Diabetes (7 questions) Flashcards
1
Q
Basic role of insulin
A
Regulates body’s balance of storage vs mobilization of body stores
2
Q
Insulin: normal stimulation vs T2DM
A
Normal: beta cells sense rise in glc levels in bloodstream, send enough insulin to lower sugar into normal range (70-105mg/dL)
T2DM: lack of adequate stimulation to lower BG to normal range
3
Q
Insulin in liver: normal vs T2DM
A
- Normal: insulin allows glc to be stored as glycogen to be later released during fasting states; promotes conversion of liver glc into fatty acids/inhibits lipolysis
- T2DM: lack of insulin or sensitivity means body thinks it’s in a fasting state when it’s not and releases glc from glycogen and FAs = high BG and free fatty acids
4
Q
Insulin in skeletal muscle: normal vs T2DM
A
normal: insulin stimulates storage of glc as muscle glycogen to be used for energy by muscle cell
T2DM: glycogen released b/c body believes it’s in fasting state, but can’t get into cells since glc transporters on cell depend on insulin
5
Q
What is the renal threshold for hyperglycemia?
A
180 mg/dL - osmotic diuresis occurs leading to significant urinary losses of F & Es
–> progressive dehydration and hyperosmolality
6
Q
Etiology of Type I DM
A
autoimmune mediated diabetes, insulin producing B-cells are destroyed by an autoimmune process.
7
Q
Additional risks associated with DMI
A
increased incidence of other autoimmune diseases such as Hashimoto’s thyroiditis, graves disease, pernicious anemia, vitiligo, celiac disease and Addison’s Disease.
8
Q
DMII etiology
A
strong family Hx - genetics & environment
9
Q
MODY etiology
A
genetic defect in the b-cell. Genetic defects in insulin action.
10
Q
Dz of exocrine pancreas that can lead to DM
A
pancreatitis, trauma, pancreatectomy, neoplasm, CF, hemochromatosis
11
Q
Medications that may cause DMII
A
steroids, HIV meds and some of the psychotropic agents may induce DM.
12
Q
Clinical manifestations of diabetes mellitus
A
- polyuria, polydipsia, polyphagia
- fatigue, blurred vision, headache, paresthesia, recurrent infections (UTI’s, candidiasis,etc.)
13
Q
Polyuria: DDx
A
- Diabetes Insipidus
- Primary Polydipsia
- UTI or Bladder Dysfunction
- Must rule out secondary causes such as
- Excess of counter-regulatory hormones
- Significant hypokalemia caused by impaired glc tolerance (IGT), diuretic use or hyperaldosteronism
- Destruction of Beta cells from pancreatitis, hemochromatosis, or drugs
14
Q
What is diabetes insipidus?
A
polyuria and polydipsia caused by inadequate secretion of vasopressin, the antidiuretic hormone (ADH). Cause is unknown, or trauma to the head which causes damage to the pituitary or a tumor. Causative factor eliminated. If not d/t damage then given vasopressin replacement therapy.
15
Q
What is primary polydipsia?
A
altered thirst perception with increased thirst and fluid intake followed by polyuria. Prevalent among patients with psychiatric history- i.e. schizophrenia.
16
Q
What is an excess of counter-regulatory hormones?
A
excess of glucagon, growth hormone, cortisol, catecholamines
17
Q
What is hyperaldosteronism?
A
production of salt retaining hormone aldosterone by an adrenal adenoma resulting in intravascular volume expansion and renin suppression.
18
Q
What is hemochromatosis
A
disease manifested with high serum iron and ferritin levels, often requiring routine phlebotomy.
19
Q
What drugs may cause polyuria?
A
e.g., corticosteroids, pentamadine, nicotinic acid, thyroid hormone, interferon, dilantin, thiazides
20
Q
Types of Diabetes Mellitus
A
- Type 1
- Type 2
- Latent Autoimmune Diabetes in Adults (LADA)
- Gestational Diabetes Mellitus
- Secondary Diabetes
- Maturity Onset Diabetes of the Young (MODY)
- Pre-Diabetes (High Risk)- impaired fasting glucose or impaired glucose tolerance
21
Q
Lab work for Dx type I DM
A
Presence of islet auto-antibodies-glutamic acid decarboxylase (GAD65), insulin autoantibody (IAA), insulinoma-associated protein 2 autoantibody (IA-2A) & zinc transporter 8 antibody (ZnT8A) and C. Peptide
22
Q
What is LADA?
