1. Identify prediabetes in patients based on impaired fasting glucose and impaired glucose tolerance values.

2. Describe mechanisms of action of medications for diabetes.

3. Prescribe a therapeutic regimen for diabetes based on data and clinical findings.

4. Describe the patient-centered medical home model.

5. Discuss parameters in a patient-centered medical home for diabetics.

Practical Strategies for Improving Diabetes Care
Steven V. Edelman, MD, Professor of Medicine, Division of Endocrinology & Metabolism, University of California, San Diego, School of Medicine

Introduction: incidence of types 1 and 2 diabetes increasing; estimated 23 million people in United States affected; >4000 people/day diagnosed with diabetes; poorly controlled diabetes can lead to complications of eye, kidney, nerve, and heart

Classification of diabetes: type 1 diabetes—in past, known as juvenile-onset, insulin-dependent, or brittle diabetes; can occur at any age (eg, patients with latent autoimmune diabetes [LADA] can become affected at age 69 yr); type 2 diabetes—in past, known as adult-onset, non-insulin-dependent, or stable diabetes; can be diagnosed in children; difficulties—type 1 diabetes commonly misdiagnosed, because some patients do not become ketoacidotic and have slower β-cell destruction (thin elderly patients may respond to oral agents initially, then quickly fail and require insulin); patients sometimes have no risk factors associated with type 2 diabetes (eg, positive family history of type 2 diabetes, dyslipidemia, hypertension)

Fasting blood glucose (FBG): normal—FBG <100 mg/dL; diabetes—≥126 mg/dL on 2 occasions; impaired fasting glucose (IFG)—100 to 126 mg/dL; indicates prediabetes

Glucose tolerance testing: diabetes—>200 mg/dL; normal—<140 mg/dL; impaired glucose tolerance (IGT)—140 to 200 mg/dL; indicates prediabetes; because of rapid β-cell destruction by circulating autoantibodies, natural history of type 1 diabetes slower than that of type 2 diabetes

Prevention of macrovascular disease: Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, Veterans Affairs Diabetes Trial (VADT), and Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial showed controlling blood glucose had no significant effect on macrovascular disease; intensive group in ACCORD trial had higher mortality rate than conventionally treated group; continue treating patients early, aggressively, and safely; control blood glucose to prevent microvascular disease, and prevent macrovascular disease with, eg, antihypertensive agents

Hemoglobin (Hb) A1C -derived average glucose (ADAG): average blood glucose calculated by (Hb A1C x 28.5)- 45.4; eg, patient with Hb A1C of 6.7% has ADAG of 146 mg/dL

Pathophysiology: pancreas— β-cells secrete glucagon; in type 2 diabetes, inappropriate hypersecretion of glucagon occurs especially after eating (can be addressed with, eg, exenatide [Byeta], pramlintide [Symlin], and dipeptidyl peptidase-IV [DDP-IV] inhibitors); liver—inappropriate hypersecretion of glucose occurs (usually at night; can be addressed with metformin [eg, Glucophage]); hepatic glucose production driven by excess glucagon; skeletal muscle and fat—insulin resistance; natural history of type 2 diabetes—in early stages, patients asymptomatic with insulin resistance and hyperinsulinemia; body adapts by increasing insulin secretion; β-cells begin to fail; hepatic glucose production increases; FBG and postprandial blood glucose increase; diagnosis usually made; diagnosis during asymptomatic stage may help slow natural history

American Diabetes Association (ADA) algorithm: if no contraindications, begin metformin immediately, then 1) add basal insulin, sulfonylurea, or insulin sensitizer, 2) use 1 of other 2 agents not used in earlier stage, 3) use more intensive insulin regimens; adding to metformin—approved by Food and Drug Administration (FDA); sulfonylurea or meglitinide; insulin secretagogue; insulin sensitizer; DPP-IV inhibitor; incretin mimetic; basal insulin

Sulfonylureas: speaker recommends against use as first-line agent (lower doses should be used later, if patient almost at goal with other agents); A Diabetes Outcome Progression Trial (ADOPT)—4500 drug-naïve patients randomized to sulfonylurea and metformin or rosiglitazone and metformin; sulfonylurea and metformin appears to work fastest, but fails over time at greater rate than metformin and rosiglitazone

Insulin sensitizers: reduce insulin resistance in skeletal muscle; lead to durable glycemic control with no hypoglycemia; raise high-density lipoprotein (HDL) levels; lower small-dense low-density lipoprotein (LDL) levels (total LDL levels may increase); concerns—weight gain; edema; precipitated congestive heart failure (CHF); bone fractures in women; rosiglitazone—controversial meta-analysis suggested rosiglitazone causes myocardial infarctions (MIs); prospective long-term studies (eg, ACCORD trial and VADT) looked at safety data and found no association between rosiglitazone and MIs; good option for prevention of diabetes in patients with prediabetes (important to treat insulin resistance early); ADOPT saw 63% relative risk reduction of rosiglitazone over sulfonylurea (32% over metformin)

