Diabetes Mellitus Flashcards
(113 cards)
1
Q
What is the general trend over time of incidence of diabetes in the US?
A
Incidence is growing
2
Q
What races/ethnicities have the greatest prevalence of DM?
A
- American Indian/Native American
- Black, non-hispanic
- Hispanic
- Asian
- White
3
Q
What epidemic is causing the current incidence of diabetes?
A
Obesity
4
Q
What are some diabetes-related complications?
A
- Lower extremity amputation
- Heart disease
- Stroke
- Neuropathy
- Diabetic eye disease
- End-stage renal disease (ESRD)
5
Q
What causes type 1 diabetes?
A
Beta cell destruction
6
Q
What causes type 2 diabetes?
A
Progressive insulin secretory defect
7
Q
What are some other types/causes of diabetes?
A
- Gestational diabetes (GDM)
- Genetic defects in beta cell function, insulin action
- Diseases of the exocrine pancreas
- Drug- or chemical-induced
8
Q
When do macrovascular changes occur? When do microvascular changes occur?
A
- Macrovascular changes occur first, even 15 years before onset of diabetes due to obesity, impaired fasting glucose, and impaired glucose tolerance
- Microvascular changes occur second, about 5 years before onset of diabetes
9
Q
What are the criteria for testing for DM or pre-DM in asymptomatic adults?
A
- Adults of any age who are overweight AND have 1+ additional risk factors:
- 1st degree relative w/ DM
- High-risk race (AA, latino, AI/NA, Asian, Pacific Islander)
- Women who had GDM
- Hx CVD
- HTN (>140/90)
- Low HDL (<35) and/or high trigs (>250)
- Women with POS (polycystic ovary syndrome)
- Physical inactivity
- Other clinical conditions associated w/ insulin resistance (severe obesity, acanthosis nigricans) - For all pts, testing should begin at age 45
If tests are normal, repeats testing at minimum q3yr. Those w/ pre-DM should be tested yearly
10
Q
What are normal results of DM testing?
A
- FPG < 100 mg/dL
- 2hr PG < 140 mg/dL
- A1c < 5.7%
11
Q
What are the criteria for diagnosing pre-DM?
A
- FPG 100-125 mg/dL
- IGT
- 2hr PG 140-199 mg/dL
- A1c 5.7-6.4%
12
Q
What are the criteria for diagnosing DM?
A
- FPG >126 mg/dL
- 2hr PG > 200 mg/dL
- Random PG > 200 mg/dL + symptoms
- A1c > 6.5%
13
Q
What are some components of the comprehensive diabetes evaluation?
A
- PMH and FH
- DM hx
- FH
- Personal history of complications and common comorbidities - SH: assess lifestyle and behavior patterns
- Medications and vaccinations
- Technology use
- History of diabetes-related complications
- Microvascular: retinopathy, nephropathy, neuropathy (sensory neuropathy, including hx foot lesions, & autonomic neuropathy, including sexual dysfunction and gastroparesis)
- Macrovascular: CHD, cerebrovascular disease, PAD
14
Q
What is some screening we should be doing in diabetics?
A
- Psychosocial (depression, anxiety, eating disorder)
- Cognitive impairment
- DSMES
- Hypoglycemia
- Pregnancy planning
15
Q
What should the physical exam involve when assessing someone with DM?
A
- Ht, Wt, BMI
- BP, including orthostatics when indicated
- Fundoscopic exam
- Thyroid palpation
- Skin exam (for acanthosis nigricans and insulin injection/infusion set insertion points
- Foot exam
16
Q
What is acanthosis nigricans?
A
- Common condition characterized by velvety, hyperpigmented plaques on the skin
- Associated with conditions causing insulin resistance, most commonly obesity & DM
- Benign, asymptomatic, cosmetic concerns are typically primary concern for tx
- Tx of underlying cause is preferred method of managmeent
17
Q
What is diabetic dermopathy?
