Understanding the Diabetes Care Process Pfizer Medical Affairs

Transcription

1 Understanding the Diabetes Care Process Pfizer Medical Affairs

2 Overview of Diabetes 1 Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both Chronic hyperglycemia is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels Abnormalities in carbohydrate, fat, and protein metabolism result from deficient action of insulin on target tissues Deficient insulin action results from inadequate insulin secretion and/or diminished tissue responses to insulin 1. American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S81-S90. 2

3 Prevalence and Burden

4 Prevalence of Diabetes in the United States Diabetes affects 29.1 million people in the US (9.3% of the population) 1 Prevalence of diabetes by age group: 1 20 years: 28.9 million (12.3%) 65 years: 11.2 million (25.9%) Diabetes is the 7 th leading cause of death in the US (2010) 1 Diabetes is the leading cause of kidney failure, nontraumatic lowerlimb amputations, and new cases of blindness among adults in the US 2 A major cause of heart disease and stroke % (8.1 million) 72.2% (21 million) Diagnosed Undiagnosed 1. Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, Atlanta, GA: U.S. Department of Health and Human Services; CDC. National Diabetes Fact Sheet: Atlanta, GA: Department of Human Services, Centers for Disease Control and Prevention;

5 Age-Adjusted Prevalence of Diagnosed Diabetes Among US Adults: Age-adjusted percentage of US adults with diagnosed diabetes. 1. CDC National Diabetes Surveillance System. Accessed February 22,

6 Age-adjusted Prevalence of Diagnosed Diabetes and Obesity Among US Adults 1 Diabetes No Data <4.5% 4.5% 5.9% 6.0% 7.4% 7.5% 8.9% >9.0% Obesity (BMI 30 kg/m 2 ) No Data <14.0% 14.0% 17.9% 18.0% 21.9% 22.0% 25.9% >26.0% 1. CDC National Diabetes Surveillance System. Accessed February 22, 2016.

7 Microvascular and Macrovascular Complications of Diabetes Microvascular Complications Retinopathy Most frequent cause of new cases of blindness among adults aged years 1 Nephropathy The leading cause of kidney failure, accounting for 44% of all new cases 2 Neuropathy 60% to 70% of people with diabetes have mild to severe forms of neuropathy 2 More than 60% of nontraumatic lower-limb amputations occur in people with diabetes 2 20% of people with diabetes have painful DPN 3 Macrovascular Complications CVD is the leading cause of morbidity and mortality for individuals with diabetes 4 CVD is the largest contributor to the direct and indirect costs of diabetes 4 Cerebrovascular Disease Coronary Heart Disease Peripheral Arterial Disease CVD = cardiovascular disease (acute coronary syndromes, myocardial infarction, stable or unstable angina, coronary/arterial revascularization, stroke, transient ischemic attack, peripheral arterial disease) 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80 2. American Diabetes Association. Fast facts : data and statistics about diabetes. FM-LYR Accessed February 22, Tesfaye S, et al. Diabetes Metab Res Rev. 2012;28(suppl 1):S8-S Fox CS. Trends Cardiovasc Med. 2010;20:90 95.

8 Economic Costs of Diabetes in the U.S. in 2012 Estimated Cost of Diagnosed Diabetes (In Billions of $) $200 $150 $100 $50 $0 Total Estimated Cost of Diagnosed Diabetes in 2012 $245 Billion $176B Direct Medical Costs $69B Reduced Productivity American Diabetes Association. Diabetes Care 2013;36: Average medical expenditures for people diagnosed with diabetes is $13,700 per year, of which $7,900 is attributed to diabetes 2.3 times higher than expenditures in the absence of diabetes Care for people with diagnosed diabetes accounts for more than 1 in 5 health care dollars in the U.S. More than half is directly attributable to diabetes. Hospital inpatient care is the single largest contributor to the attributed medical cost of diabetes (43% of total medical cost) Medications represent 28% of all health expenditures attributed to diabetes

9 Classification and Diagnosis of Diabetes

10 Etiologic Classification of Diabetes Type 1 diabetes Type 2 diabetes Gestational diabetes mellitus (GDM) Other types of diabetes 2 β-cell destruction, usually leading to absolute insulin deficiency 1 Progressive insulin secretory defect on the background of insulin resistance 1 Diabetes diagnosed in the 2 nd or 3 rd trimester of pregnancy that is not clearly overt diabetes 1 Genetic defects in β-cell function or insulin action Diseases of the exocrine pancreas Endocrinopathies Drug or chemical-induced Infections Uncommon forms of immune-mediated diabetes Genetic syndromes associated with diabetes 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22 2. American Diabetes Association. Diabetes Care 2014;37(suppl1):S81-S90.

11 Type 1 Diabetes Accounts for 5-10% of those with diabetes 1 Cellular-mediated autoimmune destruction of the β-cells of the pancreas, usually leading to absolute insulin deficiency 1 One or more markers of β-cell immune destruction are present in 85-90% of individuals when fasting hyperglycemia is detected 2 Islet cell autoantibodies 1 Autoantibodies to insulin, glutamic acid decarboxylase (GAD 65), tyrosine phosphatases IA-2, IA-2β, zinc transporter 8 (ZnT8) 1 Most likely results from an interplay of multiple genes and environmental factors 3 Rate of β-cell destruction is quite variable 1 Commonly occurs in childhood and adolescence, but it can occur at any age 1 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22 2. American Diabetes Association. Diabetes Care 2014;37(suppl 1):S81-S90 3. Ali O. Type 1 Diabetes Mellitus: Epidemiology, Genetics, Pathogenesis, and Clinical Manifestations. In: Poretsky L, ed. Principles of Diabetes Mellitus, 2 nd ed. New York, NY: Springer Science+Business Media; 2010:

