- Email: [email protected]
CME Test Answer Sheet and Evaluation Form
Clinical Cornerstone
•
ABDOHINALADIPOSITYAND
CARDIOHETABOLIC
RISK
•
Vol. 8, Supplement4
CME Test Answer Sheet and Evaluation Form for ABDOMINAL
ADIPOSITY AND CARDIOMETABOLIC
RISK
Volume 8, Supplement 4 Release Date of Activity: November 2006 Expiration Date of Activity for A M A / P R A Credit: November 30, 2008 Estimated Time to Complete this Activity: 3.5 hour(s) Get instant C M E credit(s). Complete your test online and download your certificate now!
Log on to: www.elseviercme.com/getcme/cc/00711 Please Print
Name:
Specialty:
Degree: []MD []DO []PharmD []RPh []NP []RN []BS []PA []Other: Affiliation: Street: City:
State:
Telephone:
Fax:
E-mail:
Signature:
Zip:
(All information is confidential.) C M E Credit Verification
I verify that I have spent _ _
hour(s)/___ minutes of actual time working on this CME activity.
No more than 3.5 CME credit(s) will be issued for this activity. PRETEST ASSESSMENT." Please rate your current knowledge of cardiometabolic risk associated with abdominal adiposity on a scale of 1 to 5, with 1 being the lowest and 5 the highest.
I 2 3 4 5
CMETEST (Please circle correct answers.)
1. a b c d e
4. a b
7. a b
10. a b
2. a b
5. a b c d
8. a b c d
11. a b c d e
3. a b c d e
6. a b c d e
9. a b c d e
12. a b c d
13. a b c d
COURSE EVALUATION: Please evaluate the effectiveness o f this activity by circling your choice on a scale o f 1 to 5, with 1 being the lowest and 5 the highest.
1. The role of adipose tissue as a diverse, complex, and multifunctional endocrine organ.
I 2 3 4 5
2. How insulin resistance functions as a common factor in patients with generalized and regional obesity and in patients with genetic or acquired lipodystrophies.
I 2 3 4 5
3. The impact of excess adipose tissue, adipose tissue dysfunction, and adipose tissuesecreted proteins on insulin resistance and cardiometabolic risk.
I 2 3 4 5
4. The components of the endocannabinoid system (ECS), the functional effects of ECS hyperactivation on body weight regulation, and the negative influence of endocannabinoids on the production of certain adipocytokines that contribute to insulin resistance.
I 2 3 4 5
$39
Clinical Cornerstone
•
ABDOMINALADIPOSITYAND
CARDIOMETABOLIC
RISK
•
Vol. 8, Supplement4
5. Cannabinoid type 1 receptor antagonism as an effective pharmacologic strategy to improve cardiometabolic risk factors.
1 2 3 4 5
6. How do you rate the overall quality of the activity?
1 2 3 4 5
7. How do you rate the educational content of the activity?
1 2 3 4 5
8. Was the material presented in this publication fair, objective, balanced, and free of bias in the discussion of any commercial product or service? If no, please comment:
Yes
No
Yes
No
12. Would you be willing to participate in postactivity follow-up surveys?
Yes
No
13. Would you be willing to participate in a phone, e-mail, or in-person discussion exploring ways to improve our CME activities?
Yes
No
9. Suggested topics for future activities:
10. Suggested authors for future activities:
11. After reading this publication, have you decided to change one or more aspects in the treatment of your patients? If yes, what changes will you make? If no, why not?
The EOCME thanks you for your participation in this CME activity. All information provided
intproves the scope and purpose of our programs and your patients' care.