A
- Most common skin lesion in DM
- Trauma + atrophy + chronic inflammation + poorly vascularized skin
- High correlation with retino-vascular disease and sensory neuropathy
- Asymptomatic
- Irregular, round, oval, shallow, depressed, atrophic, hyper-pigmented lesions
- Very few/many, present in crops, resolve slowly over 12-18 months
18
Q
What causes lipohypertrophy?
A
Using same sites for insulin injection
19
Q
What does a comprehensive DM foot exam look like?
A
- Inspection
- Screen for PAD (pedal pulses)
- Determination of temperature, vibration, or pinprick sensation, and a 10g monofilament sensation
20
Q
What are some risk factors for foot ulcers?
A
- Previous amputation
- Past foot ulcer hx
- Peripheral neuropathy
- Foot deformity
- Peripheral vascular disease
- Visual impairment
- Diabetic nephropathy (esp. pts on dialysis)
- Poor glycemic control
- Cigarette smoking
21
Q
What are some diagnostics tests to check in patients with diabetes?
A
A1c, if results not available in past 3 months
If not performed/available within past year
- Fasting lipid profile (total, LDL, HDL, TGs)
- LFTs
- Urine albumin excretion/urine-to-creatinine ratio
- Serum creatinine and calculated GFR
- TSH in type 1 DM, dyslipidemia, or women over the age of 50 years
- Vitamin B12 if on metformin
- Serum potassium in pts on ACE, ARB, or diuretics
22
Q
What are some refers to make for patients with diabetes?
A
- Ophthalmologist for annual dilated eye exam
- Family planning for women of reproductive age
- Registered dietician for MNT
- Diabetes self-management education/support
- Dentist for comprehensive periodontal exam
- Mental health professional if needed
23
Q
How does DSME compare to metformin?
A
- Both are highly effective, have low hypoglycemia risk, neutral wt/wt loss
- DSME does not have the side effects or cost of metformin, while it can be potentially cost saving and have high psychosocial benefit
24
Q
When are the 4 critical times to prescribe DSME for adults with type 2 DM?
A
- At diagnosis
- Annual assessment of educational, nutritional, and emotional needs
- When new complicating factors influence self-management
- When transitions of care occur
25
What is the recommended immunization schedule for diabetics?
- Routinely recommended vaccines for general population
- Pneumococcal (13-valent and 23-valent) vaccines
- Hepatitis B 3 shot series
26
What are some techniques available for health providers and patients to assess effectiveness ofmanagement plan on glycemic control?
- Patient self-monitoring of blood glucose (SMBG)
- Continuous glucose monitoring (CGM)
- A1c
27
Who should perform self-monitoring of blood glucose (SMBG)?
- Patients using intensive insulin therapies
- Patients using less frequent insulin injections or non-insulin therapies
- Patients on multiple-dose insulin (MDI) or insulin pump therapy
28
When should patients perform self-monitoring of blood glucose (SMBG)?
- Prior to meals and snacks
- Occasionally postpradial
- At bedtime
- Prior to exercise
- When they suspect low blood glucose
- After treating blood glucose until they are normoglycemic
- Prior critical tasks such as driving
29
What are the benefits of good glycemic control?
- Delayed progression of disease and associated morbidity/mortality
- Decreased rates of microvascular and neuropathic complications
- Risk reduction for cardiovascular disease
30
What are the ABCs of DM?
- A1c
- BP
- Cholesterol
31
What are the recommendations for WHEN patients should have A1c testing?
- Twice a year for patients meeting treatment goals
- Quarterly in patients whose therapy has changed or who are not meeting glycemic goals
***Point-of-care for A1c provides opportunity for more timely tx changes***
32
For which patients should we set a more stringent A1c goal of < 6.5%?
< 6.5% =
- Patients with short duration of diabetes
- Type 2 DM tx with lifestyle or metformin only
- Long life expectancy
- No significant CVD
33
For which patients should we set a reasonable A1c goal of < 7%?
Nonpregnant adults
34
For which patients should we set a less stringent A1c goal of < 8%?
- Hx severe hypoglycemia
- Limited life expectancy
- Advanced microvascular/macrovascular complications
- Extensive comorbid conditions
- Longstanding DM in whom goals are difficult to achieve
35
What are the general glycemic recommendations for nonpregnant adults with diabetes?
