Diabetes mellitus Flashcards
1
Q
Which cells in the pancreas produce Insulin?
A
- Beta cells
2
Q
Which cells in the pancreas produce glucagon?
A
- Alpha cells
3
Q
Which cells in the pancreas produce somatostatin?
A
- Delta cells
4
Q
Which cells in the pancreas produce Pancreatic polypeptide?
A
- F cells
5
Q
Is insulin anabolic or catabolic?
A
- anabolic
6
Q
What does insulin help facilitate the tissue uptake of?
A
- Glucose
- Amino acids
- fatty acids
- K+, Phos, Mg+
7
Q
Does insulin raise or lower blood glucose?
A
- Lower
8
Q
Does insulin inhibit or stimulate gluconeogenesis?
A
- Inhibits* it
9
Q
What does insulin inhibit?
A
- Gluconeogenesis, glycogenolysis, protein catabolism, lipolysis, ketogenesis
10
Q
Definition of diabetes mellitus
A
- Insufficient production of insulin by beta cells of the pancreas
11
Q
Which species get diabetes?
A
- Dogs and cats
12
Q
Diabetes in dogs
A
- Absolute insulin deficiency (seen in almost all dogs)
- Insulin-dependent (IDDM)
13
Q
Is diabetes in dogs reversible?
A
No
14
Q
Pathogenesis of diabetes in dogs
A
- Genetic predisposition + autoimmune, environmental factors/predisposing conditions
- Beta cell degeneration and destruction
- Insulin dependent diabetes mellitus
15
Q
DM in cats
A
- Relative insulin deficiency
- Non-insulin dependent (NIDDM) in 80%
- Dysfunctional Beta cells (impaired insulin secretion)
- Peripheral insulin resistance
- Cats usually need insulin but may go into remission
16
Q
Is DM reversible in cats?
A
- Yes
17
Q
Elements of DM in cats
A
- Genetic predisposition
- Predisposing factors
- Amyloid deposition (Beta cell degeneration)
- Hyperglycemia
- Glucose toxicity
18
Q
Predisposing factors that lead to insulin resistance in cats
A
- Obesity (pro-inflammatory)
- Pancreatitis (inflammation in the pancreas)
- Glucocorticoids (BIG cause)
- Progesterone (diestrus, megestrol acetate)
- Infection
- Concurrent disease
- Stress?
19
Q
Pathophysiology of DM in cats
A
- Insulin deficiency (absolute or relative)
- Decreased cellular glucose uptake and increased hepatic gluconeogenesis
- Hyperglycemia
- Glucosuria (renal threshold: BG >180-220 mg/dL)
- Polyuria (osmotic)
- Polydipsia
20
Q
Sex predisposition of DM in dogs
A
- Females are twice as common as males
21
Q
Age predisposition of DM in dogs
A
- Middle-aged
- 4-14 years old
22
Q
Breed predisposition of DM in dogs
A
- Terriers, Schnauzers, Miniature poodles, others
23
Q
Sex predisposition of DM in cats
A
- neutered males more common
24
Q
Age predisposition of DM in cats
A
- Older, >6 years
25
Breed predisposition of DM in cats
- Burmese (Australia)
- Abyssinians
- Siamese (DKA)
26
What are the most common presentations with DM?
1. "Well" Diabetic
2. Ketoacidotic
3. Hyperglycemic/hyperosmolar syndrome
27
What is the most common presentation of DM?
1. "Well" Diabetic*****
28
Ketoacidotic presentation
- Untreated or treated diabetic
- Concurrent disease --> insulin resistant
- Think about other conditions too
29
Classic signs of "Well diabetic"
- Polyuria
- Polydipsia
- Polyphagia
- Weight loss
30
Ketoacidotic presentation
- Anorexia
- Depression
- Dehydration
- Vomiting
- Look TERRIBLE
31
What are the relatively common concurrent endocrinopathies with DM in dogs?
- Hyperadrenocorticism
32
What are the relatively common concurrent endocrinopathies with DM in cats?
- Hyperthyroidism, acromegaly (cats)
33
PE findings on DM
- Hepatomegaly
- Dehydration
- Cataracts (DOGS ONLY)
- Poor coat/grooming
- Peripheral neuropathy (cats)
34
How do you diagnose DM?
- Clinical signs
- Hyperglycemia
- Glucosuria
- Based on a CBC/Chem/Urinalysis
35
DfDx for DM
- Stress (mostly in cats)
36
Other possibilities for initial CBC/Chem/UA in DM?