CME I N S T R U C T I O N S
log on to www.elseviercme.conffgetcme/cd00711. This Supplement to Clinical Cornerstone provides 3.5 free AMA PRA Category I Credits TM. Log on to the above URL to print your certificate now, or forward the Test Answer Sheet and Evaluation Form to the address shown below. Elsevier Office of Continuing Medical Education Department CC/00711 685 Route 202/206 Bridgewater, NJ 08807
Please allow 6 to 8 w e e k s for processing. A p h o t o c o p y of this form is acceptable. (Refer to pages $2-$4 for CME Information.) Responses for AMA PRA credit must be submitted by November 30, 2008.
S40
Clinical Cornerstone
•
ABDOHINALADIPOSITYAND
CARDIOHETABOLIC
RISK
•
Vol. 8, Supplement 4
CME Test Answers ABDOHINAL 1°
ADIPOSITY AND CARDIOHETABOLIC
hepatic steatosis) and skeletal muscles (leading to muscle steatosis) and, therefore, in hepatic and peripheral insulin resistance.
d°
The primaryfimction of adipose tissue is to store energy in the form of triglycerides during periods of energy excess and to release the energy during fasting or starvation as FFAs and glycerol. Hormone-sensitive lipase, an intracellular enzyme, hydrolyzes triglyceride stores in adipocytes and releases FFAs and glycerol into circulation as fuel for the whole body. FFAs released from adipose tissue contribute energy required by the skeletal muscles and substrates for triglyceride biosynthesis in hepatocytes, while glycerol contributes to gluconeogenesis in the liver or kidneys. Additional functions of adipose tissue include secretion of adipocytokines to regulate food intake, energy expenditure, fuel metabolism, and other physiologic processes. Conversion of testosterone and androstenedione to estrogen and estrone, respectively, also occurs principally in adipose tissue. Although this process, known as adipose tissue aromatization, is trivial in healthy adult men and women, with increasing body weight in older men and postmenopausal women, this process can have a substantial effect on estrogen levels. °
4°
b°
False. Although defining metabolic syndrome using criteria for generalized or regional adiposity such as body mass index and waist circumference generally may be appropriate for the population at large, patients with lipodystrophy may develop metabolic syndrome and complications related to insulin resistance (eg, type 2 diabetes, impaired glucose tolerance, hypertriglyceridemia, low levels of HDL-C, hepatic steatosis, acanthosis nigricans, polycystic ovary syndrome, and hyperuricemia) without being overtly obese. In obese patients, the amount of excess adipose tissue, as well as excess adipose tissue located in the subcutaneous truncal region and, possibly, the intra-abdominal region, determine the prevalence and severity of insulin resistance and its associated complications. In contrast, among patients with lipodystrophies, the extent of adipose tissue loss is the major determinant of insulin resistance and its complications.
ao
True. Excess adipose tissue in patients with generalized and regional obesity and markedly reduced adipose tissue in patients with various types of genetic or acquired lipodystrophies are associated with insulin resistance and its complications (eg, type 2 diabetes, hypertriglyceridemia, low levels of HDL-C, and hepatic steatosis). Early recognition of such patients, who are predisposed to metabolic complications, is critical to reducing disease burden. 3°
RISK
5°
b°
Lipodystrophies may be caused by genetic or acquired causes. Subtypes have been classified according to phenotypic and genotypic features, and the prevalence of the various components of metabolic syndrome varies among the different subtypes. Although patients with lipodystrophies have an increased prevalence of type 2 diabetes, dyslipidemia, and hepatic steatosis, a clear increase in the prevalence of hypertension has not been described. Hypertension has usually been reported after the onset of diabetic nephropathy.