- A1c < 7%
- Preprandial capillary plasma glucose 80-130 mg/dL
- Peak postprandial capillary plasma glucose <180 mg/dL
36
What is the preferred treatment for conscious individual with blood glucose < 70 mg/dL?
15-20g glucose
37
How do you define clinically significant hypoglycemia, and what preventative measures should you take as a provider?
- Blood glucose < 54 mg/dL
| - Prescribe glucagon
38
What are the signs and symptoms of hypoglycemia?
- Shakiness
- Irritability
- Confusion
- Restlessness
- Weakness
- Tachycardia
- Hunger
- Sleepiness
- Paleness
- Blurry vision
39
What does the body do at a blood sugar of 80?
Decreases insulin secretion
40
What does the body do at a blood sugar of 70?
Increases glucagon, epinephrine, ACTH (adrenocorticotrophic hormone), cortisol, and GH (growth hormone)
41
What does the body do at a blood sugar of 50?
Palpitations, sweating
42
What does the body do at a blood sugar of 40?
Decreased cognition, aberrant behavior, seizures, coma,
43
What does the body do a blood sugar of 20-10?
Neuronal cell death
44
What is the rule of 15, and what are some examples?
15 g of fast acting carbohydrates used to treat hypoglycemia
- 4 oz of fruit juice
- 15 g glucose tablets (3-4 tablets)
- 1 tube of glucose gel
- 4-6 small hard candies
- 1-2 tablespoons of honey
- 6 oz regular (not diet) soda (about half a can)
- 3 tsp table sugar
- 1/2 tube of cake mate
45
What is the next step after administering fast acting carbohydrates for hypoglycemia?
Follow with a meal or a snack
46
What do you do if a person is hypoglycemic and unable to swallow?
Administer glucagon
47
Describe the clinical pharmacology glucagon
- Increases blood glucose concentration and is used in the treatment of hypoglycemia
- Acts only on liver glycogen, converting it to glucose
48
Describe the indications and usage for glucagon
Because patients with type 1 diabetes may have less of an increase in blood glucose levels compared with a stable type 2 patient, supplementary carbohydrate should be given as soon as possible, especially to pediatric patients
49
Describe the contraindications of glucagon
- Known hypersensitivity
| - Pheochromocytoma
50
When should patients with diabetes be treated for hypertension?
> 140/90 mmHg
130/80 mmHg may be appropriate for people with high risk of CVD
51
What are first-line pharmacological therapies for patients with diabetes and hypertension?
ACE or ARB (then thiazide-type diuretic and CCB)
- For BP > 140/90 mmHg but < 160/100 mmHg, 1 medication
- For BP > 160/100 mmHg, 2 medications
52
When is it appropriate to screen lipid profile in adults with diabetes?
- At first diagnosis
- At the initial medical evaluation
- Every 5 years if under age 40, or more frequently if indicated
53
When should you reassess a diabetic after initiating a statin or other lipid-lowering therapy, or after changing statin dose?
4-12 weeks after
| Annually thereafter to monitor response to therapy
54
In regards to lipid management of diabetics, when should you intensify lifestyle therapy and optimize glycemic control?
- Elevated TGs > 150 mg/dL
| - Low HDL < 40 mg/dL (men) or < 50 mg/dL (women)
55
In high intensity statin treatment of diabetics, if LDL > 70 mg/dL despite max tolerated statin dose, what should you consider adding to their medication regimen?
LDL-lowering therapy (ezetimbe or PCSK9 inhibitor)
56
What are two examples of high intensity statin therapies?
- Atorvastatin 40-80 mg
| - Rosuvastatin 20-40 mg
57
When should aspirin therapy be used in diabetic patients?
- As secondary prevention in those with DM and history of ASCVD
- As primary prevention in those with type I or type II DM with increased risk for CVD
58
What medication should be used in patients with an aspirin allergy?
Clopidogrel
59
What is reasonable pharmacological therapy for diabetics a year after ACS?