+/- Ketonuria (not abnormal; don't be alarmed if they are well)
+/- fructosamine (will only show for animals that have been diabetic for awhile)
37
Stress Hyperglycemia
- BG normal 80-120
- Usually <250 mg/dL with SH but can go over 400 mg/dL
- Normal fructosamine
- Cause unclear
- No clinical signs of DM
38
How do you differentiate stress hyperglycemia from DM in cats?
- Recheck the BG when the cat is calm, and/or check a fructosamine level, to help rule out SH.
39
What diagnostics should be performed on all diabetics?
- CBC
- Serum biochemistry
- Urinalysis
- Urine culture
40
CBC results in Diabetics
- Usually normal
- Can be hemoconcentrated (often dehydrated)
- Infection: neutrophilia, toxic change, left shift
41
Serum chemistry changes in Diabetics
- Hyperglycemia
- Hypercholesterolemia
- Increased ALT and increased ALP (ONLY MEANS fat in the liver; be MUCH more concerned with cats than in dogs)
- +/- amylase/lipase increase (dogs)
- +/- azotemia (usually pre-renal)
42
Urinalysis changes in diabetics
- Glucosuria!
- +/- ketonuria
- +/- proteinuria (bacterial infections)
- +/- bacteriuria (not as good at putting WBCs out there)
- +/- pyuria (MAY not because they are PU/PD)
43
Urine culture in diabetics
- MANDATORY
- They have a neutrophil dysfunction
- Also sugar in their urine and decreased concentration
44
Radiographs and ultrasounds in diabetics
- Sometimes optional
- Abdominal and thoracic radiographs
- Abdominal ultrasound
- Look for the underlying/complicating disease
45
Radiographs and ultrasounds in DKA or HHS
- Necessary to identify the underlying cause
46
Other tests to consider
- exocrine pancreas
- Thyroid testing
- Hyperadrenocorticism
47
Exocrine pancreas testing in diabetics
- PLI - pancreatitis
- TLI - pancreatic insufficiency
- Chronic pancreatitis can lead to TLI and diabetes mellitus
48
Thyroid testing in diabetics for dogs
- Controversial
| - Wait until regulated before testing
49
Thyroid testing in diabetics for cats
- Assess at diagnosis of DM if you suspect
50
Hyperadrenocorticism testing in diabetics
- DO NOT test until DM is regulated
51
Is ALP commonly elevated in canine diabetics/feline diabetics/both?
- Just canine diabetics
| - Very unusual in cats
52
Goals of diabetes treatment
- Minimizing clinical signs
- Minimizing the risk of hypoglycemia
- Reducing the risk of long term complications of DM
53
What is the #1 risk of diabetes treatment?
- Hypoglycemia!
| - Much more dangerous than hyperglycemia
54
Signs of hypoglycemia
- Muscle tremors
- Weakness
- Lethargy
- Head tilt
- Dull or dazed
- Disorientation
- Ataxia
- Seizures
- Coma
55
What are some major therapeutic considerations?
- Consistency is key
- Address predisposing conditions and maintain an ideal body condition
- Exercise - consistent and regular
- Diet
- Oral hypoglycemics
- Insulin
56
Diet and exercise with DM
- Maintain ideal body condition
- Obesity can contribute to insulin resistance
- Consistent and regular (but not strenuous) exercise to improve glucose utilization
57
Dietary management for Diabetes in dogs
- Increase fiber
- Decrease simple sugars
- Decrease fat
58
Point of increasing fiber for diabetes in dogs
- Decreases glucose absorption
| - Delays gastric emptying and intestinal absorption
59
Point of decreasing fat for diabetes in dogs
- Diabetics already have derangements in fat metabolism
60
Commercial diabetes diets for dogs
- W/D, OM, R/D, DCO
61
Dietary management in cats with diabetes
- Increase protein
- Decrease carbohydrates
- Look at individual response
62
How do you decrease carbohydrates in cat diets for diabetes?
- Either by increasing protein (ideal method) or increasing fiber
63
How long do you continue diabetic cat diets?
- Continue even after they have gone into remission
64
Commercial cat diabetes diets
- W/D
- m/d
- DM
- Not great over the counter options
- People can home cook, but harder to get them nutritionally balanced
65
Fiber for thin animals with DM
- Less
66
DM obese animals additional dietary recommendations
- Weight loss
67
Raw diets in DM
- Bad idea
| - Immunosuppressed
68
Timing of insulin relative to meals
- Feed before insulin
- Dogs>>>cats
- Schedule! Consistency!
