You are leaving Medscape Education
Cancel Continue
Log in to save activities Your saved activities will show here so that you can easily access them whenever you're ready. Log in here CME & Education Log in to keep track of your credits.
 

CME

Getting to Goal in Type 2 Diabetes: Role of Postprandial Glycemic Control

  • Authors: Chairperson: Lawrence Blonde, MD, FACP, FACE; Faculty: James R. Gavin III, MD, PhD; John E. Gerich, MD
  • THIS ACTIVITY HAS EXPIRED
Start Activity


Target Audience and Goal Statement

This activity is intended for healthcare professionals treating patients with type 2 diabetes.

Health care professionals treating patients with Type 2 diabetes require continued updates about the benefits of improved glycemic control and therapeutic strategies with which it can be achieved. Information about the relationship between glycemic control and the development of both microvascular and marcrovascular disease continue to accrue. Many patients fail to meet ADA targets for glycemic control and there is often particular difficulty in achieving postprandial glycemic control.

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

  1. Describe the mechanisms by which improved glycemic control can inhibit the development and/or progression of both microvascular and macrovascular diabetic complications.
  2. Define the contribution of postprandial glucose values to overall glycemia.
  3. Integrate optimal postprandial glycemic control into treatment regimens for patients with type 2 diabetes.


Author(s)

  • Lawrence Blonde, MD, FACP, FACE

    Director, Ochsner Diabetes Clinical Research Unit, Section on Endocrinology, Diabetes and Metabolic Diseases; Associate Residency Program Director, Department of Internal Medicine, Ochsner Clinic Foundation, New Orleans, Louisiana

    Disclosures

    Disclosure: Consultant: Amylin Pharmaceuticals, Aventis, BD, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly and Company, Lifescan, Merck & Co., Inc., Merck/Shering-Plough, Novo-Nordisk, Novartis Pharmaceuticals Corporation, Pfizer; Honoraria: Amylin Pharmaceuticals, Aventis, BD, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly and Company, Lifescan, Merck & Co., Inc., Merck/Shering-Plough, Novo-Nordisk, Novartis Pharmaceuticals Corporation, Pfizer, Takeda Pharmaceuticals of America, Wyeth; Research Support: Amylin Pharmaceuticals, Aventis, BD, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly and Company, Merck & Co., Inc., Novo-Nordisk, Novartis Pharmaceuticals Corporation, Pfizer.Over the last several years, Dr. Blonde has been fortunate to be involved in industry-sponsored as well as investigator-initiated clinical trials of the majority of the new pharmacologic therapies focused on glycemic control in patients with diabetes. He has also had the opportunity to provide medical presentations

  • James R. Gavin III, MD, PhD

    President, Professor of Medicine, Morehouse School of Medicine; Chairman, National Diabetes Education Program, Atlanta, Georgia.

    Disclosures

    Disclosure: Consultant: Novartis, Eli Lilly, Aventis, Bristol-Myers Squibb, GlaxoSmithKline; Speaker?s Bureaus: Novartis, Eli Lilly, Aventis, Bristol-Myers Squibb, GlaxoSmithKline.

  • John E. Gerich, MD

    Professor of Medicine, Clinical Research Center, University of Rochester School of Medicine, Rochester, New York

    Disclosures

    Disclosure: Advisory Board: Novartis; Speaker: Novartis; Honoraria: Novartis.


Accreditation Statements

    For Physicians

  • Sponsored by Dannemiller Memorial Educational Foundation

    The Dannemiller Memorial Educational Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

    The Dannemiller Memorial Educational Foundation designates this educational activity for a maximum of 1.25 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity.

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


Instructions for Participation and Credit

There are no fees for participating in or receiving credit for this online educational activity. For information on applicability and acceptance of continuing education credit for this activity, please consult your professional licensing board.

This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit:

  1. Read the target audience, learning objectives, and author disclosures.
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score as designated at the top of the test. Medscape encourages you to complete the Activity Evaluation to provide feedback for future programming.
You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 5 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

The credit that you receive is based on your user profile.

CME

Getting to Goal in Type 2 Diabetes: Role of Postprandial Glycemic Control

Authors: Chairperson: Lawrence Blonde, MD, FACP, FACE; Faculty: James R. Gavin III, MD, PhD; John E. Gerich, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

processing....

Contributions of Fasting and Postprandial Hyperglycemia to Micro- and Macrovascular Diabetic Complications

Scope of the Problem Presented by John E. Gerich, MD

  • There has been an epidemic of type 2 diabetes in the United States and worldwide. This graphic was made up a couple years ago; we have now 18 million Americans with diabetes, more than 90% of these have type 2 diabetes, and the problem is going to get worse.