Aspirin + P2Y12 inhibitor
60
What are some risk factors for CVD in diabetics?
- Family history of ASCVD
- Hypertension
- Smoking
- Dyslipidemia
- Albuminurea
61
What medication should be used in diabetic patients with prior MI?
Beta blockers for at least two years after the event
62
When can metformin be used in patients with stable heart failure?
If estimated GFR > 30 mL/min but should be avoided in unstable or hospitalized patients with heart failure
63
When should diabetics be screened for nephropathy?
At least once a year in type 1 DM duration > 5 years and all type 2 DM
64
How do you screen diabetics for nephropathy?
- Urinary albumin (spot urinary albumin-to-creatinine ratio, UACR)
- Estimated GFR
65
What is the treatment for diabetic nephropathy?
- Optimize glucose and BP control
| - ACE or ARB when elevated urinary albumin excretion > 300 mg/day or GFR < 60 mL/min
66
What labs should be periodically minored when using ACEs, ARBs, or diuretics?
- Creatinine
| - Potassium
67
Should diabetics be placed on ACE or ARB for primary prevention of kidney disease in patients with
- Normal BP
- Normal UACR
- Normal estimated GFR?
It is not recommended
68
What is the best way to reduce the risk or slow the progression of retinopathy in diabetics?
Optimize glycemic and BP control
69
When should diabetics have dilated and comprehensive eye exams by an ophthalmologist or optometrist?
- Adults with type I DM = Within five years of DM onset
- Patients with type II DM = At time of diagnosis of DM
- If is no evidence of retinopathy for 1+ annual eye exams and glycemia is well controlled, then exams every 1 to 2 years may be considered
- If any level of retinopathy Is present, then seen at least annually
70
Who should be screened for diabetic peripheral neuropathy and when?
All diabetic patients
- Diagnosis of type 2 DM and 5 years after diagnosis of type 1 DM, then annually
- All patients should have annual 10g monofilament testing to identify feet at risk for ulcers and amputation
71
What does the assessment for distal symmetric polyneuropathy involve?
- Inspection every visit
- Neurological assessment: temperature or 10g monofilament pinprick (small-fiber function) and vibration sensation (large-fiber function)
- Vascular assessment: pulses in legs and feet
Symptoms of claudication or decreased/absent pedal pulses should be referred for further vascular assessment
72
What is the treatment for diabetic neuropathy?
- Optimize glycemic control to prevent or delay development of neuropathy
- Pregabalin (Lyrica) or duloxetine (Cymbalta) are recommended as initial pharmacological treatment for neuropathic pain in diabetes
73
What do A1c goals look like in the elderly?
< 7.5% = Otherwise healthy with few existing chronic illnesses and intact cognitive functioning
< 8-8.5% = MCI or CI or functional dependence
74
What is a big risk associated with older adults with diabetes?
Increased risk of hypoglycemia => Use medication classes with low risk hypoglycemia
75
What are the primary goals for diabetes management at the end of life?
- Palliative care: strict BP control and intense lipid management may not be necessary
- End of life: overall comfort, prevention of distressing symptoms, and preservation of quality of life and dignity
76
What are some physical factors that complicate the management of DM in older adults?
- Decreased physical activity
- Difficulty in preparing food: arthritis, tremor
- Alterations in sense: vision, taste, smell
- Difficulty in consuming food: poor digestion, dry mouth
- Altered renal and hepatic function
- Coexisting diseases: infections
- Interactions with multiple medications
77
What are some psychosocial factors that complicate the management of DM in older adults?
- Cognitive impairment
- Social isolation
- Poverty
- Psychiatric problems: depression, anxiety
- Lack of access to medical care or community resources
78
What type of language should we use in diabetes education?
Language that is:
- Neutral, nonjudgmental, and based on facts, actions, or physiology/biology
- Free from stigma
- Strengths based, respectful, inclusive, and imparts hope
- Person-centered
79
What is the most important Rx you can provide patients with DM?
Diabetes self-management education/support
80
What self-care behaviors do DM educators help?
