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Endocrinology Treatment Updates

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Mealtime Glucose Excursions and Glycemic Control in Type 2 Diabetes  CME

Edward Horton, MD

http://www.medscape.com/Medscape/Endocrinology/TreatmentUpdate/2000/tu01/public/toc-tu01.html

Valid for CME until January 7, 2001

If you cannot register online and complete the activity, you may also receive credit by mailing your completed Registration form, Post Test and Evaluation Forms to:

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Goal

The goal of this Treatment Update is to provide an overview of the pathogenesis of type 2 diabetes and how postprandial hyperglycemia affects overall glycemic control. An overview of therapeutic strategies that target physiologic mealtime insulin requirements will be presented.

Learning Objectives

Mealtime Glucose Excursions and Glycemic Control in Type 2 Diabetes is intended for physicians and pharmacists.

Upon completion of this self-study activity, participants will be able to:

  1. Outline the major metabolic defects that contribute to hyperglycemia in type 2 diabetes
  2. Describe the insulin secretory response to a meal in type 2 diabetes
  3. Explain how postprandial hyperglycemia contributes to overall glycemic control
  4. Discuss the rationale for tailoring treatment to mealtime glucose excursions
  5. Review strategies that reduce postprandial glucose excursions and, as a result, improve overall glycemic control

Eligibility for Credit

Continuing education credit will be awarded to US physicians, physician assistants, and pharmacists who successfully complete this activity as described in the section Instructions for Credit. For all other medical professionals who successfully complete this activity, Medscape will issue a Letter of Completion. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing boards.

Instructions for Credit

Participation in this self-study activity should be completed in approximately one (1) hour. There are no fees for participating and receiving CME credit for this activity. To successfully complete this activity and receive credit, participants must follow these steps during the period January 7, 2000 through January 7, 2001.

  1. Register for continuing education credit by completing the "registration" process.

  2. Read the learning objectives.

  3. Read the article text and tables, and review figures.

  4. Read, complete, and submit answers to the post test questions and evaluation questions. Participants must receive a test score of at least 70%, and respond to all evaluation questions to receive certificate by mail. Certificates will be electronically mailed to all eligible participants upon successful completion of the post test and submission of the activity evaluation for this activity. Certificates will be mailed to all eligible participants within 4-6 weeks of completion of this activity to those participants who are unable to print the certificate or who submit the post test and evaluation form for this activity using regular mail.

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Table of Contents

Abstract

Type 2 diabetes mellitus is characterized by a transition from normal glucose tolerance, to impaired glucose tolerance, to overt diabetes. There is convincing evidence that the risk of developing microvascular complications of diabetes, including retinopathy, nephropathy, and neuropathy, is related to the degree of hyperglycemia. Type 2 diabetes is also associated with an increased morbidity and mortality from macrovascular disease, including coronary artery disease, peripheral vascular disease, and stroke. Postprandial hyperglycemia contributes substantially to overall glycemic control, and in general, its role in the pathogenesis of the long-term microvascular and macrovascular complications of diabetes has been underestimated. It has been recognized that neither sulfonylureas nor regular insulin can create the appropriately brief increases in insulin secretion that normally occur in response to meals. Therefore, pharmacologic agents with a shorter onset and duration of action have been developed to more closely approximate the normal insulin response to meals to reduce postprandial hyperglycemia. This approach offers patients the ability to establish tight control of blood glucose levels and allows patients to be more flexible with their day-to-day calorie intake. This treatment update will review strategies that reduce postprandial glucose excursions and as a result, improve overall glycemic control.

