Diabetes (7 questions) Flashcards
Basic role of insulin
Regulates body’s balance of storage vs mobilization of body stores
Insulin: normal stimulation vs T2DM
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
Insulin in liver: normal vs T2DM
- 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
Insulin in skeletal muscle: normal vs T2DM
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
What is the renal threshold for hyperglycemia?
180 mg/dL - osmotic diuresis occurs leading to significant urinary losses of F & Es
–> progressive dehydration and hyperosmolality
Etiology of Type I DM
autoimmune mediated diabetes, insulin producing B-cells are destroyed by an autoimmune process.
Additional risks associated with DMI
increased incidence of other autoimmune diseases such as Hashimoto’s thyroiditis, graves disease, pernicious anemia, vitiligo, celiac disease and Addison’s Disease.
DMII etiology
strong family Hx - genetics & environment
MODY etiology
genetic defect in the b-cell. Genetic defects in insulin action.
Dz of exocrine pancreas that can lead to DM
pancreatitis, trauma, pancreatectomy, neoplasm, CF, hemochromatosis
Medications that may cause DMII
steroids, HIV meds and some of the psychotropic agents may induce DM.
Clinical manifestations of diabetes mellitus
- polyuria, polydipsia, polyphagia
- fatigue, blurred vision, headache, paresthesia, recurrent infections (UTI’s, candidiasis,etc.)
Polyuria: DDx
- 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
What is diabetes insipidus?
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.
What is primary polydipsia?
altered thirst perception with increased thirst and fluid intake followed by polyuria. Prevalent among patients with psychiatric history- i.e. schizophrenia.
What is an excess of counter-regulatory hormones?
excess of glucagon, growth hormone, cortisol, catecholamines
What is hyperaldosteronism?
production of salt retaining hormone aldosterone by an adrenal adenoma resulting in intravascular volume expansion and renin suppression.
What is hemochromatosis
disease manifested with high serum iron and ferritin levels, often requiring routine phlebotomy.
What drugs may cause polyuria?
e.g., corticosteroids, pentamadine, nicotinic acid, thyroid hormone, interferon, dilantin, thiazides
Types of Diabetes Mellitus
- 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
Lab work for Dx type I DM
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
What is LADA?
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
What is secondary diabetes?
- 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.
What is MODY?
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.
What constitutes “impaired fasting glucose”
BG 100 - 125
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.
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
How were OGTT, FPG and A1c numbers set for Dx of DM?
thresholds correlate with the presence of retinopathy, basis for these values
“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)
“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
- GDM Dx: 2+ of the following
*ACOG recommends lower threshold of 135 if high risk ethnic minority
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
PEak age for DMI
10-14 years
females 10-12, males 12-14
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.
Mainstays of mgmt for DMI
- Insulin therapy to obtain near normo-glycemia
- Diet sufficient for growth
- Exercise
- Psychological well being
- Prevention of complications
- Immunizations
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
Goal A1c for <8yo
<8 d/t risk of hypoglycemia
DMI: how often is A1c measured?
Quarterly
What is the “honeymoon period”
In DMI
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.
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
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)
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
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
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
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
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
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
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
Major goal of the mgmt of DMII
maintain normoglycemia and to prevent complications.
A1c targets in DMII
(6. 0 - 6.5%) - younger, healthier
(7. 5 - 8.0%+) - older, comorbidities, hypoglycemia prone
Preprandia BS target for DM
80-130 mg/dL
Postprandial BS target for DMII
<180 mg/dL
BP target for DMII
<140/90 in most
<130/80 in selected pts
LDL goal for DMII
< 100
w/overt CVD <70
TG goal for DMII
<150
HDL goal for DMII
>50
Urine Alb/Cr Ratio for DM II
< 30
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
Biguanides: MOA
- Activates AMP-kinase
- decrease Hepatic glucose production
- Increase insulin sensitivity – often insulin resistance is the problem & not lack of insulin
Biguanides: advantages
- Extensive experience
- No hypoglycemia
- Weight neutral
- ? decrease CVD
Biguanides: disadvantages
- Gastrointestinal
- Lactic acidosis
- B-12 deficiency
- Contraindications
Biguanides: cost
low
SUs / Meglitinides: MOA