12 Type 2 Diabetes Accounts for ~90-95% of those with diabetes 1 Due to a progressive loss of insulin secretion on the background of insulin resistance 1 Insulin resistance alone is generally insufficient to generate hyperglycemia; impaired insulin secretion is required 2 Fasting insulin levels appear normal or elevated, but are relatively low given the degree of coexisting hyperglycemia 2 Basal insulin levels eventually fail to keep up and may even decline 2 Associated with a strong genetic predisposition that is polygenic in nature 1,2 Genetic risk is largely expressed in the setting of environmental factors such as obesity and sedentary lifestyle 3 Often goes undiagnosed for years because hyperglycemia develops gradually 1 Many require insulin therapy for optimal glycemic control over time 2 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S Inzucchi SE, Sherwin RS. Type 2 Diabetes Mellitus. In: Goldman L, Schafer FM-LYR-0024 AI, ed. Goldman s Cecil Medicine. 24th ed. Philadelphia, PA: Elsevier Saunders; 2012: Nathan DM. JAMA. 2015;314(10):

13 Criteria for the Diagnosis of Diabetes 1 Fasting plasma glucose (FPG) 126 mg/dl* Fasting defined as no caloric intake for at least 8 hours OR 2-hr Plasma Glucose 200 mg/dl during OGTT* Performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water OR A1C 6.5%* Perform in lab using NGSP-certified method and standardized to the DCCT reference assay OR Random Plasma Glucose 200 mg/dl In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis * In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing NGSP = National Glycohemoglobin Standardization Program; DCCT FM-LYR-0024 = Diabetes Control and Complications Trial; OGTT = oral glucose tolerance test 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22.

14 Testing for Type 1 Diabetes Risk 1 Incidence and prevalence of type 1 diabetes is increasing Measuring islet autoantibodies in relatives of those with type 1 diabetes may identify individuals who are at risk for developing type 1 diabetes Consider referring relatives of those with type 1 diabetes for antibody testing for risk assessment in the setting of a clinical research study ( Individuals who test positive will be counseled about the risk of developing diabetes, diabetes symptoms, and DKA prevention Numerous clinical studies are being conducted to test various methods of preventing type 1 diabetes in those with evidence of autoimmunity ( 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22.

15 Testing for Type 2 Diabetes and Prediabetes in Asymptomatic Adults 1 Testing should be considered in adults of any age who are overweight or obese (BMI 25 kg/m 2 or 23 kg/m 2 in Asian Americans) and who have one or more additional risk factors for diabetes For all patients, testing should begin at age 45 years Diabetes Risk Factors Physical inactivity First-degree relative with diabetes High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander) Women who delivered a baby >9 lb or were diagnosed with GDM Hypertension ( 140/90 mmhg or on therapy) HDL cholesterol <35 mg/dl and/or triglyceride level >250 mg/dl Women with polycystic ovary syndrome A1C 5.7%, IGT, or IFG on previous testing Other conditions associated with insulin resistance (severe obesity, acanthosis nigricans) History of CVD GDM = gestational diabetes mellitus; IGT = impaired glucose FM-LYR-0024 tolerance; - 1-0IFG = impaired fasting glucose 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22.

16 Testing for Type 2 Diabetes and Prediabetes in Asymptomatic Adults 1 FPG, 2-h PG after 75-g OGTT, and A1C are equally appropriate to test for prediabetes and diabetes If results are normal, testing should be repeated at a minimum of 3-year intervals Consider more frequent testing depending on initial results and risk (e.g., those with prediabetes should be tested yearly) In patients with prediabetes or diabetes, identify and, if appropriate, treat other cardiovascular disease risk factors Consider testing in children and adolescents who are overweight or obese and have two or more additional risk factors for diabetes FPG = fasting plasma glucose; PG = plasma glucose; OGTT FM-LYR-0024 = oral glucose tolerance test; 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22.

17 Testing for Type 2 Diabetes and Prediabetes in Children and Adolescents 1 Consider testing in children and adolescents who are overweight or obese and have 2 additional risk factors BMI >85 th percentile for age and sex, weight for height >85 th percentile, or weight >120% of ideal for height Age of initiation: 10 years or at onset of puberty, if puberty occurs at a younger age Frequency: Every 3 years Diabetes Risk Factors Family history of type 2 diabetes in first- or second-degree relative Race/ethnicity: African American, Latino, Native American, Asian American, Pacific Islander Maternal history of diabetes or GDM during the child s gestation Signs of insulin resistance or conditions associated with insulin resistance acanthosis nigricans, hypertension, dyslipidemia, polycystic ovary syndrome, small-forgestational-age birth weight Persons aged 18 years; GDM = gestational diabetes mellitus 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22.

18 Categories of Increased Risk for Diabetes (Prediabetes) 1 Impaired Fasting Glucose (IFG) Fasting Plasma Glucose mg/dl ( mmol/l) * OR Impaired Glucose Tolerance (IGT) 2-hr Plasma Glucose in the 75-g OGTT mg/dl ( mmol/l) OR A1C 5.7% 6.4% For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at the higher end of the range Inform patients of their increased risk for diabetes and CVD and counsel about effective strategies to lower their risks * The World Health Organization and numerous diabetes FM-LYR-0024 organizations - define 1-0 the cutoff for IFG at 110 mg/dl (6.1 mmol/l). OGTT = oral glucose tolerance test 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S13-S22.