Introduction

Type 2 diabetes mellitus is associated with substantial morbidity and mortality from microvascular and macrovascular complications. The risk of developing diabetic microvascular complications is related to the degree of hyperglycemia, with the risk increasing at values only slightly above the normal range for hemoglobin A1c (HbA1c) and progressively increasing as hyperglycemia worsens.[1] There does not appear to be a threshold glucose level for microvascular complications that is significantly above the accepted upper limits of normal for fasting and postprandial glucose concentrations.[2-4]

Based on the results of the Diabetes Control and Complications Trial (DCCT)[4,5] in patients with type 1 diabetes, as well as the Kumomoto Study [6] and the United Kingdom Prospective Diabetes Study (UKPDS)[7] in patients with type 2 diabetes, it is generally accepted that intensive treatment that achieves normal blood glucose levels minimizes the risk of developing long-term complications of diabetes. Improving glycemic control can prevent microvascular complications of both type 1[4] and type 2 diabetes.[8] Although the relationship between macrovascular disease and glycemic control is less clear than it is for microvascular disease, hyperglycemia is a significant risk factor for developing macrovascular disease in type 2 diabetes.[2,9,10] In the UKPDS, there was a nonsignificant 16% reduction in risk of myocardial infarction in the intensively treated group compared with those treated by conventional modalities.[7]

Etiology of Hyperglycemia

In recent years, our understanding of the pathophysiology of type 2 diabetes has increased dramatically. As illustrated in Figure 1, there are 3 major metabolic defects that contribute to hyperglycemia in type 2 diabetes.[11,12]

Figure 1. Metabolic defects of type 2 diabetes.

First, insulin-stimulated glucose uptake in insulin-sensitive tissues, particularly skeletal muscle and adipose tissue, is decreased as a result of insulin resistance. Second, there is increased hepatic glucose output in the fasting state and decreased suppression of hepatic glucose output following meals. This phenomenon is thought to be a manifestation of insulin resistance in the liver and is a major contributor to both fasting and postprandial hyperglycemia. Third, a defect in beta-cell function results in abnormal insulin secretion in response to a glucose stimulus. It appears that insulin resistance and decreased beta-cell response to glucose occur early in the pathogenesis of diabetes.[13,14]

In nondiabetic individuals, the beta-cell response to an insulin secretagogue is biphasic, with an early burst of insulin release occurring during the first 10 minutes after a stimulus, followed by a second-phase insulin secretion that is characterized by a sustained increase in insulin release that may last several hours.[15] Whereas the early event appears to represent the release of preformed insulin, the later phase may reflect the release of newly synthesized insulin in response to continued beta-cell stimulation. An early defect in the development of diabetes is the loss of the early or first-phase insulin secretion following food ingestion or glucose administration.[13,16,17] This results in a delayed and late-peaking plasma insulin profile, which is associated with decreased glucose tolerance. As type 2 diabetes progresses, there is a gradual deterioration of beta-cell function that results in a loss of both the early and later phases of insulin secretion.[18]

During the early stages of type 2 diabetes, the transition from normal to impaired glucose tolerance and finally to overt type 2 diabetes is primarily associated with episodes of postprandial hyperglycemia.[19] Once diabetes is established, there is a progressive worsening of hyperglycemia in both the fasting and the postprandial state.

First-phase Insulin Secretion and Normal Glucose Tolerance

The importance of early or first-phase insulin secretion in maintaining normal glucose tolerance has been demonstrated in a number of studies. Calles-Escadon and Robbins[20] reported that a 20-minute infusion of somatostatin inhibited first-phase insulin secretion in normal volunteers and resulted in a conversion from normal to impaired glucose tolerance. In a study by Bruttomesso and colleagues,[21] the administration of lispro insulin to patients with type 2 diabetes undergoing an oral glucose tolerance test produced a rapid increase in insulin concentration, which peaked much earlier and disappeared much faster compared with regular insulin. This resulted in a significant improvement in glucose tolerance. Furthermore, because the insulin concentration rapidly decreased, it more closely simulated a normal physiologic response to a glucose challenge than was achieved by regular insulin. A more physiologic insulin response would be expected to decrease the risk for hypoglycemia during the late postprandial period and also avoid chronic hyperinsulinemia, which may be associated with weight gain, insulin resistance,[22] lipid abnormalities,[23] and hypertension[24] ; all are potential cardiovascular risk factors.

