Diabetes Treatments

Americans are estimated to have pre-diabetes, as defined by blood glucose levels new cases of diabetes were diagnosed in people aged 20 years or older, and …

Managing Type 2 Diabetes and Promoting Metabolic Cardiovascular Health:
Consensus Recommendations from an Expert Panel
Expert Panel Mitchell King, MD; Moderator
Associate Professor, Department of Family and Community Medicine Associate Dean for Academic Affairs University of Illinois at Chicago, College of Medicine at Rockford Rockford, Illinois

G Allen Crist, DO, FAAFP, CAQG
Galena and Elizabeth Offices Medical Associates Clinic Galena, Illinois

Mark Molitch, MD
Professor, Division of Endocrinology, Metabolism Molecular Medicine The Feinberg School of Medicine Northwestern University Chicago, Illinois

Terry Ridge, MSN, APRN-BC, BC-ADM
Diabetes Nurse Specialist American Health Network Indianapolis, Indiana

Learning Objectives:
I I I I I I

Identify criteria for diagnosing type 2 diabetes Describe lifestyle interventions designed to manage insulin resistance Select pharmacologic interventions to manage dyslipidemia related to insulin resistance Discuss non-pharmacologic strategies to help patients attain tight control of diabetes Describe pharmacologic strategies to help patients attain tight control of diabetes Discuss individualized lifestyle programs that enable patients at
risk for diabetes to manage weight issues

This continuing nursing education activity CEARP8948, 10/31/09 is approved for 15 contact hours by the Washington State Nurses Association, an accredited approver by the American Nurses Credentialing Centers Commission on Accreditation The Nurse Practitioner Healthcare Foundation, in collaboration with the University of Illinois at Chicago UIC College of Medicine, the Illinois Critical Access Hospital Network, and the Michigan Academy of Family Physicians, developed this activity It is made possible through an educational grant from Takeda Pharmaceuticals North America, Inc

Epidemiology and Impact
According to the American Diabetes Association ADA,1 208 million US children and adults have diabetes 62 million of whom are currently undiagnosed An additional 54 million Americans are estimated to have pre-diabetes, as defined by blood glucose levels that are higher than normal but not sufficiently elevated to be diagnosed as diabetes In 2005, 15 million new cases of diabetes were diagnosed in people aged 20 years or older, and 2 million adolescents or 1 in 6 overweight adolescents aged 12-19 had pre-diabetes If present trends continue, 1 in 3
Americans 1 in 2 minority members born in 2000 will develop diabetes in his or her lifetime The epidemic rise in the prevalence of diabetes during the previous 25 years has produced a ripple effect in terms of disease and economic burdens Diabetes is associated with numerous microvascular retinopathy, neuropathy, nephropathy and macrovascular heart disease, stroke, amputations complications Since 1987, the death rate related to diabetes has increased by 45, making the condition the fifth leading cause of death in the United States1 The total annual economic cost of diabetes was estimated to be 132 billion in 2002, including 92 billion in direct medical expenditures and nearly 41 billion in indirect costs One out of every 10 healthcare dollars spent in the United States is used for diabetes and its complications

Type 2 Diabetes: Etiology and Risk Factors
Type 2 diabetes accounts for 90 to 95 of diabetes cases Unlike type 1 diabetes, which is caused by autoimmune or idiopathic conditions, type 2 diabetes is a metabolic disorder that results from insulin resistance and progressive decline in pancreatic -cell function2 As the bodys capacity to produce sufficient quantities of insulin
decreases, blood glucose concentration rises Although the prevalence of type 2 diabetes has doubled in middle-aged adults during the past 30 years,3 this disease is no longer considered an adult-onset condition–healthcare practitioners can expect to treat adolescents, young adults, and even some children who present with diabetes or its risk factors Criteria for screening adults for type 2 diabetes are listed in Table 1; of note, many patients with type 2 diabetes present with complications that indicate disease progression prior to the onset of symptoms Children and adolescents should be tested for diabetes if they are overweight Body mass index [BMI] 85th percentile for age and sex, weight-for-height 85th percentile, or weight 120 of ideal for height and have two of the following:4 I Family history of type 2 diabetes in 1st- or 2nd-degree relative I Race/ethnicity Native American, African-American, Latino, Asian-American, Pacific Islander I Signs of insulin resistance or conditions associated with insulin resistance acanthosis nigricans, hypertension, dyslipidemia, or polycystic ovary syndrome I Maternal history of diabetes or gestational diabetes mellitus Testing should begin
at 10 years or at the onset of puberty, if puberty occurs at a younger age Children and adolescents should be tested every 2 years, preferably using fasting plasma glucose FPG
TABLE 1