19 Foundations of Care and Comprehensive Medical Evaluation

20 Comprehensive Medical Evaluation 1 A complete medical evaluation should be performed at the initial visit to: Confirm the diagnosis and classify diabetes Detect diabetes complications and potential comorbid conditions Review previous treatment and risk factor control in established diabetes Begin patient engagement in the formulation of a care management plan Develop a plan for continuing care Be aware of common comorbid conditions that may complicate diabetes management Arthritis Fatty liver disease Low testosterone Cancer Fractures Obstructive sleep apnea Cognitive impairment Hearing impairment Periodontal disease Depression Heart failure Adults who develop type 1 diabetes may develop additional autoimmune disorders (e.g., thyroid or adrenal dysfunction, celiac disease) 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

21 Components of the Comprehensive Diabetes Evaluation: Medical History 1 Age and characteristics of onset of diabetes (e.g., DKA, asymptomatic lab finding) Eating patterns, nutritional status, weight history, and physical activity habits Nutrition education and behavioral support history and needs Presence of common comorbidities, psychosocial problems, dental disease Screen for depression Screen for diabetes distress History of smoking, alcohol consumption, substance use Diabetes education, self-management, and support history/needs 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35. Review of previous treatment regimens and response to therapy (A1C records) Results of glucose monitoring & patient s use of data DKA frequency, severity, cause Hypoglycemic episodes, awareness, and frequency and causes History of increased blood pressure, increased lipids, tobacco use Microvascular complications: retinopathy, nephropathy, neuropathy Macrovascular complications: coronary heart disease, peripheral arterial disease, cerebrovascular disease

22 Components of the Comprehensive Diabetes Evaluation: Physical Examination 1 Height, weight, BMI; growth and pubertal development in children/adolescents Blood pressure determination, including orthostatic measurements when indicated Fundoscopic examination Thyroid palpation Skin examination (e.g., for acanthosis nigricans and insulin injection or infusion set insertion sites) Comprehensive foot examination Inspection Palpation of dorsalis pedis and posterior tibial pulses Presence/absence of patellar and Achilles reflexes Determination of proprioception, vibration, and monofilament sensation 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

23 Components of the Comprehensive Diabetes Evaluation: Laboratory Examination 1 A1C, if results not available within past 3 months If not performed or available within past year: Fasting lipid profile, including total, LDL, and HDL cholesterol and triglycerides, as needed Liver function tests Spot urinary albumin-to-creatinine ratio Serum creatinine and estimated glomerular filtration rate Thyroid-stimulating hormone in patients with type 1 diabetes, dyslipidemia, or women over age 50 years 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

24 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35. Components of the Comprehensive Diabetes Evaluation: Referrals 1 Eye care professional for annual dilated eye exam Family planning for women of reproductive age Registered dietitian for medical nutrition therapy Diabetes self-management education/support Dentist for comprehensive periodontal examination Mental health professional, if indicated

25 Ongoing Care Management 1 A Collaborative and Integrated Team Approach The patient, family, physician, and other health care team members should formulate the management plan Foundations of care are integral components: diabetes self-management education/support, medical nutrition therapy, smoking cessation, physical activity, immunizations, psychosocial care Enable individuals to self-manage diabetes Individualize treatment goals and plans: Age Social Situation Work/School Schedule Cultural Factors Physical Activity Health Priorities Eating Patterns Comorbidities Diabetes Complications Life expectancy Preferences for care 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

26 Diabetes Self-Management Education and Support In accordance with national standards, all people with diabetes should participate in diabetes self-management education (DSME) and diabetes self-management support (DSMS) both at diagnosis and as needed thereafter. 1 Diabetes Self-Management Education (DSME): The ongoing process of facilitating the knowledge, skills, and ability necessary for diabetes self-care. 2 Diabetes Self-Management Support (DSMS): Activities that assist the person with diabetes with implementing and sustaining the behaviors needed for ongoing self-management beyond or outside of formal self-management training. Support can be behavioral, educational, psychosocial, or clinical American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S American Diabetes Association. Diabetes Care 2014;37(suppl 1):S144-S153

27 Diabetes Self-Management Education and Support 1 Four critical time points for DSME and DSMS delivery: 1. At diagnosis 2. Annually for assessment of education, nutrition, and emotional needs 3. When new complicating factors arise that influence self-management 4. When transitions in care occur Best practice of DSME is a skill-based approach focused on helping those with diabetes to make informed selfmanagement choices Multiple studies have shown that DSME is associated with: Improved diabetes knowledge Improved quality of life Improved self-care behaviors Healthy coping Lower A1C Lower costs Lower self-reported weight DSME = diabetes self-management education DSMS = diabetes self-management support 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

28 Medical Nutrition Therapy (MNT) 1 MNT is an integral component of diabetes prevention, management, and self-management education An individualized MNT program, preferably provided by a registered dietitian, is recommended for all people with type 1 or type 2 diabetes No single ideal dietary distribution of calories among carbohydrates, proteins, and fats for people with diabetes Macronutrient distribution should be individualized while keeping total calorie and metabolic goals in mind 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

29 Physical Activity 1 Exercise is an important part of the management plan: Improves blood glucose control Contributes to weight loss Reduces cardiovascular risk factors Improves well-being Adults with diabetes: At least 150 minutes/week of moderateintensity aerobic activity (50 70% of maximum heart rate) Spread over at least 3 days/week No more than 2 consecutive days without exercise Reduce sedentary time, particularly by breaking up extended amounts of time (>90 minutes) spent sitting If not contraindicated, adults with type 2 diabetes should perform resistance training at least twice weekly Children with diabetes/prediabetes: Engage in at least 60 minutes of physical activity each day 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