Mealtime Glucose Excursions Contribute to Overall Poor Glycemic Control in Type 2 Diabetes

Frequently, guidelines and/or recommendations advise monitoring fasting plasma glucose (FPG) and HbA1c concentrations to evaluate overall glycemic control. However, FPG does not provide information about the contribution of the postprandial rise in glucose levels to overall glycemic control, and HbA1c does not provide information about the daily oscillations in blood glucose levels because it only represents the average glucose levels during the previous 2 to 3 months. Because patients are most often in a postprandial state rather than in a truly fasting state, and wide fluctuations in plasma glucose (PG) levels may occur throughout the day -- with high values 1 to 2 hours after a meal and low values before the next meal -- it may be more useful to assess postprandial glucose levels to monitor overall glycemic control. In addition, postprandial glucose levels may more closely represent the metabolic processes involved in the pathogenesis of type 2 diabetes -- insulin resistance, increased hepatic glucose output, and impaired insulin secretion.

A recent study by Avignon and colleagues,[25] evaluated the relative importance of measuring PG at different time points in assessing glucose control in patients with type 2 diabetes. A total of 66 adult patients with type 2 diabetes treated with diet or diet plus oral medications were enrolled in the study. Multiple daily blood samples were taken at 8:00 AM (fasting), 11:00 AM (1 hour before lunch), 2:00 PM (2 hours after the beginning of lunch), and 5:00 PM (5 hours after the beginning of lunch). Patients were then divided into 3 groups according to their HbA1c concentrations: less than 7%, 7% to 8.5%, and greater than 8.5%. Correlations between the various blood glucose determinations and overall glycemic control as measured by HbA1c were carried out. Figure 2 shows that the mean glycemic profile corresponds to the level of glycemic control.

Figure 2. Mean glycemic profile relative to glycemic control.

Prebreakfast PG levels had the weakest correlation, and postlunch PG levels showed the strongest. Multiple linear regression analysis of the data showed that postlunch PG and extended postlunch PG levels correlated significantly and independently with HbA1c values, whereas prebreakfast PG and prelunch PG levels did not (Figure 3).

Figure 3. Correlation between plasma glucose and HbA1c.

The results of this study indicate that good glycemic control (HbA1c concentration less than 7%) is characterized by extended postlunch PG levels that are lower than the fasting value, whereas poor glycemic control is associated with an extended postlunch PG levels higher than fasting. In other words, FPG was not a good predictor of blood glucose concentrations at other times of the day. The best correlation between PG and HbA1c was evident with the 2:00 PM and 5:00 PM samples, which represent the early and extended postlunch values. This study illustrates that postprandial increases in PG levels are better predictors of overall glycemic control than FPG and that both the early and sustained increases in PG following a meal make a significant contribution to overall glycemic control.

Postprandial Hyperglycemia and the Complications of Diabetes

Because postprandial glucose excursions contribute to the overall level of glycemic control, they are clearly related to the development of the microvascular and macrovascular complication of type 2 diabetes.

The level of postprandial hyperglycemia is associated with an increased risk of developing cardiovascular disease.[26-30] Along with meal-related glucose excursions, type 2 diabetes is also associated with a postprandial increase in lipids,[31-34] particularly very low-density lipoproteins and the activation of a prothrombotic state.[35,36]

In the majority of studies demonstrating an association between glycemia and risk for cardiovascular disease, fasting glucose or HbA1c concentrations have been used as static parameters for measuring overall glycemic control. However, in studies such as the Paris Prospective Study[37,38] and the Honolulu Heart Study,[39] increased cardiovascular risk has been seen in individuals with either impaired glucose tolerance or with increasing glucose concentrations that fall within the normal range. Because these latter groups predominantly experience postprandial increases in blood glucose levels, postprandial hyperglycemia may play an important role in determining the risk for macrovascular disease.