ADA CRITERIA FOR SCREENING FOR TYPE 2 DIABETES IN ADULTS

All individuals aged 45 years, as well as individuals aged 45 years with:
I I I I I I I I I I I I

Family history of diabetes Cardiovascular disease Overweight or obesity eg, body mass index 25 kg/m2 Sedentary lifestyle High-risk race/ethnicity eg, Latino/Hispanic, African American, Asian American, Native American, Pacific Islander Hypertension blood pressure 140/90 mm Hg Elevated triglycerides 250 mg/dL Low level of high-density lipoprotein cholesterol 35 mg/dL History of gestational diabetes or delivery of a baby weighing 9 lb Polycystic ovary syndrome Impaired fasting glucose or impaired glucose tolerance Other clinical conditions associated with insulin resistance eg, acanthosis nigricans

Source: American Diabetes Association Diabetes Care 2007;30suppl 1:S4-S41

Diagnosing Diabetes
The diagnosis of diabetes mellitus in non-pregnant adults is established on the basis of plasma glucose PG concentration, determined using one of three tests:
random PG, FPG, or 2hour 75-g oral glucose tolerance test OGTT Table 24 Because of ease of use, acceptability to patients, and cost, FPG is the preferred diagnostic test In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing on a different day
TABLE 2

DIAGNOSTIC CRITERIA FOR TYPE 2 DIABETES AND PRE-DIABETES IN NON-PREGNANT ADULTS Diabetes:
Symptoms of diabetes eg, polyuria, polydipsia, unexplained weight loss plus Random plasma glucose 200 mg/dL or Fasting plasma glucose FPG 126 mg/dL or Results of the 2-hour value on 75-g oral glucose tolerance test OGTT 200 mg/dL

Pre-diabetes:
Impaired FPG 100-125 mg/dL and/or Impaired glucose tolerance 2-hr value on 75-g OGTT, 140-199 mg/dL
Source: American Diabetes Association Diabetes Care 2007;30suppl1:S4-S41

Patients with pre-diabetes Table 2 have a high risk of developing type 2 diabetes and cardiovascular disease CVD According to the National Cholesterol Education Program Adult Treatment Panel III NCEP ATP III, a fasting glucose concentration 100 mg/dL is one diagnostic criterion for metabolic syndrome,5 which affects an estimated 47 million US adults Table 36 Whereas metabolic syndrome is not a
disease per se, it is a paradigm that reflects clustering of CVD risk factors Identification of one risk factor should therefore prompt the practitioner to search for other risk factors and begin proactive, aggressive treatment to reduce risk of future CVD5 Because of its spectrum of comorbidities, type 2 diabetes has been designated as a coronary heart disease risk equivalent by the NCEP ATP III
TABLE 3

NCEP ATP III DIAGNOSTIC FACTORS FOR METABOLIC SYNDROME IN ADULTS
Risk Factor
Waist circumference abdominal obesity I Men I Women Triglycerides High-density lipoprotein cholesterol I Men I Women Blood pressure Fasting glucose

Defining Level
102 cm 40 inches 88 cm 35 inches 150 mg/dL 169 mmol/L

40 mg/dL 104 mmol/L 50 mg/dL 129 mmol/L 130/85 mm Hg 100 mg/dL 61 mmol/L

Diagnosis is established when 3 of these risk factors are present

Originally set at 110 mg/dL by NCEP ATP III; reduced in accordance with 2003 ADA criteria for impaired fasting glucose

