The Many Faces of T2DM in Long-term Care Facilities

The Many Faces of T2DM in Long-term Care Facilities Question #1 Which of the following is a risk factor for increased hypoglycemia in older patients that may suggest the need to relax hyperglycemia treatment goals? A. Dementia B. Gastroparesis C. Living in a group home D. Obesity Patients with dementia are more likely to experience hypoglycemia. Other factors that can increase the risk of hypoglycemia in older patients include changes in mental status that impair the perception of or response to hypoglycemia, increased polypharmacy and noncompliance with medications, dependence or isolation that limits receipt of early treatment for hypoglycemia, impaired renal or hepatic metabolism, and poor oral intake. Question #2 In The Diabetes in Aging Study, which of the following was NOT among the top 3 most common nonfatal comorbidities that led experts to modify treatment goals in older patients? A. Acute hyperglycemic events B. Coronary artery disease C. Diabetes of long duration D. Hypoglycemia The risk of severe hypoglycemia likely represents the greatest barrier to type 2 diabetes mellitus (T2DM) care, particularly in older patients and in those with T2DM of long duration. Data from this study, as well as from ACCORD, ADVANCE, and VADT, showed that along with these factors, the presence of coronary artery disease or atherosclerosis was associated with a greater risk of death. Higher glycated hemoglobin (A1C) level or acute hyperglycemia was not associated with increased mortality, leading experts to recommend more relaxed goals for older patients with comorbid conditions. Question #3 At the time of diagnosis of diabetes, about how much beta-cell function is believed to be intact? A. 100% B. 90% C. 75% D. <50% 1

At the time of diagnosis, 50% to 70% of beta-cell function may already be gone. Knowing the status of a patient s beta-cell function can influence treatment selection. Many patients with long-duration T2DM, including older patients, continue to be treated with medications with mechanisms of action that require intact beta cells (eg, sulfonylureas) rather than exogenous insulin. Question #4 Which of the following is CORRECT about sliding-scale insulin? A. It combines basal insulin plus prandial insulin. B. It is the same as correction insulin. C. It uses rapid-acting insulin analogs rather than regular insulin to correct hyperglycemia while minimizing the risks of hypoglycemia. D. Its use should be discouraged because it is not physiologic in that it fails to provide basal or background insulin coverage. Combining basal insulin plus prandial insulin is called the basal-bolus concept. This approach more closely reflects physiologic insulin scenarios and is the best way to manage glycemia in long-term care facilities. The basal-bolus approach differs from a sliding-scale approach in that with the latter, rapid-acting insulin is given alone without a background of scheduled basal insulin. The use of sliding-scale insulin is to be discouraged because it is not physiologic in that it fails to provide basal or background insulin coverage, among other flaws. Correction insulin, which is insulin used with scheduled prandial and basal insulin, is an accepted form of insulin therapy. It is different from sliding-scale insulin and is based on an individual s insulin sensitivity/resistance level. Correction insulin therapy uses rapid-acting insulin analogs rather than regular insulin to correct hyperglycemia while minimizing the risks of hypoglycemia. Question #5 If deciding to recommend the use of prandial insulin to intensify therapy in older patients, which of the following approaches would you choose to minimize the risk of hypoglycemia? A. Basal-bolus therapy B. Basal-plus therapy with one injection of a rapid-acting insulin analog C. Premixed insulin (discontinue basal insulin) D. Addition of regular insulin to basal insulin The correct answer is B Basal-plus therapy with one injection of a rapid-acting insulin analog before the largest meal is a cautious way to begin to address postprandial hyperglycemia in patients not meeting A1C goals on basal insulin therapy alone. Basal-bolus therapy with multiple daily injections is associated with more hypoglycemia than basal-plus therapy. Therapy with regular (short-acting) insulin added to basal insulin is associated with more 2