Side effects seen in ADOPT: gastrointestinal (GI)—greatest with metformin; few with thiazolidinediones (TZDs) or sulfonylureas; edema—TZDs can cause fluid retention and edema (does not equate to CHF); highest in rosiglitazone group; hypoglycemia—sulfonylureas stimulate pancreas to secrete insulin; more likely in newly diagnosed type 2 diabetics; MI—for fatal MI, no clinical significant difference; for nonfatal MI, rosiglitazone and metformin equivalent; rates low; CHF—rates between metformin and rosiglitazone equal (may be associated with new diagnoses); precipitated CHF serious risk factor for patients on TZDs with low ejection fraction; stroke—same for both groups; TZDs tend to preserve β- cell failure (studies show patients maintained Hb A1C levels)

Incretin mimetics: only available form, exenatide; mechanism of action—glucose-dependent insulin secretion; glucose-dependent glucagon suppression; induces satiety and reduces appetite; controls gastric motility; benefits—Hb A1C reduction; weight loss; minimal side-effect profile; no hypoglycemia (if not used with sulfonylurea or insulin); concerns—mild nausea on initiation; pancreatitis (rare); incretin effect—when oral glucose leads to higher insulin secretion than intravenous glucose; incretin effect blunted and abnormal in type 2 diabetes; glucagon-like peptide-1 (GLP-1) most well-characterized incretin; after eating, GLP-1 released from L cells of small intestine, leading to glucose-dependent insulin secretion by pancreas; α cells suppress glucagon; appetite decreases; GLP-1 controls peristaltic motion of stomach (important in regulating glucose levels throughout day); patients with diabetes have gastric hypermotility (contributes to elevated postprandial blood glucose); in people without diabetes, glucagon decreases on glucose tolerance testing; people with type 2 diabetes have relative insulin deficiency and increased glucagon (contributes to high postprandial blood glucose)

Incretin-related therapies: hormones that mimic GLP-1 (eg, exenatide); GLP-1 analogue (not currently available); incretin enhancers (DPP-IV inhibitors; sitagliptin [Januvia]) block DPP-IV enzyme that breaks down GLP-1

3-yr exenatide extension study: Hb A1C dropped slightly >1% and maintained for 3 yr; starting with higher baseline (Hb A1C >9%) resulted in 2% reduction (Hb A1C of 7%); weight loss of 12 lb maintained for 3 yr; 84% of patients had reduction in Hb A1C and weight loss

Adding exenatide and/or basal insulin: for patients who fail metformin or 2 oral agents; studies—1) randomized patients to exenatide or insulin glargine at night; Hb A1C dropped equally in both groups (1.4%); use of basal insulin in combination with exenatide not currently indicated by FDA; insulin users gained weight while exenatide users lost weight; hypoglycemia higher with insulin; 2) patients failing oral agents placed on exenatide bid or insulin aspart (Novolog Mix 70/30; analogue mixture); glycemic control equal (exenatide group slightly better [not clinically significant]), but exenatide group had 12-lb difference in weight loss; pancreatitis and exenatide—0.34 events per 1000 patient-years; in patients with type 2 diabetes, obesity and hypertriglyceridemia often increases risk; once- weekly exenatide—study found 2% reduction in Hb A1C compared to 1.5% with exenatide, 10 µg bid; 75% of patients had Hb A1C <7%; both groups lost 8 to 9 lb; home use of exenatide—BD Ultra-Fine Mini pen needle recommended; refrigeration not required; no need to increase home glucose monitoring

Incretin enhancers: inhibit enzyme that breaks down endogenous GLP-1; benefits—once-daily oral administration; good side-effect profile; concerns—dose must be adjusted for renal insufficiency; hypersensitivity reactions (eg, Stevens-Johnson syndrome; rare); sitagliptin (Januvia)—can be used alone or in combination with metformin, thiaglitazone, or sulfonylurea; results in additive 0.6% to 0.9% reduction in HB A1C ; in patients with renal insufficiency, reduce dose by 50% to 75%, depending on creatinine clearance; available in 25-, 50-, and 100-mg tablets

Difference between DPP-IV inhibitors and incretin mimetics: both lead to significant drops in Hb A1C ; no weight loss or gain with DPP-IV inhibitors; GI side effects (eg, nausea) with incretin mimetics; no GI side effects with Januvia; both have low rates of hypoglycemia, especially when used alone; mechanisms of action different, but effects similar