Source: NCEP ATP III JAMA 2001;285:2486-2497

Care for type 2 diabetes begins at screening The initial visit should include a medical history, physical examination with foot exam and neurologic assessment, laboratory workup eg,
hemoglobin A1c [A1c], glucose, lipids, urinalysis, serum creatinine/ glomerular filtration rate, thyroid function, and an assessment of educational needs Follow-up visits should focus on management plans for metabolic control and surveillance for complications Patients with diabetes mellitus should be seen at least every 3 to 6 months to monitor progress

Establishing Tight Glycemic Control is the Key to Disease Management
The goal of diabetes management is to prevent microvascular and macrovascular complications The single most crucial factor in reducing microvascular complications is the attainment of tight glycemic control The ADA has established A1c as the primary target for glycemic control and has defined an A1c 60 as normal In its 2007 Standards of Medical Care4 http:// carediabetesjournalsorg/cgi/ reprint/30/suppl_1/S4, the ADA encourages individual patients to maintain A1c as close to normal as possible without promoting significant hypoglycemia However, the ADAs A1c goal for patients in general is 70 Although this goal may seem relaxed, data from the 1999-2000 National Health and Nutrition Examination Survey NHANES indicate that 63 of persons with diabetes are above this
level7 The benefits of tight glycemic control, as achieved through intensive therapy, in reducing complications from diabetes have been shown in prospective clinical trials, epidemiologic studies, and meta-analyses In type 1 diabetes, long-term outcomes from the Diabetes Control and Complications Trial DCCT8 and other studies indicate that improved glycemic control is associated with sustained decreased rates of microvascular retinopathy and nephropathy, macrovascular, and neuropathic complications8-11 With respect to CVD, intensive therapy in the DCCT reduced the cumulative incidence of a first cardiovascular event by 42 and the risk of non-fatal myocardial infarction MI, stroke, or CVD death by 5710 In type 2 diabetes, the epidemiologic United Kingdom Prospective Diabetes Study UKPDS demonstrated that intensive therapy significantly reduces microvascular and neuropathic complications1214 Analysis of UKPDS data indicates the potential of intensive glycemic control to reduce CVD in type 2 diabetes; each 1 decline in A1c level reduces the risk of MI, stroke, heart failure, and complications of peripheral vascular disease by 14, 12, 16, and 43, respectively14 These results are
supported by the Steno-2 Study, an open, parallel-group, 8-year study that compares targeted, multifactorial intervention eg, behavioral modification plus prophylactic aspirin therapy and pharmacologic therapy to address glycemic control, hypertension, dyslipidemia, and microalbuminuria with conventional treatment on modifiable factors for CVD in 160 persons with type 2 diabetes and microalbuminuria15 Outcome data indicate that a target-driven, long-term, intensified intervention aimed at multiple risk factors reduces the risk of CVD by 53, nephropathy by 61, retinopathy by 58, and autonomic neuropathy by 63

Cultural Factors Affect Treatment Outcomes
Patients with diabetes represent numerous ethnic backgrounds, each with unique cultural beliefs and practices that will influence the course of successful treatment Emerging studies are indicating that culturally-appropriate care can improve diabetes-related outcomes For example, initial results from the Racial and Ethnic Approaches to Community Health REACH study indicate that culturally-tailored diabetes intervention, delivered by trained community residents, significantly improves dietary and diabetes self-care behaviors among
African American and Latino adults16 When providing care, practitioners should therefore be aware of cultural considerations, including: I Educational level and health literacy I Family integration and support systems I Cultural judgments about disease and norms regarding body image I Knowledge about diabetes I Learning styles and motivational strategies I Spiritual beliefs I Nutritional preferences I Alternative/herbal practices I Language issues

Designing an Effective, Individualized Intervention
Type 2 diabetes, a chronic illness, requires continuing care and education to manage longterm complications Optimal results are achieved only when patients take an active role in managing their conditions Patients and practitioners must communicate in an interactive, collaborative, and ongoing process Ideally, care should be administered by a multidisciplinary, practitioner-facilitated team that may include a registered dietitian, a behaviorist, an exercise physiologist, an ophthalmologist, and other healthcare professionals Although access to such a team may be limited in the rural setting, it is imperative that patients maintain routine interaction with the practitioner and available
team members Certain healthcare professionals have special expertise in diabetes education; assistance in locating certified diabetes educators and creating a team is available from the American Association of Diabetes Educators at 1-800-TEAMUP4 Diabetes management consists of three overlapping components: diabetes self-management education, medical nutrition therapy, and pharmacotherapy for glycemic control and/or complications Basic principles of each category are discussed in the following sections