  • Contributions of Fasting and Postprandial Hyperglycemia to Micro- and Macrovascular Diabetic Compl

    Slide 1.

    Contributions of Fasting and Postprandial Hyperglycemia to Micro- and Macrovascular Diabetic Complications

    (Enlarge Slide)
  •  
  • Prevalence of Diabetes Mellitus

    Slide 2.

    Prevalence of Diabetes Mellitus

    (Enlarge Slide)
  • We know that the prevalence of diabetes increases as a function of age. These data show that over the age of 65 years, almost 18% of people have type 2 diabetes. Even worse, 40.8% of people have impaired glucose tolerance (IGT).

  • National Health and Nutrition Examination Survey II

    Slide 3.

    National Health and Nutrition Examination Survey II

    (Enlarge Slide)
  • Our population is aging. In 1986, 11% were over the age of 65 years. By the year 2020, that will double. So all things being equal, the problem of type 2 diabetes is going to double over the years.

  • The Aging Population

    Slide 4.

    The Aging Population

    (Enlarge Slide)

The Cost of Diabetes

  • The direct and indirect costs of diabetes are overwhelming. One in every 7 healthcare dollars is spent on someone with diabetes. The annual healthcare costs are 3-fold greater for people with diabetes than people without diabetes. Direct costs are about $85 billion. Total costs are over $100 billion.

  • Direct and Indirect Costs of Diabetes

    Slide 5.

    Direct and Indirect Costs of Diabetes

    (Enlarge Slide)
  • Where does all this money go? Not for routine follow-up visits, not for acute metabolic problems, but for the most part, it goes for the treatment of the chronic complications of diabetes.

  • Healthcare Expenditures Attributable to Diabetes

    Slide 6.

    Healthcare Expenditures Attributable to Diabetes

    (Enlarge Slide)

The Complications of Diabetes

  • Microvascular complications include retinopathy, neuropathy, and nephropathy. Then macrovascular complications include cerebrovascular disease, peripheral vascular disease, and coronary heart disease. Mainly, the macrovascular complications are the big problem in people with type 2 diabetes.

  • Complications of Diabetes

    Slide 7.

    Complications of Diabetes

    (Enlarge Slide)
  • These data show that ischemic heart disease, other heart disease, and stroke are the overwhelming causes of death in people with type 2 diabetes. For any given risk factor, the chances of getting cardiovascular disease are markedly increased in people with type 2 diabetes.

  • Reported Causes of Death in People With Diabetes

    Slide 8.

    Reported Causes of Death in People With Diabetes

    (Enlarge Slide)
  • These are data from the Multiple Risk Factor Intervention Trial (MRFIT) study, where people with and without diabetes were classified as having: no risk factors at all, only 1 risk factor, 2 risk factors, or all 3 risk factors. Risk factors were hypertension, hyperlipidemia, and smoking. For any given number of risk factors, the chances of getting cardiovascular disease are markedly increased in people with type 2 diabetes. This increased risk is related to hyperglycemia.

  • MRFIT: Impact of Diabetes on CVD Mortality

    Slide 9.

    MRFIT: Impact of Diabetes on CVD Mortality

    (Enlarge Slide)
  • There are several lines of evidence linking hyperglycemia to macrovascular disease. The first is epidemiologic data. Numerous studies have shown correlations between the frequency of cardiovascular disease and either plasma glucose levels or hemoglobin A1C (HbA1C).

  • Hyperglycemia and Macrovascular Complications

    Slide 10.

    Hyperglycemia and Macrovascular Complications

    (Enlarge Slide)
  • These data from a Finnish study compare people with HbA1C levels below 6% with those who have HbA1C levels between 6% and 7.9%. They have roughly a doubling of the incidence of cardiovascular mortality.

  • Coronary Heart Disease Incidence by HbA1c Levels in Type 2 Diabetes

    Slide 11.

    Coronary Heart Disease Incidence by HbA1c Levels in Type 2 Diabetes

    (Enlarge Slide)

Risk Associated With Postprandial Hyperglycemia

  • Is it fasting or postprandial hyperglycemia that is important? Hemoglobin A1C measures total exposure to hyperglycemia over about a 3-month period of time. Both fasting and postprandial hyperglycemia contribute to this. We have no evidence that there's anything more toxic for postprandial hyperglycemia vs fasting hyperglycemia. The relative contributions depend on the relative degree of glycemic control. When your HbA1C is very high, when you have a fasting glucose level over 200 mg/dL, most of the HbA1C will be due to fasting hyperglycemia. However, earlier in the stage of diabetes, when HbA1C levels are lower, it's going to be the postprandial values that contribute most to HbA1C.