A
Latent Autoimmune Diabetes in Adults (LADA)
- slowly progressive form of autoimmune diabetes
- adult age of Dx,
- presence of auto-antibodies (usually 1 vs DM1 has 2+)
- lack of an insulin requirement at the time of diagnosis.
- short duration of diet / PO Tx before requiring insulin.
Pt.s are usu. Thinner, lower BMI, higher A1c
23
Q
What is secondary diabetes?
A
- caused by medications such as zyprexa, abilify, (which contribute to weight gain) along with steroids, some of the meds used to treat HIV (such as Epivir, Retrovir, Norvir)
- pancreatitis, surgeries (especially involving the pancreas or organ transplantation and meds used in treatment), or diseases of the exocrine pancreas such as cystic fibrosis, ect.
24
Q
What is MODY?
A
defect in the B-cell function, characterized by onset of hyperglycemia@ an early age, generally before the age of 25 years. At least 3 different gene mutations have been identified which cause impaired insulin secretion without insulin resistance.
25
What constitutes "impaired fasting glucose"
BG 100 - 125
26
What constitutes "impaired glucose tolerance"?
2 hour plasma glucose of 140 to 199mg/dl.
That test is performed w/ a 75-g oral glucose load.
27
Diagnostic criteria for DM
* Symptoms of diabetes plus a casual/random plasma glucose _\>_ 200 mg/dl OR
* FPG_\>_126 mg/dl OR
* 2-H post-load glucose \> 200 mg/dl during an OGTT \*\* *not standard clinically*
* A1C _\>_ 6.5 %
_must repeat one of last 3 on another occasion._
*fasting = no PO intake _\>_ 8h*
28
How were OGTT, FPG and A1c numbers set for Dx of DM?
thresholds correlate with the presence of retinopathy, basis for these values
29
"One-step" Dx of GDM
* 24 to 28w gestation w/o prior overt DM
* 75-g OGTT: PG fasting, 1hr, 2hr
* Perform AM after an overnight fast of at least 8hr
* GDM Dx: any one of 3
* Fasting: ≥92 mg/dL (5.1 mmol/L)
* 1 h: ≥180 mg/dL (10.0 mmol/L)
* 2 h: ≥153 mg/dL (8.5 mmol/L)
30
"Two-step" Dx for GDM
24 to 28w gestation w/o prior overt DM
* **STEP 1**: 50-g GLT (nonfasting)
* PG at 1h (step 1)
* If 1hr PG is ≥140 mg/dL\* (7.8 mmol/L), proceed to step 2.
* **STEP 2**: 100-g OGTT (fasting)
* GDM Dx: 2+ of the following
* Fasting \>95
* 1H \>180
* 2H \>155
* 3H \>140
\**ACOG recommends lower threshold of 135 if high risk ethnic minority*
31
Does the NIH recommend the one or two step version of the OGTT for Dx of GDM?
Two step: lack of evidence for one step, and potential negative consequences for Dxing more women
32
PEak age for DMI
10-14 years
females 10-12, males 12-14
33
Whites vs other ethnic groups for risk of DM?
The risk for type 1 diabetes is higher in whites than for African-Americans, American Indians, Asians and Pacific Islanders or Hispanics, where as the opposite is true for type 2 diabetes.
34
Mainstays of mgmt for DMI
* Insulin therapy to obtain near normo-glycemia
* Diet sufficient for growth
* Exercise
* Psychological well being
* Prevention of complications
* Immunizations
35
BG goal and A1c goal for 8yo and older
SBGM: Fasting & Pre-Prandial BS 70-120
A1C goal less than 7.5% for children and older
36
Goal A1c for \<8yo
\<8 d/t risk of hypoglycemia
37
DMI: how often is A1c measured?