- Healthy eating
- Being active
- Monitoring
- Taking medication
- Problem-solving
- Healthy coping
- Reducing risks
81
Why is a plant-based whole foods dietary pattern recommended for diabetics?
1. Pathology
- Lower inflammation
- Some micronutrients have powerful anti-cancer effects
2. Nutrition: caloric density => nutrient density
- Higher in variety (spectrum of colors)
- Only complete source of micronutrients (vitamins and minerals)
- High amount of fiber (increased satiety) => improved gut microbiome
3. Environment
- Significantly reduced carbon emissions (~20% estimated by UN and WHO)
- Increased ability to feed growing world population
82
What are the physical activity guidelines for DM?
- 150 min/week moderate-to-vigorous physical activity
- No consecutive 2 days without activity
- 75 min/week vigorous physical activity
- 2-3 sessions/week resistance exercise
- Interrupt prolonged sitting q30min
- Flexibility training and balance 2-3x/week
83
What are the recommendations for smoking cessation in DM?
- Advise all pts not to use cigarettes & other tobacco products or e-cigs
- Include smoking cessation counseling & other forms of tx as routine components of DM care
84
What are some factors to consider when choosing a pharmacological agent for DM?
- Current A1c
- Duration of diabetes
- BMI
- Age of pt
- Comorbidities
- Cost of medication
- Convenience
85
What are the pharmacological recommendations for therapy for type 1 DM?
- Multiple daily injections (3-4 of basal and prandial insulin) or continuous SC insulin infusion
- Use rapid-acting analogs to reduce hypoglycemia risk
- Educate pts on how to match prandial insulin dose to carb intake, premeal glucose, and anticipated activity
- Pts who have been successfully using continuous subcutaneous insulin infusion should have continued access to this therapy after they turn 65 years old
86
What is important about potency of oral DM medications?
All oral agents require presence of some endogenous beta-cell function, as they work by either increasing insulin sensitivity of augmenting beta-cell insulin release
87
What are some of the noninsulin agents available for T2DM?
- Alpha-glucosidase inhibitors
- Amylin analogues
- Biguanides
- Bile acid sequestrants
- DPP-4 inhibitors
- Dopamine-2 agonists
- Glinides
- GLP-1 receptor agonists
- SGLT2 inhibitors
- Sulfonylureas
- Thiazolidinediones
88
What is the class, MOA, advantages/disadvantages, cost, and max dosing of metformin?
- Class: biguanides (glucophage IR/XR)
- Action: reduces hepatic glucose output (HGO)
- Advantages: extensive experience, NO hypoglycemia, reduced CVD events, weight reduction
- Disadvantages: GI side effects, vit b12 deficiency, contraindicated in CKD (GFR <30), acidosis, hypoxia, dehydration, lactic acidosis risk (rare)
- Cost: low ($10/mo)
- Max Dosing: 2000-2500 mg
- Decreases A1c 1-2%
* acidic and kidney dependent - these things go along with most metformin considerations*
89
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of sulfonylureas?
* used to be 1st choice med, 2nd gen safer than 1st gen*
- Drugs: glyburide (diabeta, gynase, micronase), glipizide (glucotrol), glimeperide (amaryl)
- Action: increase insulin secretion from beta cells by closing K-atp channels on beta-cell plasma membrane
- Advantages: extensive experience, reduced microvascular risk
- Disadvantages: *HIGHEST risk of hypoglycemia*, weight gain, high risk tx failure, renal metabolism/excretion, sulfa allergies
- Cost: low ($10/mo)
- Max Dosing: glyburide 20mg, glipizide IR 40mg/XR 20mg, glimeperide 8mg
- Decreases A1c 1-2%
90
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of meglitinides (glinides)?
- Drugs: Repaglinide (prandin), nateglinide (starlix) (before meal dosing)
- Action: rapid acting, binds to alternative sites of SU receptor, closes K-atp channels on beta-cell plasma membranes to increase insulin secretion
- Advantages: reduced postprandial glucose excursions
- Disadvantages: hypoglycemia, weight gain,, frequent dosing schedule
- Cost: mod (repaglinide $75/mo, nateglinide $120/mo)
- Max Dosing: repaglinide 16mg, nateglinide 360mg
- Decreases A1c 1-2%
91
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of thiazolidinediones (TZDs)?