d°
The underlying mechanisms by which adipose tissue disorders cause insulin resistance remain unclear; however, several hypotheses have been proposed. One hypothesis indicates that adipocytes in obese individuals are already packed, and patients with lipodystrophies are lacking sufficient adipocytes and therefore have limited capacity to store fat in nonlipodystrophic tissue. This limitation in triglyceride storage may result in aberrant storage of triglycerides in other organs, such as the liver (leading to
o
eo
During the last decade, our understanding of adipose tissue has evolved from that of an inert tissue for the storage of fat to an important player in the pathophysiology of disease. In addition to its role in the metabolic derangements that impair insulin sensitivity and result in type 2 diabetes, adipose tissue is now recognized as a dynamic endocrine $41
Clinical Cornerstone
•
ABDOMINAL
ADIPOSITY AND CARDIOMETABOLIC
RISK
•
Vol. g, Supplement4
CME Test Answers ABDOMINAL
ADIPOSITY AND CARDIOMETABOLIC
6-month study, obese nondiabetic women were given either sibutramine or orlistat to determine the effects of these agents on serum adipocytokines. Both drug regimens produced a decrease in C-reactive protein (CRP) levels and an increase in serum adiponectin. In a randomized, double-blind, placebo-controlled, Phase III clinical trial of overweight or obese patients with either hypertension or dyslipidemia, rimonabant produced significant improvements in plasma triglyceride and HDL-C levels; the ratio of total cholesterol to HDL-C; low-density lipoprotein particle size; adiponectin, insulin, and plasma CRP levels; glucose tolerance; and the proportion of patients with metabolic syndrome.
organ that has the potential to directly affect cardiovascular risk and the development of atherosclerosis. °
ao
True. Adipocytes are fat cells that secrete various bioactive proteins, collectively called adipokines or adipocytokinea'. Adipocytokines can exert local, peripheral, and central effects. Some of these bioactive proteins--for example, cytokines such as PAl-l, TNF-c~, and IL-6-contribute to a state of chronic systemic and local vascular inflammation and enhanced coagulation as the volume of adipose tissue expands. Other bioactive proteins, such as adiponectin, favorably attenuate the inflammatory milieu. 8o
11. e. One distinctive feature of endocannabinoids---endogenous CB receptor ligands--is "use-dependent synthesis." In contrast to classical neurotransmitters, endocannabinoids are not stored in vesicles. Instead, they are synthesized on demand in response to acute stimulation. The response is mediated through increased intracellular calcium concentrations that initiate endocannabinoid synthesis.
bo
As adipose tissue expands, the concentration of adiponectin decreases. Plasma concentrations of adiponectin have been observed to be significantly lower in obese persons than in persons of normal weight. Additionally, weight loss in obese individuals leads to increased adiponectin levels, whereas weight gain, and particularly an increase in visceral fat, is linked to a decrease in adiponectin levels. 9,
RISK
12. a.
Exogenous CBs and endocannabinoids increase food intake and promote weight gain in experimental animals through activation of central CB 1 receptors. Interestingly, food intake can be induced even in animals that have already been fed and by administration of endocannabinoids in brain regions not directly involved in food intake.
do
In a study by Pouliot et al, obese men and lean controls were compared with respect to risk factors for cardiovascular disease. The obese men with high visceral fat accumulation had a greater degree of glucose intolerance, increased insulin resistance, and higher triglyceride levels. They also had lower HDL-C levels than the controls.
13. a. The endocalmabinoid system may limit insulin sensitivity in skeletal muscles. Isolated skeletal muscle of rimonabant-treated obese mice was more sensitive to the effects of insulin on glucose uptake. This in vitro finding was closely linked to improved blood glucose levels in the treated animals. Future studies should determine whether improved muscle glucose uptake is due to direct effects of this agent or whether it is more related to body weight reduction and overall improvement of obesityassociated metabolic disturbances.
10. a.