    This shows the relationship of fasting and postprandial hyperglycemia to overall HbA1C over the range from less than 5% to 7.5%. Over this range, which covers the goals recommended by various groups, there is a very small increase in fasting plasma glucose levels, and a greater increase in postprandial levels. People who have HbA1C levels of 5.5% to 6% may have normal fasting plasma glucose levels, but may have a greater increase in postprandial hyperglycemia levels, and therefore these values contribute to high HbA1C.

  • Relative Changes in Fasting and Postprandial Plasma Glucose

    Slide 12.

    Relative Changes in Fasting and Postprandial Plasma Glucose

    (Enlarge Slide)
  • Is postprandial hyperglycemia a risk factor by itself if you have normal fasting plasma glucose levels? The answer is yes, we know that from epidemiologic data, but we also have this from controlled clinical trials. Let me show some of the epidemiologic data.

  • Postprandial Hyperglycemia as a Risk for CVD

    Slide 13.

    Postprandial Hyperglycemia as a Risk for CVD

    (Enlarge Slide)

Epidemiologic Data on Risk of Postprandial Hyperglycemia

  • These are data from the Paris Prospective Study. They looked at people with nondiabetic fasting plasma glucose levels of less than 140 mg/dL, and people with IGT, meaning normal fasting glucose levels and elevated 2-hour postprandial values. And the cardiovascular mortality is increased almost 2-fold.

  • Paris Prospective Study 10-Year Follow-Up: IGT Progressively Increases Risk of CHD Mortality

    Slide 14.

    Paris Prospective Study 10-Year Follow-Up: IGT Progressively Increases Risk of CHD Mortality

    (Enlarge Slide)
  • This is the Funagata Diabetes Study. They looked at cardiovascular survival by whether someone had normal glucose tolerance, IGT, or type 2 diabetes. Compared with people with normal glucose tolerance, there was a marked reduction in cardiovascular survival in people with type 2 diabetes over 7 years. But for people with IGT, after 7 years, the survival is virtually the same in both groups.

  • The Funagata Diabetes Study: Impaired Glucose Tolerance Is a CV Risk Factor

    Slide 15.

    The Funagata Diabetes Study: Impaired Glucose Tolerance Is a CV Risk Factor

    (Enlarge Slide)
  • Even scarier are the data from the Norfolk, United Kingdom cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk) study. This was a study of about 5000 people in various centers in Europe. They simply assessed cardiovascular risk factors: hypertension, hyperlipidemia, smoking, preexisting cardiovascular disease, and HbA1C. Then they looked 3 or 4 years later to see who was alive, who was dead, and what they died from. And they used, as their control group, people with HbA1C levels of 5% or below; they were given a relative risk of 1. In people who had HbA1C levels from 5% to 5.4%, there was roughly a 2.5-fold increased risk of dying from cardiovascular disease.

  • HbA1C and Mortality

    Slide 16.

    HbA1C and Mortality

    (Enlarge Slide)
  • As strange as it may seem, in this study, where they measured all these cardiovascular risk factors and HbA1C, they did not measure plasma glucose levels. So who are these people between 5% and 5.4% HbA1C? We accessed our database that had almost 500 people in it who had oral glucose tolerance tests and HbA1C levels. In the group with HbA1C of 5% or below, about 85% had normal glucose tolerance.

    In the group between 5% and 5.5%, who had 2.5-fold increased mortality in the EPIC-Norfolk study, about 37% either had IGT or type 2 diabetes. This could possibly explain the increased cardiovascular risk.

  • Characteristics of Subjects by EPIC-Norfolk HbA1C Categories, Mean ± SD

    Slide 17.

    Characteristics of Subjects by EPIC-Norfolk HbA1C Categories, Mean ± SD

    (Enlarge Slide)
  • This would be consistent with what was found in the United Kingdom Prospective Diabetes Study (UKPDS); at the time of diagnosis, people had macrovascular complications. Seventeen percent had cardiovascular complications by the time type 2 diabetes was diagnosed. You could argue they might have had diabetes for several years, but some of this cardiovascular morbidity may be related to having had IGT for several years.

  • Prevalence of Diabetic Tissue Damage at the Time of Diagnosis of Type 2 Diabetes

    Slide 18.