- Drugs: pioglitazone (actos) 1st choice, rosiglitazone (avandia)
- Action: increases insulin sensitivity, enhances insulin action everywhere (activates nucluar transcription factor PPAR-gamma)
- Advantages: low risk hypoglycemia as monotherapy, increases HDL, decreases TGs & CVD events
- Disadvantages: 3-6wks for glycemic effects, weight gain, edema/HF, bone fractures, increased risk MI
* Monitor ALT at tx start, q1mo x 12mo, then q3mo
- Cost: low/high (pioglitazone $14/mo, rosiglitazone $325/mo)
- Max Dosing: pioglitazone 45mg, rosiglitazone 8mg
- Decreases A1c 0.5-1%
92
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of alpha-glucosidase inhibitors?
- Drugs: acarbose (precose), miglitol (glyset) (take before CHO rich meals)
- Action: slows intestinal CHO digestions/absorption by intestinal enzyme inhibition
- Advantages: NO hypoglycemia, reduced post prandial glucose excursions
- Disadvantages: GI side effects (flatulence, diarrhea), modest glycemic benefit, frequent dosing schedule
- Cost: low-mod (acarbose $45/mo, miglitol $200/mo)
- Max Dosing: 300mg
- Decreases A1c 0.5-1%
93
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of
- Drugs:
- Action:
- Advantages:
- Disadvantages:
- Cost:
- Max Dosing:
94
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of bile acid sequestrants?
- Drugs: colesevelam (welchol)
- Action: binds bile acids in intestinal tract, increasing hepatic bile acid production, decreases HGP, increases incretin levels
- Advantages: rare hypoglycemia, reduces LDL
- Disadvantages: GI side effects (constipation, bloating), mod glycemic benefit, increases TGs, may reduce absorption of other meds
- Cost: high ($600/mo)
- Max Dosing: 3.75g
- Decreases A1c 0.5% (when taken w/ other glucose-lowering agents)
95
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of dopamine-2 agonists?
- Drugs: bromocriptine (cycloset)
- Action: activates dopaminergic receptors, modulates hypothalamic regulation of metabolism, increases insulin sensitivity
- Advantages: rare hypoglycemia, reduced cardiovascular events
- Disadvantages: side effects of drowsiness, N/V, HA, rhinitis, dizziness; mod glycemic effect, increases TGs, may reduced absorption of other meds (CYP3A4 interactions)
- Cost: high ($650/mo)
- Max Dosing: 4.8mg
- Decreases A1c 0.5% (when added to metformin & sulfonylurea)
96
What are some patterns?
Drugs that increase insulin sensitivity reduce CVD events
97
What are the role of SGLT transporters in the nephron?
- SGLTs are located in proximal tubule of nephron, right after Bowman's capsule
- SGLT1s are at the S3 seg of proximal tubule, where they account for 10% of glucose reabsorbtion
- SGLT2s are at the S1 seg of proximal tubule, where they account for 90% of glucose reabsorption
- A total of 180g glucose is reabsorbed at the site of the proximal tubule/day by SGLT transporters
98
How can SGLTs be targeted by pharmaceuticals to help manage diabetes?
- In T2DM, enhanced rena; glucose reabsorption contributes to hyperglycemia
- Glucose transporter SGLT2 is responsible for 90% of glucose reabsorption
- Inhibition of SGLT2: decreases glucose reabsorption, increases urinary glucose excretion
- Observe weight loss and reduction in blood pressure
99
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of SGLT2 inhibitors?