69
Oral hypoglycemics
- Acarbose
| - Glipizide
70
Acarbose
- alpha-glucosidase inhibitor
- Slows post-prandial glucose absorption
- Dogs
- Side effects in 35% are diarrhea, weight loss
71
Glipizide
- Sulfonylurea
- Stimulates beta cell secretion so must have functioning beta cells
- Only for NIDDM Type 2 cats
- Multiple side effects
72
Who would get oral hypoglycemics?
- Not DKAs
| - Anti-insulin owners
73
Response for oral hypoglycemics
- 15% good response, but some become resistant
| - 15% partial response
74
Predisposing conditions and diabetes treatment
- VERY IMPORTANT to identify and treat an predisposing conditions
75
Insulin therapy origin species
- Human
- Bovine
- Porcine
76
Formulations of insulin the delay absorption
- Protein binding
| - Crystal size
77
Starting insulin therapy for dogs
1. Vetsulin (#1) - FDA approved
2. Humulin N (longer lasting)
- Tend to do lower doses initially to avoid hypoglycemia
- Insulin availability varies
78
Starting insulin therapy for cats
1. Glargine (#1)
2. ProZinc (FDA approved)
- Animal size makes dosing quite difficult
79
Which insulins are 40 U/mL?
- Prozinc and Vetsulin
80
Which insulins are 100 U/mL?
- Almost every other kind
81
Proper handling of insulin
- Refrigerate
- ROLL insulin gently to mix, with the exception of vetsulin, which you shake
- Rotate site of injection
82
How are insulin syringes marked?
- By UNIT
- for U40, it's 20 units/0.5cc
- for U100, it's 50 units/0.5cc
83
Where do you read for an insulin dose?
- Top of the black rubber stopper on the plunger
84
What happens if you use a U100 to give the same number of units as a U40?
- Underdose
85
What if you use a U40 to give the same number of units as a U100?
- 2.5x overdose
| - This can be FATAL
86
When should you administer insulin?
- After a meal (ideally)
87
In the days after starting insulin therapy
- Check a few BGs over the next 2 days
- Change dose only if hypoglycemic
- DO NOT INCREASE DOSE BASED ON SPOT CHECKS
- Takes several days to see full effect
- BG curve 1 week later
88
When should initial glucose curve be performed?
- 1 week after starting insulin or any dose adjustment
89
What is the gold standard for monitoring insulin therapy?
- Improvement/resolution of clinical signs
- Blood glucose curves (gold standard)
- Glycosylated proteins (fructosamine and glycosylated hemoglobin)
- Urine glucose strips
90
Performing a BG curve Timeline after starting insulin
- 7 days after starting insulin for the first time, after changing the insulin dose, or after changing insulin type
- It takes that long for the body to adjust to the insulin and for consistent effects to be seen
- Don't perform when you first start insulin, as it won't be accurate
91
BG curve day at a glance
- Feed at normal time in morning at home or in hospital
- Check BG when arrives at clinic
- If appropriate - watch owner give insulin
- Check BG every 2 hours for a total of 12 hours (if BID insulin)
- Check every hour if close to or below 100
92
Parts of a BG curve
- Nadir
| - Duration
93
Nadir of a BG curve
- Time and value at which BG is lowest
| - Corresponds with peak insulin activity
94
Duration of a BG curve
- Amount of time following insulin therapy in which the BG is <250 mg/dL
- Could also define it as your target range for that individual
95
Target range for a BG curve
- ~100-250 mg/dL throughout the day
| - A little lower for cats on glargine
96
Step 1 of interpreting a BG curve
- Find blood glucose nadir and insulin duration
97
What should you do if the nadir is occurring at the right time (6 hours for a 12 hours dose) but the value is too high or too low?
Adjust the dose
98
What should you do if the nadir is occurring at the wrong time (too early or too late)?
Change the insulin type
99
What should you do if the duration is inappropriate?
- Either need to change dose or type - look at your nadir for guidance
100
Reminder to look at your pictures for glucose curves!
DO IT
101
Ideal glucose curve
- Duration of 11 or 12 hours
| - Nadir at 6 hrs, and not too high or too low
102
What amount should you adjust an insulin dose by for dogs?
- 10-25%
103
What amount should you adjust an insulin dose by for cats?
- Usually 1/2 unit per dose
| - Will get easier with experience
104
Should owners ever change insulin doses of their own accord?