Several studies have shown a better correlation between 2-hour PG concentration and the risk of cardiovascular disease than with FPG.[28,40] Furthermore, the degree of risk, which is conferred by the 2-hour PG concentration, is almost twice that associated with HbA1c.[28] Hanefeld and colleagues[30] examined the relationship between fasting glucose and postprandial glucose concentration with respect to myocardial infarction and mortality during an 11-year period in patients with type 2 diabetes. They found that although there was no significant relationship between fasting blood glucose levels and cardiovascular risk factors, there was a significant relationship between cardiovascular risk and postprandial glucose concentration.

All of this suggests that the postprandial increases in glucose concentration may produce physiologic effects that are not reflected by fasting glucose or HbA1c. Unfortunately, the assessment of fluctuations in blood glucose levels throughout the day requires frequent and invasive blood glucose testing. The measurement of 1,5-anhydro-D-glucitol has been proposed as one way to assess glucose fluctuations throughout the day, but this is not seen as a practical application.[41] The recent approval of the GlucoWatch automatic glucose biographer (Cygnus Inc, Redwood City, Calif), a device that makes frequent, noninvasive measurements of glucose possible, may facilitate intensive management of diabetes.[42]

In summary, the goal of treatment of patients with type 2 diabetes should be to achieve the best possible overall glycemic control by restoring a normal, physiologic insulin response to feeding and decreasing late postprandial insulin levels and chronic hyperinsulinemia. However, this is difficult to achieve using currently available medications because excessive postprandial increases in PG and hypoglycemia during the late postprandial or fasting state are major obstacles to achieving a completely normal blood glucose profile. Consequently, the American Diabetes Association established the target HbA1c concentration at less than 7% or as close to normal as possible (4%-6%) and recommended a need for changing the therapeutic regimen if the HbA1c concentration is higher than 8%.[43]

Improving Mealtime Glucose Control by Restoring Early Insulin Secretion in Type 2 Diabetes

Whereas sulfonylureas or insulin may adequately control fasting blood glucose levels, it is usually more challenging to modulate postprandial glucose excursions. Because neither sulfonylureas nor regular insulin appropriately simulate the postprandial insulin response to a meal, they are not ideal for managing postprandial hyperglycemia. Furthermore, because these agents produce increases in insulin levels that extend beyond the postprandial period, they may predispose the patient to hypoglycemia. The rationale for tailoring pharmacologic therapy to mealtimes is based on the importance of restoring the mealtime insulin secretion profiles of patients with type 2 diabetes to reestablish the tight control of blood glucose levels during the postprandial period. Furthermore, this approach also takes into account that most people with type 2 diabetes are overweight and are advised to reduce calorie consumption, but the risk of hypoglycemia does not allow them to be flexible about their day-to-day calorie intake.[44]

Dietary modifications may somewhat diminish postprandial hyperglycemia, but they often do not produce a satisfactory response, and therefore pharmacologic intervention is usually undertaken. Several classes of pharmacologic agents are either currently available or in clinical development for managing postprandial glucose excursions. These include alpha-glucosidase inhibitors, short-acting insulinotropic agents, rapid-acting insulin analogues, and amylin analogues.

Alpha-glucosidase Inhibitors

Alpha-glucosidase inhibitors, such as acarbose, miglitol, and voglibose, delay the digestion of complex carbohydrates by competitively inhibiting intestinal alpha-glucosidases that hydrolyze oligosaccharides into monosaccharides. By delaying the digestion and prolonging the intestinal absorption of dietary carbohydrates, these agents diminish postprandial hyperglycemia. However, because the total amount of carbohydrate absorbed is not reduced, there are no net energy losses.[45,46]

Clinical studies have shown that alpha-glucosidase inhibitors reduce postprandial glucose levels and improve overall glycemic control as indicated by HbA1c.[47-52] In addition, some studies suggest that acarbose reduces the postprandial increase in triglycerides[49] and may have beneficial effects on lipoproteins.[50] Compared with sulfonylureas, they are not associated with postprandial hypoglycemia.[51] In a comparative study of miglitol and acarbose, both agents produced comparable reductions in HbA1c concentrations.[53] When used as monotherapy, these agents may not achieve overall glycemic control in all patients, especially in those with elevated FPG levels.