    Prevalence of Diabetic Tissue Damage at the Time of Diagnosis of Type 2 Diabetes

    (Enlarge Slide)

Hyperglycemia and Cardiovascular Disease

  • How can glucose contribute to cardiovascular disease?

  • How Can Glucose Contribute to Cardiovascular Disease?

    Slide 19.

    How Can Glucose Contribute to Cardiovascular Disease?

    (Enlarge Slide)
  • We have evidence from in vitro experiments to show that there are many biochemical mechanisms to explain how hyperglycemia may lead to atherogenesis. With hyperglycemia you get glycosylation of proteins. You have more glucose moving through the polyol-hexosamine pathways. You have the generation of free radicals. All of these things can lead to an increase in protein kinase C and diacylglycerol.

    These free radicals, these compounds, and glycation can: lead to increases in plasminogen activator inhibitor-1 (PAI-1), therefore decreasing fibrinolysis; increase the production of matrix proteins in the atheroma; reduce nitric oxide (NO) production, a vasodilator that keeps the endothelium healthy; increase local generation of endothelin-1 (ET-1), which can predispose to hypertension; and increase the production of growth factors within the endothelium and subendothelium that can lead to atheroma.

    All of these things together, as the product of hyperglycemia, can lead to cell proliferation, increased coagulability, decreased fibrinolysis, decreased vasodilation, increased vascular permeability, and increased matrix formation, all known to be involved in the process of atherogenesis.

  • slide

    Slide 20.

    (Enlarge Slide)
  • Can we prevent these micro- and macrovascular complications?

  • Are These Complications Preventable?

    Slide 21.

    Are These Complications Preventable?

    (Enlarge Slide)
  • The answer is definitely yes. There have been controlled clinical trials showing that if you optimally control blood pressure, you can reduce both micro- and macrovascular complications. You can reduce macrovascular complications by optimizing control of lipids. And we've had controlled clinical trials showing that strict glycemic control can prevent these complications.

  • YES!

    Slide 22.

    YES!

    (Enlarge Slide)

Major Studies in Type 1 and Type 2 Diabetes: DCCT and UKPDS

  • The first big study was the Diabetes Control and Complications Trial (DCCT), done in people with type 1 diabetes. They were randomized to an intensive insulin regimen or, what was at the time, conventional insulin therapy. And there was about a difference of 1.9% in HbA1C levels, 7% vs 8.9%.

    The other big study was the UKPDS. This was a study of over 4000 newly diagnosed patients with type 2 diabetes who were randomized to conventional or strict metabolic control using various oral hypoglycemic agents. The difference between the intensively treated group and the conventionally treated group was only .9% HbA1C. A relatively small difference, but what a big difference it made in complications.

  • Overview of DCCT and UKPDS Parameters

    Slide 23.

    Overview of DCCT and UKPDS Parameters

    (Enlarge Slide)
  • In the DCCT, tight glycemic control decreased retinopathy by 63%, nephropathy by 39%, and neuropathy by 60%.

  • DCCT

    Slide 24.

    DCCT

    (Enlarge Slide)
  • This is an extrapolation of the data from the DCCT to show the risk of developing these complications as a function of HbA1C. When you get HbA1C down to about 7%, the relative risk compared with the normal population is about 1. This epidemiologic relationship between HbA1C and microvascular complications is the basis of the American Diabetes Association (ADA) recommending a target HbA1C of 7% or less.

  • Risk of Progression of Complications by HbA1C: DCCT

    Slide 25.

    Risk of Progression of Complications by HbA1C: DCCT

    (Enlarge Slide)
  • In the UKPDS there was a reduction in all diabetes-related endpoints and microvascular complications. The reduction in myocardial infarction (MI), 16%, was P = .052 when the data were originally reported. Many people like myself said, "P = .052, is as good as P < .05. That's significant." You had purists who said, "It was above .05, not statistically significant." There was an evaluation of the data with the final HbA1C levels, and that was statistically significant.

  • UKPDS: Conclusions From Intensive Glucose Control Study

    Slide 26.

    UKPDS: Conclusions From Intensive Glucose Control Study

    (Enlarge Slide)

Additional Studies Assessing Macrovascular Complications

  • These are data from that analysis showing the relationship between the updated HbA1C levels and fatal and nonfatal MI. For every 1% reduction in HbA1C, there was a 14% decrease in MI. These studies showed that you needed better glycemic control to prevent macrovascular disease than microvascular complications.

  • Macrovascular Complications

    Slide 27.