- No
- NEVER, EVER, EVER without instructions to do so
- Warn them about the risk of death
105
When to repeat a BG curve?
- Every 7 days until regulated
- Then in ~1 month
- Then every 3-6 months and include a urine culture
- OR if clinical signs are present
106
What can mess up a curve?
- Forgetting to give the insulin (make sure you clarify who is giving the insulin )
- Inappetence/anorexia (not eating in hospital can be a challenge)
- Vomiting
- Stress hyperglycemia (cats) - monitor with home curves, clinical signs
- Somogyi effect
107
Somogyi effect
1. ) Too much insulin
2. ) Hypoglycemia (<65 mg/dL or rapid drop)
3. ) Diabetogenic hormones take over
4. ) Rebound hyperglycemia (>300 mg/dL)
5. ) Misinterpretation...NEED A BIG CURVE!
108
Chronic monitoring for clinical signs for Diabetes
- PU/PD
| - Weight loss
109
BG curve chronic monitoring
- If clinical signs recur
- Every 3-6 months
- If stress hyperglycemia
- Home curves
110
Urine cultures for DM
- Every 6 months
111
Serum fructosamine monitoring
- Glycated proteins synthesized during insulin-independent binding of glucose to serum protein
- Indicates BG concentration during preceding 2-3 weeks
- Trends are most useful
- Measure when first regulated and then every 3-6 months
112
Serum fructosamine: which patients?
- MOST helpful in cats, as it is not affected by stress
113
Cat remission
- With insulin (and/or oral hypoglycemics) and dietary management, cats may go into remission
114
Who is remission more likely in?
- Cats intensively treated soon after (<6 months) diagnosis
- Cats that recently received glucocorticoids
- Older cats
- Cats without peripheral neuropathy
115
Estimates of remission
- 80% of cats with NIDDM if treated intensively
| - 30-40% might be more realistic estimate
116
What's the risk if a cat suddenly goes into remission?
- Hypoglycemia
117
Is relapse possible with cats that have gone into remission?
- Yes
- 25-30%
- VERY important to keep them on a low carb diet and keep the weight off
118
What is the most fatal complication of DM potentially?
- Hypoglycemia
- If they don't eat, or if they vomit, you can skip the dose or do a 1/2 dose
- They should call or check glucose at home
119
Other complicates of DM
- Insulin resistance
- Diabetic ketoacidosis
- Diabetic neuropathy
- Diabetic nephropathy
- Cataracts
120
Prevention of hypoglycemia
- If pet doesn't eat or vomits food, do not give or give reduced insulin
- Owner instructions to give Karo syrup on gums
121
What to do for a huge overdose of insulin?
- Hospitalization
- IV dextrose
- +/- other treatments as needed (should be for about 12 hours)
122
What does it suggest if you're giving a ton of insulin but still have clinical signs?
- Insulin resistance
123
What is the dose of insulin that's considered insulin resistance?
- >2U/kg insulin per dose
124
Simple explanation for insulin resistance
- Insulin storage, expiration
| - Administration (site)
125
Not-so-simple explanations for insulin resistance
- Somogyi effect (we think they're resistant, but they're actually not)
- Stealth medications (eye drops of eardrops with steroids)
- Concurrent disease (pancreatitis or other infections)
126
Conditions associated with insulin resistance
- Hyperadrenocorticism
- Exogenous steroids
- Glucocorticoids administered by any route
- Hypothyroidism or hyperthyroidism
- Pancreatitis
- Diestrus (progresterone)
- Obesity
- Neoplasia
- Acromegaly (cats >>>> dogs)
- Infections (often occult; UTI,pyoderma, pral, pneumonia, disease)
- Renal failure
- Cardiac disease
- Hepatic disease
- Insulin antibodies (last on the list)
127
What should you do if you suspect actual insulin resistance?
- Look for and treat underlying illness
128
Who gets cataracts for diabetes?
- DOGS
129
Cataracts in dogs with DM
- Secondary, lens-induced uveitis
- Surgery to remove the lens will restore vision in 75-80% of patients
- Offer treatment options early to allow for the best chance of restoring vision
- DO NOT IGNORE THEM
- May need to see an ophthalmologist for surgery
130
Diabetic neuropathy
- Rear limb weakness
- Plantigrade stance/walking on the hocks
- Unknown cause
131
Diabetic neuropathy: who gets it?