Patients should be instructed to take their dose of alpha-glucosidase inhibitor with the first bite of each meal. The principal side effects of alpha-glucosidase inhibitors are related to their effect on the gastrointestinal tract and are primarily manifested as flatulence and loose stools. They do not appear to affect the rate of gastric emptying.[54] Tolerance to these side effects usually occurs with continued administration.

Short-acting Insulinotropic Agents

Because these agents more rapidly stimulate insulin secretion compared with sulfonylureas, they simulate a more physiologic increase in mealtime insulin levels. Thus, they are primarily used for reducing postprandial hyperglycemia.

Repaglinide, a carbamoylmethyl benzoic acid derivative structurally related to meglitinide,[55] is the first short-acting insulinotropic agent approved in the United States for the treatment of type 2 diabetes. Repaglinide augments glucose-stimulated insulin secretion by closing ATP-sensitive potassium [K+(ATP)] channels on beta cells.[55] This causes depolarization of the beta cell and the opening of voltage-sensitive calcium channels allowing the influx of extracellular calcium ions, which in turn, stimulates insulin release. Repaglinide more effectively increases insulin release from islet cells incubated in vitro in the presence of D-glucose or other nutrients than in their absence.[55, 56]

Repaglinide significantly increases postprandial insulin levels and also decreases mean FPG, postprandial PG levels, and HbA1c.[57,58] It is more effective than glipizide and similar to glibeclamide and gliclazide in maintaining overall glycemic control as measured by HbA1c.[59] Patients should be instructed to take repaglinide within 15 minutes of a meal, but this time may vary from immediately preceding the meal to as long as 30 minutes before. Patients who skip a meal should be instructed to skip the dose for that meal. Conversely, if a meal is added, then patients should be instructed to add a dose.

Nateglinide, another short-acting insulinotropic agent, is an amino acid derivative that stimulates insulin secretion from pancreatic beta cells by closing K+(ATP) channels.[60] In vitro studies using rat cardiac myocytes and vascular smooth muscle cells suggest that nateglinide is more selective for beta-cell K+(ATP) channels than repaglinide and glyburide.[60] Nateglinide blunts mealtime glucose excursions, returning glucose levels to predose values 4 hours after a meal.[61]

Rapid-acting Insulin Analogues

The tendency of human insulin to self-associate under normal physiologic conditions results in a slow and prolonged absorption from the subcutaneous site of injection. This requires that regular human insulin be injected approximately 30 to 60 minutes before a meal,[62] as administration immediately before a meal produces less than optimal insulin levels during the early phase of glucose absorption and hyperinsulinemia by the time meal absorption is complete. Structural modifications of the insulin molecule have produced insulin analogues that have a weaker tendency to self-associate and, as a result, are more rapidly and reliably absorbed from the injection site. The short-acting analogues of insulin, insulin lispro and insulin aspart, were developed to provide a more physiologic insulin response to food intake.[63] These insulin analogues are usually administered within 10 to 20 minutes of a meal, allowing more flexibility in insulin dosing.

Clinical trials in patients with both type 1 and type 2 diabetes have shown that insulin lispro reduces postprandial glucose excursions.[64] A large, multinational study compared the effect of lispro injected immediately before a meal with regular human insulin, which was injected 30 to 45 minutes before eating. Postprandial glucose levels were lower in patients in the insulin lispro group.[65] When the early rise in plasma insulin was restored by the lispro analogue, postprandial glucose levels were reduced and subsequent hyperglycemia and hyperinsulinemia were prevented after an oral glucose load was compared with regular human insulin.[21] This improvement in glucose tolerance was associated with a prompter, short-lived suppression of endogenous glucose production.

