DM: Management and Therapies Flashcards
Level of plasma glucose at which symptoms of diabetes usually resolve
<200 mg/dL (11.1 mmol/L)
Guidelines for Ongoing, Comprehensive Medical Care for Patients with Diabetes:
Frequency of HbA1c testing
2-4 times/year
Guidelines for Ongoing, Comprehensive Medical Care for Patients with Diabetes:
Frequency of diabetes-related eye examination
Annual or biannual
Guidelines for Ongoing, Comprehensive Medical Care for Patients with Diabetes:
Frequency of diabetes-related foot examination
1-2 times/year by provider; daily by patient
Guidelines for Ongoing, Comprehensive Medical Care for Patients with Diabetes:
Frequency of diabetes-related neuropathy examination
Annual
Guidelines for Ongoing, Comprehensive Medical Care for Patients with Diabetes:
Frequency of diabetes-related kidney disease testing
Annual
Guidelines for Ongoing, Comprehensive Medical Care for Patients with Diabetes:
Frequency of blood pressure assessment
Quarterly
Guidelines for Ongoing, Comprehensive Medical Care for Patients with Diabetes:
Frequency of lipids assessment
Annual
Treatment Goals for Adults with Diabetes:
HbA1c (primary goal)
<7.0%
Diabetes Control and Complications Trial-based assay
Treatment Goals for Adults with Diabetes:
Preprandial capillary plasma glucose
80-130 mg/dL (4.4-7.2 mmol/L)
Treatment Goals for Adults with Diabetes:
Postprandial capillary plasma glucose (1-2 h after beginning of a meal)
<180 mg/dL (10.0 mmol/L)
Treatment Goals for Adults with Diabetes:
Blood pressure
<140/90 mmHg
Primary measures of medical nutrition therapy (MNT) are directed at:
Preventing or delaying the onset of type 2 DM in high-risk individuals by promoting weight reduction
Secondary measures of medical nutrition therapy (MNT) are directed at:
Improving glycemic control
Tertiary measures of medical nutrition therapy (MNT) are directed at:
Managing diabetes-related complications
Goal of MNT in type 1 DM:
To coordinate and match the caloric intake, both temporally and quantitatively, with the appropriate amount of insulin
Goal of MNT in type 2 DM:
Focus on weight loss and address the greatly increased prevalence of cardiovascular risk factors (hypertension, dyslipidemia, obesity) and disease in this population
Nutritional Recommendations for Adults with Diabetes or Prediabetes:
General dietary guidelines
Vegetable, fruits, whole grains, legumes, low-fat dairy products in food higher in fiber and lower in glycemic content
Nutritional Recommendations for Adults with Diabetes or Prediabetes:
Fat in diet
Mediterranean-style diet rich in monounsaturated fatty acids
Minimal trans fat consumption
Nutritional Recommendations for Adults with Diabetes or Prediabetes:
Carbohydrate in diet
- Monitor carbohydrate intake in regard to calories
- Sucrose-containing foods may be consumed with adjustments in insulin dose, but minimize intake
- Estimate grams of carbohydrate in diet (type 1 DM)
- Consider using glycemic index to predict how consumption of a particular food may affect blood glucose
- Fructose preferred over sucrose
Nutritional Recommendations for Adults with Diabetes or Prediabetes:
Other components
Reduced-calorie and nonnutritive sweeteners may be useful
Routine supplements of vitamins, antioxidants, or trace elements not supported by evidence
Sodium intake as advised for general population
ADA recommendation on exercise
150 min/week (distributed over at least 3 days) of moderate aerobic physical activity with no gaps longer than 2 days
Reminders to avoid exercise-related hyper- or hypoglycemia in type 1 DM (6)
- Monitor blood glucose before, during, and after exercise
- Delay exercise if blood glucose is >250mg/dL (14mmol/L) and ketones are present
- If the blood glucose is <100mg/dL (5.6mmol/L), ingest carbohydrate before exercising
- Monitor glucose during exercise and ingest carbohydrate to prevent hypoglycemia
- Decrease insulin doses (based on previous experience) before and after exercise and inject insulin into a nonexercising area
- Learn individual glucose responses to different types of exercise
TRUE OR FALSE: Untreated proliferative retinopathy is a relative contraindication to vigorous exercise.