Quarterly
38
What is the "honeymoon period"
In DMI
## Footnote
In first few weeks of insulin therapy common to see a “honeymoon” period when β cells recover some function. Loss of function then proceeds after a period of up to 6 months or a year.
39
Risk factors for DMII
* Obesity
* Hypertension/ Hyperlipidemia
* Having a baby _\>_ 9 lbs
* Ethnicity
* Age
* Women with prior Gestational Diabetes or PCOS
* Sedentary Lifestyle
* Impaired Glucose Tolerance or Impaired Fasting Glucose
* Vascular Disease
* first-degree relative with diabetes
* high-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)
* history of CVD
40
When should you screen adults \<45yo for DMII?
45+?
* \<45 BMI \> or equal to 25 and 1 or more risk factors
* 45+: For all patients, particularly those who are overweight or obese, testing should begin at age 45 years.
* screen now and then every 3 years (yearly if prediabetes)
41
What does the history portion of a comprehensive evaluation of DM (I or II) consist of?
* Medical History
* Age and characteristic of onset (i.e. DKA, HHS, lab finding)
* Symptoms, results of lab tests, A1C records, exams
* Eating patterns, weight Hx, growth/dev
* Medications, meal plan, SBGM, diabetes self-management ed
* Exercise Hx
* Acute complications- hypo/hyperglycemia
* Hx and treatment of other conditions
* Risk factors for CVD, other co-morbid conditions
* Family HX of Diabetes and other endocrine disorders
* Lifestyle, cultural, psychological, educational, economic factors
* Tobacco, ETOH and other controlled substance use
* Contraceptive, reproductive and sexual Hx
42
What does the PE portion of a comprehensive evaluation of DM (I or II) consist of?
* Height, weight, BMI
* BP measurement, including orthostatic when indicated
* Fundoscopic exam
* Thyroid palpation
* Skin exam (acanthosis nigricans and insulin injection sites)
* Comprehensive foot exam
43
What does the comprehensive foot exam of DM (I or II) consist of?
* Annual!
* to identify risk factors predictive of ulcers and amputations
* Inspection
* Palpation of dorsalis pedis/posterior tibial pulses
* Presence /absence of patellar and Achilles reflexes
* Determination of proprioception, vibration perception threshold using 128-Hz tuning fork, and monofilament sensation using a 10-g monofilament
44
What does the laboratory evaluation of DM (I or II) consist of?
* A1C *(if none from last 3 mths)*
* Fasting Lipid Profile
* Liver Function tests
* Spot Urine Alb/Cr ratio
* Serum Creatinine in adults (in children if proteinuria is present and calculated GFR
* TSH in all Type 1, dyslipidemia or women over age of 50 years
45
What referrals may be needed for DM pts (I or II)?
* Eye care professional for yearly dilated eye exam
* Family planning for women of reproductive age
* Registered Dietitian for MNT
* DSME
* Dentist for comprehensive periodontal exam
* Mental health professional if needed
MNT= Medical nutrition therapy
DSME=Diabetes self management education
46
Mgmt of hyperglycemia: what elements support a more stringent approach?
* Low risk associated w/hypoglycemia
* Newly Dxed DM
* Long life expectancy
* No important comorbidities
* No established vascular complications
* Resources and support system readily available
47
Mgmt of hyperglycemia: what elements support a less stringent approach?
* high risk associated w/hypoglycemia
* Long-standing DM
* Short life expectancy
* Severe comorbidities
* Severe vascular complications
* Resources and support system limited
48
Major goal of the mgmt of DMII
maintain normoglycemia and to prevent complications.