Diabetes Self-Management Education DSME
DSME is an interactive, ongoing educational process involving the person with diabetes and the educators Each patient should receive an individualized assessment, identification of personal self-management goals, an educational plan and interventions, and periodic reassessment Current ADA criteria for a DSME curriculum with successful learning outcomes include the following:17 I Description of the diabetes disease process and treatment options I Initiation of appropriate nutritional management I Incorporation of physical activity into lifestyle I Utilization of medications for therapeutic effectiveness I Monitoring of blood glucose and urine
ketones when appropriate and using the results to improve glycemic control I Preventing through risk-reduction behavior, detecting, and treating acute and chronic complications I Goal setting to promote health, and problem solving for daily living I Integration of psychosocial adjustment to daily life I Promotion of preconception care, management during pregnancy, and gestational diabetes management if applicable Persons with diabetes must self-monitor their blood glucose to prevent hypo- and hyperglycemia For those who use insulin, the ADA recommends thrice-daily monitoring For those who take oral antihyperglycemic agents, monitoring should occur sufficiently often to maintain glycemic control Blood glucose should be monitored more often when adding or modifying a therapeutic regimen

Medical Nutrition Therapy MNT
MNT, a central component of any DSME program, promotes modest 5-10 weight loss through a tailored program of lifestyle change4 Structured programs that include education, reduced intake of calories and fats, regular physical activity, and regular participant contact can facilitate long-term moderate weight loss, thereby reducing hyperglycemia, dyslipidemia, and
hypertension Monitoring the intake of carbohydrates is a key strategy to achieve glycemic control, and reducing the saturated fat intake below 7 of the total caloric intake is essential for weight maintenance Blood glucose monitoring provides the practical information to assess changes in MNT

Designing an Effective, Individualized Plan to Help Patients Maintain Weight
Combined Moderate Weight Loss and Physical Activity Lowers Diabetes/CVD Risk–Results from the Diabetes Prevention Program indicate that loss of 5-10 of body weight through lifestyle modification decreases progression to type 2 diabetes regardless of age, sex, or ethnicity18-20 According to data from the National Weight Control Registry, most persons who lost significant weight and maintained the loss for more than 1 year report engaging in high levels of physical activity 1 hour/day, eating a low-calorie, low-fat diet, eating breakfast regularly, self-monitoring their weight, and maintaining a consistent eating pattern across weekdays and weekends21 Although any intervention must be tailored to the patients needs, all strategies to lose weight safely incorporate themes of variety, proportionality, moderation, and
physical activity A Balanced Diet–For controlled weight loss, a healthful diet must create a daily caloric deficit Because each pound of adipose tissue stores approximately 3500 calories,22 a tailored diet should target a deficit of 500 to 1000 calories per day to promote loss of 1 to 2 pounds per week23 Weight loss that exceeds this rate increases health risks through the loss of water and muscle mass Therefore, practitioners should stress that nutritional balance and weight management complement weight loss; a healthful diet balances caloric intake with energy needs as part of an overall lifestyle regimen A low-calorie diet, with consideration given to the patients food preferences, is the first step Although evidencebased studies have shown calorie-restricted diets to be at least as effective as fat-restricted diets in achieving long-term weight loss in overweight and obese patients,24 the number of kcal per day necessary to maintain or lose weight depends on the patients usual caloric intake A resource for patients to help design and track a healthy personal eating/activity plan is available at the US Department of Agricultures My Pyramid website at www pyramidgov General
dietary recommendations supported by the National Heart, Lung, and Blood Institute NHLBI, the American Heart Association, the American Cancer Society, and the American Dietetic Association are presented in Table 425
TABLE 4
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GENERAL DIETARY RECOMMENDATIONS