True. Both lifestyle modification and drug therapy produce weight reductions and favorable changes in cardiovascular and metabolic risk factors. In the Finnish Diabetes Prevention Study, PAI-1 levels in patients following an intensive lifestyle modification program aimed at weight reduction, healthy diet, and increased physical activity were reduced by 31% during the first year; this reduction persisted throughout the 3-year follow-up. In a
S42
Clinical Cornerstone
•
ABDOHINALADIPOSITYAND
NOTES:
S43
C A R D I O H E T A B O L I C RISK
•
Vol. 8, Supplement 4
•
ABDOHINALADIPOSITYAND
CARDIOHETABOLIC
RISK
•
Vol. 8, Supplement4
CME Test Answer Sheet and Evaluation Form for ABDOMINAL
ADIPOSITY AND CARDIOMETABOLIC
RISK
Volume 8, Supplement 4 Release Date of Activity: November 2006 Expiration Date of Activity for A M A / P R A Credit: November 30, 2008 Estimated Time to Complete this Activity: 3.5 hour(s) Get instant C M E credit(s). Complete your test online and download your certificate now!
Log on to: www.elseviercme.com/getcme/cc/00711 Please Print
Name:
Specialty:
Degree: []MD []DO []PharmD []RPh []NP []RN []BS []PA []Other: Affiliation: Street: City:
State:
Telephone:
Fax:
E-mail:
Signature:
Zip:
(All information is confidential.) C M E Credit Verification
I verify that I have spent _ _
hour(s)/___ minutes of actual time working on this CME activity.
No more than 3.5 CME credit(s) will be issued for this activity. PRETEST ASSESSMENT." Please rate your current knowledge of cardiometabolic risk associated with abdominal adiposity on a scale of 1 to 5, with 1 being the lowest and 5 the highest.
I 2 3 4 5
CMETEST (Please circle correct answers.)
1. a b c d e
4. a b
7. a b
10. a b
2. a b
5. a b c d
8. a b c d
11. a b c d e
3. a b c d e
6. a b c d e
9. a b c d e
12. a b c d
13. a b c d
COURSE EVALUATION: Please evaluate the effectiveness o f this activity by circling your choice on a scale o f 1 to 5, with 1 being the lowest and 5 the highest.
1. The role of adipose tissue as a diverse, complex, and multifunctional endocrine organ.
I 2 3 4 5
2. How insulin resistance functions as a common factor in patients with generalized and regional obesity and in patients with genetic or acquired lipodystrophies.
I 2 3 4 5
3. The impact of excess adipose tissue, adipose tissue dysfunction, and adipose tissuesecreted proteins on insulin resistance and cardiometabolic risk.
I 2 3 4 5
4. The components of the endocannabinoid system (ECS), the functional effects of ECS hyperactivation on body weight regulation, and the negative influence of endocannabinoids on the production of certain adipocytokines that contribute to insulin resistance.
I 2 3 4 5
$39
Clinical Cornerstone
•
ABDOMINALADIPOSITYAND
CARDIOMETABOLIC
RISK
•
Vol. 8, Supplement4
5. Cannabinoid type 1 receptor antagonism as an effective pharmacologic strategy to improve cardiometabolic risk factors.
1 2 3 4 5
6. How do you rate the overall quality of the activity?
1 2 3 4 5
7. How do you rate the educational content of the activity?
1 2 3 4 5
8. Was the material presented in this publication fair, objective, balanced, and free of bias in the discussion of any commercial product or service? If no, please comment:
Yes
No
Yes
No
12. Would you be willing to participate in postactivity follow-up surveys?
Yes
No
13. Would you be willing to participate in a phone, e-mail, or in-person discussion exploring ways to improve our CME activities?
Yes
No
9. Suggested topics for future activities:
10. Suggested authors for future activities:
11. After reading this publication, have you decided to change one or more aspects in the treatment of your patients? If yes, what changes will you make? If no, why not?
The EOCME thanks you for your participation in this CME activity. All information provided
intproves the scope and purpose of our programs and your patients' care.
CME I N S T R U C T I O N S
log on to www.elseviercme.conffgetcme/cd00711. This Supplement to Clinical Cornerstone provides 3.5 free AMA PRA Category I Credits TM. Log on to the above URL to print your certificate now, or forward the Test Answer Sheet and Evaluation Form to the address shown below. Elsevier Office of Continuing Medical Education Department CC/00711 685 Route 202/206 Bridgewater, NJ 08807
Please allow 6 to 8 w e e k s for processing. A p h o t o c o p y of this form is acceptable. (Refer to pages $2-$4 for CME Information.) Responses for AMA PRA credit must be submitted by November 30, 2008.