30 Physical Activity Considerations 1 Customize the regimen to the individual s needs Consider patient s age and previous physical activity level Start high-risk patients with short periods of low-intensity exercise and slowly increase intensity and duration Routine screening of asymptomatic diabetic patients for coronary artery disease is not recommended Perform a careful history and assess other CV risk factors Assess patients for conditions that could contraindicate certain types of exercise or predispose to injury * Consider ingesting added carbohydrate if pre-exercise glucose levels are <100 mg/dl in individuals taking insulin and/or insulin secretagogues * Uncontrolled hypertension, autonomic neuropathy, peripheral neuropathy, history of foot lesions, unstable proliferative retinopathy 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

31 Exercise in the Presence of Complications Retinopathy Peripheral Neuropathy Vigorous aerobic or resistance exercise may be contraindicated with proliferative diabetic retinopathy or severe nonproliferative diabetic retinopathy 1 Individuals with peripheral neuropathy and without acute ulceration may participate in moderate weightbearing exercise 2 Moderate-intensity walking may not lead to increased risk of foot ulcers or reulceration in those with peripheral neuropathy who use proper footwear 1 All individuals with peripheral neuropathy should wear proper footwear and examine their feet daily to detect lesions early 1 Anyone with a foot injury or open sore should be restricted to non weight-bearing activities 1 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S Colberg SR, et al. Diabetes Care. 2010;33:e147-e167.

32 Exercise in the Presence of Complications 1 Autonomic Neuropathy Albuminuria and Nephropathy Increased risk of exercise-induced injury or adverse events through: Decreased cardiac responsiveness to exercise Postural hypotension Impaired thermoregulation Impaired night vision due to impaired papillary reaction Greater susceptibility to hypoglycemia Cardiovascular autonomic neuropathy is an independent risk factor for cardiovascular death and silent myocardial ischemia Individuals with autonomic neuropathy should undergo cardiac investigation before beginning physical activity more intense than that to which they are accustomed No evidence that vigorous exercise increases the rate of progression of diabetic kidney disease No need for specific exercise restrictions 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

33 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35. Smoking Cessation Individuals with diabetes who smoke have a higher risk of cardiovascular disease, premature death, and microvascular complications of diabetes 1 Routine and thorough assessment of tobacco use is essential to prevent smoking or encourage cessation 1 Advise all patients not to use cigarettes, other tobacco products, or e-cigarettes 1 Include smoking cessation counseling and other forms of treatment as a routine component of diabetes care 1

34 Immunization 1 Provide routine vaccinations for all children and adults with diabetes 1 Influenza Vaccine Annually in all patients with diabetes 6 months of age 2 Pneumococcal Vaccine Hepatitis B Vaccine All patients with diabetes 2 years of age 1 Refer to Recommendations of the Advisory Committee on Immunization Practices (ACIP) for complete information regarding vaccine administration schedules and sequencing by age group 3 Unvaccinated adults with diabetes years of age 1 Consider in unvaccinated adults with diabetes who are 60 years of age 1 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S MMWR. 2015;64(30): Pneumococcal ACIP Vaccine Recommendations. Accessed April 1, 2016.

35 Psychosocial Assessment and Care 1 The patient s psychological and social situation should be addressed in the medical management of diabetes. Psychosocial screening and follow-up may include: Attitudes about the illness Expectations for medical management & outcomes Affect/mood General and diabetes-related quality of life Resources (financial, social, emotional) Psychiatric history Routinely screen for psychosocial problems: Depression, anxiety, diabetes-related distress, eating disorders, cognitive impairment Older adults ( 65 years) should be considered for evaluation of cognitive function and depression screening and treatment. Patients with comorbid diabetes and depression should receive a stepwise collaborative care approach for the management of depression 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S23-S35.

36 Glycemic Targets

37 Self-Monitoring of Blood Glucose (SMBG) 1 Allows patients to evaluate their individual response to therapy and assess whether glycemic targets are being achieved Results can be a useful tool for guiding medical nutrition therapy and physical activity, preventing hypoglycemia, and adjusting medications The patient s needs and goals should dictate SMBG frequency & timing Provide ongoing instruction and regular evaluation of SMBG technique, results, and the patient s ability to use SMBG data to adjust therapy Intensive Insulin Regimens a Consider SMBG: Prior to meals and snacks Occasionally postprandially At bedtime Prior to exercise When low blood glucose is suspected After treating low blood glucose until normoglycemic Prior to critical tasks (e.g., driving) Basal Insulin or Noninsulin Therapies Results may help guide treatment decisions and/or self-management Should be prescribed as part of a broader educational context Insufficient evidence regarding when to prescribe SMBG and how often testing is needed a Multiple-dose insulin or insulin pump therapy 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46.

38 Continuous Glucose Monitoring (CGM) 1 When used properly, CGM in conjunction with intensive insulin regimens is a useful tool to lower A1C in selected adults (aged 25 years) with type 1 diabetes CGM may be helpful in children, teens, and younger adults, although evidence for A1C lowering is less strong May be a supplemental tool to SMBG in those with: Hypoglycemia unawareness Frequent hypoglycemic episodes Success correlates with adherence to ongoing use of the device Assess individual readiness for continuing use of CGM prior to prescribing Robust diabetes education, training, and support are required for optimal CGM implementation and ongoing use 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46.

39 A1C Testing 1 Per Perform the A1C test: At least two times a year in patients who are meeting treatment goals and have stable glycemic control Quarterly in patients whose therapy has changed or who are not meeting glycemic goals A1C reflects average glycemia over several months and has strong predictive value for diabetes complications Use of point-of-care testing for A1C provides the opportunity for more timely treatment changes A1C does not provide a measure of hypoglycemia or glycemic variability 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46.