5-7 servings of fruits and vegetables per day 6 or more servings of whole grain products per day Less than 6 grams of salt per day 25-30 grams of fiber per day Less than 300 mg of cholesterol per day At least 64 ounces of water per day Fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats Fats and oils with 2 grams or less of saturated fat per tablespoon eg, canola oil, olive oil, margarines Limited intake of high calorie/low nutrition foods, such as soft drinks and candy Limited intake of foods high in saturated fat or cholesterol, such as full-fat milk products, fatty meats, tropical oils, and egg yolks No more than one alcoholic drink 12 oz of beer, 4 oz of wine, or 15 oz of 80-proof spirits per day for women; no more than 2 alcoholic drinks per day for men

I

Vitamin supplements may be required to meet all recommended dietary allowances Sample food exchange lists and
strategies are available from the NHLBI at http://wwwnhlbinihgov/guidelines/obesity/practgdehtm26 For further consultation, a registered dietitian can be located by calling the American Dietetic Association at 1-800-366-1655 Physical Activity–Physical activity eg, exercise, walking, sports, common chores increases muscle mass and metabolic rate, and an active lifestyle decreases risk factors for CVD, type 2 diabetes, and dyslipidemia18,20,27-29 The National Academy of Sciences Institute of Medicine suggests 60 minutes of moderately-intense activity eg, walking or

jogging 4-5 mph, bicycling, golf, social dance, tennis, low-impact aerobics performed daily, in addition to activities required by a sedentary lifestyle30 However, some activity is preferable to no activity, and patients with type 2 diabetes and no cardiovascular restrictions should begin modestly eg, 30 minutes/day for 5 days/week to facilitate compliance The daily allotment of aerobic activity can be obtained piecemeal to achieve health benefits and can be incorporated into many daily routines eg, using stairs, parking farther away from work, walking at lunch time Any patient who is starting an activity program should
be evaluated for cardiovascular fitness prior to commencement Evidence-Based Practice Recommendation: Healthcare practitioners should include exercise as an intervention for persons with type 2 diabetes because exercise significantly improves glycemic control and reduces visceral adipose tissue and plasma triglycerides even in the absence of weight loss31 Behavioral Considerations–Successful weight management requires that patients take responsibility for their actions Numerous patient factors, including motivation level, support systems, time, and attitude toward physical activity can influence adherence to a given regimen Adherence relies on accountability; therefore, patients must be encouraged to use all possible tools to maintain momentum Suggested strategies to facilitate adherence to a regimen include: Keep a daily diet/exercise diary I Identify and, where possible, avoid high-risk situations I Reward success I Identify a social network and support system eg, family and friends, established organizations such as Weight WatchersTM I Set realistic goals and a specific plan For those patients who are undertaking lifestyle transitions but do not wish to join established social
support groups, the practitioner should schedule frequent follow-up visits to assess progress
I

Pharmacotherapy
Because -cell decline is progressive in type 2 diabetes, most patients cannot maintain glycemic control through lifestyle changes alone Pharmacologic intervention for hyperglycemia traditionally begins with supplemental oral monotherapy, although most patients who receive a traditional oral agent will ultimately require additional agents oral or insulin32,33 Regardless of initial interventions, practitioners should treat all patients with type 2 diabetes aggressively Moreover, if control is not achieved with first-line therapy, additional agents should be used, as combination therapy enhances glycemic control relative to monotherapy Although the ADA does not endorse a specific timetable for introducing additional agents, a consensus statement issued by the ADA and the European Association for the Study of Diabetes recommends measuring A1c every 3 months until it is 7 and at least every 6 months thereafter34 Therefore, practitioners should titrate doses upward and add additional agents rapidly over several months to attain glycemic goals and reduce risks of long-term
complications Considerations for choosing an oral medication are listed here:
I I I I I I

Efficacy for glycemic reduction Mechanism of action Side effects/contraindications Associated metabolic changes Patient adherence Cost