The degree of self-association of insulin aspart is similar to that of insulin lispro. Insulin aspart is absorbed twice as fast and it produces maximum insulin leves that are approximately twice as high compared with human insulin.[66] In patients with type 1 diabetes, insulin aspart significantly improved postprandial blood glucose control after lunch and dinner and significantly reduced the occurrence of hypoglycemic episodes requiring third-party intervention.[67]

Amylin Analogues

Amylin is a pancreatic hormone produced by the beta cell and cosecreted with insulin in response to various secretagogues. Amylin delays gastric emptying and inhibits postprandial glucagon secretion. In individuals with type 2 diabetes, the decline in amylin secretory response correlates with reduced pancreatic beta-cell activity.[68] However, the short half-life limits the use of amylin. These limitations have been overcome by the advent of pramlintide, an analogue of amylin.

Recent clinical studies in patients with type 1 diabetes indicate that pramlintide produces a significant decrease in mean PG and postprandial glucose concentration despite comparable insulin level.[69] In patients with type 2 diabetes, pramlintide produced a decrease in HbA1c.[70] However, the clinical usefulness of pramlintide in type 2 diabetes remains to be defined.

Summary

An early defect in the development of diabetes is the loss of the early or first-phase insulin response to meals. This results in a delayed and late-peaking plasma insulin profile, which is associated with decreased glucose tolerance. Increasing evidence suggests that controlling postprandial hyperglycemia improves glycemic control, and it is well known that achieving this slows or prevents the development of diabetic complications. The rationale for the development of rapid-acting agents that reduce postprandial glucose excursions is based on providing a more physiologic insulin response to meals. This approach provides patients with type 2 diabetes the ability to more easily establish tight glycemic control and offers them the flexibility of modulating calorie intake without the increased risk of hypoglycemia.

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  51. Johnston PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL. Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocrinol Metab. 1998;83:1515-1522.
  52. Holman RR, Steemson J, Turner RC. Post-prandial glycaemic reduction by an alpha-glucosidase inhibitor in type 2 diabetic patients with therapeutically attained basal normoglycaemia. Diabetes Res. 1991;18:149-153.
  53. Rybka J, Goke B, Sissmann J. European Comparative Study of 2 alpha-glucosidase inhibitors, miglitol and acarbose. In: Program and abstracts of the 59th Annual Meeting of the American Diabetes Association; June 18-22, 1999; San Diego, Calif; Abstract 433.
  54. Kawagishi T, Nishizawa Y, Taniwaki H, et al. Relationship between gastric emptying and an alpha-glucosidase inhibitor effect on postprandial hyperglycemia in NIDDM patients. Diabetes Care. 1997;20:1529-1532.
  55. Malaisse WJ. Mechanism of action of a new class of insulin secretagogues. Exp Clin Endocrinol Diabetes. 1999;4:S140-S143.
  56. Bakkali-Nadi A, Malaisse-Lagae F, Malaisse WJ. Insulinotropic action of meglitinide analogs: concentration-response relationship and nutrient dependency. Diabetes Res. 1994;27:81-87.
  57. Marbury T, Huang WC, Strange P, Lebovitz H. Repaglinide versus glyburide: a one-year comparison trial. Diabetes Res Clin Pract. 1999;43:155-166.
  58. Goldberg RB, Einhorn D, Lucas CP, et al. A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes. Diabetes Care. 1998;21:1897-1903.
  59. Gomis R. Repaglinide as monotherapy in Type 2 diabetes. Exp Clin Endocrinol Diabetes. 1999;107:S133-S135.
  60. Hu S, Wang S, Dunning BE. Tissue selectivity of antidiabetic agent nateglinide: study on cardiovascular and beta-cell K(ATP) channels. J Pharmacol Exp Ther. 1999;291:1372-1379.
  61. Hirschberg Y, McLeod J, Gareffa S, Spratt D. Pharmacodynamics and dose response of nateglinide in type 2 diabetics. In: Program and abstracts of the 59th Annual Meeting of the American Diabetes Association; June 18-22, 1999; San Diego, Calif; Abstract 430.
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Mealtime Glucose Excursions and Glycemic Control in Type 2 Diabetes  CME

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Mealtime Glucose Excursions and Glycemic Control in Type 2 Diabetes  CME

Post Test

Click on the appropriate response. A test score of 70% or greater is required for accreditation.