49
A1c targets in DMII
(6. 0 - 6.5%) - younger, healthier
(7. 5 - 8.0%+) - older, comorbidities, hypoglycemia prone
50
Preprandia BS target for DM
80-130 mg/dL
51
Postprandial BS target for DMII
\<180 mg/dL
52
BP target for DMII
\<140/90 in most
\<130/80 in selected pts
53
LDL goal for DMII
\< 100
w/overt CVD \<70
54
TG goal for DMII
\<150
55
HDL goal for DMII
\>50
56
Urine Alb/Cr Ratio for DM II
\< 30
57
Pharmacologic options for DMII
* Sulfonylureas
* Non-Sulfonylurea Insulin Secretagogues
* Biguanides
* Thiazolidinediones
* α-Glucosidase Inhibitors
* Insulin
* DPP-4 Inhibitors
* Incretin Mimetics (GLP-1)/ Amylin Analogues
* SGLT-2 Inhibitors
58
Biguanides: MOA
* Activates AMP-kinase
* decrease Hepatic glucose production
* Increase insulin sensitivity – *often insulin resistance is the problem & not lack of insulin*
59
Biguanides: advantages
* Extensive experience
* No hypoglycemia
* Weight neutral
* ? decrease CVD
60
Biguanides: disadvantages
* Gastrointestinal
* Lactic acidosis
* B-12 deficiency
* Contraindications
61
Biguanides: cost
low
62
SUs / Meglitinides: MOA
* Closes KATP channels
* Stimulate insulin release through β cells
Meg: Quick peak, short duration compared to sulfonylureas
63
SUs / Meglitinides: Advantages
* Extensive experience
* decrease Microvasc. risk
64
SUs / Meglitinides: Disadvantages
* Hypoglycemia
* Weight gain
* Low durability
* ? Ischemic preconditioning
65
SUs / Meglitinides: Cost
Low
66
TZDs: MOA
* PPAR-g activator
* increase**** insulin sensitivity
67
TZDs: advantages
* No hypoglycemia
* Durability
* decreased TGs, increased HDL-C
* ? decreased CVD (pio)
68
TZDs disadvantages
* Gastrointestinal
* Dosing frequency
* Modest decrease in A1c
69
TZDs cost
high
70
a-GIs: MOA
* Inhibits a-glucosidase
* Slows carbohydrate absorption
71
a-GIs: Advantages
* No hypoglycemia
* Nonsystemic
* decreased Post-prandial glucose
* ? decreasedCVD events
72
a-GIs: Cost
Moderate
73
DPP-4 Inhibitors: MOA
* Inhibits DPP-4, suppress glucagon secretion
* Increases GLP-1, GIP, Increase glucose-dependent insulin release
74
DPP-4 inhibitors: Advantages
* No hypoglycemia
* Well tolerated
75
DPP-4 Inhibitors: disadvantages
* Modest decrease A1c
* ? Pancreatitis
* Urticaria
76
DPP-4 Inhibitors: cost
high
77
GLP-1 receptor agonists: MOA
* Activates GLP-1 R
* increased Insulin, decreased glucagon
* decreased gastric emptying
* increased **** satiety
78
GLP-1 receptor agonists: Advantages
* Weight loss
* No hypoglycemia
* ? Beta cell mass
* ? CV protection
79
GLP-1 receptor agonists: Disadvantages
* GI
* ? Pancreatitis
* Medullary ca
* Injectable
80
GLP-1 receptor agonists: cost
high
81
Amylin mimetics: MOA
* Activates amylin receptor
* decreased glucagon
* decreased gastric emptying
* increased satiety
82
Amylin mimetics: advantages
* Weight loss
* decreased PPG
83
Amylin mimetics: Disadvantages
* GI
* Modest decrease A1c
* Injectable
* Hypo w/ insulin
* Dosing frequency
84
Amylin mimetics: Cost
high
85
SGLT2 Inhibitors: MOA
* ****increased urinary excretion of glucose
* decreased reabsorption of glucose prox. segment of the convoluted tubule
## Footnote
*sodium / glc cotransporter 2*
86
SGLT2 Inhibitors: Advantages
* Weight loss
* No hypoglycemia
87
SGLT2 Inhibitors: Disadvantages
* UTIs
* Genital infections
88
SGLT2 Inhibitors: Cost
high
89
Can a point of care A1c be used for Dx?
No!
90
How do you titrate metformin and what do you tell pt when you start them on metformin?
MOA, SE, Titrate up by 500 mg in a week, take with the first bite of food or with meals
91
How often should BG be checked for pts using multiple insulin injections or insulin pump Tx?