- Drugs: canagliflozin (invokana), dapagliflozin (farxiga), empagliflozin (jardiance)
- Action: blocks glucose reabsorption by kidney, increasing glucosuria, inhibits SGLT2 in the proximal nephron
- Advantages: NO hypoglycemia, weight loss, BP reduction, lower CVD rate & mortality in pts w/ CVD
- Disadvantages: GU infections, angioedema/urticaria & other immune-mediated dermatological effects, increased LDL, increased creatinine, DKA, ?acute pancreatitis, ?increase HF hospitalizations
- Cost: high ($430/mo)
- Max Dosing: canagliflozin 300mg, dapagliflozin 10mg, empagliflozin 25mg
- Decreases A1c 1%
100
What is the incretin effect and how does it related to diabetics?
In pts w/ T2DM:
1. The incretin effect severely reduced
- Insulinotropic effects of GIP are virtually absent
- Insulinotropic effects of GLP-1 are at least partially preserved
(endogenous GLP-1-mediated insulin secretion does not compensate for loss of insulinotropic activity of GIP)
- Defective glucagon suppression produces hyperglucagonemia (fasting and post-nutrient state)
2. Defective incretin-mediated stimulation contributes to defective insulin secretion
101
Name the functions of GLP-1 in the human
GLP-1 is secreted upon the ingestions of food (broken down by DPP-IV)
- Promotes satiety and reduces appetite
- Work on alpha cells to reduce postprandial glucagon secretion => reduced glucagon reduces hepatic glucose output
- Work on beta cells to enhance glucose-dependent insulin secretion
- Work on stomach to help regulate gastric emptying
102
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of GLP-1 agonists?
- Drugs: INJECTED exenatide (byetta qd, bydureon q1wk), liraglutide (victoza), albiglutide (tanzeum), lixisenatide (adlyxin), dulaglutide (trulicity)
- Action: incretin memtic GLP-1 analog, not recognized by DPP-IV, activates GLP-1 receptors to increase insulin secretion, reduced glucagon secretion, slow gastric emptying, and increase satiety
- Advantages: rare hypoglycemia, weight loss, reduced postprandial glucose, decreases some CV risk factors, associated w/ lower CVD event & mortality
- Disadvantages: injectable, GI side effects (N/V/D), increased HR, ?acute pancreatitis
- Cost: high
- Max Dosing: ?
- Decreases A1c 0.5-1.6%
103
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of DPP-IV inhibitors?
- Drugs: sitagliptin (januvia), saxagliptin (onglyza), linaliptin (tradjenta), alogliptin (nesina)
- Action: increases insulin secretion & reduces glucagon secretion (glucose dependent), inhibits DPP-IV activity increasing postprandial active incretin (GLP-1, GIP concentrations)
- Advantages: rare hypoglycemia, well tolerated
- Disadvantages: angioedema/urticaria & other immune-mediated dermatological effects, ?acute pancreatitis, ?increase HF hospitalizations
- Cost: high (sitagliptin $380/mo, saxa $385/mo, lina $380/mo, alo $195/mo)
- Max Dosing: sitagliptin 100mg, saxa 5mg, lina 5mg alo 25mg
- Decreases A1c 0.6-0.9%
104
What is the MOA, example drugs, advantages/disadvantages, cost, and max dosing of amylin mimetics?
- Drugs: pramlintide (symlin)
- Action: activates amylin receptors, reduces glucagon secretion, slows gastric emptying, increases satiety
- Advantages: reduces postprandial glucose excursion, weight loss
- Disadvantages: injectable, GI side effects (N/V), angioedema/urticaria & other immune-mediated dermatological effects, ?acute pancreatitis, ?HF hospitalizations
- Cost: high ($2,000/mo)
- Max Dosing: 120mcg/dose (360mg/day)
- Decreases A1c ~0.36% when added to insulin w/wo metformin and/or sulfonylurea
105
Algorithm for adding or intensifying insulin...