40 Mean Glucose Levels for Specified A1C Levels A1C-Derived Average Glucose (ADAG) Trial 1 A1C (%) Estimated Average Glucose mg/dl mmol/l Estimates are based on ~2,700 glucose measurements over 3 months per A1C measurement in 507 adults with type 1, type 2, and no diabetes. 1 The correlation between A1C and average glucose was A calculator for converting A1C into estimated average glucose (eag) is available at Nathan DM, et al. Diabetes Care. 2008;31: American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46.

41 Mean Glucose Levels for Specified A1C Levels 1 Fasting, Premeal, Postmeal, and Bedtime A1C (%) Mean Fasting Glucose (mg/dl) Mean Premeal Glucose (mg/dl) Mean Postmeal Glucose (mg/dl) Mean Bedtime Glucose (mg/dl) < SMBG data from 470 of the ADAG study participants (237 with type 1 diabetes and 147 with type 2 diabetes) were used to determine the average fasting, premeal, 90-minute postmeal, and bedtime blood glucose for predefined target HbA1c groups between 5.5 and 8.5%. 1. Wei N, et al. Diabetes Care. 2014;37:

42 Glycemic Recommendations for Nonpregnant Adults with Diabetes 1 A1C <7.0%* Preprandial capillary plasma glucose Peak postprandial capillary plasma glucose mg/dl* ( mmol/l) <180 mg/dl* (<10.0 mmol/l) * More or less stringent glycemic goals may be appropriate for individual patients. Goals should be individualized based on: Duration of diabetes Known CVD or advanced microvascular complications Age/Life expectancy Hypoglycemia unawareness Comorbid conditions Individual patient considerations Postprandial glucose may be targeted if A1C goals are not met despite reaching preprandial glucose goals. Postprandial glucose measurements should be made 1-2 hours after the beginning of the meal, generally peak levels in patients with diabetes. 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46

43 Glycemic Goals in Adults 1 Achieving an A1C target <7%: Reduces microvascular complications Reduces mortality in patients with type 1 diabetes Is associated with long-term reduction in macrovascular disease (if implemented soon after the diagnosis of diabetes) More Stringent (<6.5%) A1c Goals (if achieved without significant hypoglycemia or other adverse effects) Short duration of diabetes Type 2 diabetes treated with lifestyle or metformin only Long life expectancy No significant cardiovascular disease 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46 Less Stringent (<8%) A1c Goals History of severe hypoglycemia Limited life expectancy Advanced microvascular or macrovascular complications Extensive co-morbid conditions Long-standing diabetes when the general goal is difficult to attain despite education, monitoring, and drug treatment

44 Approach to the Management of Hyperglycemia 1 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46

45 Hypoglycemia 1 Individuals at risk for hypoglycemia should be asked about symptomatic and asymptomatic hypoglycemia at each encounter Glucose (15 20 g) a is the preferred treatment for the conscious individual: Repeat treatment if SMBG shows continued hypoglycemia 15 minutes after initial treatment Consume a meal or snack to prevent recurrence after SMBG returns to normal Glucagon should be prescribed for all individuals at increased risk of severe hypoglycemia b Instruct caregivers/family members on administration a Any form of carbohydrate that contains glucose may be used b Severe hypoglycemia is defined as hypoglycemia requiring assistance from another person SMBG = self-monitoring of blood glucose 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46

46 Hypoglycemia Hypoglycemia unawareness (or hypoglycemia-associated autonomic failure) is characterized by deficient counterregulatory hormone release and a diminished autonomic response 1 A form of functional sympathoadrenal failure that is most often caused by recent iatrogenic hypoglycemia 2 Partly reversible by avoidance of hypoglycemia 2 Hypoglycemia unawareness or one or more episodes of severe hypoglycemia: 1 Re-evaluate the treatment regimen Insulin-treated patients: Raise glycemic targets for at least several weeks to partially reverse hypoglycemia unawareness and to reduce risk of future episodes 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S39-S46 2. Seaquist ER, et al. Diabetes Care :

47 Approaches to Glycemic Treatment

48 Pharmacological Therapy for Type 1 Diabetes* Use multiple-dose insulin (MDI) injections (3-4 injections per day of basal and prandial insulin) or continuous subcutaneous insulin infusion (CSII) 1 Consider educating individuals to match prandial insulin dose to carbohydrate intake, premeal blood glucose, and anticipated physical activity 1 Most individuals should use insulin analogs to reduce hypoglycemia risk 1 Consider use of a sensor-augmented low glucose threshold suspend pump for patients with frequent nocturnal hypoglycemia and/or hypoglycemia unawareness 1 * Recommended for most people with type 1 diabetes 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S52-S59

49 Pharmacological Therapy for Type 2 Diabetes 1 Lifestyle Changes Change metformin to Biguanide if necessary Metformin Preferred initial pharmacological agent for type 2 diabetes Added at, or soon after, diagnosis, if tolerated and not contraindicated Consider insulin therapy, with or without other agents Add a second oral agent, a GLP-1 receptor agonist, or basal insulin In newly diagnosed patients with markedly symptomatic and/or elevated blood glucose levels or A1C If monotherapy does not achieve or maintain the A1C target after 3 months Consider initiating therapy with a dual combination when A1C is 9% Many patients with type 2 diabetes eventually require and benefit from insulin therapy. GLP-1 = glucagon-like peptide 1 Considerations when choosing pharmacological therapy: Patient preferences Efficacy Comorbidities Weight Potential side effects FM-LYR-0024 Cost Hypoglycemia risk For your personal use. Not for 1. further American distribution Diabetes Association. Diabetes Care 2016;39(suppl 1):S52-S59

50 Antihyperglycemic Therapy Oral agents & non-insulin injectables * 1 Biguanides Meglitinides Sulfonylureas α-glucosidase inhibitors Thiazolidinediones Amylin mimetics DPP-4 inhibitors Bile acid sequestrants SGLT-2 inhibitors Dopamine-2 agonists GLP-1 receptor agonists Insulins 1 Rapid-acting analogs Intermediate-acting Lispro, Aspart, Glulisine Human NPH Short-acting Basal insulin analogs Human Regular Glargine, Detemir * Agents in bold on the left are the most popular in the U.S. Agents on the right are less commonly used and may be considered in certain circumstances American Diabetes Association. Diabetes Care 2016;39(suppl 1):S52-S59 2. Inzucchi SE, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes slide deck. Accessed April 1, 2016.