The six major classes of oral antihyperglycemic agents are detailed below

Insulin Secretagogues: Sulfonylureas Glimepiride, Glipizide, Glyburide and Meglitinides Nateglinide, Repaglinide–By depolarizing -cell membranes, secretagogues promote insulin release, thereby increasing the circulating insulin concentration35 Sulfonylurea SU agents decrease A1c levels by 1-2,12,36,37 although they vary slightly in duration of action or metabolism38,39 Weight gain and hypoglycemia are common side effects of SU therapy12,40 Dosing regimens vary among members of this class, but glucose-lowering effects plateau after half of the maximal dose is reached37,41 Although SUs are approved as monotherapy and in combination with all other oral agent classes and insulin, practitioners should exercise caution in cases of severe renal or hepatic impairment The meglitinides have a comparatively short metabolic half-life42 As a consequence, insulin stimulation tends to be brief, and
the efficacy of these agents is most pronounced postprandially Thus, dosing schedules must be coordinated with meals For glycemic control, repaglinide is similar to the SUs,19,43 although nateglinide appears to be less efficacious44 Adverse effects of meglitinides are similar but less pronounced than those of SUs However, caution must be exercised in patients with impaired liver or kidney function because insufficient clearance may lead to elevated plasma concentrations of these agents Meglitinides are approved as monotherapy or in combination with metformin Metformin–Metformin reduces hepatic glucose production in the presence of insulin, thereby reducing insulin resistance;45 it lowers A1c concentrations 1-246,47 Metformin use is not associated with weight gain and is associated with much less hypoglycemia than is SU therapy,48-50 decreased lipid levels,51 and an amelioration in vascular reactivity52 Adverse effects, including abdominal pain, nausea, and diarrhea,48 may be minimized with slow titration of dose and food consumption However, metformin use is discouraged in patients at increased risk for lactic acidosis,52 including those with renal impairment The agent is approved
as monotherapy and in combination with SUs, insulin, and thiazolidinediones TZDs Thiazolidinediones Pioglitazone, Rosiglitazone–TZDs increase insulin-stimulated glucose uptake by skeletal muscle cells and adipose tissue53,54 TZDs are similar to SUs and metformin for lowering A1c level 1-255,56 TZD therapy has been shown to elevate high-density lipoprotein cholesterol concentration while lowering triglycerides57,58 Side effects, including wei ght gain and edema, are more common in patients who receive TZD with insulin59 TZDs are approved as monotherapy and in combination with metformin, SUs, and insulin pioglitazone only A recent metaanalysis has associated rosiglitazone with an increased risk of MI and death from cardiovascular causes60 However, an interim analysis of data from the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes RECORD trial mean follow-up: 375 years found no evidence of any increase in death from either cardiovascular causes or all causes61 Although trial data were insufficient to determine whether the drug was associated with increased risk of MI, rosiglitazone was associated with an increased risk of heart failure Patients
with hepatic impairment or advanced heart failure should therefore not receive TZD therapy Rosiglitazone, as compared with glyburide and metformin, has also been associated with an increased fracture risk in women with type 2 diabetes;33 whether this is a TZD class effect is currently under debate

-Glucosidase Inhibitors Acarbose, Miglitol—Glucosidase inhibitors AGIs competitively inhibit the action of -glucosidase, an enzyme in the intestinal tract that breaks down complex carbohydrates and polysaccharides In doing so, carbohydrate absorption is lowered and subsequent removal enhanced62 AGIs lower A1c levels 05-1 relative to placebo63,64 and exert minimal effect on fasting glucose levels but a more pronounced effect on postprandial levels AGIs do not promote weight gain or hypoglycemia, although flatulence, abdominal discomfort, and diarrhea may be sufficiently severe to discontinue use AGIs are approved for monotherapy and in combination with SUs
Incretin Mimetics Exenatide–Secreted at the ingestion of food, incretins such as glucagon-like peptide-1 GLP-1 modulate numerous metabolic functions, including enhancing glucose-dependent insulin secretion from cells, regulating
gastric emptying, promoting satiety, and decreasing postprandial glucagon secretion, which in turn reduces hepatic glucose output65-68 Based on a salivary protein found in the Gila monster, exenatide is a synthetic incretin mimetic that binds to known human GLP-1 receptors on -cells in vitro Exenatide is indicated as adjunctive therapy for patients with type 2 diabetes who are taking metformin, an SU, a TZD, metforminSU, or metforminTZD In clinical studies, addition of exenatide 10 g bid to metformin, an SU, or metforminSU regimens reduces A1c level an additional 08 to 1029,69-71 Furthermore, use of exenatide has been associated with sub-