TRUE, because this may lead to vitreous hemorrhage or retinal detachment.
Glycated hemoglobin (HbA1c) reflects the glycemic history over the previous ___ months
2-3 (Because erythrocytes have an average life span of 120 days)
Glycemic level in the preceding month contributes about __% to the HbA1c value.
50%
HbA1c approximation of mean plasma glucose
HbA1c 6% = 126 mg/dL HbA1c 7% = 154 mg/dL HbA1c 8% = 183 mg/dL HbA1c 9% = 212 mg/dL HbA1c 10% = 240 mg/dL HbA1c 11% = 269 mg/dL HbA1c 12% = 298 mg/dL
*Remember HbA1c 6% is equal to 126 mg/dL, then +28 thereafter
Clinical conditions leading to abnormal RBC parameters that may alter the HbA1c result (5)
Hemoglobinopathies, anemias, reticulocytosis, transfusion, and uremia
Fructosamine assaycan be used to assess the glycemic status. It measures glycated ______
Albumin
Fructosamine assay reflects the glycemic status over the prior _________
2 weeks
measures glycated albumin
General guidelines for glycemic control and CVD risk (4)
- Early in the course of type 2 diabetes when the CVD risk is lower, improved glycemic control likely leads to improved cardiovascular outcome, but this benefit may occur more than a decade after a period of improved glycemic control
- Intense glycemic control in individuals with established CVD or at high risk for CVD is not advantageous, and may be deleterious, over a follow-up of 3-5 years
- Hypoglycemia in such high-risk populations (elderly, CVD) should be avoided
- Improved glycemic control reduces microvascular complications of diabetes even if it does not improve macrovascular complications like CVD
Usual insulin formulation in the US:
- In general
- Short-acting
- Long acting
- Most insulin U-100 (100 units/mL)
- Short acting U-200 (200 units/mL)
- Long-acting U-300 (300 units/mL)
Insulin lispro is an insulin analogue with the following amino acid modification:
28th and 29th amino acids (lysine and proline) on the insulin B chain have been reversed by recombinant DNA technology
Insulin glargine is a biosynthetic human insulin that differs from normal insulin in that:
Asparagine is replaced by glycine at amino acid 21, and two arginine residues are added to the C terminus of the B chain, leading to the formation of microprecipitates at physiologic pH in subcutaneous tissue
Insulin detemir has a long duration of action because:
It has a fatty acid side chain that reversibly binds to albumin and prolongs its action by slowing absorption and catabolism
Insulin degludec has a long duration of action because:
It has a modification and extension in the carboxy-terminal terminus of the B chain, which forms multihexamers in subcutaneous tissue and ends albumin
Guidelines in mixing insulins (4)
- Mix the different insulin formulations in the syringe immediately before injection (inject within 2 min after mixing)
- Do not store insulin as a mixture
- Follow the same routine in terms of insulin mixing and administration to standardize the physiologic response to injected insulin
- Do not mix insulin glargine, detemir, or degludec with other insulins
What do we need to check prior to the use of inhaled insulin
Forced expiratory volume in 1 second (FEV1)
Because it can cause bronchospasm and cough, and hence should not be used in individuals with lung disease or who smoke
What are the short-acting insulins, and what are their onset, peak, and effective duration?
(Onset --- Peak --- Duration in Hours) Aspart <0.25 --- 0.5-1.5 --- 2-4 Glulisine <0.25 --- 0.5-1.5 --- 2-4 Lispro <0.25 --- 0.5-1.5 --- 2-4 Regular 0.5-1.0 --- 2-3 --- 3-6 Inhaled human insulin 0.5-1.0 --- 2-3 --- 3
What are the long-acting insulins, and what are their onset, peak, and effective duration?
(Onset --- Peak --- Duration in Hours) Degludec 1-9 --- minimal peak --- 42 Detemir 1-4 --- minimal peak --- 12-24 Glargine 2-4 --- minimal peak --- 20-24 NPH 2-4 --- 4-10 --- 10-16
How many minutes before a meal should the short-acting and regular insulins be injected?