51 Cardiovascular Disease and Risk Management

52 Cardiovascular Disease and Diabetes Cardiovascular disease (CVD) is the major cause of morbidity and mortality for individuals with diabetes 1 Patients with diabetes are two to four times more likely to develop CVD than those without diabetes 2 As many as 80% of patients with type 2 DM will develop CVD. More than 60% of these patients will die from CVD. 2 Hypertension and dyslipidemia commonly coexist with type 2 DM and are clear risk factors for CVD 1 Diabetes itself confers independent risk 1 Controlling individual risk factors will prevent or slow CVD. Large benefits are seen when multiple risk factors are addressed globally American Diabetes Association. Diabetes Care 2016;39(suppl 1):S60-S71 2. Shannon RP. Eur Heart J Suppl. 2012;14(suppl B):B1-B3,

53 Hypertension/Blood Pressure Control 1 Blood Pressure Goal: <140/90 mmhg Lower targets (<130/80 mmhg) may be appropriate for certain individuals if they can be achieved without undue treatment burden Measure blood pressure at every routine visit. Confirm elevated blood pressure on a separate day. >120/80 mmhg: Advise on lifestyle changes Reduce sodium intake Moderation of alcohol intake Reduce excess body weight Increased physical activity Confirmed BP 140/90 mmhg: Initiate drug therapy Regimen should include either an ACE inhibitor or angiotensin II receptor blocker. If one class is not tolerated, substitute the other. Multiple-drug therapy is generally required to achieve blood pressure targets 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S60-S71

54 Dyslipidemia/Lipid Management 1 In adults, a screening lipid profile is reasonable at first diagnosis, at the initial medical evaluation, and/or at age 40 years and periodically (e.g., every 1-2 years) thereafter To improve lipid profile in patients with diabetes, recommend lifestyle modification, focusing on: Reduction of saturated fat, trans fat, cholesterol intake Increase of n-3 fatty acids, viscous fiber, plant stanols/sterols Weight loss (if indicated) and increased physical activity Intensify lifestyle therapy and optimize glycemic control for: Triglyceride levels >150 mg/dl and/or HDL cholesterol <40 mg/dl in men and <50 mg/dl in women For patients with fasting triglyceride levels > 500 mg/dl, evaluate for secondary causes and consider medical therapy to reduce the risk of pancreatitis 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S60-S71

55 Age <40 years Recommendations for Statin Treatment in People with Diabetes years >75 years None ASCVD Risk Factor(s)** ASCVD Risk Factors None ASCVD Risk Factors ASCVD ACS and LDL cholesterol >50mg/dL in patients who cannnot tolerate high-dose statins None ASCVD Risk Factors ASCVD ACS and LDL cholesterol >50mg/dL in patients who cannnot tolerate high-dose statins 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S60-S71 Recommended Statin Dose* None Moderate or High High Moderate High High Moderate + ezetimibe Moderate Moderate or High High Moderate + ezetimibe * In addition to lifestyle therapy ** ASCVD risk factors include LDL cholesterol 100 mg/dl, high blood pressure, smoking, and overweight and obesity, family history of premature ASCVD For patients of all ages with diabetes and overt CVD, high-intensity statin therapy should be added to lifestyle therapy

56 Antiplatelet Agents 1 Primary Prevention with Aspirin mg/day Consider in those with type 1 or type 2 diabetes at increased CVD risk (10-year CVD risk of >10%) with no increased risk of bleeding Includes most men or women with diabetes aged 50 years with one or more major risk factors (hypertension, smoking, dyslipidemia, family history of premature ASCVD, albuminuria) Use clinical judgment for those <50 years of age with multiple other risk factors (10-year CVD risk of 5-10%) Not recommended for those at low risk (10-year CVD risk <5%) Men or women <50 years with no major additional ASCVD risk factors Secondary Prevention with Aspirin mg/day: Adults with Diabetes and a History of ASCVD Use clopidogrel 75mg/day with documented aspirin allergy 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S60-S71

57 Microvascular Complications and Foot Care

58 Diabetic Kidney Disease 1 Diabetic kidney disease occurs in 20-40% of patients with diabetes and is the single leading cause of end-stage renal disease (ESRD). At least once a year, assess urinary albumin (e.g., spot urinary albumin-to-creatinine ratio) and estimate glomerular filtration rate In patients with type 1 diabetes with duration of 5 years In all patients with type 2 diabetes In all patients with comorbid hypertension Optimize glucose and blood pressure control (<140/90 mmhg) to reduce the risk or slow progression of diabetic kidney disease When estimated glomerular filtration rate is <60 ml/min/1.73m 2, evaluate and manage potential complications of chronic kidney disease 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80