3+ times daily
92
How often should BG be checked for pts using less freqent insulin injections, noninsulin tx, or medical nutrition therapy alone?
could be a useful guide, but no specific number given and may not be truly useful / cost-effective if not on insulin
93
What does HbA1c reflect?
reflects mean glycemia over the preceding 2-3 months
94
How often should A1c be checked?
adults at target: q6mths
kids: q3mths
95
How is glycemic control best judged?
combination of the patient’s self blood glc monitoring (SBGM) and the current A1C result
96
Meaning of A1c values - 6 to 12%
6 % 126 mg/dl
7 % 154 mg/dl
8 % 183 mg/dl
9 % 212 mg/dl
10 % 240 mg/dl
11 % 269 mg/dl
12 % 298 mg/dl
97
What are the general recommendations of medical nutrition therapy?
* **Individualized** meal planning include optimization of food choices to meet recommended dietary allowance/dietary reference intake for all micronutrients as needed to achieve treatment goals.
* For people with diabetes, it is unlikely one optimal mix of macronutrients for meal plans exists
* The best mix of carbohydrate, protein, and fat appears to vary depending on individual circumstances
98
Goals of Medical Nutrition Therapy
_Metabolic Control and Balance_
* Maintenance of as near-normal blood glucose levels as possible
* Prevention and treatment of acute and long-term complications of diabetes
* Achievement of optimal serum lipid levels
* Improvement of overall health through optimal nutrition
* Adequate calories for maintaining/attaining reasonable weights for adults, normal growth and development in children and adolescents, increased metabolic needs during pregnancy and lactation, or recovery from catabolic illnesses
99
Physical Acivity recommendatons for adults
* Adults 150 minutes of moderate physical activity over 3 days/ week….no 2 consecutive days w/o exercise
* resistance training twice a week (w/o contraindications)
* In Type 1 adjust the therapeutic regimen to allow safe participation in all forms of physical activity.
100
IZs for patients with DM
* Provide an influenza vaccine annually to all diabetic patients ≥6 months of age
* Administer pneumococcal polysaccharide vaccine 23 (PPSV23) to all diabetic patients ≥2 years
* For those _\>_ 65 not previously vaccinated receive the pneumococcal conjugate vaccine 13 (PCV13) followed by the PPSV23 in 6-12 months
* For those _\>_ 65 previously vaccinated PPSV23, receive \>12 months the PCV13
* Other indications for repeat vaccination: nephrotic syndrome, chronic renal disease, immunocompromised states
* Hepatitis B per CDC recommendations (19-59, consider 60+)
101
Recommended pharm therapy for diabetes & htn
ACEi or ARB
2+ drugs at max dose for BP targets
1+ antiHTN at bedtime
102
DMI + proteinuria + ACEi - outcome?
* ACEI’s were associated with a 50% reduction in the risk of death, dialysis, and transplantation.
103
How should neuropathy be screened for in DM pts?
How often?
* All patients should be screened for distal symmetric polyneuropathy (DPN) and for signs and symptoms of cardiovascular autonomic neuropathy
* At diagnosis of type 2 DM with 5 years after diagnosis of type 1
* At least annually thereafter using simple clinical tests
104
Oral therapies for neuropathy
Lyrica, Cymbalta, Gabapentin
Alpha lipoic Acid 600-1200mg QD
105
How / when should initial retinopathy screenings be done?
* Initial dilated and comprehensive eye examination by an ophthalmologist or optometrist
* Adults and children aged 10 years or older
with type 1 diabetes
* Within 5 years after diabetes onset
* Patients with type 2 diabetes
* Shortly after diagnosis of diabetes
- Women with preexisting diabetes/pregnancy
106
How / when should follow-up screenings be done for diabetic retinopathy?
* for type 1 and type 2 diabetic patients should be repeated annually by an ophthalmologist or optometrist
* Less frequent exams (every 2-3 years) may be considered following 1+ normal eye exams, if recommended by eye care professional
* Examinations will be required more frequently if retinopathy is progressing (B)
107
Eye exams in women with preexisting diabetes who are pregnant or planning to get pregnant - when and how?