    Macrovascular Complications

    (Enlarge Slide)
  • I mentioned earlier about IGT as a risk factor for cardiovascular disease. There was a study called the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM). It was designed to see if the use of an alpha-glucosidase inhibitor, which only works on postprandial hyperglycemia, could prevent people with IGT from progressing to overt type 2 diabetes.

    They also looked at the development of cardiovascular disease during the 3-year study. The progression to type 2 diabetes was reduced, but also the development of cardiovascular events was reduced by 50%. This was just by treating postprandial hyperglycemia. We know that once people have cardiovascular complications, good control matters.

  • Effect of Acarbose on the Development of Cardiovascular Disease

    Slide 28.

    Effect of Acarbose on the Development of Cardiovascular Disease

    (Enlarge Slide)
  • The Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study took patients in Sweden who were in coronary care units with MIs, and randomized them to an intensive basal-bolus insulin regimen or their conventional treatment. The people who were placed on the basal-bolus intensive regimen had in-hospital reduction of cardiovascular mortality, and it was reduced more and more over time. At 5 years, the relative reduction in cardiovascular mortality was increased. So even in established macrovascular disease, good glycemic control matters.

  • DIGAMI

    Slide 29.

    DIGAMI

    (Enlarge Slide)
  • Perhaps one of the mechanisms is the improvement in cardiovascular risk factors. These are data from 4 different studies that looked at the effect of improving glycemic control in people with type 2 diabetes by use of insulin regimens on various cardiovascular risk factors. There's a reduction in triglycerides, low-density lipoprotein (LDL) cholesterol, and very low density lipoprotein (VLDL), an increase in high-density lipoprotein (HDL), a reduction in apolipoprotein B, a reduction in blood pressure, a reduction in insulin resistance, a reduction in albuminuria, an improvement in endothelial function, a decrease in C-reactive protein (CRP), a decrease in PAI-1, and a decrease in thromboxane generation.

  • Effects of Improved Glycemic Control on Cardiovascular Risk Factors

    Slide 30.

    Effects of Improved Glycemic Control on Cardiovascular Risk Factors

    (Enlarge Slide)

Achieving Glycemic Goals in Type 2 Diabetes

  • The goals of glycemic control. The ADA, primarily based on evidence regarding microvascular complications, recommends HbA1C below 7%. The International Diabetes Federation (IDF) and the American Association of Clinical Endocrinologists (AACE), taking into consideration that you need stricter glycemic control to prevent macrovascular complications, recommend a target of less than 6.5%.

  • Glycemic Goals for T2DM

    Slide 31.

    Glycemic Goals for T2DM

    (Enlarge Slide)
  • What do we have to do to get to an HbA1C of 6.5%? Going back to that database that I mentioned earlier, we accessed people who had HbA1C levels between 6% and 6.5% and compared them with people with levels between 6.5% and 7%. All of these people had diabetes, but were under no treatment other than diet at the time.

    What's the difference between these 2 groups? Fasting plasma glucose levels are near normal. They're not different between the 2 groups. Postprandial hyperglycemia, there's the difference. So to take a patient with HbA1C between 7% and 7.5% and move them below 7%, to 6.5%, it's going to take concentrating on treating postprandial hyperglycemia because people in those HbA1C ranges have normal fasting glucose levels.

  • Characteristics of Individuals With HbA1C Values 6.0% to 6.5% and 6.6% to 7.0%, Respectively

    Slide 32.

    Characteristics of Individuals With HbA1C Values 6.0% to 6.5% and 6.6% to 7.0%, Respectively, Mean ± SD

    (Enlarge Slide)
  • How good are we at getting good glycemic control? These are data from National Health and Nutrition Examination Survey III (NHANES III), and only 38% of people on oral agents achieved HbA1C below 7%. It's even worse with insulin, 27%. This shows that we're not using enough of the pills, or people who should be on insulin are still on pills. Looking at insulin, you have to draw the conclusion that either insulin doesn't work or we're not using it aggressively. We know from studies such as the DCCT that insulin does work.

  • Percentage of Adults With Type 2 Diabetes by HbA1C Level

    Slide 33.

    Percentage of Adults With Type 2 Diabetes by HbA1C Level

    (Enlarge Slide)
  • NHANES III ended in 1994. At that time we were basically limited to sulfonylurea treatment and conventional insulins: regular insulin, neutral protamine Hagedorn (NPH), and mixtures. Since that time we have had the introduction of numerous new agents, many of which work via different mechanisms, many of which are better than our old preparations. And with these new tools we should be able to get better glycemic control than we have in the past.

  •  New Treatment Modalities Available

    Slide 34.

    New Treatment Modalities Available

    (Enlarge Slide)