59 ACE Inhibitor or ARB Therapy for Diabetic Kidney Disease 1 Strongly recommended for nonpregnant patients with urinary albumin excretion 300 mg/day and/or estimated GFR <60 ml/min/1.73m 2 Recommended for nonpregnant patients with modestly elevated urinary albumin excretion ( mg/day). Not recommended for primary prevention of diabetic kidney disease in patients with normal blood pressure, normal urinary albumin-tocreatinine ratio (<30 mg/g), and normal estimated GFR Periodically monitor serum creatinine and potassium levels when ACE inhibitors, ARBs, or diuretics are used Continue monitoring UACR in patients with albuminuria treated with an ACE inhibitor or ARB to assess response to treatment and progression of diabetic kidney disease 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80 ARB = angiotensin receptor blocker GFR = glomerular filtration rate

60 Management of CKD in Diabetes 1 GFR (ml/min/1.73 m 2 ) All Patients Recommended Management Yearly measurement of creatinine, UACR, potassium Referral to a nephrologist if possibility for nondiabetic kidney disease exists (duration of type 1 diabetes <10 years, persistent albuminuria, abnormal findings on renal ultrasound, resistant hypertension, rapid fall in GFR, or active urinary sediment on ultrasound) Consider the need for dose adjustment of medications Monitor egfr every 6 months Monitor electrolytes, bicarbonate, hemoglobin, calcium, phosphorus, parathyroid hormone at least yearly Assure vitamin D sufficiency Consider bone density testing Referral for dietary counseling Monitor egfr every 3 months Monitor electrolytes, bicarbonate, calcium, phosphorus, parathyroid hormone, hemoglobin, albumin, weight every 3 6 months Consider the need for dose adjustment of medications <30 Referral to a nephrologist 1. American Diabetes Association. Diabetes Care 2016;39(suppl For your 1):S72-S80 personal use. Not for further distribution

61 Diabetic Retinopathy 1 The most frequent cause of new cases of blindness among adults aged years Prevalence strongly related to the duration of diabetes and level of glycemic control. Optimize glycemic, blood pressure, and lipid control to reduce the risk or slow progression of retinopathy Initial dilated and comprehensive eye examination by an ophthalmologist or optometrist Type 1 DM: Within 5 years after the onset of diabetes Type 2 DM: At the time of the diabetes diagnosis Subsequent exams are generally repeated annually for patients with minimalt o no retinopathy 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80

62 Diabetic Retinopathy Screening 1 If there is no evidence of retinopathy for one or more annual eye exams, then exams every 2 years may be considered If any level of diabetic retinopathy is present, subsequent examinations should be repeated annually by an ophthalmologist or optometrist More frequent exams are required if retinopathy is progressing or sight-threatening Women with preexisting diabetes who are planning pregnancy or who have become pregnant Comprehensive eye exam before pregnancy or in the first trimester Counseled on risk of development and/or progression of diabetic retinopathy Monitor every trimester and for 1 year postpartum as indicated by the degree of retinopathy 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80

63 Diabetic Retinopathy Treatment 1 Promptly refer patients with any level of macular edema, severe nonproliferative diabetic retinopathy (NPDR), or any proliferative diabetic retinopathy (PDR) Laser photocoagulation therapy is indicated to reduce risk of vision loss in patients with: High risk PDR Some cases of severe NPDR Intravitreal injections of anti-vascular endothelial growth factor (VEGF) therapy are indicated for center-involved diabetic macular edema Retinopathy is not a contraindication to aspirin therapy for cardioprotection (no increased risk of retinal hemorrhage) 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80

64 Neuropathy Diabetic neuropathies are heterogeneous, affecting different parts of the nervous system with diverse clinical manifestations 1 The most prevalent neuropathies are diabetic peripheral neuropathy and autonomic neuropathy 2 Diabetic Peripheral Neuropathy (DPN) 1 Common symptoms are pain, dysesthesias, and numbness Up to 50% may be asymptomatic and at risk for insensate injury to their feet Autonomic Neuropathy 1 Hypoglycemia unawareness, resting tachycardia, orthostatic hypotension gastroparesis, constipation, diarrhea, fecal incontinence, erectile dysfunction, neurogenic gladder, and sudomotor dysfunction Cardiovascular autonomic neuropathy (CAN) is an independent risk factor for CV mortality 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80 2. American Diabetes Association. Diabetes Care 2015;38(suppl 1):S58-66

65 Neuropathy Screening and Management 1 All patients should be screened for DPN starting at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes and at least annually thereafter 1 Careful history and 10-g monofilament and at least one of the following: pinprick sensation, vibration sensation, ankle reflexes 2 Symptoms and signs of autonomic neuropathy should be assessed in patients with microvascular and neuropathic complications 1 Optimize glucose control to prevent or delay neuropathy in type 1 diabetes and slow progression in type 2 diabetes 1 Assess and treat patients to reduce pain related to DPN and symptoms of automatic neuropathy and to improve the quality of life 1 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80 2. Boulton AJ, et al. Diabetes Care. 2008;31(8):

66 Foot Care 1 Amputation and foot ulceration, which are consequences of diabetic neuropathy and/or peripheral arterial disease (PAD), are common and represent major causes of morbidity and disability in people with diabetes. Perform a comprehensive foot evaluation each year to identify risk factors for ulcers and amputations Obtain a prior history of ulceration, amputation, Charcot foot, angioplasty or vascular surgery, cigarette smoking, retinopathy, and renal disease Assess current symptoms of neuropathy (pain, burning, numbness) and vascular disease (leg fatigue, claudication) Examination should include: Inspection of the skin Assessment of foot deformities Neurological assessment 10-g monofilament plus pinprick sensation, vibration sensation, or ankle reflexes Vascular assessment pulses in the legs and feet 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80

