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Diabetes Mellitus
Diabetes Mellitus
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TYPE 1 DIABETES
Cause:
a. Autoimmune destruction of B-islet cells leading to:
i. No insulin production
ii. Hyperglycermia
iii. Ketoacidosis
iv. Glucosuria osmotic diuresis dehydration
v. End organs damaged
vi. Shift from CHO to fat and protein metabolism (causing ketoacidosis and gluconeogenesis)
b. Chronic syndrome
Epidemiology:
a. Mc in Scandinavian and N. European
b. Rising incidence
c. Peaks at school age and again at puberty
d. M=F
Etiology:
a. 1/3 genes, 2/3 environment
b. Genes associated:
i. HLA- DR3
ii. HLA- DR4
iii. ICA
iv. GAD65
v. IAA
vi. IA-2
vii. ZnT8
Features of Disease:
a. Decreased insulin so you need to supplement
b. Normal/thin body weight due to it being a catabolic disorder
c. Slow to rapid onset
d. Response to PO drugs is uncommon
e. Increased plasma glucagon
f. Pancreatic B cells do not respond to insulinogenic stim- need exogenous insulin
g. Immune mediated or Idiopathic
i. Immune: 95%
1. Type 1A
2. Infectious causes- rubella, mumps, cows milk, etc
3. Hygiene hypothesis
ii. Idiopathic- 5%
1. Asian/Africans
2. No evidence of autoimmunity
S/Sx:
a. Polyuria
b. Polydipsia
c. Polyphagia
d. Blurred vision
e. Weight loss (first due to decrease in water, later due to muscle wasting)
f. Hypotension (decreased plasma volume)
g. Weakness (from K loss and muscle catabolism)
h. Paresthesia
i. Candida infections
j. Ketoacidosis fruity breath
k. LOC if uncontrolled!
Labs:
a. Urine
i. Glycosuria Diastix held in urine stream or dipped in cup
VIII.
IX.
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1. The Longer-acting insulin analogs (detemir, glargine) cannot be mixed with regular
insulin or the rapidly acing insulin analogs.
2. NPL (neutral protamine lispro- which has the same effects and duration as NPH) plus
lispro
a. Humalog mix 75/25
b. Humalog mix 50/50
c. Novolog mix70/30
f. Administration:
i. Syringe and needle
1. Injection into loose skin- abdomen, thicgh, upper arms, flanks, upper buttocks
2. Rotation of sites to avoid delayed absorption when fibrosis or lipohypertrophy occurs
a. Recommended to limit to a specific body region and then rotate between sites in
that region- to avoid different absorptions of the insulin.
ii. Pen injector
iii. Insulin pumps (subcutaneous delivery)
iv. Inhaled- controversial
1. Exubera
v. Administration of insulin should be based on self monitoring blood glucose levels and multiple
injections/day
1. QD or BID injections do not work well
g. Pancreas Transplant
i. Often done with a kidney transplant simultaneously
h. Islet cell transplant- only for type 1 diabetes
Complications of Insulin therapty:
a. Hypoglycemia
i. Near 54 mg/dl autonomic Sxs
1. Tachycardia, palpitations, sweats, shakes, nausea, hunger
ii. Near 50 mg/dl neurogenic Sxs
1. Irritability, confusion, blurred vision, headache, trouble speaking, syncope or seizure
iii. With multiple episodes of hypogly, neurogenic Sxs are first, called hypoglycemic unawareness.