S40
Clinical Cornerstone
•
ABDOHINALADIPOSITYAND
CARDIOHETABOLIC
RISK
•
Vol. 8, Supplement 4
CME Test Answers ABDOHINAL 1°
ADIPOSITY AND CARDIOHETABOLIC
hepatic steatosis) and skeletal muscles (leading to muscle steatosis) and, therefore, in hepatic and peripheral insulin resistance.
d°
The primaryfimction of adipose tissue is to store energy in the form of triglycerides during periods of energy excess and to release the energy during fasting or starvation as FFAs and glycerol. Hormone-sensitive lipase, an intracellular enzyme, hydrolyzes triglyceride stores in adipocytes and releases FFAs and glycerol into circulation as fuel for the whole body. FFAs released from adipose tissue contribute energy required by the skeletal muscles and substrates for triglyceride biosynthesis in hepatocytes, while glycerol contributes to gluconeogenesis in the liver or kidneys. Additional functions of adipose tissue include secretion of adipocytokines to regulate food intake, energy expenditure, fuel metabolism, and other physiologic processes. Conversion of testosterone and androstenedione to estrogen and estrone, respectively, also occurs principally in adipose tissue. Although this process, known as adipose tissue aromatization, is trivial in healthy adult men and women, with increasing body weight in older men and postmenopausal women, this process can have a substantial effect on estrogen levels. °
4°
b°
False. Although defining metabolic syndrome using criteria for generalized or regional adiposity such as body mass index and waist circumference generally may be appropriate for the population at large, patients with lipodystrophy may develop metabolic syndrome and complications related to insulin resistance (eg, type 2 diabetes, impaired glucose tolerance, hypertriglyceridemia, low levels of HDL-C, hepatic steatosis, acanthosis nigricans, polycystic ovary syndrome, and hyperuricemia) without being overtly obese. In obese patients, the amount of excess adipose tissue, as well as excess adipose tissue located in the subcutaneous truncal region and, possibly, the intra-abdominal region, determine the prevalence and severity of insulin resistance and its associated complications. In contrast, among patients with lipodystrophies, the extent of adipose tissue loss is the major determinant of insulin resistance and its complications.
ao
True. Excess adipose tissue in patients with generalized and regional obesity and markedly reduced adipose tissue in patients with various types of genetic or acquired lipodystrophies are associated with insulin resistance and its complications (eg, type 2 diabetes, hypertriglyceridemia, low levels of HDL-C, and hepatic steatosis). Early recognition of such patients, who are predisposed to metabolic complications, is critical to reducing disease burden. 3°
RISK
5°
b°
Lipodystrophies may be caused by genetic or acquired causes. Subtypes have been classified according to phenotypic and genotypic features, and the prevalence of the various components of metabolic syndrome varies among the different subtypes. Although patients with lipodystrophies have an increased prevalence of type 2 diabetes, dyslipidemia, and hepatic steatosis, a clear increase in the prevalence of hypertension has not been described. Hypertension has usually been reported after the onset of diabetic nephropathy.