hypoglycemia than use of prandial insulin analogs because regular insulin has a longer onset and offset of action and must be given 30 minutes prior to a meal (and counts on the patient eating), whereas rapid-acting insulin can be given just prior to eating. Premixed insulin combines a prandial and basal insulin in a single injection and is therefore a convenient, simple option for addressing fasting and postprandial hyperglycemia, but it is a fixed-dose combination and thus requires regularity of meals/carbohydrate ingestion, which is sometimes difficult to ensure in older patients. Premixed insulin is associated with higher risks of hypoglycemia because it requires regularity of routine. Question #6 All of the following are features of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) EXCEPT: A. May reduce the dose needed of basal insulin B. May result in weight loss or at least in no weight gain C. Similar efficacy to insulin without hypoglycemia risks D. Well tolerated with low risk of adverse effects GLP-1 RAs have been compared with insulin and have been found to result in generally comparable A1C reductions with less hypoglycemia and without the weight gain typically observed with insulin therapy. The major adverse effect of GLP-1 RAs are gastrointestinal in nature (primarily nausea and diarrhea), which decline with treatment persistence. When used with basal insulin, the short-acting exenatide and the once-daily liraglutide have improved A1C levels, have sometimes reduced the doses needed of basal insulin, and have diminished weight. Question #7 All of the following are CORRECT regarding postprandial hyperglycemia EXCEPT: A. Dipeptidyl peptidase-4 (DPP-4) inhibitors target postprandial hyperglycemia. B. Loss of postprandial glycemic control precedes stepwise deterioration of fasting glucose with worsening diabetes. C. Postprandial hyperglycemia predominates at higher A1C levels. D. Postprandial hyperglycemia is linked with macrovascular complications. The correct answer is C Current treatment recommendations suggest the addition of DPP-4 inhibitors, GLP-1 RAs, or prandial insulin for treatment intensification when basal insulin is no longer effective in achieving treatment goals. Postprandial plasma glucose is the predominant contributor in patients with satisfactory to good control of diabetes (lower A1C levels). Loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes. Postprandial hyperglycemia has been independently linked to a greater risk of cardiovascular (CV) (macrovascular) complications. 3

Question #8 Which of the following agents is NOT metabolized by the kidney and does not have dosing alterations in patients with renal impairment? A. Exenatide B. Dulaglutide C. Glyburide D. Sitagliptin E. Canagliflozin The correct answer is B Exenatide is renally metabolized and is contraindicated in patients with severe renal impairment or end-state renal disease. Liraglutide is not renally metabolized but is broken down through enzymatic degradation. The newer once-weekly GLP-1 RAs, dulaglutide and albiglutide, do not require dose adjustment in patients with renal impairment. All of the DPP-4 inhibitors except linagliptin are renally metabolized and require dose adjustment depending on the level of renal impairment. SGLT-2 inhibitors work via the kidney, and therefore it is not surprising that dose adjustment is necessary depending on the level of renal function. The sulfonylurea glyburide is metabolized in the kidney to an active metabolite that is also dependent on kidney function for metabolism; it should be avoided in patients with chronic kidney disease. Question #9 Which of the following is an example of a duplicative mechanism of action drug-drug interaction that should be brought to the attention of the prescribing clinician? A. GLP-1 RA + DPP-4 inhibitor B. Metformin + GLP-1 RA C. Insulin + SGLT-2 inhibitor D. Metformin + thiazolidinedione Patients generally should not be treated concurrently with a GLP-1 RA and a DPP-4 inhibitor. Although there are differences between the two classes of medications, both act on the incretin system. These agents share some basic mechanisms of action, but DPP-4 inhibitors do not slow gastric emptying rate, promote satiety, or reduce food intake, and so do not promote weight loss. However, the use of the two together would be considered duplicating some basic therapeutic actions. It is better to use combination therapies with agents that have complementary mechanisms of action, such as some of the other combinations listed. Question #10 Which of the following is the most common cause of death for patients with T2DM that clinicians should be aware of when considering the adverse-effect profile of antihyperglycemic agents? 4

A. CV disease B. End-stage renal disease C. Nondiabetic ketoacidosis D. Stroke Because CV disease (CVD) is the major cause of death for patients with T2DM, attention to CV risk factors and choice of antihyperglycemic agents with good CV safety is especially important. Some sulfonylureas increase CV risk presumably by preventing protective ischemic cardiac preconditioning. Rosiglitazone increases risk of myocardial infarction and death possibly by increasing serum triglycerides and LDL-cholesterol levels. GLP-1 RAs have been shown to improve some CV risk factors, such as lowering blood pressure and improving lipid profiles. Only insulin-sensitizing drugs such as metformin and pioglitazone have been consistently shown to reduce CV risk. 5