1. Beta-blockers can mask Sxs, use Beta-1 selectives instead
iv. In insulin-taking Pts comes from 3 factors
1. Behavioral issues
2. Counter-regulatory issues
3. Complications of diabetes
v. Treatment
1. Pt carries Dextrosol tabs/juice and avoids OJ or Soda
2. Glucagon 1 mg amp for IM or SQ injection (Glucagon Kit)
3. D/50 50 ml IV
b. Lipodystrophy at Injection Site
i. Atrophy of subcutaneous fatty tissue to disfiguring excavations, from an immune reaction
ii. Lipohypertrophy effects of insulin being deposited in the same location repeatedly
Diet
a. Insulin-dependent pts need exchange lists, carbohydrate counting, timed meals and snacks.
b. Obese, mild hyperglycemic pts need weight reduction by calorie restriction.
c. >50% of pts. Non-compliant w/ diet!
d. CMDT 2015 says generally:
i. Limit carbs to 45-65% daily calories
ii. Limit fat to 25-35% daily calories
iii. Limit protein to 10-35% of daily calories
iv. Limit cholesterol to 300 mg/d or 200 /d if LDL > 100mg/dL
e. Fiber
i. May reduce hyperglycemia
ii. May reduce blood cholesterol
f. Glycemic Index
i. Low index foods result in lower glucose levels after meals
XI.
XII.
g. Artificial sweeteners
i. Do help limit hyperglycemia
Prebreakfast hyperglycemia
a. Somogyi effect
i. Nocturnal hypoglycemia (40 at 3 AM) leads to surge of hormones that produces an elevated
glucose by 7 am (200)
ii. Tx:
1. Skip dinner time intermediate insulin and add a lower dose insulin or eat more food HS
b. Dawn Phenomenon
i. Reduced tissue sensitivity to insulin between 5 and 7 am (150(
ii. Tx: incrase pump basal infusion rate from 0.7 U/hr to 0.8 U/hr from 3 am to 8 am
Chronic Complications of Type 1 diabetes
a. Ocular:
i. Cataracts
ii. Glaucoma
iii. Retinopathy
1. Non-Proliferative
a. Microaneurysms, dot hemorrhages, exudates, retinal edema
2. Proliferative
a. Growth of new capillaries and fibrous tissue in retina
b. One of the leading causes of blindness
b. Renali. Diabetic nephropathy
1. Initially manifested by protein-uria, then as kidney function continues to decline, urea
and creatinine accumulate in the blood
c. CVmore of a problem in type 2 diabetes
d. Neuropathy
i. Peripheral
1. Distal symmetric polyneuropathy- stocking-glove pattern of
2. Isolated peripheral neuropathy- sudden onset, affects vision and extremities
3. Painful neuropathy- hyperesthesia
a. Burning skin at night
4. Sensory portion is lost first
ii. Autonomic
1. Postural HTN
2. Loss of valsalva response
3. Gastroparesis
4. Diarrhea
5. Urinary Retention
6. Impotence
a. Erectile dysfunction
i. Medical
1. Sildenafil (Viagra)
2. Vardenafil (Levitra)
3. Taladafil (Cialis
a. cGMP specific phosphodesterase type 5 (ODES)
inhibitors impair breakdown of cGMP to improve
achieving and maintaining and erection
b. Do not use with nitrates (TNG tabs or paste)
4. Penile injections with papaverine or alprostadil (urethral pellets)
ii. Mechanical
1. External vacuum therapy and tension ring
iii. Surgical
1. Implanted balloons with pumps
iii. Skin and mucous membranes:
1. Chronic pyogenic infections
2. Shin spots
3. Candida infections
e. Diabetic Coma
i. Hypoglycemia from excessive insulin or oral diabetic agents
1. Treat w/ D50 50 ml IV or Glucagon 1 mg IM if no IV (as per earlier slide)
ii. Hyperglycemic coma associated with
1. Severe insulin deficiency (diabetic ketoacidosis) or
2. Mild to moderate insulin deficiency (hyperglycemic hyperosmolar state)
f. Diabetic Ketoacidosis (DKA)
i. Essentials of Diagnosis
1. Hyperglycemia > 250 mg/dL
2. Acidosis, aterial pH < 7.3
3. Serum bicarb < 15 meq/L
4. Serum positive for ketones
ii. Basics
1. True medical emergency, 5% mortality in under 40 age group, >20% in elderly or
delayed TX
2. May be first sign of Type 1 DM, even in the elderly
3. May come from:
a. Increased insulin requirement in Infection, Trauma, MI or Surgery
b. Complication of insulin pump TX (1 per 80 Pt-mos of TX)