- Closes KATP channels
- Stimulate insulin release through β cells
Meg: Quick peak, short duration compared to sulfonylureas
SUs / Meglitinides: Advantages
- Extensive experience
- decrease Microvasc. risk
SUs / Meglitinides: Disadvantages
- Hypoglycemia
- Weight gain
- Low durability
- ? Ischemic preconditioning
SUs / Meglitinides: Cost
Low
TZDs: MOA
- PPAR-g activator
- increase insulin sensitivity
TZDs: advantages
- No hypoglycemia
- Durability
- decreased TGs, increased HDL-C
- ? decreased CVD (pio)
TZDs disadvantages
- Gastrointestinal
- Dosing frequency
- Modest decrease in A1c
TZDs cost
high
a-GIs: MOA
- Inhibits a-glucosidase
- Slows carbohydrate absorption
a-GIs: Advantages
- No hypoglycemia
- Nonsystemic
- decreased Post-prandial glucose
- ? decreasedCVD events
a-GIs: Cost
Moderate
DPP-4 Inhibitors: MOA
- Inhibits DPP-4, suppress glucagon secretion
- Increases GLP-1, GIP, Increase glucose-dependent insulin release
DPP-4 inhibitors: Advantages
- No hypoglycemia
- Well tolerated
DPP-4 Inhibitors: disadvantages
- Modest decrease A1c
- ? Pancreatitis
- Urticaria
DPP-4 Inhibitors: cost
high
GLP-1 receptor agonists: MOA
- Activates GLP-1 R
- increased Insulin, decreased glucagon
- decreased gastric emptying
- increased satiety
GLP-1 receptor agonists: Advantages
- Weight loss
- No hypoglycemia
- ? Beta cell mass
- ? CV protection
GLP-1 receptor agonists: Disadvantages
- GI
- ? Pancreatitis
- Medullary ca
- Injectable
GLP-1 receptor agonists: cost
high
Amylin mimetics: MOA
- Activates amylin receptor
- decreased glucagon
- decreased gastric emptying
- increased satiety
Amylin mimetics: advantages
- Weight loss
- decreased PPG
Amylin mimetics: Disadvantages
- GI
- Modest decrease A1c
- Injectable
- Hypo w/ insulin
- Dosing frequency
Amylin mimetics: Cost
high
SGLT2 Inhibitors: MOA
- increased urinary excretion of glucose
- decreased reabsorption of glucose prox. segment of the convoluted tubule
sodium / glc cotransporter 2
SGLT2 Inhibitors: Advantages
- Weight loss
- No hypoglycemia
SGLT2 Inhibitors: Disadvantages
- UTIs
- Genital infections
SGLT2 Inhibitors: Cost
high
Can a point of care A1c be used for Dx?
No!
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
How often should BG be checked for pts using multiple insulin injections or insulin pump Tx?
3+ times daily
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
What does HbA1c reflect?
reflects mean glycemia over the preceding 2-3 months
How often should A1c be checked?
adults at target: q6mths
kids: q3mths
How is glycemic control best judged?
combination of the patient’s self blood glc monitoring (SBGM) and the current A1C result
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
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
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
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.
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+)
Recommended pharm therapy for diabetes & htn
ACEi or ARB
2+ drugs at max dose for BP targets
1+ antiHTN at bedtime
DMI + proteinuria + ACEi - outcome?
- ACEI’s were associated with a 50% reduction in the risk of death, dialysis, and transplantation.
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
Oral therapies for neuropathy
Lyrica, Cymbalta, Gabapentin
Alpha lipoic Acid 600-1200mg QD
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
- Adults and children aged 10 years or older
- Women with preexisting diabetes/pregnancy
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)
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
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
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
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
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
Initial total daily dose for insulin, Type I?
0.4-1.0 u/kg of body weight
How many insulin injections per day recommended for DMI?
- Initially 3-4 injections per day in Type 1
- Basal –Bolus Therapy is recommended
How many insulin doses for DMII initially recommended?
Initially as bedtime insulin
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)
What are the intermediate acting insulins?
- NPH (Humulin – Eli Lilly, Novolin – Novo Nordisk)
What are the long acting insulins?
Detemir (Levemir® - Novo Nordisk)
Glargine (Lantus® - Sanofi Aventis)
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)
Rapid-Acting: OPD
O: 5-10min
P: 3/4 - 1hr
D: 2hrs
Regular insulin: OPD
O: 0-1h
P: 2-4h
D: 4-6h
NPH: OPD
O: 1-4h
P: 6-10h
D: 12-20h
Detemir / Glargine: OPD
O: 1-2h
P: none
D: 24h
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
What are the three classes of hypoglycemia?
Mild, moderate, severe
What symptoms characterize mild hypoglycemia?
hunger weakness, shakiness, diaphoresis, pallor, tachycardia, irritability, difficulty concentrating
What symptoms characterize moderate hypoglycemia?
Impaired CNS function, decreased thinking ability, increased anger, irritability, some changes in mental status, may be able to treat.
What symptoms characterize severe hypoglycemia?
confusion, drowsiness, progression to seizure activity
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.