stantial weight loss and improvement in some markers of cardiovascular risk29,69-71 Exenatide is resistant to inactivation by dipeptidyl peptidase-4 DPP-4 DPP-4 Inhibitors Sitagliptin–Once released, GLP-1 is rapidly degraded by DPP472 In randomized, double-blind, placebo-controlled studies in normoglycemic healthy males73 and middle-aged obese subjects,74 the DPP-4 inhibitor sitagliptin increased postprandial GLP-1 concentration without causing hypoglycemia or weight gain Sitagliptin is approved as monotherapy or as adjunctive therapy with
metformin or a TZD; in all of these scenarios, this agent reduces A1c level an additional 1075-77 In 2007, the US Food and Drug Administration approved a metformin/sitagliptin combination oral agent Evidence-Based Practice Recommendation: Healthcare practitioners should consider metformin monotherapy as first-line therapy for overweight or obese persons with type 2 diabetes because this agent promotes a significant benefit for glycemic control, weight control, dyslipidemia, and diastolic blood pressure a strong benefit for lowering A1c when compared with placebo and diet, and a moderate benefit for its effect on glycemic control, low-density lipoprotein cholesterol, and BMI or weight when compared with SUs31

Combination Therapy and Insulin
Aggressive treatment to target is the primary strategy to control type 2 diabetes, and healthcare practitioners must monitor and change treatment modalities to maximize benefits Each consecutive oral agent can reduce A1c by an additional 1 to 2 After two oral agents have been prescribed, however, the decision regarding choice of a third agent must be determined on an individual basis For most patients, the combination of metformin and an SU
represents a simple and cost-effective initial strategy For patients with marked insulin resistance, metformin plus a TZD is appropriate If these strategies fail to lower A1c below 7, a third agent or insulin should be added Although insulin may be prescribed at any point in therapy,69,78 insulin is rarely used as a first-line agent, primarily because of fears that it may promote weight gain12 However, weight gain can be minimized through diet and exercise Although insulin may promote the occasional hypoglycemic reaction–a common element of diabetes control– serious hypoglycemic reactions are rare Insulin varieties differ in their onset length of time before insulin begins lowering blood glucose, peak time time during which insulin provides maximum effect, and duration of action Based on these characteristics, insulins are classified as rapid-, short-, intermediate-, or long-acting Table 5
TABLE 5

INSULINS
Rapid-acting Short-acting
Regular 30 min 2-3 hr 3-6 hr

Intermediateacting
NPH 2-4 hr 4-12 hr 12-18 hr

Long-acting Basal
Glargine, Detemir 1 hr — 18-28 hr

Trade Names Onset Post-Injection Peak Time Duration

Lispro, Aspart, Glulisine 5-10 min 1 hr 2-4 hr

Adapted from:
American Diabetes Association The Basics of Insulin http://wwwdiabetesorg/type-1-diabetes/basicsjsp

Rapid-acting insulins should be injected immediately before a meal because they are absorbed quickly and peak rapidly In contrast, basal insulins provide a near-constant insulin supply Insulins glargine and detemir have relatively rapid onsets 1 hour and provide a steady action that mimics natural basal insulin secretion Thus, a combination of a long-acting and a rapid-acting insulin can achieve proper insulin peaking at mealtimes Patients with type 1 diabetes always require a basal insulin along with mealtime, shorter-acting insulins Patients with type 2 diabetes, however, may be treated with basal or prandial insulins plus oral agents or with combinations of the two insulins When starting a basal insulin regimen, patients should add a single evening dose 10 U or 01 U/kg at bedtime, whereas oral agents should be continued at their same dosages Insulin dose should be titrated according to fasting glucose concentration, and the dose may be increased 2 U every 3 to 5 days as needed to achieve glycemic control Premixed insulins, consisting of 70 NPH/30 regular, 75 lispro protamine/25
lispro, or 70 NPA/30 aspart,

are options to be given at dinner for some patients Insulin may be administered using standard syringes or with portable pens, which provide greater accuracy Although injection remains the standard mode of administration, inhaled rapid-acting insulin has recently become available This product may be used alone, with oral agents, or with longer-acting insulins Practitioners must allay common concerns about insulin, namely, that it is addictive and that its use will lead to type 1 diabetes Although insulin is often more convenient to use than oral agents, many patients fear self-administration of insulin and feel instinctively that its use signals the end stages of the disease By moving aggressively toward insulin administration, practitioners ensure that patients instead view insulin as an expedient tool to attain glycemic control