* Comprehensive eye examination
* Counseled on risk of development and/or progression of diabetic retinopathy
* Eye examination should occur in the first trimester (B)
* Close follow-up throughout pregnancy
* For 1 year postpartum
108
How should nephropathy be screened for in DM?
* Assess urine albumin excretion annually
* In type 1 diabetic patients with diabetes duration of ≥5 years
* In all type 2 diabetic patients at diagnosis
* Measure serum creatinine at least annually
* In all adults with diabetes regardless of degree of urine albumin excretion
* Serum creatinine should be used to estimate GFR and stage level of chronic kidney disease, if present
109
Significance of high triglycerides in the setting of hyperglycemia
TRIG elevation may be related to the high glucose and once it normalizes the TRIG may normalize, but keep an eye on the lipids
110
Indications for Insulin Therapy in Patients With Type 2 Diabetes
* Maximal doses of oral agents do not control glucose levels
* Periods of acute injury, stress, infection, or surgery
* Presence of weight loss, ketonemia and/or ketonuria and/or severe hyperglycemic symptoms
* Pregnancy
* Renal disease
* Allergy or serious reaction to sulfa drugs
111
Recommendations for Insulin Therapy for Type 1?
Most people with type 1 diabetes should
* Be treated with MDI injections (3–4 injections per day of basal and prandial insulin) or continuous subcutaneous insulin infusion (CSII)
* Be educated in how to match prandial insulin dose to carbohydrate intake, premeal blood glucose, and anticipated activity
* Use insulin analogs to reduce hypoglycemia risk
112
Initial total daily dose for insulin, Type I?
0.4-1.0 u/kg of body weight
113
How many insulin injections per day recommended for DMI?
* Initially 3-4 injections per day in Type 1
* Basal –Bolus Therapy is recommended
114
How many insulin doses for DMII initially recommended?
Initially as bedtime insulin
115
What are the rapid / short acting insulins?
* Aspart (Novolog® - Novo Nordisk)
* Lispro (Humalog® - Eli Lilly)
* Glulisine (Apidra® - Sanofi Aventis)
* Regular Insulin ( Humulin – Eli Lilly, Novolin – Novo Nordisk)
116
What are the intermediate acting insulins?
* NPH (Humulin – Eli Lilly, Novolin – Novo Nordisk)
117
What are the long acting insulins?
Detemir (Levemir® - Novo Nordisk)
Glargine (Lantus® - Sanofi Aventis)
118
What are the mixed acting insulins?
* Humalog® 75/25 (Eli Lilly)
* Novolog® 70/30 (Novo Nordisk)
* 70/30 Mix ( Novolin -Novo Nordisk, Humulin – Eli Lilly)
119
Rapid-Acting: OPD
O: 5-10min
P: 3/4 - 1hr
D: 2hrs
120
Regular insulin: OPD
O: 0-1h
P: 2-4h
D: 4-6h
121
NPH: OPD
O: 1-4h
P: 6-10h
D: 12-20h
122
Detemir / Glargine: OPD
O: 1-2h
P: none
D: 24h
123
Treatmnt for hypoglycemia
* 15-30 gms of simple carbohydrate orally
* Check BG in 15-20 minutes
* Can repeat in 15 minutes with 10 -15 gm
* Snack of 1 protein and 1 carbohydrate 30 minutes later
* If severe and able to swallow then 30-45 gms simple carbohydrate
* If unable to swallow glucagon SQ
* IV Glucose
124
What are the three classes of hypoglycemia?
Mild, moderate, severe
125
What symptoms characterize mild hypoglycemia?
hunger weakness, shakiness, diaphoresis, pallor, tachycardia, irritability, difficulty concentrating
126
What symptoms characterize moderate hypoglycemia?
Impaired CNS function, decreased thinking ability, increased anger, irritability, some changes in mental status, may be able to treat.
127
What symptoms characterize severe hypoglycemia?
confusion, drowsiness, progression to seizure activity
128
Criteria for prediabetes Dx?
* FPG 100 to 125 mg/dL
OR
* 2-h PG in the 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT)
OR
* A1C 5.7–6.4%
\*For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher ends of the range.