- Cats > dogs
132
Cause of diabetic neuropathy
- Unknown
133
Treatment for diabetic neuropathy
- Improved glucoregulation
| - May not fully reverse
134
Diabetic nephropathy
- Glomerular dysfunction
- Proteinuria
- Progression to failure
- Cause unknown - multifactorial
135
What is diabetic ketoacidosis?
- Life threatening, acute complication of untreated diabetes mellitus
- VERY LIFE THREATENING (though most common and most rapidly fatal complication of DM is still hypoglycemia)
136
What triggers DKA?
1. Marked insulin deficiency
2. Concurrent cause of insulin resistance (e.g. infection, pancreatitis, cancer, diestrus, glucocorticoids or progesterone)
137
Underlying pathogenesis of DKA
- Insulin is not present to facilitate glucose uptake by cells
- Cells are starved for energy so turn to alternative energy sources (FFAs, liver manufactures ketone bodies)
- Contributing factors: excess glucagon, cortisol, fasting, dehydration
138
What leads to the acidosis in DKA?
- Ketone bodies overwhelm the body's buffering capacity
139
What leads to the dehydration in DKA?
- Glucose and ketones accumulate in urine leading to osmotic diuresis
140
Clinical signs/Clinical Pathologic Abnormalities of DKA PRIMARY
- Diabetes + Ketonuria + "illness"
- Hyperglycemia
- Acidosis
141
DKA CBC abnormalities
- Non-regenerative anemia, left shift neutrophilia, or thrombocytosis (~50% of dogs)
- Neutrophilia and Heinz body formation (common in cats due to ketones)
142
Chemistry changes DKA
- Increased ALP (almost all dogs)
- ALT elevation
- Cholesterol elevation
- Azotemia (Cats > dogs)
- Hypokalemia (often not able to take up potassium and phosphorus into cells; need insulin to take up potassium and phosphorus)
- Hypophosphatemia (see hypokalemia)
- Hypomagnesemia
Hyponatremia (pseudo due to expanded vascular volume?)
- Hypochloremia
143
DKA treatment?
- Emergency!
- Correct fluid deficit
- Correct insulin deficit and reverse ketone formation
- Correct electrolyte and acid base abnormalities
- Supportive care
- Identify and correct underlying disorders
144
What is one of the most important aspects of resolving DKA?
- Identify and correct the underlying disease
145
What is something you should let owners know if their pet has DKA?
- Make sure the owner is aware of the financial and time commitments of managing a diabetic prior to initiating treatment
146
1st priority of DKA treatment
- REHYDRATE
- Delay insulin administration for at least 1-2 hours
- Isotonic fluids
- Correct deficit over 24 hours
147
What are the two things that fluids help do for treating DKA?
- Correct acid-base abnormalities
| - May have some effect on lowering glucose levels
148
Goal of insulin in DKA treatment
- Decrease BG slowly over 6-12 hours
149
How should you give insulin with you're doing DKA treatment?
- Short-acting and short duration (regular)
| - IV CRI or intermittent IM method
150
What range should you maintain BG for DKA treatment?
- Moderate range (~200's) to allow for continual administration of insulin
- Dextrose may be added to fluids to maintain BG and allow for insulin administration
151
Acidosis Treatment
- Fluid therapy and resolution of ketones should correct acidosis eventually
- +/- Bicarbonate (??) can be used to more rapidly correct acidosis if needed, but it's controversial
152
Bicarbonate opponents
- Fluid therapy will correct in patient with reasonable renal function
153
Bicarbonate proponents
- May prevent deleterious effects of acidemia
| - Acidemia is very detrimental
154
How often should you be monitoring BG in DKA?
- Every 1-2 hours
155
What else should you be monitoring with DKA?
- Potassium, phosphorus, other electrolytes, blood gases
156
How often should you be monitoring electrolytes, blood gases, potassium, and phosphorus?
- Every 4-6 hrs initially then less frequently with improvement
- Insulin will drive K and Phos into cells so even if normal initially, can plummet dramatically with treatment
- Supplement as needed
157
How often should you monitor urine ketones in DKA?
- Every 24 hours
158
Things to be monitoring in DKA summary
- BG every 1-2 hrs
- Potassium, phosphorus, other electrolytes, blood gases every 4-6 hours
- Urine ketones every 24 hours
159
Complications of DKA treatment
- Generally result from over-aggressive insulin therapy or fluids and inadequate monitoring
- Hypoglycemia
- Cerebral edema
- Hypokalemic complications
- Hypophosphatemic complications