1. Start basal insulin
- If A1c < 8%, TDD 0.1-0.2u/kg
- If A1c > 8%, TDD 0.2-0.3u/kg
2. Insulin titration q2-3days to reach glycemic goal
- Fixed regimen: increase TDD by 2 u
- Adjustable regimen:
~ FBG > 180: add 20% of TDD
~ FBG 140-180: add 10% of TDD
~ FBG 110-139: add 1 u
- If hypoglycemia, reduce TDD by:
~ BG < 70: 10-20%
~ BG <40: 20-40%
*Consider d/c or reducing sulfonylurea after starting basal insulin
*Glucemic goal:
- <7% for most pts, fasting & premeal BG < 110, absense of hypoglycemia
- A1c & FBG targets adjustd based on age, duration of DM, presence of comorbidities, & hypoglycemia risk
*If glycemic goal not met with basal insulin, add GLP-1 RA, DPP-4I, or SGLT-2I, or intensify w/ prandial control
3. Add prandial insulin
- Basal plus 1 before biggest meal, if not met plus 2, if not met plus 3 - start 10% of basal dose or 5 u
- Basal bolus: begin prandial insulin before each meal, 50% basal, 50% prandial, TDD 0.3-0.5u/kg - start 50% of TDD in 3 doses before meals
4. Insulin titration q2-3days to reach glycemic goal
- Increase prandial dose by 10% of 1-2u if 2h PPG of premeal glucose > 140
- If hypoglycemia, reduce TDD basal &/ prandial insulin by:
~ BG consistently < 70: 10-20%
~ Severe hypoglycemia (requiring assistance from another person) of BG < 40: 20-40%
106
Why is there a need for newer insulins?
1. NPH, in the same dose by the same person in the same site at the same time of the day under the same conditions can vary up to 50% absorption
2. Glargine & Detemir
- Still slight peak
- Hypoglycemia
- Some variability
- In some cases BID injections
- More injections = less adherence
3. Smoother, flatter, more constant profiles needed
- Lower intra-patient variability
- Increased adherence
- Less hypoglycemia
- Less wt gain
4. Newer insulins have greater adherence
- Glargine 300: dose is given qd but has 3hr window it can be given
- Degludec: if dose missed can give next day if 8 hr window before next dose
107
What are the different types of insulins?
```
Basal:
- NPH - biggest spike of them all
- Glargine (also Glargine 300)
- Detemir
- Degludec
Basal-prandial: Regular U-500
Prandial:
- Aspart
- Glulisine
- Lispro
- Inhaled insulin
```
108
What are some thing sto keep in mind with NPH?
- More ppl ahve to swtich to NPH due to cost
- Be prepared if switching from NPH to go down in dose until glycemic control established
- Pt demonstrates how to use vial and syringe
- Pt understands mixing (rolling technique)
- Help pts be more aware of activity levels, meals/snacks, & possibility of greater nighttime hypoglycemia
109
Titration for glargine
Start w/ 10 u & adjust weekly
- 100-120: add 2u
- 120-140: add 4u
- 140-160: add 6u
- > 180: add 8u
110
Why add GLP-1 RA w basal insulin?
- Improved A1c (comparable to adding prandial insulin)
- Added lowering of FPG
- Beneficial effects of PPG
- Lowers risk of hypoglycemia compared to increase basal insulin alone or adding prandial insulin
- Less weight gain
111
What are the rules for GLP-1 RA + basal insulin and vice versa?
- If adding GLP-1 RA to basal insulin, downward titration of basal insulin in suggested => reduction of basal insulin dose reduces risk of hypoglycemia and weight gain
- Adding basal insulin to GLP-1 obviates the need for downward titration of basal insulin
* Both provide safer and easier way to achieving control
112
When should you start insulin?
1. FPG > 250
2. A1c > 10%
3. Random plasma glucose > 300
4. Not meeting glycemic goals with oral hypoglycemics
5. Oral hypoglycemics are contraindicated
6. Hyperglycemia + ketonuria OR metabolic acidosis OR sx DM w/ polyuria, polydipsia, wt loss
113
Framework for treating hyperglycemia in older adults
1. Healthy
- A1c < 7.5%
- FPG 90-130
- Bedtime glucose 90-150
2. Complex (multiple comorbidities, 2+ IADL impairments, MCI)
- A1c < 8%
- FPG 90-150
- Bedtime glucose 100-180
3. Very complex (end stage, 2+ ADL impairments, mod-sev CI)
- A1c < 8.5%
- FPG 100-180
- Bedtime glucose 110-200