67 Foot Care Recommendations 1 Patients with a history of ulcers or amputations, foot deformities, insensate feet, and peripheral arterial disease should have their feet examined at every visit. Refer patients with symptoms of claudication or decreased or absent pedal pulses for ankle-brachial index (ABI) testing and for further vascular assessment A multidisciplinary approach is recommended for individuals with foot ulcers and high-risk feet Refer patients who smoke or who have a history of prior lower extremity complications, loss of protective sensation (LOPS), structural abnormalities, or peripheral arterial disease to foot care specialists for ongoing preventive care and lifelong surveillance Provide general foot self-care education to all patients with diabetes 1. American Diabetes Association. Diabetes Care 2016;39(suppl 1):S72-S80

68 Quality Programs

69 2016 Diabetes Physician Quality Reporting System Measures: Hemoglobin A1c, Retinopathy, Eye Exam Diabetes: Hemoglobin A1c Poor Control (#1) 1 (NQS Domain: Effective Clinical Care) Diabetic Retinopathy (#19) 1 (NQS Domain: Communication and Care Coordination) Diabetes: Eye Exam (#117) 1 (NQS Domain: Effective Clinical Care) Percentage of patients years of age with diabetes who had hemoglobin A1c >9.0% during the measurement period (A Cross-Cutting Measure) 2 Percentage of patients aged 18 years and older with a diagnosis of diabetic retinopathy who had a dilated macular or fundus exam performed with documented communication to the physician who manages the patient s ongoing care regarding the findings of the exam at least once within 12 months Percentage of patients years of age with diabetes who had a retinal or dilated eye exam by an eye care professional during the measurement period or a negative retinal or dilated eye exam (no evidence of retinopathy) in the 12 months prior to the measurement period Providers who do not satisfactorily report data on quality measures for covered professional services will be subject to a 2% negative payment adjustment to Medicare Part B Physician Fee Schedule covered services beginning in Program participation during a calendar year will affect payments after two years (i.e., 2016 program participation will affect 2018 payments) Centers for Medicare and Medicaid Services PQRS Individual Claims Registry Measure Specifications. Instruments/PQRS/MeasuresCodes.html. Accessed April 1, Centers for Medicare and Medicaid Services Cross-Cutting Measures List. Accessed April 1, Centers for Medicare and Medicaid Services. Payment Adjustment Information. Information.html. Accessed April 1, 2016.

70 2016 Diabetes Physician Quality Reporting System Measures: Nephropathy, Cardiovascular Disease Diabetes: Medical Attention for Nephropathy (#119) 1 (NQS Domain: Effective Clinical Care) The percentage of patients years of age with diabetes who had a nephropathy screening test or evidence of nephropathy during the measurement period Coronary Artery Disease: ACEi or ARB Therapy Diabetes or Left Ventricular Systolic Dysfunction (#118) 1 (NQS Domain: Effective Clinical Care) Percentage of patients aged 18 years and older with a diagnosis of coronary artery disease seen within a 12 month period who also have diabetes OR a current or prior Left Ventricular Ejection Fraction < 40% who were prescribed ACEi or ARB therapy Statin Therapy for the Prevention and Treatment of Cardiovascular Disease (#438) 1 (NQS Domain: Effective Clinical Care) Percentage of patients who were prescribed or on statin therapy during the measurement period: Diagnosis of clinical ASCVD LDL-C level 190 mg/dl Adults aged years with a diagnosis of diabetes with LDL-C level = mg/dl (NEW MEASURE in 2016) Providers who do not satisfactorily report data on quality measures for covered professional services will be subject to a 2% negative payment adjustment to Medicare Part B Physician Fee Schedule covered services beginning in Program participation during a calendar year will affect payments after two years (i.e., 2016 program participation will affect 2018 payments). 3 ACEi = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; ASCVD = atherosclerotic cardiovascular disease; LDL-C = low-density lipoprotein cholesterol 1. Centers for Medicare and Medicaid Services PQRS Individual Claims Registry Measure Specifications. Instruments/PQRS/MeasuresCodes.html. Accessed April 1, Centers for Medicare and Medicaid Services. Payment Adjustment Information. Information.html. Accessed April 1, 2016.

71 2016 Diabetes Physician Quality Reporting System Measures: Foot Care Diabetic Foot and Ankle Care, Peripheral Neuropathy Neurological Evaluation (#126) 1 Percentage of patients 18 years with a diagnosis of diabetes mellitus who had a neurological examination of their lower extremities within 12 months 10-g monofilament plus one of the following: vibration using 128-Hz tuning fork, pinprick sensation, ankle reflexes, or vibration perception threshold) Diabetic Foot and Ankle Care, Ulcer Prevention Evaluation of Footwear (#127) 1 Percentage of patients aged 18 years and older with a diagnosis of diabetes mellitus who were evaluated for proper footwear and sizing Diabetes: Foot Exam (#163) 2 Percentage of patients aged years with diabetes who had a foot examination during the measurement period Examination through visual inspection, sensory exam with monofilament, and pulse exam (Reportable via EHR only in 2016; Claims/Registry Reporting Method Removed) Providers who do not satisfactorily report data on quality measures for covered professional services will be subject to a 2% negative payment adjustment to Medicare Part B Physician Fee Schedule covered services beginning in Program participation during a calendar year will affect payments after two years (i.e., 2016 program participation will affect 2018 payments) Centers for Medicare and Medicaid Services PQRS Individual Claims Registry Measure Specifications. Instruments/PQRS/MeasuresCodes.html. Accessed April 1, Centers for Medicare and Medicaid Services PQRS Measures List. Accessed April 1, Centers for Medicare and Medicaid Services. Accessed April 1, Centers for Medicare and Medicaid Services. Payment Adjustment Information. Information.html. Accessed April 1, 2016.