Resources for Patients and Practitioners
Numerous resources regarding the management of type 2 diabetes and the maintenance of cardiovascular and metabolic health are available for patients and healthcare practitioners Table 6 lists various online resources, including their web addresses and their special
features

Conclusion
The Expert Panel endorses an approach to diabetes management that includes aggressive treat-to-target strategies and involves patients in the process of their disease management as early as possible At the first sign of risk factors, practitioners should suggest lifestyle changes designed to prevent the onset of diabetes and CVD Because patients must ultimately assume an active role in monitoring their daily conditions, education from a team of qualified practitioners is a vital component of disease management Each case of diabetes is unique, and practitioners must monitor progress and modify interventions as necessary Type 2 diabetes is a progressive disease that will likely require insulin use; therefore, patients should be made comfortable with this inevitability By using this approach, risk for future CVD can be reduced and quality of life can be enhanced for patients living with this disease I

Faculty Disclosures
Mitchell King, MD, reports no conflict of interest G Allen Crist, DO, FAAFP CAQG, reports stock ownership in Pfizer , Mark Molitch, MD, has received grant support from Sanofi-Aventis and Amgen, serves on the speakers bureaus for Sanofi-Aventis,
Merck Co, and Abbott Laboratories, and is a consultant for Sanofi-Aventis, Abbott, and Pfizer Terry Ridge, MSN, APRN-BC, BC-ADM, serves on the speakersbureaus for Amylin Pharmaceuticals, Novartis, Eli Lilly, and Pfizer

For Continuing Nursing Education Credit: Go to: https://wwwnurseslearningcom/courses/make_test2cfm?CourseKey3940

TABLE 6

ONLINE RESOURCES FOR PATIENTS AND PROVIDERS
URL
wwwdiabetesorg

Organization
American Diabetes Association

Resources
General information about diabetes Nutrition and recipes Weight loss/ exercise strategies Preventive tools risk calculators Current statistics and research findings Nutrition fact sheets and information Registered dietitian locator Professional development materials Healthy lifestyle patient materials Culturally-appropriate tools and information Discussion of CVD warning signs Information on lipidemias, diabetes, hypertension Weight-Control Information Network diet and physical activity guidelines; obesity-related clinical trials and research; Spanish language format National Diabetes Information Clearinghouse 100 publications, including easy-to-read and Spanish language Resources geared toward parents, children,
high-risk ethnic populations Multiple language formats Spanish, Asian, Pacific Islander Patient education tools for providers Detailed dietary guidelines Personalized meal plans and calculators Diet quality and activity level assessment tools Guidelines for exercise and diabetes Networking and support Goal-setting guidelines

American Dietetic Association

wwweatrightorg

American Heart Association

wwwamericanheartorg

National Institute of Diabetes and Digestive and Kidney Diseases

wwwniddknihgov

National Diabetes Education Program

wwwndepnihgov

US Department of Agriculture; Center for Nutrition Policy and Promotion

wwwpyramidgov

Diabetes Exercise and Sports Association

wwwdiabetes-exerciseorg/indexasp

Partnership for Healthy Weight Management DLife

wwwconsumergov/weightloss

wwwdlifecom

Resources for persons with diabetes nutrition, blood sugar management Personalized meal manager Support forums

Copyright NPHF 2007

References
1 American Diabetes Association Diabetes Statistics Available at: http://wwwdiabetesorg/ diabetes-statisticsjsp 2 American Diabetes Association Diagnosis and classification of diabetes mellitus Diabetes Care 2007;30suppl 1:S42-S47 3
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