I.

II.

III.

IV.

V.

VI.

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

ii. Ketonuria Ketostix dipped in urine, or in urine stream

b. Blood
i. Random Plasma Glucose
1. < 100 OK
2. 100 do FPG (fasting plasma glucose)
ii. Fasting (8 hrs) Blood Glucose
1. < 100 OK
2. Between 100 and 125, repeat FPG (more than a week but less than a month)
3. Twice bet. 100 and 125 = impaired glucose tolerance (pre-diabetes) but may do GTT
4. 126 2 times, no more glucose challenges or tests -> DM!
iii. GTT (coming back into vogue)
1. 75 g glucose in 300 ml H2O, post-overnight fast and 3 days of 150-200 g carbohydrate
diet. Do in AM.
2. 2 hr sample < 140 wnl
3. 2 hr sample 140 to 199 impaired glucose tolerance
4. 2 hr sample 200 DM!
5. False positives not uncommon
iv. Glycated Hemoglobin (HgbA1c)
1. Office-based machine uses capillary tube sample with results in 9 or fewer minutes.
2. Normal range is 3.5% to 6%
3. Elevated blood glucose permanently raises HbA1c for the life-span of the RBC
4. RBCs last up to 120 days. So, they show glycemia over preceding 8-12 weeks
5. Test HbA1c q 3-4 mos in both types of diabetics.
a. OK to use for screening.
v. The shift to A1c
1. ADA endorses HbA1c as Dx test for DM
2. A cutoff value of 6.5% was chosen because the risk for retinopathy increases
substantially above this value.
3. Advantages
a. No fasting
b. Lower variability than FGT or OGTT
c. Looks back 3 mos.
4. How to use A1c
a. 5.7-6.4 is prediabetes
b. Repeat A1c unless Pt. symptomatic & BG > 200
c. Dont use in hemoglobinopathies
d. Test should comply with Nat GlycoHgb Standardization prog. of DCCT

vi. Serum Fructosamine- main use is in pregnant women

1. Glycosylated albumin
2. Normal range: 1.5 -2.4 mmol/L or 205 285 mg/dl
3. Half-life is only 2 weeks

4. Used When A1c unreliable

a. Recent bleed or hemolytic anemia
b. Short time frame needed like for glycemic state at time of conception in preg.
woman
vii. Self-monitoring of blood glucose
1. Pt puts drop of blood on test strip, then inserts into glucometer, reading comes in few secs
to several minutes
2. Cost for machine is $Free - $100
3. Test strips are 50-75 cents each
4. Fingertip blood shows glucose changes 5-20 mins. faster than arm blood could be a
factor in rapidly developing hypoglycemia
viii. Lipoprotein abnormalities
1. Mainly seen in obese type 2 with insulin resistance
2. Circulating lipoproteins are just as dependent on insulin as is the plasma glucose.
3. Called diabetic dyslipidemia
4. Trigs are 300-400 mg/dL (<150 mg/dL wnl)
5. HDL < 30 mg/dL (40-60 mg/dL wnl)
6. Causes microvascular disease
7. Weight loss and glucose control usually fix the problem.
VII.

VIII.

Features for diagnosis

a. Polyuria, polydipsia, polyphagia, weight loss associated with random plasma glucose >200 mg/dL, FPG >
126 on more than on occasion
i. Less than a month apart but at least a week apart
b. Ketonemia, ketonuria, or both
c. Islet autoantibodies are frequently present
d. FHx
Tx:
a. Goals of treatment:
i. Prevent acute illness
ii. Reduce risk of long term complications
b. Insulin is for type 1 diabetics and some type 2 diabetics
c. Types: human insulin (only kind available in the US); Pork/animal insulin (not available in the US)
d. U100 in 10 ml vial/ u500 in 5 mL vial (in the hospital)
e. 3 preps:
i. Short acting (regular)
1. Types:
a. Regular Insulin (onset: 30 minutes; Duration: 5-7 hours
i. Continuous drip in DKA/perioperative
ii. No pumps
iii. Take 60 minutes before meals
b. Rapid Acting insulin: Onset 20 minutes
1. Lispro (Humalog)- used in insulin pumps
2. Aspart (novolog)
3. Giulisine (Apirdra)4. Take 20 minutes before meal
ii. Long Acting:
1. NPH- intermediate acting
a. Onset: 2-5 hours; duration: 10-20 hours
2. Glargine
a. Onset is slow; duration: 24 hours
3. Detemir
a. Onset is slow; duration 17 hours
iii. Mixed preps: used because intermediated inuslins require several hours to reach adequate
therapeutic levels, requiring supplements of regular or rapidly acting insulin analogs preprandially

IX.

X.

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

3.
4.
5.
ii. Basics
1.
2.
3.

No acidosis, arterial pH > 7.3

Serum bicarb > 15 meq/L
Normal anion gap (<14 meq/L)

Second most common form of hyperglycemic coma.