d°
The underlying mechanisms by which adipose tissue disorders cause insulin resistance remain unclear; however, several hypotheses have been proposed. One hypothesis indicates that adipocytes in obese individuals are already packed, and patients with lipodystrophies are lacking sufficient adipocytes and therefore have limited capacity to store fat in nonlipodystrophic tissue. This limitation in triglyceride storage may result in aberrant storage of triglycerides in other organs, such as the liver (leading to
o
eo
During the last decade, our understanding of adipose tissue has evolved from that of an inert tissue for the storage of fat to an important player in the pathophysiology of disease. In addition to its role in the metabolic derangements that impair insulin sensitivity and result in type 2 diabetes, adipose tissue is now recognized as a dynamic endocrine $41
Clinical Cornerstone
•
ABDOMINAL
ADIPOSITY AND CARDIOMETABOLIC
RISK
•
Vol. g, Supplement4
CME Test Answers ABDOMINAL
ADIPOSITY AND CARDIOMETABOLIC
6-month study, obese nondiabetic women were given either sibutramine or orlistat to determine the effects of these agents on serum adipocytokines. Both drug regimens produced a decrease in C-reactive protein (CRP) levels and an increase in serum adiponectin. In a randomized, double-blind, placebo-controlled, Phase III clinical trial of overweight or obese patients with either hypertension or dyslipidemia, rimonabant produced significant improvements in plasma triglyceride and HDL-C levels; the ratio of total cholesterol to HDL-C; low-density lipoprotein particle size; adiponectin, insulin, and plasma CRP levels; glucose tolerance; and the proportion of patients with metabolic syndrome.
organ that has the potential to directly affect cardiovascular risk and the development of atherosclerosis. °
ao
True. Adipocytes are fat cells that secrete various bioactive proteins, collectively called adipokines or adipocytokinea'. Adipocytokines can exert local, peripheral, and central effects. Some of these bioactive proteins--for example, cytokines such as PAl-l, TNF-c~, and IL-6-contribute to a state of chronic systemic and local vascular inflammation and enhanced coagulation as the volume of adipose tissue expands. Other bioactive proteins, such as adiponectin, favorably attenuate the inflammatory milieu. 8o
11. e. One distinctive feature of endocannabinoids---endogenous CB receptor ligands--is "use-dependent synthesis." In contrast to classical neurotransmitters, endocannabinoids are not stored in vesicles. Instead, they are synthesized on demand in response to acute stimulation. The response is mediated through increased intracellular calcium concentrations that initiate endocannabinoid synthesis.
bo
As adipose tissue expands, the concentration of adiponectin decreases. Plasma concentrations of adiponectin have been observed to be significantly lower in obese persons than in persons of normal weight. Additionally, weight loss in obese individuals leads to increased adiponectin levels, whereas weight gain, and particularly an increase in visceral fat, is linked to a decrease in adiponectin levels. 9,
RISK
12. a.
Exogenous CBs and endocannabinoids increase food intake and promote weight gain in experimental animals through activation of central CB 1 receptors. Interestingly, food intake can be induced even in animals that have already been fed and by administration of endocannabinoids in brain regions not directly involved in food intake.
do
In a study by Pouliot et al, obese men and lean controls were compared with respect to risk factors for cardiovascular disease. The obese men with high visceral fat accumulation had a greater degree of glucose intolerance, increased insulin resistance, and higher triglyceride levels. They also had lower HDL-C levels than the controls.
13. a. The endocalmabinoid system may limit insulin sensitivity in skeletal muscles. Isolated skeletal muscle of rimonabant-treated obese mice was more sensitive to the effects of insulin on glucose uptake. This in vitro finding was closely linked to improved blood glucose levels in the treated animals. Future studies should determine whether improved muscle glucose uptake is due to direct effects of this agent or whether it is more related to body weight reduction and overall improvement of obesityassociated metabolic disturbances.
10. a.
True. Both lifestyle modification and drug therapy produce weight reductions and favorable changes in cardiovascular and metabolic risk factors. In the Finnish Diabetes Prevention Study, PAI-1 levels in patients following an intensive lifestyle modification program aimed at weight reduction, healthy diet, and increased physical activity were reduced by 31% during the first year; this reduction persisted throughout the 3-year follow-up. In a
S42
Clinical Cornerstone
•
ABDOHINALADIPOSITYAND
NOTES:
S43
C A R D I O H E T A B O L I C RISK
•
Vol. 8, Supplement 4