Short-acting insulin analogues: Just before a meal (<10 mins) - sometimes injected just after a meal if with gastroparesis or unpredictable food intake
Regular insulin: 30-45 minutes prior to a meal
Insulin requirement in type 1 DM in general
0.4-1 units/kg per day divided into multiple doses, with ~50% given as basal insulin
Common insulin to carbohydrate ratio in type 1 DM
1 unit insulin per 10-15 g of carbohydrate
General assumptions on the effect of insulin regimen on self-monitored blood glucose (4)
- The fasting glucose is primarily determined by the prior evening long-acting insulin
- The prelunch glucose is a function of the morning short-acting insulin
- The presupper glucose is a function of the morning long-acting insulin
- The bedtime glucose is a function of the presupper, short-acting insulin
What is the “dawn phenomenon”?
It refers to periodic episodes of hyperglycemia occurring in the early morning that is caused by the release of growth hormone, cortisol, and catecholamines, that is not adequately counteracted due to decreased insulin secretion (not from Harrison’s)
What is the “Somogyi effect”?
It refers to hyperglycemia in the morning that occurs as a compensatory response to hypoglycemia during sleep (hence also called rebound hyperglycemia) (not from Harrison’s)
Agents Used for Treatment of Type 1 or Type 2 Diabetes
PLEASE READ TABLE 397-5 ON PAGE 2866 (hahaha)
Which 2 agents cause a 1-2% reduction in HbA1c?
Biguanides and Sulfonylureas
Which intervention leads to a 1-3% reduction in HbA1c?
Medical nutrition therapy and physical activity
Which anti-DM medication causes vitamin B12 deficiency?
Biguanides (metformin)
Which anti-DM medication causes angioedema or urticarial and immune-mediated dermatologic effects?
DPP-IV inhibitors (i.e. sitagliptin, vildagliptin, linagliptin)
Which anti-DM medication causes fractures and macular edema?
Thiazolidinediones (i.e. pioglitazone, rosiglitazone)
Which anti-DM medication causes peripheral edema and CHF?
Thiazolidinediones (i.e. pioglitazone, rosiglitazone)
Which anti-DM medication is contraindicated in CHF?
Thiazolidinediones (i.e. pioglitazone, rosiglitazone)
Which anti-DM medication is contraindicated in people who take agents that slow GI motility?
Amylin agonists (i.e. pramlintide) and GLP-1 receptor agonists (i.e. exenatide, liraglutaide)
Which anti-DM medication is contraindicated in medullary carcinoma of the thyroid, multiple endocrine neoplasia, and pancreatic disease?
GLP-1 receptor agonists (i.e. exenatide, liraglutaide)
Mechanism of action of biguanides
Decrease hepatic glucose production
Mechanism of action of alpha-glucosidase inhibitors
Decrease GI glucose absorption
Mechanism of action of dipeptidyl peptidase IV inhibitors
Prolong endogenous GLP-1 action; Increase insulin and decrease glucagon
Mechanism of action of insulin secretagogues
Increase insulin secretion
Mechanism of action of sodium-glucose cotransporter 2 inhibitors
Increase renal glucose excretion
Mechanism of action of thiazolidinediones
Decrease insulin resistance, increase glucose utilization (by binding to the peroxisome proliferator-activated receptor gamma (PPAR-gamma) nuclear receptor)
Mechanism of action of amylin agonists
Slow gastric emptying, decrease glucagon
Mechanism of action of GLP-1 receptor agonists
Increase insulin, decrease glucagon, slow gastric emptying, satiety
Mechanism of action of insulin
Increase glucose utilization, decrease hepatic glucose production, and other anabolic actions
Mechanism of action of medical nutrition therapy and physical activity
Decrease insulin resistance, increase insulin secretion
TRUE OR FALSE: Biguanides and thiazolidinediones are effective in type 1 DM and can be used for severely ill individuals with type 2 DM.
FALSE
Glucose-lowering agents other than insulin (with the exception of amylin analogue) are ineffective in type 1 DM and should not be used for glucose management of severely ill individuals with type 2 DM.