Formerly Hyperglycemic, hyperosmolar, non-ketotic coma.
Severe hyperglycemia in the absence of significant ketosis, w/ hyperosmolality and
dehydration.
4. Hyperosmolality (>310 mosm/kg) and dehydration
5. Occurs in mild or occult DM
6. Most patients are at least middle-aged to elderly
7. Mortality 10 times higher than DKA
a. Pts older, sicker and DX often delayed
b. Prompt therapy reduces death from 50% to baseline for existing other conditions
iii. Pathogenesis
1. A partial or relative insulin deficiency reduces glucose utilization by muscle, fat, and
liver
2. Hyperglucagonemia raises hepatic glucose output
3. With massive glycosuria, obligatory water loss ensues.
4. Dehydration results.
5. As plasma volume contracts, renal insufficiency develops, renal glucose loss falls
6. Glucose rises further
7. Severe hyperosmolality develops that causes mental confusion and finally coma.
8. A convenient method of estimating effective serum osmolality is: (normal values in
humans are 280300 mosm/kg):
a. Mosm/kg = 2[Na+] + (Glucose (mg/dL)/18)
iv. Signs & Sx
1. Onset insidious over days or weeks
2. Weakness, polyuria, and polydipsia
3. Reduced fluid intake not uncommon due to either inappropriate lack of thirst, nausea, or
inaccessibility of fluids to elderly, bedridden patients.
4. Lethargy and confusion develop, progressing to convulsions and deep coma.
5. PE
a. Profound dehydration
b. Lethargic or comatose patient
c. No Kussmaul respirations.
i. No acidosis for the body to try to compensate for.
v. Treatment
1. Fluid Replacement
a. Fluid deficit often 610 L.
b. If hypotension and oliguria, start with 0.9% saline...
c. Else, 0.45% saline preferable because body fluids markedly hyperosmolar
d. Up to 46 L of fluid in the first 810 hours.
e. Monitor for proper sodium and water replacement.
f. Once blood glucose reaches 250 mg/dL, switch to 5% dextrose in either water,
0.45% saline solution, or 0.9% saline solution.
g. Dextrose infusion should be adjusted to maintain glycemic levels of 250300
mg/dL
h. End point of fluid therapy is to restore urinary output to 50 mL/h or more.
2. Insulin
a. Give loading dose, 0.1 unit/kg
b. Then insulin infusion of 0.1 unit/kg/h, titrated to lower blood glucose levels by
5070 mg/dL per hour.
3. Potassium
a. With the absence of acidosis, hyperkalemia may be absent unless associated renal
failure is present.

b. Because it declines rapidly from insulin's effect on driving potassium

intracellularly, start potassium replacement earlier than in ketotic patients.
c. Potassium chloride (10 mEq/L) can be added to the initial bottle of fluids
4. Phosphate
a. If severe hypophosphatemia (serum phosphate < 1 mg/dL) develops during
insulin therapy, phosphate replacement can be given at 3 mmol/h

Type 2 Diabetes:
I.

II.

III.

I.

II.

III.

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

IV.

V.

VI.
VII.

2. 6070% of North Americans, Europeans, or Africans

3. Near 100% among Pima Indians or Pacific Islanders from Nauru or Samoa.
d. 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
b. Chronic skin infections
i. Candida infections
c. Babies >9 lbs, polyhydramnios, preeclampsia, fetal loos
d. Central adipose
i. Waist circumference: >40 in males; >35 in females
e. Acanthosis Nigricans- armpit and back of neck
f. Polyuria
g. Polydipsia
h. Polyphagia
i. Associated with HTN, dyslipidemia, atherosclerosis
j. Not associated with ketonuria/weight loss/DKA
Labs/Dx criteria: SAME AS WITH TYPE 1 DIABETES
Tx:
a. Six classes
i. Insulin secretion stimulants
ii. Those that alter insulin action on liver, muscle & fat
iii. Those that reduce intestinal absorption of glucose
iv. Incretin Mimics or Prolongers
v. Those that inhibit reabsorption of filtered glucose in the kidney
vi. Other: glucagon suppression & slowing gastric emptying
b. Oral Drugs
i. Insulin stimulants Others
1. Meglitinide Analogs Repaglinide
2. D-Phenylalanine Derivitive - Nateglinide
ii. Insulin action alterers
1. Biguanide (Metformin) works in the liver
a. Improve FPG & Post Prandial hyperglycemia (after a meal)
b. 1st LINE DRUG! Start at Dx of DM
c. Often 500 mg tid w/meals or 850-1000mg breakfast & dinner
2. Thiazolidinediones (rosiglitazone [Avandia] and pioglitazone [Actos]) sensitize
peripheral muscle and fat tissue to insulin
a. Use as mono Tx or w/ Metformin, sulfonylureas or insulin per CMDT

VIII.

IX.

X.

XI.

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.

b. Chronic skin infections

i. Candida infections
c. Babies >9 lbs, polyhydramnios, preeclampsia, fetal loos
d. Central adipose
i. Waist circumference: >40 in males; >35 in females
e. Acanthosis Nigricans- armpit and back of neck
f. Polyuria
g. Polydipsia
h. Polyphagia
i. Associated with HTN, dyslipidemia, atherosclerosis
j. Not associated with ketonuria/weight loss/DKA
Labs/Dx criteria: SAME AS WITH TYPE 1 DIABETES
Tx:
a. Six classes
i. Insulin secretion stimulants
ii. Those that alter insulin action on liver, muscle & fat
iii. Those that reduce intestinal absorption of glucose
iv. Incretin Mimics or Prolongers
v. Those that inhibit reabsorption of filtered glucose in the kidney
vi. Other: glucagon suppression & slowing gastric emptying
b. Oral Drugs
i. Insulin stimulants Others
1. Meglitinide Analogs Repaglinide
2. D-Phenylalanine Derivitive - Nateglinide
ii. Insulin action alterers
1. Biguanide (Metformin) works in the liver
a. Improve FPG & Post Prandial hyperglycemia (after a meal)
b. 1st LINE DRUG! Start at Dx of DM
c. Often 500 mg tid w/meals or 850-1000mg breakfast & dinner
2. Thiazolidinediones (rosiglitazone [Avandia] and pioglitazone [Actos]) sensitize
peripheral muscle and fat tissue to insulin
a. Use as mono Tx or w/ Metformin, sulfonylureas or insulin per CMDT
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

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