes Care
 Biochemistry Urine Analysis- Protein/Sugar/Ketones
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Look for microalbuminurea in patients
with DM duration greater than 10 yrs.
Early sign of kidney involvement
FBS/PPBS/RBS
HbA1c (~6% or less)
Lipid profile
BUN & Creatinine
Red flagsSugars less than 50
Sugars greater than 250
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OthersECG/ Stress test
Doppler vascular studies
Ophthalmic studies for cataracts/
retinal issues
FGIDs (functional gastro intestinal
disorders)
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Diabetic Foot! Charcot!
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Diabetic Foot Care
 Visual inspection, palpation of the foot, vascular and neurologic
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assessment, dermatologic assessment, motor
examination, and determination of range of motion of the foot and ankle.
Look for:
Healing injuries, bruising, or skin disturbances; bunions, hammertoes, a rocker
bottom foot, or Achilles contracture
Vascular skin changes: stasis dermatitis, skin atrophy, hair loss, nail changes, or
clear areas of decreased perfusion; dryness, scaling, swelling, thickening of the
tissues, and the temperature of the foot
Presence or absence of pedal pulses, and degree of sensory loss (neuropathy)
Check the toe web spaces for evidence of tinea pedis, maceration,
fissures, or ulceration. Global erythema and swelling may represent Charcot
changes or cellulitis
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Diabetic Foot Care
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Neurologic status: (50% affected)
Recent onset of pain, numbness, tingling, or other
paresthesias?
Subjective sensory tests, with comparison to the contralateral
limbLoss of the Achilles deep tendon reflex
128-hz tuning fork
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Define neuropathy!
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Peripheral neuropathypain or loss of feeling in the toes, feet, legs, hands, and arms
 Proximal neuropathy (amyotrophy)
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pain in the thighs, hips, or buttocks, leading to weakness in the legs
Focal neuropathydysfunction of one group or a group of nerves, resulting in muscle weakness
or pain
Distal symmetrical polyneuropathy- ‘stocking-and-glove’ type
most common
Cranial neuropathy- acute-onset diplopia with ptosis and
papillary sparing associated with an ipsilateral headache
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Risk factors for the development of diabetic
neuropathy
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Modifiable risk factors
Obesity
Hypertriglyeridemia
Cigarette smoking
Hypertension
Elevated A1C
Glycemic variability
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Nonmodifiable risk factors
Duration of diabetes
Age
Family history of neuropathic
disease
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Drugs used in treating neuropathy:
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Antidepressants: Duloxetine/ Venlafaxine/ Tricyclics (TCAs)
Anticonvulsants: Pregabalin/ Gabapentin/ Carbamazepine/
Lamotrigine/ Topiramate/
Opioids: Oxycodone CR/ Tramadol/
Topical agents: Capsaicin/ Lidocaine Patch
Miscellaneous: Magnesium oxide
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