iii. Signs & Sx
1. Polyuria, polydypsia, fatigue, N/V, mild hypothermia, drowsiness (common), dry mucous
membranes, tachypnea (Kussmaul respirations), fruity breath odor, hypotension,
tachycardia, abd. pain/tenderness
2. Frank coma in 10% of cases
iv. Labs
1. Glucose 350-900 mg/dL
2. Hyperkalemia 5-8 mEq/l (wnl 3.5-5.1)
3. Serum ketosis
4. Urine ketosis 4+
5. Glycosuria 4+
6. Hyponatremia of 130 (135-145 mEq/l)
7. Leukocytosis w/ left shift if caused by infection
8. Fluids often down by 100 mL/kg (wnl 42 L 70 kg person)
v. Treatment
1. Prevent by educating pt
2. Admit to ICU
3. Monitor VS, urine output, urine glucose and ketones, blood glucose, bicarbonate and
acetone, arterial pH, serum osmolality (to 280-300 mosm/kg) BUN and lytes
4. Fluids (down 4-5L)
a. IV 0.9% saline, 1 L/hr first 2 hours, then 300-400 mL/hr
b. When glucose <250 mg/dL switch to D5-containing solution
5. Regular Insulin IV
a. Start w/ loading dose bolus of 0.1 U/kg, then
b. 0.1U/kg/hr until glucose is <250 mg/dL, then maintain glucose at 250-300.
6. Potassium [3.5-5.2] 10-30 mEq/h starting 2nd to 3rd hour (flows out of cells initially
and back in with treatment, so levels can drop if not replaced.)
7. Bicarb? Controversial for pH 7.0 amps 1 or 2 in1 L 0.45% saline and monitor pH.
8. Phosphate [2.4-4.1] only if level falls below 1 mg/dL give 3-4 mmol/hr (65 kg person)
for 5 hrs max. MR X 1 prn.
9. Treat infection or other cause!
g. Hyperglycemic Hyperosmolar State
i. Essentials of Diagnosis
1. Hyperglycemia > 600 mg/dL
2. Serum osmolality > 310 mosm/kg
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ii. Basics
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Type 2 Diabetes:
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Cause:
a. Diminished target tissue sensitivity to insulin
i. Plasma insulin is elevated in early stage in an attempt to compensate
ii. Plasma insulin decreases in late- stage
b. Obesity has become most important environmental factor causing insulin resistance
c. Circulating endogenous insulin is suffienent enough to prevent ketoacidosis but is inadequate to prevent
hyperglycemia
d. Systems affected: CV, endocrine/metabolic, neurological, renal
Epidemiology:
a. M=F
b. Age- used to be disease of adults but now is occurring in children/adolescents
c. Prevalence increases with age
d. Accounts for most of diabetics in the US (90%)
Etiology:
a. Genetic and environmental factors combine to cause both insulin resistance and beta cell loss
b. Genetics:
i. Strong genetic component to the disease
ii. After age 40, concordance in identical twins is >70% at 1 yr after 1st twin Dxd.
c. Environment:
i. Obesity is the most important environmental factor causing insulin resistance.
ii. Degree and prevalence of obesity varies among racial groups
1. 30% of Chinese and Japanese
2. 6070% of North Americans, Europeans, or Africans
3. Near 100% among Pima Indians or Pacific Islanders from Nauru or Samoa.
Type 2 Diabetes:
Cause:
a. Diminished target tissue sensitivity to insulin
i. Plasma insulin is elevated in early stage in an attempt to compensate
ii. Plasma insulin decreases in late- stage
b. Obesity has become most important environmental factor causing insulin resistance
c. Circulating endogenous insulin is suffienent enough to prevent ketoacidosis but is inadequate to prevent
hyperglycemia
d. Systems affected: CV, endocrine/metabolic, neurological, renal
Epidemiology:
a. M=F
b. Age- used to be disease of adults but now is occurring in children/adolescents
c. Prevalence increases with age
d. Accounts for most of diabetics in the US (90%)
Etiology:
a. Genetic and environmental factors combine to cause both insulin resistance and beta cell loss
b. Genetics:
i. Strong genetic component to the disease
ii. After age 40, concordance in identical twins is >70% at 1 yr after 1st twin Dxd.