How frequently can we escalate metformin dose and what is the maximally tolerated dose?
Every 1-2 weeks
2000 mg daily
Recommendation of the National Institute for Health and Clinical Excellence in the United Kingdom on the use of metformin in decreased GFR
Metformin may be safe at GFR >30 mL/min, with a reduced dose when the GFR is <45 mL/min
All sulfonylureas have a low affinity for the isoform of ATP-sensitive potassium channels in the myocardium and the brain, and hence might increase CV risk, EXCEPT
Glyburide
Second-generation sulfonylureas differ from first-generation such that…
More rapid onset of action
Better coverage of postprandial glucose rise
Shorter half-life (may require more than once a day dosing)
Exenatide, a GLP-1 analogue, is a synthetic version of a peptide initially identified in which body secretion of which animal?
Saliva of the Gila monster (exendin-4)
What is the limiting side effect of GLP-1 receptor agonists?
Nausea
Which oral DM medication may increase levels of sulfonylureas and increase the incidence of hypoglycemia?
Alpha glucosidase inhibitors
The prototype of this class of drugs has been withdrawn from the US market due to reports of hepatotoxicity and an association with an idiosyncratic liver reaction
Thiazolidinediones (prototype is troglitazone)
The sodium-glucose co-transporter 2 is expressed in which part of the kidney?
Proximal convoluted tubule
SGLT2 inhibitors are associated with how much reduction in the systolic blood pressure?
3-6 mmHg
Which anti-DM medication is contraindicated in patients with type 1 DM or pancreatogenic forms of DM associated with insulin deficiency?
SGLT2 inhibitors (because inhibition of SGLT2 on the alpha cell may lead to increased glucagon and consequently liver production of glucose and ketones)
Which anti-DM meds have been associated with a possible increased risk of bladder cancer?
Dapagliflozin and Pioglitazone
Which bile-acid binding resin, which has been approved for treatment of type 2 DM, should be used cautiously in patients with a tendency for hypertriglyceridemia?
Colesevelam
What is the usual initial dose and timing of insulin in type 2 DM?
Long acting insulin 0.2-0.4 U/kg per day given in the evening or just before bedtime (then adjusted in 10% increments as dictated by SMBG)
Which of the oral anti-DM meds are more effective in type 2 DM?
Insulin secretagogues, biguanides, GLP-1 receptor agonists, and thiazolidinediones improve glycemic control to a similar degree (1-2% reduction in HbA1c) and are more effective than alpha-glucosidase inhibitors, DPP-IV inhibitors, and SGLT2 inhibitors.
Which of the oral anti-DM meds have a more immediate effect?
Insulin secretagogues, GLP-1 receptor agonists, DPP-IV inhibitors, alpha glucosidase inhibitors, and SGLT2 inhibitors begin to lower the plasma glucose immediately, whereas the glucose-lowering effects of the biguanides and thiazolidinediones are delayed by weeks.
Which oral anti-DM meds do not directly cause hypoglycemia?
Biguanides Alpha glucosidase inhibitors GLP-1 receptor agonists DPP-IV inhibitors Thiazolidinediones SGLT2 inhibitors
What is the ADA recommendation on metabolic/bariatric surgery?
ADA clinical guidelines state that metabolic surgery should be considered in individuals with type 2 DM and a BMI 30 kg/m2 if hyperglycemia is inadequately controlled despite optimal medical therapy
Which anti-DM meds cause weight gain?
Insulin
Insulin secretagogues
Thiazolidinediones
What are the indications for measuring ketones in individuals with type 1 DM?
- When plasma glucose >250 mg/dL
- During a concurrent illness
- Nausea, vomiting, abdominal pain
Which is preferred for ketone testing, blood or urine?
Blood measurement of beta-hydroxybutyrate is preferred over urine testing with nitroprusside-based assays that measure only acetoacetate and acetone.
Which between DKA and HHS is more frequently seen in type 1 and type 2 DM?
Type 1 DM - DKA
Type 2 DM - HHS
What is the pathophysiology behind DKA?
