Diabetes Master Class

Later this month you will be meeting with Dr. Schubart for the Diabetes Master Class.   The goals of the sessions are to solidify our knowledge of the basics of diabetes treatment and to challenge us to become more expert in the treatment of this common condition.

To attain these goals, we will read the latest recommendations of the ADA in detail, improving our familiarity with the large clinical trials that constitute the basis of the recommendations.  The 2014 guidelines promulgated by the ADA are careful to distinguish recommendations based on the results of large RCTs from those based on expert opinion, to differentiate between what is known and what is not yet known.  The older, trialed and true treatments have brought improvements in important outcomes, however  reductions in mortality and macrovascular complications have proven difficult to come by; older agents also appear not to reverse or retard the underlying pathophysiology – insulin resistance and progressive beta cell loss.  In recognition of these difficulties, the guidelines “allow” use of newer agents for which the evidence base is necessarily incomplete.

Everyone should complete the test below prior to the class.  You are encouraged, indeed required, to do the test in an “open book” fashion.  Read the guidelines summary and recommendations in detail.  Also read the attached article by DeFronzo et al in which they describe a different approach, based more on what is known about the pathophysiology of diabetes than the results of large clinical trials.   Google and PubMed.  Work together.  Ask anyone you like.  Please turn in a copy of your answers at the beginning of the class.

In addition to completing the test, each of you will be assigned one of the questions.  You will lead a discussion of the question.  You may prepare a powerpoint or a handout if you’d like.

Many of the questions below, though in multiple choice format, are not standard multiple choice.  There are often multiple correct choices.  For cxample the queston may ask “Which of the following is true?”  and B and C may both be true while A,D, and E are not.  Try to get them all right.

Here is the ADA “Standards of Medical Care in Diabetes – 2014”: Dia Care-2014–S14-80

Here is the DeFronzo article “Pathophysiologic Approach to Therapy in Patients with Newly Diagnosed Type 2 Diabetes” Dia Care-2013-DeFronzo-S127-38

1. Metformin is the first line agent for oral treatment of Type II Diabetes because:

A. It is the most powerful in terms of lowering HbA1c
B.  It has been shown to reduce mortality more than other oral agents
C.  It is the only oral agent that has been shown to reduce macrovascular complications.
D.  It causes less weight gain than other oral agents
E.  It is the only oral agent shown not to lose its potency with longterm use.
F. It does not cause hypoglycemia.
G. It directly targets the primary pathophysiologic mechanism underlying Type II Diabetes
H. It has been shown to delay the need to begin insulin longer than other oral agents
I. All of the above

2.  What is the incretin effect?

3.  Regarding incretin mimetics, select all of the answers below that are true:

A. GLIP, GIP, and GLIP-1 are the identified incretin hormones
B. Glipizide targets both GLIP and GLIP-1.
C. The frequency of dosing of incretin mimetics from most frequent to least frequent is: byetta, victoza, byurdeon
D. The most frequent side effect is nausea.
E. They work by accelerating gastric emptying, stimulating insulin secretion by islet cells, and suppressing glucagon secretion

4.  Match the diabetes drug with its mechanism:

Drugs

Mechanisms of Action
A. Acarbose 1. Insulin secretagogue
B. Glimepride 2. Amylin analogue – suppresses glucagon secretion, delays gastric emptying
C. Metformin 3, SGLT2 inhibitor; reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.
D. Pioglitazone 4. Alpha glucosidase inhibitor – works in the intestines to slow the digestion of some carbohydrates so that after-meal blood glucose peaks are not so high
E. Victoza 5. GLP-1 analogue – inhibits glucagon secretion, delays gastric emptying, enhances insulin secretion
F. Invokana 6. reduces hepatic gluconeogenesis and glycogenolysis, as well as enhancing peripheral glucose uptake and enhancing insulin sensitivity
G. Nateglinide 7. Decreases  insulin resistance by causing conformational change in insulin receptors in muscle
H. Pramlintide 8. Sensitizes muscle, fat and liver cells to the effects of insulin (both endogenous and exogenous insulin) by modulating the peroxisome proliferator‐activated receptor gamma

 

5 Which of the following drugs have a mechanism of action that targets postprandial elevations of glucose?

A. Exenatide
B. Prandin
C. Postprandin
D. Insulin Glargine
E. Insulin aspart
F. Acarbose
G. Metformin
H. Invokana

6. In studies investigating the effects of bariatric surgery on Type II DM, the rates of remission from procedures involving intestinal bypass is:

A. 0-10%
B. 10-20%
C. 20-30%
D. 40-50%
E. >50%

7. Try to quantify the risk of side effects of various diabetes medications by giving hazard ratios, relative risk, and/or number needed to harm:

A. What is the risk of bladder cancer with use of actos?
B.  What is the risk of pancreatitis from using byetta?
C.  What is the risk of medullary carcinoma of the thyroid with use of victoza?
D.  What is the risk of pancreatitis and pancreatic cancer with use of Januvia?
E.  What is the risk of lactic acidosis with use of metformin in patients with creatinine between 1.5-2.0?

8.  Which of the following are true regarding sulfonylureas?

A. The ADA recommends them as the next drug to add on if metformin alone provides insufficient control.
B. They are usually ineffective when the patient requires more than minimal doses of insulin to control fasting blood sugar.
C. They maintain their effect after other oral agents have failed to control diabetes.
D. They are more effective in IFG than IGT.

9.  Match the clinical trial with the conclusion:

 

Trial

Conclusion
A. ACCORD 1. With intensive glucose control, the incidence of microvascular complications in Type I diabetics is reduced.
B. ACCORD – BP 2. With intensive glucose control, the incidence of microvascular complications in Type II diabetics is reduced.
C. ACCORD – Lipid 3. The addition of fenofibrate to statin therapy did not reduce the incidence of macrovascular complications
D. STENO – 2 4.  Poorly controlled diabetic veterans randomized to intensive glucose control (HbA1c < 6) did not have reduced macrovascular outcomes compared to those randomized to usual care.
E. DCCT 5.  Lifestyle interventions (modest weight loss and moderate increase in exercise) were more effective than metformin in preventing progression of pre-diabetes to diabetes and both were more effective than placebo.
F. UKDPS 6.  Older (>55 yo) diabetics with a history of microvascular or macrovascular complications or at least one other risk factor for vascular randomized to intensive glucose control (HbA1c < 6.5) did not have fewer macrovascular events than those randomized to usual care
G. DPP 7.  Diabetics with either a history of cardiovascular events or significant cardiovascular risk who were randomized to intensive treatment (A1c < 6.0) had an increase in CV mortality and overall mortality over those treated in the usual care (A1C of7.0‐7.9%) arm
H. ADVANCE 8.  Diabetics with either a history of cardiovascular events or significant cardiovascular risk who were treated to target BP of 120/80 did not have fewer CV events than those treated to target BP of 140/90
I. VADT 9.  In diabetics with persistent microalbuminuria  intensive multifactorial invertention with tight glucose regulation and the use of RAAS blockers, ASA, and statins  had sustained beneficial effects with respect to vascular complications and mortality over those treated with usual care.