c. Environment:
i. Obesity is the most important environmental factor causing insulin resistance.
ii. Degree and prevalence of obesity varies among racial groups
1. 30% of Chinese and Japanese
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b. Since Fall 2010 use either TZD with caution. Black box warns they can
cause/worsen CHF. Consider cardiology consult. THEN Fall 2013 Black Box
GONE!
iii. Glucose absorption inhibitors
1. Acarbose [Precose] & Miglitol [Glyset] frequent complaint is diarrhea and flatus.
iv. Incretin Mimics 1
1. GLP-1 Receptor Agonists
a. Exenatide (Byetta) (SC 60 min. ac bfst & dinner) comes from Gila Monster
venomous saliva.
b. Liraglutide (Victoza) (SC qd) GLP1 synthetic GLP-1 analog
i. Approval for weight loss
v. Incretin Mimics 2
1. DPP-4 Inhibitors (Oral Meds)
a. Stimulates insulin without causing hypoglycemia
b. Suppresses glucagon and limits PP hyperglycemia
2. Sitagliptin (Januvia)
3. Saxagliptin (Onglyza)
4. Linagliptin (Tradjenta)
5. Alogliptin (Nesina)
vi. Serum-glucose co-transporter 2 inhibitors
1. Dapagliflozin (Farixga in U.S. just this year)
a. Inhibits 90% of glucose resorption in the kidney, causes glycosuria, lowering
plasma glucose levels
b. Caution: Chronic kidney disease (CKD) reduces efficacy
c. Other Drugs
i. Pramlintide [Symlin]
1. Inject just pre-prandial
2. Delays gastric emptying
3. Suppresses Glucagon
4. Decreases appetite
ii. Bromocriptine & Colesevelam not recommended for DM by CMDT 2015.
DIET:
a. Weight loss is important with type 2 diabetes
b. Same recommendations as type 1 diabetes
Complications: SAME AS TYPE 1 DIABETES
a. Obese-Resistant
i. Mainly Insulin resistant early in disease
1. Progressive loss of B-cell function occurs later in disease
ii. Visceral (i.e. omental and mesenteric) fat vs not-subcutaneous fat.
Features of Disease:
a. Visceral fat- more common in males
i. Associated to insulin resistance
b. Subcutaneous fat- more common in females
i. Less associated to insulin resistance
c. Fat cells secrete Adipokines- these affect the sensitivity of tissues to insulin
i. Adiponectin- increases sensitivity to insulin
ii. Tumor necrosis factor- inactivates insulin receptors
1. Decrease insulin sensitivity
iii. Resistin- interferes with insulin action on glucose and glucose metabolism
1. Decrease insulin sensitivity
d. Hyperglycemia can also cause a build up of hexosamines in muscle/fat tissue and inhibit glucose transport
into the cells- this is called acquired glucose toxicity
e. Correcting hyperglycemia can reverse this acquired insulin resistance
S/Sx
a. Can be asx
XII.
XIII.
XIV.
XV.
c. Other Drugs
i. Pramlintide [Symlin]
1. Inject just pre-prandial
2. Delays gastric emptying
3. Suppresses Glucagon
4. Decreases appetite
ii. Bromocriptine & Colesevelam not recommended for DM by CMDT 2015.
DIET:
a. Weight loss is important with type 2 diabetes
b. Same recommendations as type 1 diabetes
Complications: SAME AS TYPE 1 DIABETES