1. Which of the following metabolic defects usually is NOT associated with type 2 diabetes?
  A. Decreased insulin-stimulated glucose uptake in skeletal muscle and adipose tissue
B. Decreased hepatic glucose output in the fasting state
C. Decreased suppression of hepatic glucose output following meals
D. Reduced beta-cell function resulting in abnormal insulin secretion in response to a glucose stimulus
2. A recent study by Avignon and colleagues (Diabetes Care. 1997;20:1822-1826) demonstrated that:
  A. Patients are more often in the fasting state than the postprandial state
B. Prebreakfast plasma glucose (PG) had the strongest correlation with HbA1c levels
C. HbA1c levels lower than 7% are characterized by extended postlunch PG levels that are lower than the fasting PG
D. Only the sustained increases in PG following a meal make a significant contribution to overall glycemic control
3. Tailoring pharmacologic therapy for type 2 diabetes to target mealtime insulin secretion:
  A. Is intended to simulate the normal postprandial insulin response to meals
B. Predisposes patients to hypoglycemia
C. Primarily reduces fasting PG levels
D. Requires that patients maintain a constant calorie intake to prevent hypoglycemia
4. Which of the following statements regarding alpha-glucosidase inhibitors is FALSE?
  A. Alpha-glucosidase inhibitors are not effective as monotherapy for patients with severely elevated fasting PG
B. Patients should take acarbose 30-60 minutes before each meal
C. Alpha-glucosidase inhibitors do not delay gastric emptying
D. Compared with sulfonylureas, alpha-glucosidase inhibitors are not associated with postprandial hypoglycemia
5. Which of the following statements about short-acting insulinotropic agents is FALSE?
  A. Repaglinide and nateglinide augment glucose-stimulated insulin secretion by opening ATP-sensitive potassium channels on beta cells
B. Nateglinide blunts mealtime glucose excursions, returning glucose levels to predose values 4 hours after a meal
C. In vitro studies show that repaglinide is less effective in increasing insulin release in the absence of nutrients
D. Patients who skip a meal should be instructed to skip their dose of repaglinide for that meal

Mealtime Glucose Excursions and Glycemic Control in Type 2 Diabetes  CME

Evaluation

Scale: 5 = Excellent 4 = Good 3 = Satisfactory 2 = Fair 1 = Poor

1. How would you rate how well you can achieve the following learning objectives?
a. Outline the major metabolic defects that contribute to hyperglycemia in type 2 diabetes
5 4 3 2 1
b. Describe the insulin secretory response to a meal in type 2 diabetes
5 4 3 2 1
c. Explain how postprandial hyperglycemia contributes to overall glycemic control
5 4 3 2 1
d. Discuss the rationale for tailoring treatment to mealtime glucose excursions
5 4 3 2 1
e. Review strategies that reduce postprandial glucose excursions and, as a result, improve overall glycemic control
5 4 3 2 1

2. How would you rate the relevance of activity content to the objectives?
5 4 3 2 1
3. How would you rate the faculty's effectiveness (clarity and organization) in presenting the material?
5 4 3 2 1
4. How would you rate the content?
a. Will definitely change the way you practice
b. Challenged you to think about the topics
c. Applicable to your practice; a good review
d. Of limited use in your practice
e. Not applicable to your practice
5. How well did this activity meet the goal of providing state-of-the-art information on the pathogenesis of type 2 diabetes and how postprandial hyperglycemia affects overall glycemic control?
5 4 3 2 1
6. Were your personal objectives for taking this activity met?
5 4 3 2 1
7. How long did this session actually take you to complete?
a. .25 - .50 hrs
b. .50 - 1.0 hrs
c. 1.0 - 1.5 hrs
d. 1.5 - 2.0 hrs
e. More than 2.0 hrs
8. What other continuing education topics would be of value to you? Please offer any additional comments.

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