DKA results from relative or absolute insulin deficiency combined with counterregulatory hormone excess (glucagon, catecholamines, cortisol, and growth hormone).
Enzyme that is crucial for regulating fatty acid transport into the mitochondria, where beta oxidation and conversion to ketone bodies occur
Carnitine palmitoyltransferase I
Primary laboratory findings in DKA
- Hyperglycemia (glucose >250 mg/dL)
- Ketosis
- Metabolic acidosis (serum bicarbonate <15 mmol/L with increased anion gap)
During hyperglycemia, how much is sodium decreased?
1.6 mmol/L (1.6 meq) reduction in serum sodium for each 5.6 mmol/L (100mg/dL) rise in serum glucose
Which medications can cause a false-positive reaction to the nitroprusside test?
Captopril and penicillamine
Fluid replacement in DKA
2-3L of 0.9% saline over first 1-3 h (10-20ml/kg per hour); then 0.45% saline at 250-500ml/h; then 5% glucose and 0.45% saline at 150-250 ml/h when plasma glucose reaches 250 mg/dL
Initial insulin given in DKA
Short-acting regular insulin 0.1units/kg IV, then 0.1units/kg per hour by continuous IV infusion
Usual rate of improvement of hyperglycemia in DKA
4.2-5.6 mmol/L (50-100mg/dL) per hour
What is the major nonmetabolic complication of DKA therapy?
Cerebral edema (most often develops in children as DKA is resolving; caused by overreplacement of free water and rapid normalization of serum glucose)
What is the underlying pathophysiology in HHS?
Relative insulin deficiency and inadequate fluid intake
Most notable laboratory findings in HHS
- Marked hyperglycemia (>1000 mg/dL)
- Hyperosmolality (>350 mosmol/L)
- Prerenal azotemia
Which RCT found an increased mortality rate and a greater number of episodes of severe hypoglycemia with very strict glycemic control in ICU patients compared to a moderate glycemic control?
Normoglycemia in Intensive Care Evaluation Survival Using Glucose Algorithm Regulation (NICE-SUGAR)
ADA recommendations on the glycemic goals for hospitalizated patients
- In critically or non-critically ill patients: 140-180 mg/dL
- In selected patients: 110-140 mg/dL with avoidance of hypoglycemia
When can we safely discontinue insulin infusion after giving long-acting insulin? (hours)
2-4 hours after giving long-acting insulin
In order for DM to be called “steroid-induced diabetes”, new-onset hyperglycemia must occur during chronic treatment with supraphysiologic doses of glucocorticoid defined as…
> 5mg of prednisone or equivalent
(Effects of glucocorticoids on glucose homeoastasis are dose-related, usually reversible, and most pronounced in the postprandial period)
True or False: Glucose and insulin cross the placenta and affect the developing fetus.
False. Glucose readily crosses the placenta but insulin does not.
Increased insulin requirements in pregnancy is caused by
Marked insulin resistance
Which oral anti-DM meds have shown efficacy and no toxicity in pregnant patients in some studies?
Metformin and glyburide
Which class of HIV medications have been associated with a centripetal accumulation of fat, accumulation of fat in the dorsocervical region, loss of extremity fat, decreased insulin sensitivity, and dyslipidemia?
Protease inhibitors
Amino acid modification in insulin glulisine
The asparagine at position B3 is replaced by lysine and the lysine in position B29 is replaced by glutamic acid (not from Harrison’s)
Amino acid modification in insulin aspart
The proline at position B28 is replaced with the charged aspartic acid (not from Harrison’s)
This class of drugs reduce insulin resistance by binding to the peroxisome proliferator-activated receptor gamma (PPAR-gamma) nuclear receptor
Thiazolidinediones (i.e. pioglitazone, rosiglitazone)
Which class of anti-DM meds promote a redistribution of fat from central to peripheral locations?
Thiazolidinediones (i.e. pioglitazone, rosiglitazone)
Thiazolidinediones reduce insulin resistance by binding to which receptor?
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) nuclear receptor
Sodium-glucose co-transporter 2 is expressed almost exclusively in which part of the kidney?
Proximal convoluted tubule