Basal insulin: suppresses hepatic glucose production; improves morning blood glucose; minimum weight gain and risk for hypoglycemia; effective way to start insulin therapy in patients with type 2 diabetes; insulin suspension, isophane (NPH), insulin detemir, or insulin glargine (Lantus) traditionally used at bedtime; occasionally, premixed insulin used before dinner; treat-to-target study—patients failing oral therapy received NPH or insulin glargine; in 18 wk, mean Hb A1C dropped from 8.6% to <7.0%; NPH and insulin glargine highly effective, but significant reduction of mild hypoglycemia at night seen with NPH (no difference in severe hypoglycemia); starting therapy—patients need 0.5 units/ kg (eg, patient who weighs 220 lb starting on 10 units, needs 40-50 units); follow-up within 1 wk; when blood glucose begins to rise, allow patient to “take over in their own algorithm” to avoid discouragement; patient self-directed titration—motivates testing; set individual goal; increase dose by 1 unit/day until morning blood glucose at goal; provide instructions; insulin pens convenient and protect insulin against heat and light which can reduce potency of insulin

Treatment strategies: change over time; start with metformin; add 1 to 3 oral agents; treat patients with progressed disease (eg, exhausted pancreas) similarly to type 1 diabetes (ie, use basal insulin and fast-acting insulin before meals); polypharmacy—patients commonly need, eg, 3 drugs for diabetes, 1 drug for cholesterol, and 3 blood pressure (BP) agents; educate patients about safety and efficacy of natural and herbal products; make therapeutic changes earlier (eg, treat patient as Hb A1C approaches 7%, not 8%-9%); insulin pumps—effective for type 2 diabetes; allow different basal rates; amount of bolus can be adjusted depending on meal; continuous glucose monitoring— important for patients with type 1 diabetes and subset of patients with type 2 diabetes; available manufacturers and/ or systems include Dexcom, Medtronic MiniMed, Guardian, and Abbott FreeStyle Navigator; benefits patients with type 1 diabetes, insulin-requiring type 2 diabetes, frequent severe hypoglycemia, or gestational diabetes

Quality-driven Care for Diabetic Patients
Mary Elizabeth Roth, MD, MBA, Associate Chief Academic Officer, Geisinger Health System, Wilkes Barre, PA

Patient-centered medical home model: approach to providing comprehensive primary care for people of all ages and medical conditions; way for physician-led medical practices chosen by patients to integrate health care services for patients who confront complex and confusing health care systems; quality improvement is hallmark of new system; patient actively involved in decision making; emphasizes new communication techniques (eg, e-mail, electronic system for patients to monitor laboratory test results) to inform patients about progression of diabetes; quality improvement involves patient and family

Diabetes care: competency issue; difficult for patients whose lifestyles include high-carbohydrate, high-fat diets and no exercise to transition to healthy behaviors that support management of diabetes

5 As of patient education: 1) assess patients’ health risks; 2) advise patients on what might be best for their care; be clear, and personalize care; 3) agree; talk to patients about what they want to do; listen and agree on steps; 4) assist patients in planning and performing behavioral changes to achieve diabetic control; 5) arrange; facilitate, eg, group education, exercise memberships

Parameters of Diabetes Physicians Recognition Program: certified by National Committee for Quality Assurance (NCQA) and ADA; Hb A1 C control—should be <7%; consider what percentage of patients have Hb A1C >9% (indicates poor control); BP control—consider percentage of patients with BP >140/90 mm Hg vs <130/80 mm Hg; LDL control—in high-risk patients, LDL should be <70 mg/dL; according to ADA, LDL should be <100 mg/dL in all persons with diabetes; consider percentage of patients with LDL >130 mg/dL; percentage of patients who undergo yearly eye examinations; frequency and thoroughness of foot examinations; yearly nephropathology assessment (eg, checking for microalbuminuria); assessment of tobacco smoking status and cessation advice or treatment; considerations— whether practice chooses to put medical home in place that uses parameters of care from NCQA or ADA; how family physicians, office staff, and others can activate medical home to facilitate best care; other aspects of care to lower risk for microvascular and macrovascular disease

Pneumococcal vaccines: speaker’s facility—in March 2006, ≈53% of patients had received pneumococcal vaccine; evidence-based medicine suggests all diabetics (especially patients >65 yr of age) should be vaccinated; reminders to physicians to address vaccine during routine care important (eg, helpful to give vaccine at same time as influenza vaccine); in April 2008, 80% to 87% of patients with diabetes, patients >65 yr of age, and patients >65 yr of age at high risk (eg, patients with coronary artery disease); between October 1 and December 31, 4000 to 5000 people received pneumococcal vaccine at time of influenza vaccination; parameter of care of individual physician, site, and system

Reaching parameters of best practice: consider incentive program; speaker’s facility—≈2.4% of patients had 9 of 9 parameters met (projected goal, 1.6%); concept of medical home is personal communication with physician to keep within best practice guidelines and lower ultimate costs to increase better quality outcomes